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High-intensity statins may cut risk of joint replacement
TORONTO – comparing nearly 180,000 statin users with an equal number of propensity-matched nonusers, Jie Wei, PhD, reported at the OARSI 2019 World Congress.
Less intensive statin therapy was associated with significantly less need for joint replacement surgery in rheumatoid arthritis patients, but not in those with osteoarthritis, she said at the meeting, sponsored by the Osteoarthritis Research Society International.
“In summary, statins may reduce the risk of joint replacement, especially when given at high strength and in people with rheumatoid arthritis,” said Dr. Wei, an epidemiologist at Massachusetts General Hospital, Boston, and Central South University in Changsha, Hunan, China.
She was quick to note that this study can’t be considered the final, definitive word on the topic, since other investigators’ studies of the relationship between statin usage and joint replacement surgery for arthritis have yielded conflicting results. However, given the thoroughly established super-favorable risk/benefit ratio of statins for the prevention of cardiovascular morbidity and mortality, the possibility of a prospective, randomized, controlled trial addressing the joint surgery issue is for ethical reasons a train that’s left the station.
Dr. Wei presented an analysis drawn from the U.K. Clinical Practice Research Datalink for the years 1989 through mid-2017. The initial sample included the medical records of 17.1 million patients, or 26% of the total U.K. population. From that massive pool, she and her coinvestigators zeroed in on 178,467 statin users and an equal number of non–statin-user controls under the care of 718 primary care physicians, with the pairs propensity score-matched on the basis of age, gender, locality, comorbid conditions, nonstatin medications, lifestyle factors, and duration of rheumatoid arthritis or osteoarthritis. The mean age of the matched pairs was 62 years, 52% were women, and the mean prospective follow-up was 6.5 years.
The use of high-intensity statin therapy – for example, atorvastatin at 40-80 mg/day or rosuvastatin (Crestor) at 20-40 mg/day – was independently associated with a 21% reduction in the risk of knee or hip replacement surgery for osteoarthritis and a 90% reduction for rheumatoid arthritis, compared with statin nonusers. Notably, joint replacement surgery for osteoarthritis was roughly 25-fold more common than for rheumatoid arthritis.
Statin therapy overall, including the more widely prescribed low- and intermediate-intensity regimens, was associated with a 23% reduction in joint replacement surgery for rheumatoid arthritis, compared with statin nonusers, but had no significant impact on surgery for the osteoarthritis population.
A couple of distinguished American rheumatologists in the audience rose to voice reluctance about drawing broad conclusions from this study.
“Bias, as you’ve said yourself, is a bit of a concern,” said David T. Felson, MD, professor of medicine and public health and director of clinical epidemiology at Boston University.
He was troubled that the study design was such that anyone who filled as few as two statin prescriptions during the more than 6-year study period was categorized as a statin user. That, he said, muddies the waters. Does the database contain information on duration of statin therapy, and whether joint replacement surgery was more likely to occur when patients were on or off statin therapy? he asked.
It does, Dr. Wei replied, adding that she will take that suggestion for additional analysis back to her international team of coinvestigators.
“It seems to me,” said Jeffrey N. Katz, MD, “that the major risk of potential bias is that people who were provided high-intensity statins were prescribed that because they were at risk for or had cardiac disease.”
That high cardiovascular risk might have curbed orthopedic surgeons’ enthusiasm to operate. Thus, it would be helpful to learn whether patients who underwent joint replacement were less likely to have undergone coronary revascularization or other cardiac interventions than were those without joint replacement, according to Dr. Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.
Dr. Wei agreed that confounding by indication is always a possibility in an observational study such as this. Identification of a plausible mechanism by which statins might reduce the risk of joint replacement surgery in rheumatoid arthritis – something that hasn’t happened yet – would help counter such concerns.
She noted that a separate recent analysis of the U.K. Clinical Practice Research Datalink by other investigators concluded that statin therapy started up to 5 years following total hip or knee replacement was associated with a significantly reduced risk of revision arthroplasty. Moreover, the benefit was treatment duration-dependent: Patients on statin therapy for more than 5 years were 26% less likely to undergo revision arthroplasty than were those on a statin for less than 1 year (J Rheumatol. 2019 Mar 15. doi: 10.3899/jrheum.180574).
On the other hand, Swedish investigators found that statin use wasn’t associated with a reduced risk of consultation or surgery for osteoarthritis in a pooled analysis of four cohort studies totaling more than 132,000 Swedes followed for 7.5 years (Osteoarthritis Cartilage. 2017 Nov;25[11]:1804-13).
Dr. Wei reported having no financial conflicts regarding the study, which was supported by the National Clinical Research Center of Geriatric Disorders in Hunan, China, and several British universities.
SOURCE: Sarmanova A et al. Osteoarthritis cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.
TORONTO – comparing nearly 180,000 statin users with an equal number of propensity-matched nonusers, Jie Wei, PhD, reported at the OARSI 2019 World Congress.
Less intensive statin therapy was associated with significantly less need for joint replacement surgery in rheumatoid arthritis patients, but not in those with osteoarthritis, she said at the meeting, sponsored by the Osteoarthritis Research Society International.
“In summary, statins may reduce the risk of joint replacement, especially when given at high strength and in people with rheumatoid arthritis,” said Dr. Wei, an epidemiologist at Massachusetts General Hospital, Boston, and Central South University in Changsha, Hunan, China.
She was quick to note that this study can’t be considered the final, definitive word on the topic, since other investigators’ studies of the relationship between statin usage and joint replacement surgery for arthritis have yielded conflicting results. However, given the thoroughly established super-favorable risk/benefit ratio of statins for the prevention of cardiovascular morbidity and mortality, the possibility of a prospective, randomized, controlled trial addressing the joint surgery issue is for ethical reasons a train that’s left the station.
Dr. Wei presented an analysis drawn from the U.K. Clinical Practice Research Datalink for the years 1989 through mid-2017. The initial sample included the medical records of 17.1 million patients, or 26% of the total U.K. population. From that massive pool, she and her coinvestigators zeroed in on 178,467 statin users and an equal number of non–statin-user controls under the care of 718 primary care physicians, with the pairs propensity score-matched on the basis of age, gender, locality, comorbid conditions, nonstatin medications, lifestyle factors, and duration of rheumatoid arthritis or osteoarthritis. The mean age of the matched pairs was 62 years, 52% were women, and the mean prospective follow-up was 6.5 years.
The use of high-intensity statin therapy – for example, atorvastatin at 40-80 mg/day or rosuvastatin (Crestor) at 20-40 mg/day – was independently associated with a 21% reduction in the risk of knee or hip replacement surgery for osteoarthritis and a 90% reduction for rheumatoid arthritis, compared with statin nonusers. Notably, joint replacement surgery for osteoarthritis was roughly 25-fold more common than for rheumatoid arthritis.
Statin therapy overall, including the more widely prescribed low- and intermediate-intensity regimens, was associated with a 23% reduction in joint replacement surgery for rheumatoid arthritis, compared with statin nonusers, but had no significant impact on surgery for the osteoarthritis population.
A couple of distinguished American rheumatologists in the audience rose to voice reluctance about drawing broad conclusions from this study.
“Bias, as you’ve said yourself, is a bit of a concern,” said David T. Felson, MD, professor of medicine and public health and director of clinical epidemiology at Boston University.
He was troubled that the study design was such that anyone who filled as few as two statin prescriptions during the more than 6-year study period was categorized as a statin user. That, he said, muddies the waters. Does the database contain information on duration of statin therapy, and whether joint replacement surgery was more likely to occur when patients were on or off statin therapy? he asked.
It does, Dr. Wei replied, adding that she will take that suggestion for additional analysis back to her international team of coinvestigators.
“It seems to me,” said Jeffrey N. Katz, MD, “that the major risk of potential bias is that people who were provided high-intensity statins were prescribed that because they were at risk for or had cardiac disease.”
That high cardiovascular risk might have curbed orthopedic surgeons’ enthusiasm to operate. Thus, it would be helpful to learn whether patients who underwent joint replacement were less likely to have undergone coronary revascularization or other cardiac interventions than were those without joint replacement, according to Dr. Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.
Dr. Wei agreed that confounding by indication is always a possibility in an observational study such as this. Identification of a plausible mechanism by which statins might reduce the risk of joint replacement surgery in rheumatoid arthritis – something that hasn’t happened yet – would help counter such concerns.
She noted that a separate recent analysis of the U.K. Clinical Practice Research Datalink by other investigators concluded that statin therapy started up to 5 years following total hip or knee replacement was associated with a significantly reduced risk of revision arthroplasty. Moreover, the benefit was treatment duration-dependent: Patients on statin therapy for more than 5 years were 26% less likely to undergo revision arthroplasty than were those on a statin for less than 1 year (J Rheumatol. 2019 Mar 15. doi: 10.3899/jrheum.180574).
On the other hand, Swedish investigators found that statin use wasn’t associated with a reduced risk of consultation or surgery for osteoarthritis in a pooled analysis of four cohort studies totaling more than 132,000 Swedes followed for 7.5 years (Osteoarthritis Cartilage. 2017 Nov;25[11]:1804-13).
Dr. Wei reported having no financial conflicts regarding the study, which was supported by the National Clinical Research Center of Geriatric Disorders in Hunan, China, and several British universities.
SOURCE: Sarmanova A et al. Osteoarthritis cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.
TORONTO – comparing nearly 180,000 statin users with an equal number of propensity-matched nonusers, Jie Wei, PhD, reported at the OARSI 2019 World Congress.
Less intensive statin therapy was associated with significantly less need for joint replacement surgery in rheumatoid arthritis patients, but not in those with osteoarthritis, she said at the meeting, sponsored by the Osteoarthritis Research Society International.
“In summary, statins may reduce the risk of joint replacement, especially when given at high strength and in people with rheumatoid arthritis,” said Dr. Wei, an epidemiologist at Massachusetts General Hospital, Boston, and Central South University in Changsha, Hunan, China.
She was quick to note that this study can’t be considered the final, definitive word on the topic, since other investigators’ studies of the relationship between statin usage and joint replacement surgery for arthritis have yielded conflicting results. However, given the thoroughly established super-favorable risk/benefit ratio of statins for the prevention of cardiovascular morbidity and mortality, the possibility of a prospective, randomized, controlled trial addressing the joint surgery issue is for ethical reasons a train that’s left the station.
Dr. Wei presented an analysis drawn from the U.K. Clinical Practice Research Datalink for the years 1989 through mid-2017. The initial sample included the medical records of 17.1 million patients, or 26% of the total U.K. population. From that massive pool, she and her coinvestigators zeroed in on 178,467 statin users and an equal number of non–statin-user controls under the care of 718 primary care physicians, with the pairs propensity score-matched on the basis of age, gender, locality, comorbid conditions, nonstatin medications, lifestyle factors, and duration of rheumatoid arthritis or osteoarthritis. The mean age of the matched pairs was 62 years, 52% were women, and the mean prospective follow-up was 6.5 years.
The use of high-intensity statin therapy – for example, atorvastatin at 40-80 mg/day or rosuvastatin (Crestor) at 20-40 mg/day – was independently associated with a 21% reduction in the risk of knee or hip replacement surgery for osteoarthritis and a 90% reduction for rheumatoid arthritis, compared with statin nonusers. Notably, joint replacement surgery for osteoarthritis was roughly 25-fold more common than for rheumatoid arthritis.
Statin therapy overall, including the more widely prescribed low- and intermediate-intensity regimens, was associated with a 23% reduction in joint replacement surgery for rheumatoid arthritis, compared with statin nonusers, but had no significant impact on surgery for the osteoarthritis population.
A couple of distinguished American rheumatologists in the audience rose to voice reluctance about drawing broad conclusions from this study.
“Bias, as you’ve said yourself, is a bit of a concern,” said David T. Felson, MD, professor of medicine and public health and director of clinical epidemiology at Boston University.
He was troubled that the study design was such that anyone who filled as few as two statin prescriptions during the more than 6-year study period was categorized as a statin user. That, he said, muddies the waters. Does the database contain information on duration of statin therapy, and whether joint replacement surgery was more likely to occur when patients were on or off statin therapy? he asked.
It does, Dr. Wei replied, adding that she will take that suggestion for additional analysis back to her international team of coinvestigators.
“It seems to me,” said Jeffrey N. Katz, MD, “that the major risk of potential bias is that people who were provided high-intensity statins were prescribed that because they were at risk for or had cardiac disease.”
That high cardiovascular risk might have curbed orthopedic surgeons’ enthusiasm to operate. Thus, it would be helpful to learn whether patients who underwent joint replacement were less likely to have undergone coronary revascularization or other cardiac interventions than were those without joint replacement, according to Dr. Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.
Dr. Wei agreed that confounding by indication is always a possibility in an observational study such as this. Identification of a plausible mechanism by which statins might reduce the risk of joint replacement surgery in rheumatoid arthritis – something that hasn’t happened yet – would help counter such concerns.
She noted that a separate recent analysis of the U.K. Clinical Practice Research Datalink by other investigators concluded that statin therapy started up to 5 years following total hip or knee replacement was associated with a significantly reduced risk of revision arthroplasty. Moreover, the benefit was treatment duration-dependent: Patients on statin therapy for more than 5 years were 26% less likely to undergo revision arthroplasty than were those on a statin for less than 1 year (J Rheumatol. 2019 Mar 15. doi: 10.3899/jrheum.180574).
On the other hand, Swedish investigators found that statin use wasn’t associated with a reduced risk of consultation or surgery for osteoarthritis in a pooled analysis of four cohort studies totaling more than 132,000 Swedes followed for 7.5 years (Osteoarthritis Cartilage. 2017 Nov;25[11]:1804-13).
Dr. Wei reported having no financial conflicts regarding the study, which was supported by the National Clinical Research Center of Geriatric Disorders in Hunan, China, and several British universities.
SOURCE: Sarmanova A et al. Osteoarthritis cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.
REPORTING FROM OARSI 2019
Key clinical point: High-intensity statin therapy may reduce need for joint replacement in arthritis.
Major finding: The risk of knee or hip replacement surgery for rheumatoid arthritis was slashed by 90%, and by 21% for osteoarthritis.
Study details: This study included nearly 180,000 statin users propensity score-matched to an equal number of nonusers and prospectively followed for a mean of 6.5 years.
Disclosures: The study was supported by the National Clinical Research Center of Geriatric Disorders at Central South University in Hunan, China, and by several British universities. The presenter reported having no financial conflicts of interest.
Source: Sarmanova A et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S78-S79. Abstract 77.
Walk-in ultrasound helps to avoid unnecessary steroids for giant cell arteritis
BIRMINGHAM, England – More than half of all patients referred to a fast-track giant cell arteritis (GCA) clinic that offers a walk-in ultrasonography service avoided use of glucocorticoids, according to a report given at the annual conference of the British Society for Rheumatology.
The clinic, an initiative run by the University Hospital Coventry and Warwickshire (UHCW) NHS Trust for the past 6 years, provides same-day diagnosis and treatment for suspected GCA.
“Walk-in ultrasound helps to avoid steroids completely in a significant proportion of patients,” said study author and presenter Shirish Dubey, MBBS, a consultant rheumatologist at the UHCW NHS Trust. Of 652 patients seen at the UHCW GCA fast-track clinic between 2014 and 2017, 143 (22%) were diagnosed with GCA. Over 400 had not been exposed to glucocorticoids and 369 (57%) were able to avoid unnecessary glucocorticoid use in the cohort, Dr. Dubey reported.
The old NHS paradigm for managing patients with suspected GCA was that when they presented to their primary care physicians, they would be started on immediate glucocorticoid therapy while waiting for an urgent specialist referral. However, that referral could take anywhere from a couple of days to a couple of weeks to happen, Dr. Dubey explained. Patients would then undergo possible temporal artery biopsy (TAB) and only then, following confirmation of a GCA diagnosis, would a management plan be agreed upon.
UCHW introduced its fast-track pathway for the diagnosis of GCA in mid-2013. The pathway called for patients with suspected GCA aged 50 years or older who had two or more features present, such as an abrupt, new-onset headache or facial pain, scalp pain and tenderness, jaw claudication, or visual symptoms. Primary care physicians could make urgent referrals to the service via an on-call rheumatology trainee or ophthalmology senior house officer.
“Patients are normally steroid-naive and seen on the same day,” Dr. Dubey said. Doppler ultrasound of the temporal artery results in around 80% of diagnoses, with TAB still needed in some cases.
One of the downsides of the fast-track process perhaps is the increasing number of referrals. “One thing we find is that we have become a glorified headache service,” Dr. Dubey said. However, many patients do not have GCA and, when there is a low clinical probability and the ultrasound is negative, the patient is usually reassured and discharged with no need for glucocorticoids. Although the number of referrals have increased – 98 patients in 2014, 154 in 2015, 123 in 2016, and 277 in 2017 – the number of those diagnosed with GCA has remained around the same.
To see how ultrasound was faring in real-life practice, the UHCW NHS Trust team compared Doppler ultrasound findings against the final clinical diagnosis for the period 2014 to 2017. A sensitivity of just under 48% and specificity of 98% was recorded. The positive and negative predictive values were 87% and 88%, respectively.
The specificity of ultrasound was lower than that reported previously in the literature, the UHCW NHS Trust team pointed out in its abstract, but it does compare similarly with other real-world studies. The use of glucocorticoids affected the ultrasound results, with better sensitivity (55%) when these drugs were not used prior to the scan.
The use of TAB versus a clinical diagnosis in 100 patients seen over the same time period showed it had a sensitivity of 37% and a specificity of 100%, with positive and negative predictive values of 100% and 62%. The sensitivity of TAB is again low, Dr. Dubey said, but that could be because TAB is performed only when the diagnosis is uncertain.
This was an unselected cohort of patients, but overall there were good positive and negative predictive values. The UHCW NHS Trust team suggested that ultrasound can assist and reassure clinicians trying to diagnose or exclude GCA in their patients.
Regular multidisciplinary team meetings including rheumatology, ophthalmology, and vascular Doppler physiologists are key to the fast-track service, Dr. Dubey pointed out.
Despite the shortcomings of the retrospective study, Dr. Dubey stressed that the team was confident that none of the patients who had been ruled out as having GCA were subsequently diagnosed as having GCA.
Importantly, he said, the use of ultrasound had made a big difference in cost; the group plans to formally evaluate costs of ultrasound versus TAB.
The study received no commercial funding. Dr. Dubey had no conflicts of interest to disclose.
SOURCE: Pinnell J et al. Rheumatology. 2019;58(suppl 3):Abstract 038.
BIRMINGHAM, England – More than half of all patients referred to a fast-track giant cell arteritis (GCA) clinic that offers a walk-in ultrasonography service avoided use of glucocorticoids, according to a report given at the annual conference of the British Society for Rheumatology.
The clinic, an initiative run by the University Hospital Coventry and Warwickshire (UHCW) NHS Trust for the past 6 years, provides same-day diagnosis and treatment for suspected GCA.
“Walk-in ultrasound helps to avoid steroids completely in a significant proportion of patients,” said study author and presenter Shirish Dubey, MBBS, a consultant rheumatologist at the UHCW NHS Trust. Of 652 patients seen at the UHCW GCA fast-track clinic between 2014 and 2017, 143 (22%) were diagnosed with GCA. Over 400 had not been exposed to glucocorticoids and 369 (57%) were able to avoid unnecessary glucocorticoid use in the cohort, Dr. Dubey reported.
The old NHS paradigm for managing patients with suspected GCA was that when they presented to their primary care physicians, they would be started on immediate glucocorticoid therapy while waiting for an urgent specialist referral. However, that referral could take anywhere from a couple of days to a couple of weeks to happen, Dr. Dubey explained. Patients would then undergo possible temporal artery biopsy (TAB) and only then, following confirmation of a GCA diagnosis, would a management plan be agreed upon.
UCHW introduced its fast-track pathway for the diagnosis of GCA in mid-2013. The pathway called for patients with suspected GCA aged 50 years or older who had two or more features present, such as an abrupt, new-onset headache or facial pain, scalp pain and tenderness, jaw claudication, or visual symptoms. Primary care physicians could make urgent referrals to the service via an on-call rheumatology trainee or ophthalmology senior house officer.
“Patients are normally steroid-naive and seen on the same day,” Dr. Dubey said. Doppler ultrasound of the temporal artery results in around 80% of diagnoses, with TAB still needed in some cases.
One of the downsides of the fast-track process perhaps is the increasing number of referrals. “One thing we find is that we have become a glorified headache service,” Dr. Dubey said. However, many patients do not have GCA and, when there is a low clinical probability and the ultrasound is negative, the patient is usually reassured and discharged with no need for glucocorticoids. Although the number of referrals have increased – 98 patients in 2014, 154 in 2015, 123 in 2016, and 277 in 2017 – the number of those diagnosed with GCA has remained around the same.
To see how ultrasound was faring in real-life practice, the UHCW NHS Trust team compared Doppler ultrasound findings against the final clinical diagnosis for the period 2014 to 2017. A sensitivity of just under 48% and specificity of 98% was recorded. The positive and negative predictive values were 87% and 88%, respectively.
The specificity of ultrasound was lower than that reported previously in the literature, the UHCW NHS Trust team pointed out in its abstract, but it does compare similarly with other real-world studies. The use of glucocorticoids affected the ultrasound results, with better sensitivity (55%) when these drugs were not used prior to the scan.
The use of TAB versus a clinical diagnosis in 100 patients seen over the same time period showed it had a sensitivity of 37% and a specificity of 100%, with positive and negative predictive values of 100% and 62%. The sensitivity of TAB is again low, Dr. Dubey said, but that could be because TAB is performed only when the diagnosis is uncertain.
This was an unselected cohort of patients, but overall there were good positive and negative predictive values. The UHCW NHS Trust team suggested that ultrasound can assist and reassure clinicians trying to diagnose or exclude GCA in their patients.
Regular multidisciplinary team meetings including rheumatology, ophthalmology, and vascular Doppler physiologists are key to the fast-track service, Dr. Dubey pointed out.
Despite the shortcomings of the retrospective study, Dr. Dubey stressed that the team was confident that none of the patients who had been ruled out as having GCA were subsequently diagnosed as having GCA.
Importantly, he said, the use of ultrasound had made a big difference in cost; the group plans to formally evaluate costs of ultrasound versus TAB.
The study received no commercial funding. Dr. Dubey had no conflicts of interest to disclose.
SOURCE: Pinnell J et al. Rheumatology. 2019;58(suppl 3):Abstract 038.
BIRMINGHAM, England – More than half of all patients referred to a fast-track giant cell arteritis (GCA) clinic that offers a walk-in ultrasonography service avoided use of glucocorticoids, according to a report given at the annual conference of the British Society for Rheumatology.
The clinic, an initiative run by the University Hospital Coventry and Warwickshire (UHCW) NHS Trust for the past 6 years, provides same-day diagnosis and treatment for suspected GCA.
“Walk-in ultrasound helps to avoid steroids completely in a significant proportion of patients,” said study author and presenter Shirish Dubey, MBBS, a consultant rheumatologist at the UHCW NHS Trust. Of 652 patients seen at the UHCW GCA fast-track clinic between 2014 and 2017, 143 (22%) were diagnosed with GCA. Over 400 had not been exposed to glucocorticoids and 369 (57%) were able to avoid unnecessary glucocorticoid use in the cohort, Dr. Dubey reported.
The old NHS paradigm for managing patients with suspected GCA was that when they presented to their primary care physicians, they would be started on immediate glucocorticoid therapy while waiting for an urgent specialist referral. However, that referral could take anywhere from a couple of days to a couple of weeks to happen, Dr. Dubey explained. Patients would then undergo possible temporal artery biopsy (TAB) and only then, following confirmation of a GCA diagnosis, would a management plan be agreed upon.
UCHW introduced its fast-track pathway for the diagnosis of GCA in mid-2013. The pathway called for patients with suspected GCA aged 50 years or older who had two or more features present, such as an abrupt, new-onset headache or facial pain, scalp pain and tenderness, jaw claudication, or visual symptoms. Primary care physicians could make urgent referrals to the service via an on-call rheumatology trainee or ophthalmology senior house officer.
“Patients are normally steroid-naive and seen on the same day,” Dr. Dubey said. Doppler ultrasound of the temporal artery results in around 80% of diagnoses, with TAB still needed in some cases.
One of the downsides of the fast-track process perhaps is the increasing number of referrals. “One thing we find is that we have become a glorified headache service,” Dr. Dubey said. However, many patients do not have GCA and, when there is a low clinical probability and the ultrasound is negative, the patient is usually reassured and discharged with no need for glucocorticoids. Although the number of referrals have increased – 98 patients in 2014, 154 in 2015, 123 in 2016, and 277 in 2017 – the number of those diagnosed with GCA has remained around the same.
To see how ultrasound was faring in real-life practice, the UHCW NHS Trust team compared Doppler ultrasound findings against the final clinical diagnosis for the period 2014 to 2017. A sensitivity of just under 48% and specificity of 98% was recorded. The positive and negative predictive values were 87% and 88%, respectively.
The specificity of ultrasound was lower than that reported previously in the literature, the UHCW NHS Trust team pointed out in its abstract, but it does compare similarly with other real-world studies. The use of glucocorticoids affected the ultrasound results, with better sensitivity (55%) when these drugs were not used prior to the scan.
The use of TAB versus a clinical diagnosis in 100 patients seen over the same time period showed it had a sensitivity of 37% and a specificity of 100%, with positive and negative predictive values of 100% and 62%. The sensitivity of TAB is again low, Dr. Dubey said, but that could be because TAB is performed only when the diagnosis is uncertain.
This was an unselected cohort of patients, but overall there were good positive and negative predictive values. The UHCW NHS Trust team suggested that ultrasound can assist and reassure clinicians trying to diagnose or exclude GCA in their patients.
Regular multidisciplinary team meetings including rheumatology, ophthalmology, and vascular Doppler physiologists are key to the fast-track service, Dr. Dubey pointed out.
Despite the shortcomings of the retrospective study, Dr. Dubey stressed that the team was confident that none of the patients who had been ruled out as having GCA were subsequently diagnosed as having GCA.
Importantly, he said, the use of ultrasound had made a big difference in cost; the group plans to formally evaluate costs of ultrasound versus TAB.
The study received no commercial funding. Dr. Dubey had no conflicts of interest to disclose.
SOURCE: Pinnell J et al. Rheumatology. 2019;58(suppl 3):Abstract 038.
REPORTING FROM BSR 2019
VA system lags in getting DMARDs to veterans with inflammatory arthritis
MADISON, WISC. – Only half of United States veterans with inflammatory arthritis received disease-modifying medication within 90 days of diagnosis if they received care within the Veterans Health Administration, according to a study presented at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
Over the study period, 58.2% of all inflammatory arthritis patients began a disease-modifying antirheumatic drug (DMARD) within 12 months of diagnosis. Rates of DMARD initiation were similar for patients with rheumatoid arthritis (RA, 57.7%) and psoriatic arthritis (PsA, 64.3%), said the first author of the poster presentation, Sogol S. Amjadi, DO, a resident physician at Bingham Memorial Hospital, Blackfoot, Idaho.
However, at 12 months after diagnosis, only 29.6% of ankylosing spondylitis (AS) patients had not been started on a DMARD. “The ankylosing spondylitis group really had the lowest DMARD initiation over time,” said Dr. Amjadi in an interview.
The study used diagnosis codes and natural language processing to look for incident cases of the three inflammatory arthritides (IAs) among patients receiving care within the Veterans Health Administration from 2007 through 2015.
In all, 12,118 patients with incident IA were identified. Of these, 9,711 had RA, 1,472 had PsA, and 935 had AS. Patients were mostly (91.3%) male, with a mean age of 63.7 years.
Over the study period, 41.2% of IA patients were dispensed a DMARD within 30 days of diagnosis, and 50% received a DMARD within 90 days of diagnosis. Patients with PsA or RA had similar rates of DMARD prescription within 30 days of diagnosis (about 42% and 43%, respectively).
The investigators discovered in their analysis that another factor in prompt treatment was access to specialty care.“Timely access to a rheumatology provider is likely important for early DMARD treatment,” wrote Dr. Amjadi and her coauthors in the poster accompanying the presentation. Of patients who did receive a DMARD, 82.7% had received rheumatology specialty care before nonbiologic DMARD dispensing, as had 90.0% of patients receiving biologic DMARDs. Over the entire study period, about 10% of all IA patients had biologic DMARD exposure.
There was a trend over time for increased DMARD dispensing, said the investigators. “The percentage of IA patients with DMARD exposure during the 12-month follow-up period increased from 48.8% in 2008 to 66.4% in 2015.”
For AS patients, early DMARD prescribing rates rose from about 20% in 2007 to nearly 30% in 2015. “DMARD treatment rates during the initial 12 months after diagnosis increased between 2007 and 2015, but nontreatment remained common, particularly in patients with AS,” wrote the investigators. “Delays in treatment for inflammatory arthritis are associated with unfavorable outcomes, including impaired quality of life, irreversible joint damage, and disability.”
The authors reported no conflicts of interest and no outside sources of funding.
MADISON, WISC. – Only half of United States veterans with inflammatory arthritis received disease-modifying medication within 90 days of diagnosis if they received care within the Veterans Health Administration, according to a study presented at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
Over the study period, 58.2% of all inflammatory arthritis patients began a disease-modifying antirheumatic drug (DMARD) within 12 months of diagnosis. Rates of DMARD initiation were similar for patients with rheumatoid arthritis (RA, 57.7%) and psoriatic arthritis (PsA, 64.3%), said the first author of the poster presentation, Sogol S. Amjadi, DO, a resident physician at Bingham Memorial Hospital, Blackfoot, Idaho.
However, at 12 months after diagnosis, only 29.6% of ankylosing spondylitis (AS) patients had not been started on a DMARD. “The ankylosing spondylitis group really had the lowest DMARD initiation over time,” said Dr. Amjadi in an interview.
The study used diagnosis codes and natural language processing to look for incident cases of the three inflammatory arthritides (IAs) among patients receiving care within the Veterans Health Administration from 2007 through 2015.
In all, 12,118 patients with incident IA were identified. Of these, 9,711 had RA, 1,472 had PsA, and 935 had AS. Patients were mostly (91.3%) male, with a mean age of 63.7 years.
Over the study period, 41.2% of IA patients were dispensed a DMARD within 30 days of diagnosis, and 50% received a DMARD within 90 days of diagnosis. Patients with PsA or RA had similar rates of DMARD prescription within 30 days of diagnosis (about 42% and 43%, respectively).
The investigators discovered in their analysis that another factor in prompt treatment was access to specialty care.“Timely access to a rheumatology provider is likely important for early DMARD treatment,” wrote Dr. Amjadi and her coauthors in the poster accompanying the presentation. Of patients who did receive a DMARD, 82.7% had received rheumatology specialty care before nonbiologic DMARD dispensing, as had 90.0% of patients receiving biologic DMARDs. Over the entire study period, about 10% of all IA patients had biologic DMARD exposure.
There was a trend over time for increased DMARD dispensing, said the investigators. “The percentage of IA patients with DMARD exposure during the 12-month follow-up period increased from 48.8% in 2008 to 66.4% in 2015.”
For AS patients, early DMARD prescribing rates rose from about 20% in 2007 to nearly 30% in 2015. “DMARD treatment rates during the initial 12 months after diagnosis increased between 2007 and 2015, but nontreatment remained common, particularly in patients with AS,” wrote the investigators. “Delays in treatment for inflammatory arthritis are associated with unfavorable outcomes, including impaired quality of life, irreversible joint damage, and disability.”
The authors reported no conflicts of interest and no outside sources of funding.
MADISON, WISC. – Only half of United States veterans with inflammatory arthritis received disease-modifying medication within 90 days of diagnosis if they received care within the Veterans Health Administration, according to a study presented at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
Over the study period, 58.2% of all inflammatory arthritis patients began a disease-modifying antirheumatic drug (DMARD) within 12 months of diagnosis. Rates of DMARD initiation were similar for patients with rheumatoid arthritis (RA, 57.7%) and psoriatic arthritis (PsA, 64.3%), said the first author of the poster presentation, Sogol S. Amjadi, DO, a resident physician at Bingham Memorial Hospital, Blackfoot, Idaho.
However, at 12 months after diagnosis, only 29.6% of ankylosing spondylitis (AS) patients had not been started on a DMARD. “The ankylosing spondylitis group really had the lowest DMARD initiation over time,” said Dr. Amjadi in an interview.
The study used diagnosis codes and natural language processing to look for incident cases of the three inflammatory arthritides (IAs) among patients receiving care within the Veterans Health Administration from 2007 through 2015.
In all, 12,118 patients with incident IA were identified. Of these, 9,711 had RA, 1,472 had PsA, and 935 had AS. Patients were mostly (91.3%) male, with a mean age of 63.7 years.
Over the study period, 41.2% of IA patients were dispensed a DMARD within 30 days of diagnosis, and 50% received a DMARD within 90 days of diagnosis. Patients with PsA or RA had similar rates of DMARD prescription within 30 days of diagnosis (about 42% and 43%, respectively).
The investigators discovered in their analysis that another factor in prompt treatment was access to specialty care.“Timely access to a rheumatology provider is likely important for early DMARD treatment,” wrote Dr. Amjadi and her coauthors in the poster accompanying the presentation. Of patients who did receive a DMARD, 82.7% had received rheumatology specialty care before nonbiologic DMARD dispensing, as had 90.0% of patients receiving biologic DMARDs. Over the entire study period, about 10% of all IA patients had biologic DMARD exposure.
There was a trend over time for increased DMARD dispensing, said the investigators. “The percentage of IA patients with DMARD exposure during the 12-month follow-up period increased from 48.8% in 2008 to 66.4% in 2015.”
For AS patients, early DMARD prescribing rates rose from about 20% in 2007 to nearly 30% in 2015. “DMARD treatment rates during the initial 12 months after diagnosis increased between 2007 and 2015, but nontreatment remained common, particularly in patients with AS,” wrote the investigators. “Delays in treatment for inflammatory arthritis are associated with unfavorable outcomes, including impaired quality of life, irreversible joint damage, and disability.”
The authors reported no conflicts of interest and no outside sources of funding.
REPORTING FROM SPARTAN 2019
Key clinical point:
Major finding: Overall, 58.2% of inflammatory arthritis patients received a DMARD within the first year of diagnosis.
Study details: Retrospective review of 12,118 incident cases of inflammatory arthritis in the Veterans Health Administration during the period from 2007 through 2015.
Disclosures: The authors reported no conflicts of interest and no outside sources of funding.
Source: Amjadi SS et al. SPARTAN 2019.
Emerging data support anabolic-first regimens for severe osteoporosis
LOS ANGELES – In the opinion of Felicia Cosman, MD, the current state of osteoporosis treatment is fraught with clinical challenges.
First, most patients at highest risk for future fractures are not being treated. “In fact, fewer than 25% of patients with new clinical fractures are treated for their underlying disease,” Dr. Cosman, professor of medicine at Columbia University, New York, said at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists (AACE).
“One of the reasons doctors are not treating these patients is that many of them do not have a T-score in the osteoporosis range. There’s a misunderstanding here. A fracture that occurs in people with low bone mass in the setting of minimal trauma – such as a fall from standing height – meets the criteria for the clinical diagnosis of osteoporosis and qualifies a person for being at high risk of more fractures. This is likely because bone weakness or fragility is related not just to quantitative aspects, but also to structural and qualitative aspects that cannot be measured as easily.”
Another problem is that some of the highest-risk patients are those with a vertebral fracture. “However, vertebral fractures are particularly difficult to find and treat because they’re often asymptomatic and we’re not [identifying] these patients,” she said. “Targeted screening [with] spine imaging to find vertebral fractures is probably as important as BMD [bone mineral density] testing.”
To complicate matters, Dr. Cosman said that clinicians and patients “misunderstand the balance between benefits and risks of osteoporosis medications and they don’t consider the risk of not treating the underlying disease. Lastly, there’s little evidence to help guide long-term strategies. Guidelines across medical specialties are incredibly inconsistent. With the exception of guidelines from AACE, the one thing that they’re very consistent about is underrecognizing the value of anabolic therapy for people with severe osteoporosis.”
It is well known that previous bone fracture is the most important risk factor for a future fracture, but the recency of the fracture is also important. In a recent study, researchers followed 377,561 female Medicare beneficiaries with a first fracture for up to 5 years (Osteoporos Int. 2019;30[1]:79-92). They found that at 1 year, the risk of another fracture was 10%. The fracture risk rose to 18% at 2 years, and to 31% at 5 years. “I like to think of this as the osteoporosis emergency,” said Dr. Cosman, co–editor-in-chief of Osteoporosis International. “We need to treat these people right away to prevent more fractures and related disability, morbidity, and mortality.”
According to data from pivotal trials, the anabolic agents teriparatide, abaloparatide, and romosozumab appear to produce more rapid and larger effects against all fractures, compared with even the best antiresorptive agents. “However, comparing across studies can be problematic, because the different populations have varying baseline characteristics and different underlying risk,” Dr. Cosman said. “The protocols and the outcome definitions might be different. It’s better to compare anabolic agents with antiresorptive agents in head-to-head trials, and we now have a few of these.”
Two trials are older studies in which fracture outcomes were not the primary endpoints. One study evaluated a population of patients with glucocorticoid-induced osteoporosis and found that over 18 months, teriparatide reduced vertebral fractures by 90%, compared with alendronate (N Engl J Med. 2007;357[20]:2028-39). The other trial focused on a population of patients with acute, painful vertebral fractures. It found that over 1 year, teriparatide reduced vertebral fractures by 50%, compared with risedronate (Osteoporos Int. 2012;23[8]:2141-50). Two more recent studies compared anabolic and antiresorptive therapies on fracture outcomes as primary endpoints in patients with prevalent fractures. The VERO trial compared teriparatide with risedronate (Lancet. 2018;391[10117]:230-40), and ARCH compared romosozumab with alendronate (N Engl J Med. 2017;377[15]:1417-27).
In VERO, 1,360 patients with a prevalent vertebral fracture were randomized to receive teriparatide or risedronate for 2 years. At 12 months, the proportion of patients with a new vertebral fracture was 3.1% and 6% in the teriparatide and risedronate groups, respectively, a pattern that held true at 24 months (6.4% vs. 12%). The study also showed that the number of nonvertebral fractures was significantly lower in teriparatide-treated patients, compared with those on risedronate. In ARCH, 4,093 postmenopausal women at high risk of fracture were randomized to receive romosozumab or alendronate for 1 year and then followed for a median period of 33 months. At 12 months, the proportion of patients with a new vertebral fracture was 4% and 6.3% in the romosozumab and alendronate groups, respectively, a pattern that held true at 24 months (6.2% vs. 11.9%).
“These trials showed that the antifracture effects are faster and larger with anabolic agents, compared with antiresorptive agents,” Dr. Cosman said. “They also showed that antifracture effects are sustained after transition to antiresorptive therapy.” In ARCH, both nonvertebral and hip fracture incidences were lower in the romosozumab group, compared with the alendronate group.
The trials demonstrated that improving total hip BMD is associated with improved bone strength and resistance to fracture, yet treatment sequence matters. “The greatest BMD gains of the hip are seen when anabolic agents are used first-line, followed by a potent antiresorptive agent,” she said.
Dr. Cosman offered a strategy for patients on potent antiresorptive agents who need anabolic medication. In patients on bisphosphonates, especially with an incident hip fracture or very low hip BMD, consider combination therapy with initiation of teriparatide or abaloparatide, along with an antiresorptive agent. “There are very little data addressing patients on denosumab, but I would suggest perhaps adding teriparatide or abaloparatide in this population, and continuing denosumab,” she said. “That could lead to BMD gain. Switching to romosozumab might also be an option. But, if possible, use an anabolic agent first. The role of anabolic medication for osteoporosis is evolving as evidence continues to suggest superior benefit of anabolic-first regimens for high-risk patients.”
Dr. Cosman disclosed that she has received advising, consulting, and speaking fees from Amgen and Radius. She has received consulting fees from Tarsa and research grants and medication from Amgen.
LOS ANGELES – In the opinion of Felicia Cosman, MD, the current state of osteoporosis treatment is fraught with clinical challenges.
First, most patients at highest risk for future fractures are not being treated. “In fact, fewer than 25% of patients with new clinical fractures are treated for their underlying disease,” Dr. Cosman, professor of medicine at Columbia University, New York, said at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists (AACE).
“One of the reasons doctors are not treating these patients is that many of them do not have a T-score in the osteoporosis range. There’s a misunderstanding here. A fracture that occurs in people with low bone mass in the setting of minimal trauma – such as a fall from standing height – meets the criteria for the clinical diagnosis of osteoporosis and qualifies a person for being at high risk of more fractures. This is likely because bone weakness or fragility is related not just to quantitative aspects, but also to structural and qualitative aspects that cannot be measured as easily.”
Another problem is that some of the highest-risk patients are those with a vertebral fracture. “However, vertebral fractures are particularly difficult to find and treat because they’re often asymptomatic and we’re not [identifying] these patients,” she said. “Targeted screening [with] spine imaging to find vertebral fractures is probably as important as BMD [bone mineral density] testing.”
To complicate matters, Dr. Cosman said that clinicians and patients “misunderstand the balance between benefits and risks of osteoporosis medications and they don’t consider the risk of not treating the underlying disease. Lastly, there’s little evidence to help guide long-term strategies. Guidelines across medical specialties are incredibly inconsistent. With the exception of guidelines from AACE, the one thing that they’re very consistent about is underrecognizing the value of anabolic therapy for people with severe osteoporosis.”
It is well known that previous bone fracture is the most important risk factor for a future fracture, but the recency of the fracture is also important. In a recent study, researchers followed 377,561 female Medicare beneficiaries with a first fracture for up to 5 years (Osteoporos Int. 2019;30[1]:79-92). They found that at 1 year, the risk of another fracture was 10%. The fracture risk rose to 18% at 2 years, and to 31% at 5 years. “I like to think of this as the osteoporosis emergency,” said Dr. Cosman, co–editor-in-chief of Osteoporosis International. “We need to treat these people right away to prevent more fractures and related disability, morbidity, and mortality.”
According to data from pivotal trials, the anabolic agents teriparatide, abaloparatide, and romosozumab appear to produce more rapid and larger effects against all fractures, compared with even the best antiresorptive agents. “However, comparing across studies can be problematic, because the different populations have varying baseline characteristics and different underlying risk,” Dr. Cosman said. “The protocols and the outcome definitions might be different. It’s better to compare anabolic agents with antiresorptive agents in head-to-head trials, and we now have a few of these.”
Two trials are older studies in which fracture outcomes were not the primary endpoints. One study evaluated a population of patients with glucocorticoid-induced osteoporosis and found that over 18 months, teriparatide reduced vertebral fractures by 90%, compared with alendronate (N Engl J Med. 2007;357[20]:2028-39). The other trial focused on a population of patients with acute, painful vertebral fractures. It found that over 1 year, teriparatide reduced vertebral fractures by 50%, compared with risedronate (Osteoporos Int. 2012;23[8]:2141-50). Two more recent studies compared anabolic and antiresorptive therapies on fracture outcomes as primary endpoints in patients with prevalent fractures. The VERO trial compared teriparatide with risedronate (Lancet. 2018;391[10117]:230-40), and ARCH compared romosozumab with alendronate (N Engl J Med. 2017;377[15]:1417-27).
In VERO, 1,360 patients with a prevalent vertebral fracture were randomized to receive teriparatide or risedronate for 2 years. At 12 months, the proportion of patients with a new vertebral fracture was 3.1% and 6% in the teriparatide and risedronate groups, respectively, a pattern that held true at 24 months (6.4% vs. 12%). The study also showed that the number of nonvertebral fractures was significantly lower in teriparatide-treated patients, compared with those on risedronate. In ARCH, 4,093 postmenopausal women at high risk of fracture were randomized to receive romosozumab or alendronate for 1 year and then followed for a median period of 33 months. At 12 months, the proportion of patients with a new vertebral fracture was 4% and 6.3% in the romosozumab and alendronate groups, respectively, a pattern that held true at 24 months (6.2% vs. 11.9%).
“These trials showed that the antifracture effects are faster and larger with anabolic agents, compared with antiresorptive agents,” Dr. Cosman said. “They also showed that antifracture effects are sustained after transition to antiresorptive therapy.” In ARCH, both nonvertebral and hip fracture incidences were lower in the romosozumab group, compared with the alendronate group.
The trials demonstrated that improving total hip BMD is associated with improved bone strength and resistance to fracture, yet treatment sequence matters. “The greatest BMD gains of the hip are seen when anabolic agents are used first-line, followed by a potent antiresorptive agent,” she said.
Dr. Cosman offered a strategy for patients on potent antiresorptive agents who need anabolic medication. In patients on bisphosphonates, especially with an incident hip fracture or very low hip BMD, consider combination therapy with initiation of teriparatide or abaloparatide, along with an antiresorptive agent. “There are very little data addressing patients on denosumab, but I would suggest perhaps adding teriparatide or abaloparatide in this population, and continuing denosumab,” she said. “That could lead to BMD gain. Switching to romosozumab might also be an option. But, if possible, use an anabolic agent first. The role of anabolic medication for osteoporosis is evolving as evidence continues to suggest superior benefit of anabolic-first regimens for high-risk patients.”
Dr. Cosman disclosed that she has received advising, consulting, and speaking fees from Amgen and Radius. She has received consulting fees from Tarsa and research grants and medication from Amgen.
LOS ANGELES – In the opinion of Felicia Cosman, MD, the current state of osteoporosis treatment is fraught with clinical challenges.
First, most patients at highest risk for future fractures are not being treated. “In fact, fewer than 25% of patients with new clinical fractures are treated for their underlying disease,” Dr. Cosman, professor of medicine at Columbia University, New York, said at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists (AACE).
“One of the reasons doctors are not treating these patients is that many of them do not have a T-score in the osteoporosis range. There’s a misunderstanding here. A fracture that occurs in people with low bone mass in the setting of minimal trauma – such as a fall from standing height – meets the criteria for the clinical diagnosis of osteoporosis and qualifies a person for being at high risk of more fractures. This is likely because bone weakness or fragility is related not just to quantitative aspects, but also to structural and qualitative aspects that cannot be measured as easily.”
Another problem is that some of the highest-risk patients are those with a vertebral fracture. “However, vertebral fractures are particularly difficult to find and treat because they’re often asymptomatic and we’re not [identifying] these patients,” she said. “Targeted screening [with] spine imaging to find vertebral fractures is probably as important as BMD [bone mineral density] testing.”
To complicate matters, Dr. Cosman said that clinicians and patients “misunderstand the balance between benefits and risks of osteoporosis medications and they don’t consider the risk of not treating the underlying disease. Lastly, there’s little evidence to help guide long-term strategies. Guidelines across medical specialties are incredibly inconsistent. With the exception of guidelines from AACE, the one thing that they’re very consistent about is underrecognizing the value of anabolic therapy for people with severe osteoporosis.”
It is well known that previous bone fracture is the most important risk factor for a future fracture, but the recency of the fracture is also important. In a recent study, researchers followed 377,561 female Medicare beneficiaries with a first fracture for up to 5 years (Osteoporos Int. 2019;30[1]:79-92). They found that at 1 year, the risk of another fracture was 10%. The fracture risk rose to 18% at 2 years, and to 31% at 5 years. “I like to think of this as the osteoporosis emergency,” said Dr. Cosman, co–editor-in-chief of Osteoporosis International. “We need to treat these people right away to prevent more fractures and related disability, morbidity, and mortality.”
According to data from pivotal trials, the anabolic agents teriparatide, abaloparatide, and romosozumab appear to produce more rapid and larger effects against all fractures, compared with even the best antiresorptive agents. “However, comparing across studies can be problematic, because the different populations have varying baseline characteristics and different underlying risk,” Dr. Cosman said. “The protocols and the outcome definitions might be different. It’s better to compare anabolic agents with antiresorptive agents in head-to-head trials, and we now have a few of these.”
Two trials are older studies in which fracture outcomes were not the primary endpoints. One study evaluated a population of patients with glucocorticoid-induced osteoporosis and found that over 18 months, teriparatide reduced vertebral fractures by 90%, compared with alendronate (N Engl J Med. 2007;357[20]:2028-39). The other trial focused on a population of patients with acute, painful vertebral fractures. It found that over 1 year, teriparatide reduced vertebral fractures by 50%, compared with risedronate (Osteoporos Int. 2012;23[8]:2141-50). Two more recent studies compared anabolic and antiresorptive therapies on fracture outcomes as primary endpoints in patients with prevalent fractures. The VERO trial compared teriparatide with risedronate (Lancet. 2018;391[10117]:230-40), and ARCH compared romosozumab with alendronate (N Engl J Med. 2017;377[15]:1417-27).
In VERO, 1,360 patients with a prevalent vertebral fracture were randomized to receive teriparatide or risedronate for 2 years. At 12 months, the proportion of patients with a new vertebral fracture was 3.1% and 6% in the teriparatide and risedronate groups, respectively, a pattern that held true at 24 months (6.4% vs. 12%). The study also showed that the number of nonvertebral fractures was significantly lower in teriparatide-treated patients, compared with those on risedronate. In ARCH, 4,093 postmenopausal women at high risk of fracture were randomized to receive romosozumab or alendronate for 1 year and then followed for a median period of 33 months. At 12 months, the proportion of patients with a new vertebral fracture was 4% and 6.3% in the romosozumab and alendronate groups, respectively, a pattern that held true at 24 months (6.2% vs. 11.9%).
“These trials showed that the antifracture effects are faster and larger with anabolic agents, compared with antiresorptive agents,” Dr. Cosman said. “They also showed that antifracture effects are sustained after transition to antiresorptive therapy.” In ARCH, both nonvertebral and hip fracture incidences were lower in the romosozumab group, compared with the alendronate group.
The trials demonstrated that improving total hip BMD is associated with improved bone strength and resistance to fracture, yet treatment sequence matters. “The greatest BMD gains of the hip are seen when anabolic agents are used first-line, followed by a potent antiresorptive agent,” she said.
Dr. Cosman offered a strategy for patients on potent antiresorptive agents who need anabolic medication. In patients on bisphosphonates, especially with an incident hip fracture or very low hip BMD, consider combination therapy with initiation of teriparatide or abaloparatide, along with an antiresorptive agent. “There are very little data addressing patients on denosumab, but I would suggest perhaps adding teriparatide or abaloparatide in this population, and continuing denosumab,” she said. “That could lead to BMD gain. Switching to romosozumab might also be an option. But, if possible, use an anabolic agent first. The role of anabolic medication for osteoporosis is evolving as evidence continues to suggest superior benefit of anabolic-first regimens for high-risk patients.”
Dr. Cosman disclosed that she has received advising, consulting, and speaking fees from Amgen and Radius. She has received consulting fees from Tarsa and research grants and medication from Amgen.
EXPERT ANALYSIS FROM AACE 2019
Ankylosing spondylitis patients taking COX-2 inhibitors may see fewer cardiovascular events
MADISON, WISC. – Patients with ankylosing spondylitis had a small but significant reduction in risk for cardiovascular events if they were taking cyclooxygenase-2 (COX-2) inhibitors, according to a new systematic review and meta-analysis.
The reduced risk observed in this analysis (risk ratio, 0.48; 95% confidence interval, 0.33-0.70) contrasts with the increased risk for cardiovascular events seen with COX-2 inhibitor use in the general population, said Paras Karmacharya, MBBS, speaking in an interview at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN). The overall effect was highly statistically significant (P = .0001), and the finding provides “reassuring” data for a population that’s known to have an elevated risk for cardiovascular events, he said.
“[W]e found in the subgroup analysis that COX-2 inhibitors were associated with a reduced risk of cardiovascular events as a whole,” an association also seen when looking just at ischemic stroke, Dr. Karmacharya said. “So that was sort of surprising; in the general population, there are some concerns about using COX-2 inhibitors.”
Looking at data for the nine studies that met criteria for inclusion in the meta-analysis, Dr. Karmacharya, a rheumatology fellow at the Mayo Clinic, Rochester, Minn., and his collaborators calculated risk ratios for a composite outcome of all cardiovascular events (CVE) for all individuals taking NSAIDs, compared with individuals with ankylosing spondylitis (AS) who were not taking NSAIDs. Here, they found a relative risk of 0.94 (95% CI, 0.50-1.75; P = .84).
Next, the investigators calculated a relative risk of 0.78 for the composite CVE outcome just for those taking nonselective NSAIDs (95% CI, 0.44-1.38; P = .40).
Along with NSAIDs, Dr. Karmacharya and his coauthors also looked at the relationship between tumor necrosis factor inhibitors (TNFIs) and cardiovascular events. They found a significantly increased risk for the composite endpoint among AS patients taking TNFIs (RR, 1.60; 95% CI, 1.05-2.41; P = .03), but the comparison was limited to only one study.
In their analysis, the investigators also broke out risk of acute coronary syndrome (ACS)/ischemic heart disease. “The only place where we found some increased risk was ACS and ischemic heart disease, and that was with nonselective NSAIDS,” Dr. Karmacharya said (RR, 1.21; 95% CI, 1.06-1.39; P = .005). No significant changes in relative risk for ACS and ischemic heart disease were seen for the total group of NSAID users, for the subgroups taking COX-2 inhibitors, or for those taking TNFIs.
Finally, the investigators found a relative risk of 0.58 for stroke among the full group of NSAID users and a relative risk of 0.59 for those taking COX-2 inhibitors, but no reduced risk for the subgroup taking nonselective NSAIDs (P = .02, .04, and .37, respectively).
“While NSAIDs are known to be associated with an increased risk of CVE in the general population, whether the anti-inflammatory effects of NSAIDs reduce or modify the CVE risk in AS is controversial,” Dr. Karmacharya and his collaborators wrote. In this context, the meta-analysis provides a useful perspective for rheumatologists who care for AS patients, Dr. Karmacharya said: “I think it’s important, because most of these patients are on NSAIDs long-term.”
However, all of the studies included in the meta-analysis were observational, with no randomized, controlled trials meeting inclusion criteria. Also, some analyses presented in the poster involved as few as two studies, so findings should be interpreted with caution, he added. “We don’t have a lot of studies included in the analysis. ... so we need more data for sure, but I think what data we have so far look reassuring.”
Dr. Karmacharya reported that he had no conflicts of interest, and reported no outside sources of funding.
MADISON, WISC. – Patients with ankylosing spondylitis had a small but significant reduction in risk for cardiovascular events if they were taking cyclooxygenase-2 (COX-2) inhibitors, according to a new systematic review and meta-analysis.
The reduced risk observed in this analysis (risk ratio, 0.48; 95% confidence interval, 0.33-0.70) contrasts with the increased risk for cardiovascular events seen with COX-2 inhibitor use in the general population, said Paras Karmacharya, MBBS, speaking in an interview at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN). The overall effect was highly statistically significant (P = .0001), and the finding provides “reassuring” data for a population that’s known to have an elevated risk for cardiovascular events, he said.
“[W]e found in the subgroup analysis that COX-2 inhibitors were associated with a reduced risk of cardiovascular events as a whole,” an association also seen when looking just at ischemic stroke, Dr. Karmacharya said. “So that was sort of surprising; in the general population, there are some concerns about using COX-2 inhibitors.”
Looking at data for the nine studies that met criteria for inclusion in the meta-analysis, Dr. Karmacharya, a rheumatology fellow at the Mayo Clinic, Rochester, Minn., and his collaborators calculated risk ratios for a composite outcome of all cardiovascular events (CVE) for all individuals taking NSAIDs, compared with individuals with ankylosing spondylitis (AS) who were not taking NSAIDs. Here, they found a relative risk of 0.94 (95% CI, 0.50-1.75; P = .84).
Next, the investigators calculated a relative risk of 0.78 for the composite CVE outcome just for those taking nonselective NSAIDs (95% CI, 0.44-1.38; P = .40).
Along with NSAIDs, Dr. Karmacharya and his coauthors also looked at the relationship between tumor necrosis factor inhibitors (TNFIs) and cardiovascular events. They found a significantly increased risk for the composite endpoint among AS patients taking TNFIs (RR, 1.60; 95% CI, 1.05-2.41; P = .03), but the comparison was limited to only one study.
In their analysis, the investigators also broke out risk of acute coronary syndrome (ACS)/ischemic heart disease. “The only place where we found some increased risk was ACS and ischemic heart disease, and that was with nonselective NSAIDS,” Dr. Karmacharya said (RR, 1.21; 95% CI, 1.06-1.39; P = .005). No significant changes in relative risk for ACS and ischemic heart disease were seen for the total group of NSAID users, for the subgroups taking COX-2 inhibitors, or for those taking TNFIs.
Finally, the investigators found a relative risk of 0.58 for stroke among the full group of NSAID users and a relative risk of 0.59 for those taking COX-2 inhibitors, but no reduced risk for the subgroup taking nonselective NSAIDs (P = .02, .04, and .37, respectively).
“While NSAIDs are known to be associated with an increased risk of CVE in the general population, whether the anti-inflammatory effects of NSAIDs reduce or modify the CVE risk in AS is controversial,” Dr. Karmacharya and his collaborators wrote. In this context, the meta-analysis provides a useful perspective for rheumatologists who care for AS patients, Dr. Karmacharya said: “I think it’s important, because most of these patients are on NSAIDs long-term.”
However, all of the studies included in the meta-analysis were observational, with no randomized, controlled trials meeting inclusion criteria. Also, some analyses presented in the poster involved as few as two studies, so findings should be interpreted with caution, he added. “We don’t have a lot of studies included in the analysis. ... so we need more data for sure, but I think what data we have so far look reassuring.”
Dr. Karmacharya reported that he had no conflicts of interest, and reported no outside sources of funding.
MADISON, WISC. – Patients with ankylosing spondylitis had a small but significant reduction in risk for cardiovascular events if they were taking cyclooxygenase-2 (COX-2) inhibitors, according to a new systematic review and meta-analysis.
The reduced risk observed in this analysis (risk ratio, 0.48; 95% confidence interval, 0.33-0.70) contrasts with the increased risk for cardiovascular events seen with COX-2 inhibitor use in the general population, said Paras Karmacharya, MBBS, speaking in an interview at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN). The overall effect was highly statistically significant (P = .0001), and the finding provides “reassuring” data for a population that’s known to have an elevated risk for cardiovascular events, he said.
“[W]e found in the subgroup analysis that COX-2 inhibitors were associated with a reduced risk of cardiovascular events as a whole,” an association also seen when looking just at ischemic stroke, Dr. Karmacharya said. “So that was sort of surprising; in the general population, there are some concerns about using COX-2 inhibitors.”
Looking at data for the nine studies that met criteria for inclusion in the meta-analysis, Dr. Karmacharya, a rheumatology fellow at the Mayo Clinic, Rochester, Minn., and his collaborators calculated risk ratios for a composite outcome of all cardiovascular events (CVE) for all individuals taking NSAIDs, compared with individuals with ankylosing spondylitis (AS) who were not taking NSAIDs. Here, they found a relative risk of 0.94 (95% CI, 0.50-1.75; P = .84).
Next, the investigators calculated a relative risk of 0.78 for the composite CVE outcome just for those taking nonselective NSAIDs (95% CI, 0.44-1.38; P = .40).
Along with NSAIDs, Dr. Karmacharya and his coauthors also looked at the relationship between tumor necrosis factor inhibitors (TNFIs) and cardiovascular events. They found a significantly increased risk for the composite endpoint among AS patients taking TNFIs (RR, 1.60; 95% CI, 1.05-2.41; P = .03), but the comparison was limited to only one study.
In their analysis, the investigators also broke out risk of acute coronary syndrome (ACS)/ischemic heart disease. “The only place where we found some increased risk was ACS and ischemic heart disease, and that was with nonselective NSAIDS,” Dr. Karmacharya said (RR, 1.21; 95% CI, 1.06-1.39; P = .005). No significant changes in relative risk for ACS and ischemic heart disease were seen for the total group of NSAID users, for the subgroups taking COX-2 inhibitors, or for those taking TNFIs.
Finally, the investigators found a relative risk of 0.58 for stroke among the full group of NSAID users and a relative risk of 0.59 for those taking COX-2 inhibitors, but no reduced risk for the subgroup taking nonselective NSAIDs (P = .02, .04, and .37, respectively).
“While NSAIDs are known to be associated with an increased risk of CVE in the general population, whether the anti-inflammatory effects of NSAIDs reduce or modify the CVE risk in AS is controversial,” Dr. Karmacharya and his collaborators wrote. In this context, the meta-analysis provides a useful perspective for rheumatologists who care for AS patients, Dr. Karmacharya said: “I think it’s important, because most of these patients are on NSAIDs long-term.”
However, all of the studies included in the meta-analysis were observational, with no randomized, controlled trials meeting inclusion criteria. Also, some analyses presented in the poster involved as few as two studies, so findings should be interpreted with caution, he added. “We don’t have a lot of studies included in the analysis. ... so we need more data for sure, but I think what data we have so far look reassuring.”
Dr. Karmacharya reported that he had no conflicts of interest, and reported no outside sources of funding.
REPORTING FROM SPARTAN 2019
Key clinical point: Individuals with ankylosing spondylitis (AS) who took cyclooxygenase 2 (COX-2) inhibitors had a reduced risk of cardiovascular events, compared with AS patients who were not using COX-2 inhibitors.
Major finding: Individuals with AS taking COX-2 inhibitors had a risk ratio of 0.48 for cardiovascular events (95% CI, 0.33-0.70; P = .001).
Study details: Systematic review and meta-analysis of nine observational studies that variably examined the association between NSAID use and tumor necrosis factor inhibitor use and cardiovascular events among individuals with AS.
Disclosures: The authors reported no conflicts of interest and no outside sources of funding.
Source: Karmacharya P. et al. SPARTAN 2019.
New JIA, JIA-associated uveitis guidelines address knowledge gaps
while attempting to address gaps in the clinical screening, monitoring, and treatment of these diseases.
The first guideline – which was published simultaneously in Arthritis Care & Research and Arthritis & Rheumatology – offered 39 recommendations for treating children and adolescents with JIA and nonsystemic polyarthritis, sacroiliitis, and enthesitis. Due to the low quality of the supporting evidence, 31 of the recommendations were labeled as conditional.
“While these recommendations are intended to address common clinical situations, all treatment decisions must be individualized, with consideration of the unique aspects of each patient’s presentation, medical history, and preferences,” wrote first author Sarah Ringold, MD, of Seattle Children’s Hospital and her coauthors.
These recommendations serve as updates to an initial set on JIA treatment in 2011 and a 2013 addition on the treatment of systemic arthritis. In addition, the ACR has since adopted the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to generate its recommendations, which was described in an interview with Dr. Ringold as providing “greater transparency around the decisions made during the recommendation development process.”
“An important difference from the 2011 guidelines is that is that initial NSAID monotherapy is no longer recommended for children with polyarthritis, given the established benefits of early initiation of DMARD [disease-modifying antirheumatic drug] therapy for these patients,” she added. “In addition, these guidelines also support inactive disease as a treatment goal for children with polyarthritis, with treatment escalation recommended for patients with low disease activity.”
As general recommendations for patients with JIA and polyarthritis, the coauthors strongly recommend using triamcinolone hexacetonide over triamcinolone acetonide for intraarticular glucocorticoid injections, along with using infliximab in combination with a DMARD. Despite the quality of the supporting evidence being very low, they also strongly recommend against adding chronic low-dose glucocorticoids to treatment because of well-known adverse effects like growth suppression, weight gain, osteopenia, and cataract.
Other strong recommendations include choosing treatment with an NSAID in children and adolescents with JIA and active sacroiliitis; adding a tumor necrosis factor inhibitor (TNFi) rather than continued NSAID monotherapy and avoiding methotrexate monotherapy in children and adolescents with active sacroiliitis despite NSAIDs; and choosing NSAID treatment in children and adolescents with JIA and active enthesitis.
Recommendations on JIA with associated uveitis
The second guideline – also published in Arthritis Care & Research and Arthritis & Rheumatology – focused on the screening, monitoring, and treatment of JIA with associated uveitis. Their 19 recommendations serve as updates to 2006 recommendations from the American Academy of Pediatrics on routine ophthalmic screening in children with arthritis and 2012 recommendations from the German Uveitis in Childhood Study Group on proposed ophthalmic screening schedules, neither of which addressed the monitoring of children with an established diagnosis of uveitis or the treatment of uveitis.
“Although the quality of evidence was very low, and most recommendations were therefore conditional, this guideline fills an important clinical gap in the care of children with JIA-associated uveitis and may be updated as better evidence becomes available,” wrote first author Sheila T. Angeles-Han, MD, of the Cincinnati Children’s Hospital Medical Center and her coauthors.
Their strong recommendations include ophthalmic monitoring at least every 3 months in children and adolescents with JIA and controlled uveitis on stable therapy; monitoring within 1 month after each change of topical glucocorticoids in patients who are tapering or discontinuing that treatment; and monitoring within 2 months of changing systemic therapy for patients who are tapering or discontinuing that treatment.
They also strongly recommend education on the warning signs of acute anterior uveitis for children and adolescents with spondyloarthritis, along with tapering topical glucocorticoids before systemic therapy in children and adolescents with JIA and chronic anterior uveitis who are still on 1-2 drops a day of glucocorticoids.
“Our biggest message is that it is critical that uveitis is controlled, since persistent active uveitis can lead to sight-threatening complications and permanent vision loss,” Dr. Angeles-Han said in an interview. “It is important that ocular inflammation is controlled early, exposure to long-term topical glucocorticoids is limited, and that systemic treatment is started promptly.
“We also emphasize that close communication and collaboration between pediatric rheumatologists and ophthalmologists is important to ensure optimal vision outcomes,” she added.
These guidelines also factored in feedback from a patient and parent panel, particularly in regard to recommendations with a low level of supporting evidence.
“This partnership highlighted the importance of incorporating parent and patient preferences into treatment decisions and the need for shared decision-making approaches,” Dr. Ringold said.
Both guidelines were supported by the American College of Rheumatology and the Arthritis Foundation. Several authors reported support from the National Institutes of Health, the Rheumatology Research Foundation, and the Fundación Bechara. Several authors also reported receiving consulting and speaking fees, along with research grants, from numerous pharmaceutical companies.
SOURCES: Ringold S et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23870 ; Angeles-Han ST et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23871 .
while attempting to address gaps in the clinical screening, monitoring, and treatment of these diseases.
The first guideline – which was published simultaneously in Arthritis Care & Research and Arthritis & Rheumatology – offered 39 recommendations for treating children and adolescents with JIA and nonsystemic polyarthritis, sacroiliitis, and enthesitis. Due to the low quality of the supporting evidence, 31 of the recommendations were labeled as conditional.
“While these recommendations are intended to address common clinical situations, all treatment decisions must be individualized, with consideration of the unique aspects of each patient’s presentation, medical history, and preferences,” wrote first author Sarah Ringold, MD, of Seattle Children’s Hospital and her coauthors.
These recommendations serve as updates to an initial set on JIA treatment in 2011 and a 2013 addition on the treatment of systemic arthritis. In addition, the ACR has since adopted the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to generate its recommendations, which was described in an interview with Dr. Ringold as providing “greater transparency around the decisions made during the recommendation development process.”
“An important difference from the 2011 guidelines is that is that initial NSAID monotherapy is no longer recommended for children with polyarthritis, given the established benefits of early initiation of DMARD [disease-modifying antirheumatic drug] therapy for these patients,” she added. “In addition, these guidelines also support inactive disease as a treatment goal for children with polyarthritis, with treatment escalation recommended for patients with low disease activity.”
As general recommendations for patients with JIA and polyarthritis, the coauthors strongly recommend using triamcinolone hexacetonide over triamcinolone acetonide for intraarticular glucocorticoid injections, along with using infliximab in combination with a DMARD. Despite the quality of the supporting evidence being very low, they also strongly recommend against adding chronic low-dose glucocorticoids to treatment because of well-known adverse effects like growth suppression, weight gain, osteopenia, and cataract.
Other strong recommendations include choosing treatment with an NSAID in children and adolescents with JIA and active sacroiliitis; adding a tumor necrosis factor inhibitor (TNFi) rather than continued NSAID monotherapy and avoiding methotrexate monotherapy in children and adolescents with active sacroiliitis despite NSAIDs; and choosing NSAID treatment in children and adolescents with JIA and active enthesitis.
Recommendations on JIA with associated uveitis
The second guideline – also published in Arthritis Care & Research and Arthritis & Rheumatology – focused on the screening, monitoring, and treatment of JIA with associated uveitis. Their 19 recommendations serve as updates to 2006 recommendations from the American Academy of Pediatrics on routine ophthalmic screening in children with arthritis and 2012 recommendations from the German Uveitis in Childhood Study Group on proposed ophthalmic screening schedules, neither of which addressed the monitoring of children with an established diagnosis of uveitis or the treatment of uveitis.
“Although the quality of evidence was very low, and most recommendations were therefore conditional, this guideline fills an important clinical gap in the care of children with JIA-associated uveitis and may be updated as better evidence becomes available,” wrote first author Sheila T. Angeles-Han, MD, of the Cincinnati Children’s Hospital Medical Center and her coauthors.
Their strong recommendations include ophthalmic monitoring at least every 3 months in children and adolescents with JIA and controlled uveitis on stable therapy; monitoring within 1 month after each change of topical glucocorticoids in patients who are tapering or discontinuing that treatment; and monitoring within 2 months of changing systemic therapy for patients who are tapering or discontinuing that treatment.
They also strongly recommend education on the warning signs of acute anterior uveitis for children and adolescents with spondyloarthritis, along with tapering topical glucocorticoids before systemic therapy in children and adolescents with JIA and chronic anterior uveitis who are still on 1-2 drops a day of glucocorticoids.
“Our biggest message is that it is critical that uveitis is controlled, since persistent active uveitis can lead to sight-threatening complications and permanent vision loss,” Dr. Angeles-Han said in an interview. “It is important that ocular inflammation is controlled early, exposure to long-term topical glucocorticoids is limited, and that systemic treatment is started promptly.
“We also emphasize that close communication and collaboration between pediatric rheumatologists and ophthalmologists is important to ensure optimal vision outcomes,” she added.
These guidelines also factored in feedback from a patient and parent panel, particularly in regard to recommendations with a low level of supporting evidence.
“This partnership highlighted the importance of incorporating parent and patient preferences into treatment decisions and the need for shared decision-making approaches,” Dr. Ringold said.
Both guidelines were supported by the American College of Rheumatology and the Arthritis Foundation. Several authors reported support from the National Institutes of Health, the Rheumatology Research Foundation, and the Fundación Bechara. Several authors also reported receiving consulting and speaking fees, along with research grants, from numerous pharmaceutical companies.
SOURCES: Ringold S et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23870 ; Angeles-Han ST et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23871 .
while attempting to address gaps in the clinical screening, monitoring, and treatment of these diseases.
The first guideline – which was published simultaneously in Arthritis Care & Research and Arthritis & Rheumatology – offered 39 recommendations for treating children and adolescents with JIA and nonsystemic polyarthritis, sacroiliitis, and enthesitis. Due to the low quality of the supporting evidence, 31 of the recommendations were labeled as conditional.
“While these recommendations are intended to address common clinical situations, all treatment decisions must be individualized, with consideration of the unique aspects of each patient’s presentation, medical history, and preferences,” wrote first author Sarah Ringold, MD, of Seattle Children’s Hospital and her coauthors.
These recommendations serve as updates to an initial set on JIA treatment in 2011 and a 2013 addition on the treatment of systemic arthritis. In addition, the ACR has since adopted the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to generate its recommendations, which was described in an interview with Dr. Ringold as providing “greater transparency around the decisions made during the recommendation development process.”
“An important difference from the 2011 guidelines is that is that initial NSAID monotherapy is no longer recommended for children with polyarthritis, given the established benefits of early initiation of DMARD [disease-modifying antirheumatic drug] therapy for these patients,” she added. “In addition, these guidelines also support inactive disease as a treatment goal for children with polyarthritis, with treatment escalation recommended for patients with low disease activity.”
As general recommendations for patients with JIA and polyarthritis, the coauthors strongly recommend using triamcinolone hexacetonide over triamcinolone acetonide for intraarticular glucocorticoid injections, along with using infliximab in combination with a DMARD. Despite the quality of the supporting evidence being very low, they also strongly recommend against adding chronic low-dose glucocorticoids to treatment because of well-known adverse effects like growth suppression, weight gain, osteopenia, and cataract.
Other strong recommendations include choosing treatment with an NSAID in children and adolescents with JIA and active sacroiliitis; adding a tumor necrosis factor inhibitor (TNFi) rather than continued NSAID monotherapy and avoiding methotrexate monotherapy in children and adolescents with active sacroiliitis despite NSAIDs; and choosing NSAID treatment in children and adolescents with JIA and active enthesitis.
Recommendations on JIA with associated uveitis
The second guideline – also published in Arthritis Care & Research and Arthritis & Rheumatology – focused on the screening, monitoring, and treatment of JIA with associated uveitis. Their 19 recommendations serve as updates to 2006 recommendations from the American Academy of Pediatrics on routine ophthalmic screening in children with arthritis and 2012 recommendations from the German Uveitis in Childhood Study Group on proposed ophthalmic screening schedules, neither of which addressed the monitoring of children with an established diagnosis of uveitis or the treatment of uveitis.
“Although the quality of evidence was very low, and most recommendations were therefore conditional, this guideline fills an important clinical gap in the care of children with JIA-associated uveitis and may be updated as better evidence becomes available,” wrote first author Sheila T. Angeles-Han, MD, of the Cincinnati Children’s Hospital Medical Center and her coauthors.
Their strong recommendations include ophthalmic monitoring at least every 3 months in children and adolescents with JIA and controlled uveitis on stable therapy; monitoring within 1 month after each change of topical glucocorticoids in patients who are tapering or discontinuing that treatment; and monitoring within 2 months of changing systemic therapy for patients who are tapering or discontinuing that treatment.
They also strongly recommend education on the warning signs of acute anterior uveitis for children and adolescents with spondyloarthritis, along with tapering topical glucocorticoids before systemic therapy in children and adolescents with JIA and chronic anterior uveitis who are still on 1-2 drops a day of glucocorticoids.
“Our biggest message is that it is critical that uveitis is controlled, since persistent active uveitis can lead to sight-threatening complications and permanent vision loss,” Dr. Angeles-Han said in an interview. “It is important that ocular inflammation is controlled early, exposure to long-term topical glucocorticoids is limited, and that systemic treatment is started promptly.
“We also emphasize that close communication and collaboration between pediatric rheumatologists and ophthalmologists is important to ensure optimal vision outcomes,” she added.
These guidelines also factored in feedback from a patient and parent panel, particularly in regard to recommendations with a low level of supporting evidence.
“This partnership highlighted the importance of incorporating parent and patient preferences into treatment decisions and the need for shared decision-making approaches,” Dr. Ringold said.
Both guidelines were supported by the American College of Rheumatology and the Arthritis Foundation. Several authors reported support from the National Institutes of Health, the Rheumatology Research Foundation, and the Fundación Bechara. Several authors also reported receiving consulting and speaking fees, along with research grants, from numerous pharmaceutical companies.
SOURCES: Ringold S et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23870 ; Angeles-Han ST et al. Arthritis Care Res. 2019 Apr 25. doi: 10.1002/acr.23871 .
FROM ARTHRITIS CARE & RESEARCH
Intradermal etanercept improves discoid lupus
BIRMINGHAM, ENGLAND – Intradermal delivery of a tumor necrosis factor inhibitor (TNFi) could offer patients with discoid lupus erythematosus (DLE) a much-needed additional treatment option, according to results of a phase 2, “proof-of-concept” study.
Overall, 14 (56%) of the 25 patients in the study achieved a 20% or greater reduction in disease activity from baseline to week 12 via intradermal injection of etanercept (Enbrel), which was assessed via the modified limited Score of Activity and Damage in DLE (ML-SADDLE). About half (48%) and one-fifth (20%) also achieved greater reductions of 50% and 70%, respectively.
“Discoid lupus is a chronic form of cutaneous lupus. Usually it occurs in visible areas like the face and scalp, causing scarring, so it’s really disabling and affects patients’ quality of life,” observed the lead study investigator Md Yuzaiful Md Yusof, MBChB, PhD, NIHR Academic Clinical Lecturer at the University of Leeds, England.
“It’s also one of the most resistant manifestations of lupus,” he said during a poster presentation at the annual conference of the British Society for Rheumatology. “Usually, when people have discoid lupus, the dermatologist gives antimalarial treatment, but only 50% of people respond to these drugs. So, what happens to the rest of them?” Basically, it is trial and error, Dr. Md Yusof said; some patients may be given disease-modifying antirheumatic drugs and in some patients this may work well, but in others there may be toxicity that contraindicates treatment.
B-cell therapy with rituximab (Rituxan) has not been successful, he said. In a previous study of 35 patients with refractory discoid lupus, none of the patients responded to rituximab and half of them actually flared after taking the drug.
There is a pathologic case for using anti-TNF therapy in DLE, but the use of TNFis is not without concern. Such treatment can increase antinuclear antibody production and make lupus worse. “In order to overcome this, as the lesion is quite small, we don’t need to use a systemic approach,” Dr. Md Yusof explained in an interview. “If you give directly, it should just be confined to the lesion and not absorbed, that’s the whole idea of thinking outside the box.” He noted that if it worked, such treatment would be for inducing remission and not for maintenance.
The study, “Targeted therapy using intradermal injection of etanercept for remission induction in discoid lupus erythematosus” (TARGET-DLE) was designed to test the validity of using intradermal rather than subcutaneous TNFi therapy in patients with discoid lupus.
Dr. Md Yusof noted that only 25 patients needed to be recruited into the single-arm, prospective trial as a “Simon’s two-stage minimized design” was used (Control Clin Trials. 1989;10[1]:1-10). This involved treating the first few patients to see if a response occurred and if it did, carrying on with treating the others, but if no response occurred in at least two patients, the trial would stop completely.
Adult patients were eligible for inclusion if they had one or more active DLE lesions and had not responded to antimalarial treatment. Stable doses of DMARDs and up to 10 mg of oral prednisolone daily was permitted if already being taken prior to entering the study.
Etanercept was injected intradermally around the most symptomatic lesion once a week for up to 12 weeks. The dosage was determined based on the radius of the selected discoid lesion. Over an 18-month period, all 25 patients were recruited, including 18 women. The median age of patients was 47 years, and six had systemic lupus erythematosus. The median number of prior DMARDs was 5 but ranged from 1 to 16, indicating a very resistant patient population.
The primary endpoint was at least 6 of the 25 patients having at least a 20% reduction in ML-SADDLE at week 12; 14 (56%) patients achieved this.
“We didn’t use CLASI [Cutaneous Lupus Area and Severity Index Activity Score] because that only includes erythema and atrophy,” Dr. Md Yusof explained. “In discoid lupus, induration is quite important as well, so that’s why we used ML-SADDLE. We called it ‘modified limited’ because the original SADDLE score is based on the whole organ score, but we only calculated the one lesion that we wanted to treat.”
In addition to meeting the primary endpoint, several secondary endpoints were met, including significant improvements in scores on visual analog scales as determined by pre- and posttreatment scoring by physicians (53.1 mm vs. 23.2 mm; P less than .001) and patients (56.9 mm vs. 29.7 mm; P = .001). Mean Dermatology Life Quality Index (DLQI) score significantly improved between pre- and post treatment, as did blood perfusion under the skin based on laser Doppler imaging and infrared thermography. However, no difference was seen with optical coherence tomography.
“There were only four grade 3/4 toxicities, and importantly, none of the SLE patients got worse, and none with DLE only converted into SLE,” Dr. Md Yusof reported. Of the four grade 3/4 adverse events, two were chest infections, one was heart failure, and one was a worsening of chilblains.
“It was a full-powered phase 2 trial, and because it was positive, now we can go to phase 3 trial,” he added.
Before conducting a phase 3 trial, however, Dr. Md Yusof wants to refine how the TNFi is delivered. Perhaps an intradermal patch with microneedles could be used. This would be left on the skin for a short amount of time to allow drug delivery and then removed. It could help ensure that all patients comply with treatment and perhaps even self-administer, he noted.
“The median compliance rate was 80%, which is not too bad, but I think when we come to run a phase 3 trial, I’m looking to improve the drug delivery,” he said. Changing the delivery method will need to be validated before a phase 3 trial can be started.
The study was not commercially funded. Dr. Md Yusof had no disclosures. Pfizer provided the study drug free of charge.
SOURCE: Md Yusof MY et al. Rheumatology. 2019;58(suppl 3): Abstract 244. doi: 10.1093/rheumatology/kez107.060.
BIRMINGHAM, ENGLAND – Intradermal delivery of a tumor necrosis factor inhibitor (TNFi) could offer patients with discoid lupus erythematosus (DLE) a much-needed additional treatment option, according to results of a phase 2, “proof-of-concept” study.
Overall, 14 (56%) of the 25 patients in the study achieved a 20% or greater reduction in disease activity from baseline to week 12 via intradermal injection of etanercept (Enbrel), which was assessed via the modified limited Score of Activity and Damage in DLE (ML-SADDLE). About half (48%) and one-fifth (20%) also achieved greater reductions of 50% and 70%, respectively.
“Discoid lupus is a chronic form of cutaneous lupus. Usually it occurs in visible areas like the face and scalp, causing scarring, so it’s really disabling and affects patients’ quality of life,” observed the lead study investigator Md Yuzaiful Md Yusof, MBChB, PhD, NIHR Academic Clinical Lecturer at the University of Leeds, England.
“It’s also one of the most resistant manifestations of lupus,” he said during a poster presentation at the annual conference of the British Society for Rheumatology. “Usually, when people have discoid lupus, the dermatologist gives antimalarial treatment, but only 50% of people respond to these drugs. So, what happens to the rest of them?” Basically, it is trial and error, Dr. Md Yusof said; some patients may be given disease-modifying antirheumatic drugs and in some patients this may work well, but in others there may be toxicity that contraindicates treatment.
B-cell therapy with rituximab (Rituxan) has not been successful, he said. In a previous study of 35 patients with refractory discoid lupus, none of the patients responded to rituximab and half of them actually flared after taking the drug.
There is a pathologic case for using anti-TNF therapy in DLE, but the use of TNFis is not without concern. Such treatment can increase antinuclear antibody production and make lupus worse. “In order to overcome this, as the lesion is quite small, we don’t need to use a systemic approach,” Dr. Md Yusof explained in an interview. “If you give directly, it should just be confined to the lesion and not absorbed, that’s the whole idea of thinking outside the box.” He noted that if it worked, such treatment would be for inducing remission and not for maintenance.
The study, “Targeted therapy using intradermal injection of etanercept for remission induction in discoid lupus erythematosus” (TARGET-DLE) was designed to test the validity of using intradermal rather than subcutaneous TNFi therapy in patients with discoid lupus.
Dr. Md Yusof noted that only 25 patients needed to be recruited into the single-arm, prospective trial as a “Simon’s two-stage minimized design” was used (Control Clin Trials. 1989;10[1]:1-10). This involved treating the first few patients to see if a response occurred and if it did, carrying on with treating the others, but if no response occurred in at least two patients, the trial would stop completely.
Adult patients were eligible for inclusion if they had one or more active DLE lesions and had not responded to antimalarial treatment. Stable doses of DMARDs and up to 10 mg of oral prednisolone daily was permitted if already being taken prior to entering the study.
Etanercept was injected intradermally around the most symptomatic lesion once a week for up to 12 weeks. The dosage was determined based on the radius of the selected discoid lesion. Over an 18-month period, all 25 patients were recruited, including 18 women. The median age of patients was 47 years, and six had systemic lupus erythematosus. The median number of prior DMARDs was 5 but ranged from 1 to 16, indicating a very resistant patient population.
The primary endpoint was at least 6 of the 25 patients having at least a 20% reduction in ML-SADDLE at week 12; 14 (56%) patients achieved this.
“We didn’t use CLASI [Cutaneous Lupus Area and Severity Index Activity Score] because that only includes erythema and atrophy,” Dr. Md Yusof explained. “In discoid lupus, induration is quite important as well, so that’s why we used ML-SADDLE. We called it ‘modified limited’ because the original SADDLE score is based on the whole organ score, but we only calculated the one lesion that we wanted to treat.”
In addition to meeting the primary endpoint, several secondary endpoints were met, including significant improvements in scores on visual analog scales as determined by pre- and posttreatment scoring by physicians (53.1 mm vs. 23.2 mm; P less than .001) and patients (56.9 mm vs. 29.7 mm; P = .001). Mean Dermatology Life Quality Index (DLQI) score significantly improved between pre- and post treatment, as did blood perfusion under the skin based on laser Doppler imaging and infrared thermography. However, no difference was seen with optical coherence tomography.
“There were only four grade 3/4 toxicities, and importantly, none of the SLE patients got worse, and none with DLE only converted into SLE,” Dr. Md Yusof reported. Of the four grade 3/4 adverse events, two were chest infections, one was heart failure, and one was a worsening of chilblains.
“It was a full-powered phase 2 trial, and because it was positive, now we can go to phase 3 trial,” he added.
Before conducting a phase 3 trial, however, Dr. Md Yusof wants to refine how the TNFi is delivered. Perhaps an intradermal patch with microneedles could be used. This would be left on the skin for a short amount of time to allow drug delivery and then removed. It could help ensure that all patients comply with treatment and perhaps even self-administer, he noted.
“The median compliance rate was 80%, which is not too bad, but I think when we come to run a phase 3 trial, I’m looking to improve the drug delivery,” he said. Changing the delivery method will need to be validated before a phase 3 trial can be started.
The study was not commercially funded. Dr. Md Yusof had no disclosures. Pfizer provided the study drug free of charge.
SOURCE: Md Yusof MY et al. Rheumatology. 2019;58(suppl 3): Abstract 244. doi: 10.1093/rheumatology/kez107.060.
BIRMINGHAM, ENGLAND – Intradermal delivery of a tumor necrosis factor inhibitor (TNFi) could offer patients with discoid lupus erythematosus (DLE) a much-needed additional treatment option, according to results of a phase 2, “proof-of-concept” study.
Overall, 14 (56%) of the 25 patients in the study achieved a 20% or greater reduction in disease activity from baseline to week 12 via intradermal injection of etanercept (Enbrel), which was assessed via the modified limited Score of Activity and Damage in DLE (ML-SADDLE). About half (48%) and one-fifth (20%) also achieved greater reductions of 50% and 70%, respectively.
“Discoid lupus is a chronic form of cutaneous lupus. Usually it occurs in visible areas like the face and scalp, causing scarring, so it’s really disabling and affects patients’ quality of life,” observed the lead study investigator Md Yuzaiful Md Yusof, MBChB, PhD, NIHR Academic Clinical Lecturer at the University of Leeds, England.
“It’s also one of the most resistant manifestations of lupus,” he said during a poster presentation at the annual conference of the British Society for Rheumatology. “Usually, when people have discoid lupus, the dermatologist gives antimalarial treatment, but only 50% of people respond to these drugs. So, what happens to the rest of them?” Basically, it is trial and error, Dr. Md Yusof said; some patients may be given disease-modifying antirheumatic drugs and in some patients this may work well, but in others there may be toxicity that contraindicates treatment.
B-cell therapy with rituximab (Rituxan) has not been successful, he said. In a previous study of 35 patients with refractory discoid lupus, none of the patients responded to rituximab and half of them actually flared after taking the drug.
There is a pathologic case for using anti-TNF therapy in DLE, but the use of TNFis is not without concern. Such treatment can increase antinuclear antibody production and make lupus worse. “In order to overcome this, as the lesion is quite small, we don’t need to use a systemic approach,” Dr. Md Yusof explained in an interview. “If you give directly, it should just be confined to the lesion and not absorbed, that’s the whole idea of thinking outside the box.” He noted that if it worked, such treatment would be for inducing remission and not for maintenance.
The study, “Targeted therapy using intradermal injection of etanercept for remission induction in discoid lupus erythematosus” (TARGET-DLE) was designed to test the validity of using intradermal rather than subcutaneous TNFi therapy in patients with discoid lupus.
Dr. Md Yusof noted that only 25 patients needed to be recruited into the single-arm, prospective trial as a “Simon’s two-stage minimized design” was used (Control Clin Trials. 1989;10[1]:1-10). This involved treating the first few patients to see if a response occurred and if it did, carrying on with treating the others, but if no response occurred in at least two patients, the trial would stop completely.
Adult patients were eligible for inclusion if they had one or more active DLE lesions and had not responded to antimalarial treatment. Stable doses of DMARDs and up to 10 mg of oral prednisolone daily was permitted if already being taken prior to entering the study.
Etanercept was injected intradermally around the most symptomatic lesion once a week for up to 12 weeks. The dosage was determined based on the radius of the selected discoid lesion. Over an 18-month period, all 25 patients were recruited, including 18 women. The median age of patients was 47 years, and six had systemic lupus erythematosus. The median number of prior DMARDs was 5 but ranged from 1 to 16, indicating a very resistant patient population.
The primary endpoint was at least 6 of the 25 patients having at least a 20% reduction in ML-SADDLE at week 12; 14 (56%) patients achieved this.
“We didn’t use CLASI [Cutaneous Lupus Area and Severity Index Activity Score] because that only includes erythema and atrophy,” Dr. Md Yusof explained. “In discoid lupus, induration is quite important as well, so that’s why we used ML-SADDLE. We called it ‘modified limited’ because the original SADDLE score is based on the whole organ score, but we only calculated the one lesion that we wanted to treat.”
In addition to meeting the primary endpoint, several secondary endpoints were met, including significant improvements in scores on visual analog scales as determined by pre- and posttreatment scoring by physicians (53.1 mm vs. 23.2 mm; P less than .001) and patients (56.9 mm vs. 29.7 mm; P = .001). Mean Dermatology Life Quality Index (DLQI) score significantly improved between pre- and post treatment, as did blood perfusion under the skin based on laser Doppler imaging and infrared thermography. However, no difference was seen with optical coherence tomography.
“There were only four grade 3/4 toxicities, and importantly, none of the SLE patients got worse, and none with DLE only converted into SLE,” Dr. Md Yusof reported. Of the four grade 3/4 adverse events, two were chest infections, one was heart failure, and one was a worsening of chilblains.
“It was a full-powered phase 2 trial, and because it was positive, now we can go to phase 3 trial,” he added.
Before conducting a phase 3 trial, however, Dr. Md Yusof wants to refine how the TNFi is delivered. Perhaps an intradermal patch with microneedles could be used. This would be left on the skin for a short amount of time to allow drug delivery and then removed. It could help ensure that all patients comply with treatment and perhaps even self-administer, he noted.
“The median compliance rate was 80%, which is not too bad, but I think when we come to run a phase 3 trial, I’m looking to improve the drug delivery,” he said. Changing the delivery method will need to be validated before a phase 3 trial can be started.
The study was not commercially funded. Dr. Md Yusof had no disclosures. Pfizer provided the study drug free of charge.
SOURCE: Md Yusof MY et al. Rheumatology. 2019;58(suppl 3): Abstract 244. doi: 10.1093/rheumatology/kez107.060.
REPORTING FROM BSR 2019
Experts agree on optimal use of MRI in axSpA
BIRMINGHAM, ENGLAND – An evidence-based approach coupled with expert consensus has been used to determine the best way to use MRI for the diagnosis of axial spondyloarthritis (axSpA).
Working under the auspices of the British Society for Spondyloarthritis (BRITSpA), a task force of nine rheumatologists and nine musculoskeletal radiologists with an interest in axSpA developed a set of seven recommendations that provide guidance on how to best to acquire and then interpret MRI images of the spine and sacroiliac joints.
The recommendations, which were published online (Rheumatology. 2019 May 2. doi: 10.1093/rheumatology/kez173), cover how to perform MRI when axSpA is suspected, such as by imaging both the sacroiliac joints and the spine, and provide guidance on the sequences and order of MRI planes to be used, and what features may increase the diagnostic confidence of axSpA.
The recommendations are as follows:
• When requesting an MRI for suspected axSpA, imaging of both the sacroiliac joints and the spine is recommended.
• T1-weighted and fat-suppressed, fluid-sensitive sequences are recommended for suspected axSpA.
• The minimum protocol when requesting an MRI for suspected axSpA should include sagittal images of the spine with extended lateral coverage and images of the sacroiliac joints that are in an oblique coronal plane to the joint.
• In the sacroiliac joints, the presence of bone marrow edema, fatty infiltration, or erosion is suggestive of the diagnosis of axSpA. The presence of more than one of these features increases the diagnostic confidence of axSpA.
• In the spine, the presence of multiple corner inflammatory lesions and/or multiple corner fatty lesions increases the diagnostic confidence of axSpA.
• In the sacroiliac joints and/or spine, the presence of characteristic new bone formation increases the diagnostic confidence of axSpA.
• The full range and combination of active and structural lesions of the sacroiliac joints and spine should be taken into account when deciding if the MRI scan is suggestive of axSpA or not.
The recommendations “are intended to standardize practice around the use of MRI,” said Alexis Jones, MBBS, MS (Rheumatology), a senior clinical research fellow at University College London Hospitals NHS Foundation Trust. She presented the recommendations on behalf of the expert task force at the annual conference of the British Society for Rheumatology.
“MRI has become an essential tool in axial spondyloarthritis. It facilitates earlier diagnoses and therefore has allowed for earlier initiation of treatment. It can be used to monitor the burden of inflammation and may predict response to therapy,” Dr. Jones said. Despite this, “there is significant inconsistency in the use of MRI” in clinical practice.
For instance, a survey performed in the United Kingdom (J Rheumatol. 2017;44[6]:780-5) highlighted the need for better collaboration between rheumatology and radiology departments to identify axSpA MRI lesions and develop appropriate protocols.
That survey showed that a quarter of radiologists were not aware of the term axSpA, and just 31% and 25%, respectively, were aware of Assessment of Spondyloarthritis international Society (ASAS) criteria for a positive MRI of the sacroiliac joints and spine. Furthermore, 18% of radiologists did not recognize bone marrow edema as a diagnostic feature of axSpA.
The heterogeneity in the performance of MRI in clinical practice could lead to a delay in diagnosis and potentially misdiagnosis, the task force’s lead author and consultant rheumatologist, Pedro Machado, MD, said in an interview.
“I think everyone has been focusing on demonstrating the value of MRI in the condition but then they forgot to look at the standardization aspect,” said Dr. Machado, who works at University College Hospital and the National Hospital for Neurology and Neurosurgery in London.
With that in mind, the BRITSpA-endorsed task force was set up and met to determine the scope of the recommendations. They looked at the evidence for the use of MRI in the diagnosis of axSpA and used two overarching principles to draft the recommendations: 1) the diagnosis of axSpA is based on clinical, laboratory, and imaging features; 2) Some patients with axSpA have isolated inflammation of the sacroiliac joints or spine.
“All of the recommendations were met with a high level of agreement, indicating a strong consensus” among rheumatologists and radiologists, Dr. Jones noted.
“These recommendations can be immediately applied to clinical practice,” said Dr. Machado, who noted that they should standardize practice and decrease heterogeneity around the use of MRI. “This will help ensure a more informed and consistent approach to the diagnosis of axSpA.”
One of the potential impacts of the recommendations, if followed, is that they may actually help to reduce health care costs, Dr. Machado suggested, because an optimized protocol would be used, making MRI more cost effective by not including sequences that do not add value in the condition.
The next task is to share the recommendations more widely and make sure they are applied in clinical practice.
A systematic literature review on which the recommendations were based was published simultaneously with the conference presentation (Rheumatology. 2019 May 2. doi: 10.1093/rheumatology/kez172).
The work was supported by BRITSpA. The authors had no relevant disclosures.
SOURCE: Bray TJP et al. Rheumatology 2019;58(suppl 3): Abstract 033. doi: 10.1093/rheumatology/kez105.032.
BIRMINGHAM, ENGLAND – An evidence-based approach coupled with expert consensus has been used to determine the best way to use MRI for the diagnosis of axial spondyloarthritis (axSpA).
Working under the auspices of the British Society for Spondyloarthritis (BRITSpA), a task force of nine rheumatologists and nine musculoskeletal radiologists with an interest in axSpA developed a set of seven recommendations that provide guidance on how to best to acquire and then interpret MRI images of the spine and sacroiliac joints.
The recommendations, which were published online (Rheumatology. 2019 May 2. doi: 10.1093/rheumatology/kez173), cover how to perform MRI when axSpA is suspected, such as by imaging both the sacroiliac joints and the spine, and provide guidance on the sequences and order of MRI planes to be used, and what features may increase the diagnostic confidence of axSpA.
The recommendations are as follows:
• When requesting an MRI for suspected axSpA, imaging of both the sacroiliac joints and the spine is recommended.
• T1-weighted and fat-suppressed, fluid-sensitive sequences are recommended for suspected axSpA.
• The minimum protocol when requesting an MRI for suspected axSpA should include sagittal images of the spine with extended lateral coverage and images of the sacroiliac joints that are in an oblique coronal plane to the joint.
• In the sacroiliac joints, the presence of bone marrow edema, fatty infiltration, or erosion is suggestive of the diagnosis of axSpA. The presence of more than one of these features increases the diagnostic confidence of axSpA.
• In the spine, the presence of multiple corner inflammatory lesions and/or multiple corner fatty lesions increases the diagnostic confidence of axSpA.
• In the sacroiliac joints and/or spine, the presence of characteristic new bone formation increases the diagnostic confidence of axSpA.
• The full range and combination of active and structural lesions of the sacroiliac joints and spine should be taken into account when deciding if the MRI scan is suggestive of axSpA or not.
The recommendations “are intended to standardize practice around the use of MRI,” said Alexis Jones, MBBS, MS (Rheumatology), a senior clinical research fellow at University College London Hospitals NHS Foundation Trust. She presented the recommendations on behalf of the expert task force at the annual conference of the British Society for Rheumatology.
“MRI has become an essential tool in axial spondyloarthritis. It facilitates earlier diagnoses and therefore has allowed for earlier initiation of treatment. It can be used to monitor the burden of inflammation and may predict response to therapy,” Dr. Jones said. Despite this, “there is significant inconsistency in the use of MRI” in clinical practice.
For instance, a survey performed in the United Kingdom (J Rheumatol. 2017;44[6]:780-5) highlighted the need for better collaboration between rheumatology and radiology departments to identify axSpA MRI lesions and develop appropriate protocols.
That survey showed that a quarter of radiologists were not aware of the term axSpA, and just 31% and 25%, respectively, were aware of Assessment of Spondyloarthritis international Society (ASAS) criteria for a positive MRI of the sacroiliac joints and spine. Furthermore, 18% of radiologists did not recognize bone marrow edema as a diagnostic feature of axSpA.
The heterogeneity in the performance of MRI in clinical practice could lead to a delay in diagnosis and potentially misdiagnosis, the task force’s lead author and consultant rheumatologist, Pedro Machado, MD, said in an interview.
“I think everyone has been focusing on demonstrating the value of MRI in the condition but then they forgot to look at the standardization aspect,” said Dr. Machado, who works at University College Hospital and the National Hospital for Neurology and Neurosurgery in London.
With that in mind, the BRITSpA-endorsed task force was set up and met to determine the scope of the recommendations. They looked at the evidence for the use of MRI in the diagnosis of axSpA and used two overarching principles to draft the recommendations: 1) the diagnosis of axSpA is based on clinical, laboratory, and imaging features; 2) Some patients with axSpA have isolated inflammation of the sacroiliac joints or spine.
“All of the recommendations were met with a high level of agreement, indicating a strong consensus” among rheumatologists and radiologists, Dr. Jones noted.
“These recommendations can be immediately applied to clinical practice,” said Dr. Machado, who noted that they should standardize practice and decrease heterogeneity around the use of MRI. “This will help ensure a more informed and consistent approach to the diagnosis of axSpA.”
One of the potential impacts of the recommendations, if followed, is that they may actually help to reduce health care costs, Dr. Machado suggested, because an optimized protocol would be used, making MRI more cost effective by not including sequences that do not add value in the condition.
The next task is to share the recommendations more widely and make sure they are applied in clinical practice.
A systematic literature review on which the recommendations were based was published simultaneously with the conference presentation (Rheumatology. 2019 May 2. doi: 10.1093/rheumatology/kez172).
The work was supported by BRITSpA. The authors had no relevant disclosures.
SOURCE: Bray TJP et al. Rheumatology 2019;58(suppl 3): Abstract 033. doi: 10.1093/rheumatology/kez105.032.
BIRMINGHAM, ENGLAND – An evidence-based approach coupled with expert consensus has been used to determine the best way to use MRI for the diagnosis of axial spondyloarthritis (axSpA).
Working under the auspices of the British Society for Spondyloarthritis (BRITSpA), a task force of nine rheumatologists and nine musculoskeletal radiologists with an interest in axSpA developed a set of seven recommendations that provide guidance on how to best to acquire and then interpret MRI images of the spine and sacroiliac joints.
The recommendations, which were published online (Rheumatology. 2019 May 2. doi: 10.1093/rheumatology/kez173), cover how to perform MRI when axSpA is suspected, such as by imaging both the sacroiliac joints and the spine, and provide guidance on the sequences and order of MRI planes to be used, and what features may increase the diagnostic confidence of axSpA.
The recommendations are as follows:
• When requesting an MRI for suspected axSpA, imaging of both the sacroiliac joints and the spine is recommended.
• T1-weighted and fat-suppressed, fluid-sensitive sequences are recommended for suspected axSpA.
• The minimum protocol when requesting an MRI for suspected axSpA should include sagittal images of the spine with extended lateral coverage and images of the sacroiliac joints that are in an oblique coronal plane to the joint.
• In the sacroiliac joints, the presence of bone marrow edema, fatty infiltration, or erosion is suggestive of the diagnosis of axSpA. The presence of more than one of these features increases the diagnostic confidence of axSpA.
• In the spine, the presence of multiple corner inflammatory lesions and/or multiple corner fatty lesions increases the diagnostic confidence of axSpA.
• In the sacroiliac joints and/or spine, the presence of characteristic new bone formation increases the diagnostic confidence of axSpA.
• The full range and combination of active and structural lesions of the sacroiliac joints and spine should be taken into account when deciding if the MRI scan is suggestive of axSpA or not.
The recommendations “are intended to standardize practice around the use of MRI,” said Alexis Jones, MBBS, MS (Rheumatology), a senior clinical research fellow at University College London Hospitals NHS Foundation Trust. She presented the recommendations on behalf of the expert task force at the annual conference of the British Society for Rheumatology.
“MRI has become an essential tool in axial spondyloarthritis. It facilitates earlier diagnoses and therefore has allowed for earlier initiation of treatment. It can be used to monitor the burden of inflammation and may predict response to therapy,” Dr. Jones said. Despite this, “there is significant inconsistency in the use of MRI” in clinical practice.
For instance, a survey performed in the United Kingdom (J Rheumatol. 2017;44[6]:780-5) highlighted the need for better collaboration between rheumatology and radiology departments to identify axSpA MRI lesions and develop appropriate protocols.
That survey showed that a quarter of radiologists were not aware of the term axSpA, and just 31% and 25%, respectively, were aware of Assessment of Spondyloarthritis international Society (ASAS) criteria for a positive MRI of the sacroiliac joints and spine. Furthermore, 18% of radiologists did not recognize bone marrow edema as a diagnostic feature of axSpA.
The heterogeneity in the performance of MRI in clinical practice could lead to a delay in diagnosis and potentially misdiagnosis, the task force’s lead author and consultant rheumatologist, Pedro Machado, MD, said in an interview.
“I think everyone has been focusing on demonstrating the value of MRI in the condition but then they forgot to look at the standardization aspect,” said Dr. Machado, who works at University College Hospital and the National Hospital for Neurology and Neurosurgery in London.
With that in mind, the BRITSpA-endorsed task force was set up and met to determine the scope of the recommendations. They looked at the evidence for the use of MRI in the diagnosis of axSpA and used two overarching principles to draft the recommendations: 1) the diagnosis of axSpA is based on clinical, laboratory, and imaging features; 2) Some patients with axSpA have isolated inflammation of the sacroiliac joints or spine.
“All of the recommendations were met with a high level of agreement, indicating a strong consensus” among rheumatologists and radiologists, Dr. Jones noted.
“These recommendations can be immediately applied to clinical practice,” said Dr. Machado, who noted that they should standardize practice and decrease heterogeneity around the use of MRI. “This will help ensure a more informed and consistent approach to the diagnosis of axSpA.”
One of the potential impacts of the recommendations, if followed, is that they may actually help to reduce health care costs, Dr. Machado suggested, because an optimized protocol would be used, making MRI more cost effective by not including sequences that do not add value in the condition.
The next task is to share the recommendations more widely and make sure they are applied in clinical practice.
A systematic literature review on which the recommendations were based was published simultaneously with the conference presentation (Rheumatology. 2019 May 2. doi: 10.1093/rheumatology/kez172).
The work was supported by BRITSpA. The authors had no relevant disclosures.
SOURCE: Bray TJP et al. Rheumatology 2019;58(suppl 3): Abstract 033. doi: 10.1093/rheumatology/kez105.032.
REPORTING FROM BSR 2019
Could that back pain be caused by ankylosing spondylitis?
CASE
A 38-year-old man presents to your primary care clinic with chronic low back stiffness and pain. You have evaluated and treated this patient for this complaint for more than a year. His symptoms are worse in the morning upon wakening and improve with activity and anti-inflammatory medications. He denies any trauma or change in his activity level. His medical history includes chronic insertional Achilles pain and plantar fasciopathy, both for approximately 2 years. The patient reports no systemic or constitutional symptoms, and no pertinent family history.
How would you proceed with his work-up?
Ankylosing spondylitis (AS) is a form of arthritis that primarily affects the spine and sacroiliac joints. It is the most common spondyloarthropathy (SpA)—a family of disorders that also includes psoriatic arthritis; arthritis associated with inflammatory bowel disease; reactive arthritis; and juvenile SpA.1 AS is most prevalent in Caucasians and may affect 0.1% to 1.4% of the population.2
Historically, a diagnosis of AS required radiographic evidence of inflammation of the axial spine or sacrum that manifested as chronic stiffness and back pain. However, the disease can also be mild or take time for radiographic evidence to appear. So an umbrella term emerged—axial spondyloarthritis (axSpA)—that includes both AS and the less severe form, called nonradiographic axSpA (nr-axSpA). While patients with AS exhibit radiographic abnormalities consistent with sacroiliitis, patients with early, or nr-axSpA, do not have radiographic abnormalities of the sacroiliac (SI) joint or axial spine.
In clinical practice, the distinction between AS and nr-axSpA has limited impact on the management of individual patients. However, early recognition, intervention, and treatment in patients who do not meet radiographic criteria for AS can improve patient-oriented outcomes.
The family physician (FP)’s role. It is not necessary that FPs be able to make a definitive diagnosis, but FPs should:
- be able to recognize the symptoms of inflammatory back pain (IBP);
- know which radiographic and laboratory studies to obtain and when;
- know the Assessment of SpondyloArthritis international Society (ASAS) criteria3 that assist in identifying patients at risk for axSpA; and
- know when to refer moderate- to high-risk patients to rheumatologists for assistance with the diagnosis.
FPs should have a high index of suspicion in any patient who has chronic back pain (> 3 months) with other features of SpA, and should pay special attention to young adult patients (< 45 years) who have IBP features.
Continue to: Definitive data to show...
Definitive data to show what percentage of patients with nr-axSpA progress to AS are lacking. However, early identification of AS is important, as those who go undiagnosed have increased back pain, stiffness, progressive loss of mobility, and decreased quality of life. In addition, patients diagnosed after significant sacroiliitis is visible are less responsive to treatment.4
What follows is a review of what you’ll see and the tools that will help with diagnosis and referral.
The diagnosis dilemma
In the past, the modified New York criteria have been used to define AS, but they require the presence of both clinical symptoms and radiographic findings indicative of sacroiliitis for an AS designation.5,6 Because radiographic sacroiliitis can be a late finding in axSpA and nonexistent in nr-asSpA, these criteria are of limited clinical utility.
To assist in early identification, the ASAS published criteria to classify patients with early axSpA prior to radiographic manifestations.3 While not strictly diagnostic, these criteria combine patient history that includes evidence of IBP, human leukocyte antigen (HLA)-B27 positivity, and radiography to assist health care providers in identifying patients who may have axSpA and need prompt referral to a rheumatologist.
Easy to miss, even with evidence. It takes an average of 5 to 7 years for patients with radiographic evidence of AS to receive the proper diagnosis.7 There are several reasons for this. First, the axSpA spectrum encompasses a small percentage of patients who present to health care providers with back pain. In addition, many providers overlook the signs and symptoms of IBP, which are a hallmark of the condition. And finally, as stated earlier, true criteria for the diagnosis of axSpA do not exist.
Continue to: In addition...
In addition, AS predominantly affects people in the third and fourth decades of life, but as many as 5% of patients of all ages with chronic back pain (> 3 months) can be classified as having AS.8 In patients who have IBP features, 14% can be classified as having axSpA.9 Therefore, it is important to recognize the features of IBP (TABLE 110). The presence of 4 of the 5 of IBP features has a sensitivity of 77% and a specificity of 91.7% for IBP.10
A different kind of back pain. The vast majority of patients presenting with low back pain will have features of mechanical back pain, which include improvement with rest, mild and short-lived morning stiffness and/or pain upon waking, and the absence of inflammatory markers. Those with axSpA, on the other hand, are more likely to report improvement of pain with exercise, no improvement with rest, and pain at night with improvement upon rising. While the presence of IBP features alone isn’t diagnostic for nr-axSpA or AS, such features should increase your suspicion, especially when such features are present in younger patients.
Physical exam findings
Physical exam findings are neither sensitive nor specific for the diagnosis of an axSpA disorder, but can help build a case for one. The physical exam can also assist in identifying comorbid conditions including uveitis, psoriasis, dactylitis, and enthesitis. Experts do not recommend using serial measurements of axial range of motion because they are time-consuming, and normative values are highly variable.
On examination of the peripheral joints and feet, note any swollen, tender, or deformed joints, as well as any dactylitis. Although any enthesis can be affected in axSpA, the insertional points of the Achilles and the plantar fascia are the most typical,1 so pay particular attention to these areas. On skin exam, note any evidence of psoriatic manifestations. Refer all patients with suspected uveitis to an ophthalmologist for confirmation of the diagnosis.
Lab studies: Not definitive, but helpful
No laboratory studies confirm a diagnosis of nr-axSpA or AS; however, 2 studies—C-reactive protein (CRP) and HLA-B27—are important, as levels are listed as part of ASAS’s axSpA features (TABLE 23) and are factors that should be considered when deciding whether a referral is needed (TABLE 311). As such, HLA-B27 and CRP testing should be performed in all patients suspected of having an axSpA spectrum disorder.
Continue to: HLA-B27 is...
HLA-B27 is positive in 70% to 95% of patients with axSpA and can help build a case for the disorder.6,12 CRP is useful too, as an elevated CRP has important treatment implications (more on that in a bit).6
Other diagnoses in the differential include: degenerative disc disease, lumbar spondylosis, congenital vertebral anomalies, and osteoarthritis of the SI joint, bone metastasis, or primary bone tumors.1
Start with plain x-rays. The American College of Radiology (ACR) published appropriateness criteria for obtaining x-rays in patients suspected of having axSpA.13 Plain x-rays of the spine and SI joint are recommended for the initial evaluation. Magnetic resonance imaging (MRI) of the SI joint and/or spine should be obtained if the initial x-rays are negative or equivocal. Patient symptomology and/or exam findings determine whether to include the SI joint and/or spine. If the patient has subjective and objective findings concerning for pathology of both, then an MRI of the spine and SI joint is warranted.
Alternatively, computed tomography (CT) can be substituted if MRI is unavailable. In patients with known axSpA, surveillance radiography should not occur more often than every 2 years.6
Timely referral is essential
Timely referral to a rheumatologist is an essential part of early diagnosis and treatment. Advances in treatment options for axSpA have become available in recent years and offer new hope for patients.
Continue to: As the presence of IBP...
As the presence of IBP features portends a 3-fold increase in the risk for axSpA,8 we propose an approach to the referral of patients with IBP features that deviates slightly from the ASAS algorithm. We believe it is within the scope of FPs to recognize IBP features, order appropriate ancillary studies, start a trial of nonsteroidal anti-inflammatory drugs (NSAIDs), and follow-up with patients in 2 to 4 weeks to review results and evaluate treatment response. As such, all patients < 45 years old with IBP symptoms (TABLE 110) for 3 months or longer should be sent for laboratory workup (HLA-B27, CRP) and plain radiographs of the sacroiliac joints and lumbar spine.
Older patients, patients with IBP features for < 3 months, or patients < 45 years with IBP that have negative lab testing and negative radiographs should start an exercise program, be treated with an NSAID, and be assessed for ASAS spondyloarthritis features (TABLE 23).
Any patient with positive lab testing, positive radiographs, or ≥ 1 ASAS axSpA features should be referred to Rheumatology (TABLE 311). Patients with a negative radiograph should be evaluated with an MRI of the SI joints or spine (driven by pain location) and referred to Rheumatology if positive.
Keep in mind that not all patients fit neatly into an algorithm or a classification system. Therefore, we recommend that any patient with IBP features who fails to improve after 3 months of an exercise program, for whom you have a high index of suspicion for possible axSpA spectrum disease, receive appropriate ancillary studies and referral for expert consultation.
Exercise and NSAIDs form the basis of treatment
The purpose of treating patients with a suspected axSpA spectrum disorder is to decrease pain and stiffness, improve function and quality of life, and, ideally, halt or slow progression of disease. The only modifiable predictor of progression to axSpA is smoking; as such, encourage tobacco cessation if appropriate.14
Continue to: Nonpharmacologic treatment...
Nonpharmacologic treatment, such as regular aerobic exercise and strength training, should be prescribed for all patients with axSpA.6 Regular exercise is helpful in improving lower back pain, function, and spinal mobility. Combination endurance and strength-training programs are associated with the greatest benefits, and aquatic therapy is better than land-based therapy for pain.15 That said, recommend land-based exercises over no exercise when pool-based therapy is unavailable.
NSAIDs (eg, ibuprofen 200-800 mg at variable frequency, up to a maximum dose of 2400 mg/d; naproxen 250-500 mg bid) are the core treatment for patients with axSpA, as they improve pain, function, and quality of life.6 Both traditional NSAIDs and cyclooxygenase II (COX-II) inhibitors are effective; no differences in efficacy exist between the classes.6,15,16
NSAIDs have been shown to be as safe as placebo for up to 12 weeks of continuous use in patients without gastritis or renal disease.16 In patients with a gastrointestinal comorbidity, use NSAIDs cautiously.17
If adequate pain relief is not obtained after 2 to 4 weeks of NSAID use, try a different NSAID prior to escalating treatment.6 More research is needed to evaluate the effect of NSAIDs on spinal radiographic progression of disease because of conflicting results of existing studies.16
Unlike with other rheumatologic disorders, oral glucocorticoids and traditional disease-modifying anti-rheumatic drugs (DMARDs) are not effective in axSpA and should not be prescribed.18
Continue to: Other agents
Other agents. In patients who continue to have symptoms, or cannot tolerate 12 weeks of NSAIDs, newer biologic DMARDs may be considered. Tumor necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i) have shown the best efficacy.18,19 In patients with AS, these medications improve pain and function, increase the chance of achieving partial remission of symptoms, and reduce CRP levels and MRI-detectable inflammation of the SI joint and/or spine.1,19 At this time, these medications are reserved for use in patients with clinical symptoms consistent with, and radiographic evidence of, axSpA, or in patients with nr-axSpA who have elevated CRP levels.18
For patients diagnosed with axSpA, an elevated CRP, short symptom duration (or young age), and inflammation noted on MRI seem to be the best predictors of a good response to TNFi.20 All patients in whom biologic DMARDS are considered should be referred to a rheumatologist because of cost, potential adverse effects, and stringent indications for use.
Surveil disease progression to prevent complications
We don’t yet know if progression of axSpA is linear or if the process can be slowed or halted with timely treatment. We do know that the natural history of structural progression is low in patients with early nr-axSpA.
Examples of validated online tools that can assist in measuring patient response to treatment and/or progression of disease follow.21 They can be used alone or in combination to help monitor treatment and progression of disease.
- The Ankylosing Spondylitis Disease Activity Score (ASDAS) (https://www.asas-group.org/clinical-instruments/asdas-calculator/). This measure of disease activity uses a 5-item patient assessment and CRP level measurement.
- The Bath Ankylosing Spondylitis Functional Index (BASFI) (http://basdai.com/BASFI.php). The BASFI consists of 8 items pertaining to everyday function and 2 items assessing the ability of patients to cope with everyday life.
- The Ankylosing Spondylitis Quality of Life Scale (ASQoL; http://oml.eular.org/sysModules/obxOml/docs/ID_32/ASQoL%20Questionnaire%20English.pdf).The ASQoL is an 18-item questionnaire related to the impact of disease on sleep, mood, motivation, and activities of daily living, among others.
Comorbidities. Patients with axSpA have an increased lifetime risk for cardiovascular disease, osteoporosis, fracture, inflammatory bowel disease, and iritis.6 Acute back pain in a patient with axSpA should be evaluated for a fracture and not automatically deemed an axSpA flare.13 Obtain a CT scan of the spine for all patients with known spine ankyloses who are suspected of having a fracture (because of the low sensitivity of plain radiography).13
Continue to: Prognosis
Prognosis. AS is a progressive long-term medical condition. Patients may experience progressive spinal deformity, hip joint or sacroiliac arthroses, or neurologic compromise after trauma. Reserve surgical referral for patients with spinal deformity that significantly affects quality of life and is severe or progressing despite nonpharmacologic and pharmacologic measures. Refer patients with an unstable spinal fracture for surgical intervention.6
Advise patients of available local, national, and international support groups. The National Ankylosis Spondylitis Society (NASS) based in the United Kingdom and the Spondylitis Association of America (SAA) are patient-friendly, nonprofit organizations that provide resources and information to people to help them learn about and cope with their condition.
CASE
You diagnose IBP in this patient and proceed with a work-up. You order x-rays of the back and SI joint, a CRP level, and an HLA-B27 test. X-rays and laboratory studies are negative. The patient is encouraged by your recommendation to start an aerobic and strength training home exercise program. In addition, you prescribe naproxen 500 mg bid and ask the patient to return in 1 month.
On follow-up he states that the naproxen is working well to control his pain. Upon further chart review and questioning, the patient confirms a history of chronic plantar fasciosis and psoriasis that he has controlled with intermittent topical steroids. He denies visual disturbances or gastrointestinal complaints. You refer him to a rheumatologist, where biologic agents are discussed but not prescribed at this time.
CORRESPONDENCE
Carlton J Covey, MD, FAAFP, Nellis Family Medicine Residency Program, 4700 Las Vegas Blvd. North, Nellis AFB, NV 89191; carlton.j.covey.mil@mail.mil
1. Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet. 2017;390:73-84.
2. Lawrence R, Helmick C, Arnett F, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 1998;41:778-799.
3. Rudwaleit M, van der Heijde D, Landewe R, et al. The development of assessment of spondyloarthritis international society classification criteria for axial spondyloarthritis (part II); validation and final selection. Ann Rheum Dis. 2009;68:777-783.
4. Seo MR, Baek HL, Yoon HH, et al. Delayed diagnosis is linked to worse outcomes and unfavorable treatment responses in patients with axial spondyloarthritis. Clin Rheumatol. 2015;34:1397-1405.
5. van der Linden SM, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27:361-68.
6. National Institute for Health and Care Excellence. NICE Guideline, No. 65. Spondyloarthritis in over 16s: diagnosis and management. February 2017. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0091652/. Accessed April 24, 2019.
7. Dincer U, Cakar E, Kiralp MZ, et al. Diagnosis delay in patients with ankylosing spondylitis: possible reasons and proposals for new diagnostic criteria. Clin Rheumatol. 2008:27:457-462.
8. Underwood MR, Dawes P. Inflammatory back pain in primary care. Br J Rheumatol. 1995;34:1074-1077.
9. Strand V, Singh J. Evaluation and management of the patient with suspected inflammatory spine disease. Mayo Clin Proc. 2017;92:555-564.
10. Sieper J, van der Heijde D, Landewe R, et al. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS). Ann Rheum Dis. 2009;68:784-788.
11. Poddubnyy D, van Tubergen A, Landewe R, et al. Development of ASAS-endorsed recommendation for the early referral of patients with a suspicion of axial spondyloarthritis. Ann Rheum Dis. 2015;74:1483-1487.
12. Rostom S, Dougados M, Gossec L. New tools for diagnosing spondyloarthropathy. Joint Bone Spine. 2010;77:108-114.
13. Bernard SA, Kransdorf MJ, Beaman FD, et al. ACR appropriateness criteria chronic back pain suspected sacroiliitis-spondyloarthropathy. J Am Coll Radiol. 2017;14:S62-S70.
14. Dougados M, Demattei C, van den Berg R, et al. Rate and predisposing factors for sacroiliac joint radiographic progression after a two-year follow-up period in recent-onset spondyloarthritis. Arthritis Rheumatol. 2016;68:1904-1913.
15. Regel A, Sepriano A, Baraliakos X, et al. Efficacy and safety of non-pharmacological treatment: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis. RMD Open. 2017;3:e000397.
16. Kroon FPB, van der Burg LRA, Ramiro S, et al. Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis). Cochrane Database Syst Rev. 2015;7:CD010952.
17. Radner H, Ramiro S, Buchbinder R, et al. Pain management for inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and other spondyloarthritis) and gastrointestinal or liver comorbidity. Cochrane Database Syst Rev. 2012;1:CD008951.
18. van der Heijde D, Ramiro S, Landewe R, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017;76:978-991.
19. Maxwell LJ, Zochling J, Boonen A, et al. TNF-alpha inhibitors for ankylosing spondylitis. Cochrane Database Syst Rev. 2015;4:CN005468.
20. Sieper J, Poddubnyy D. New evidence on the management of spondyloarthritis. Nat Rev Rheumatol. 2016;12:282-295.
21. Zochling J. Measures of symptoms and disease status in ankylosing spondylitis. Arthritis Care Res. 2011;63:S47-S58.
CASE
A 38-year-old man presents to your primary care clinic with chronic low back stiffness and pain. You have evaluated and treated this patient for this complaint for more than a year. His symptoms are worse in the morning upon wakening and improve with activity and anti-inflammatory medications. He denies any trauma or change in his activity level. His medical history includes chronic insertional Achilles pain and plantar fasciopathy, both for approximately 2 years. The patient reports no systemic or constitutional symptoms, and no pertinent family history.
How would you proceed with his work-up?
Ankylosing spondylitis (AS) is a form of arthritis that primarily affects the spine and sacroiliac joints. It is the most common spondyloarthropathy (SpA)—a family of disorders that also includes psoriatic arthritis; arthritis associated with inflammatory bowel disease; reactive arthritis; and juvenile SpA.1 AS is most prevalent in Caucasians and may affect 0.1% to 1.4% of the population.2
Historically, a diagnosis of AS required radiographic evidence of inflammation of the axial spine or sacrum that manifested as chronic stiffness and back pain. However, the disease can also be mild or take time for radiographic evidence to appear. So an umbrella term emerged—axial spondyloarthritis (axSpA)—that includes both AS and the less severe form, called nonradiographic axSpA (nr-axSpA). While patients with AS exhibit radiographic abnormalities consistent with sacroiliitis, patients with early, or nr-axSpA, do not have radiographic abnormalities of the sacroiliac (SI) joint or axial spine.
In clinical practice, the distinction between AS and nr-axSpA has limited impact on the management of individual patients. However, early recognition, intervention, and treatment in patients who do not meet radiographic criteria for AS can improve patient-oriented outcomes.
The family physician (FP)’s role. It is not necessary that FPs be able to make a definitive diagnosis, but FPs should:
- be able to recognize the symptoms of inflammatory back pain (IBP);
- know which radiographic and laboratory studies to obtain and when;
- know the Assessment of SpondyloArthritis international Society (ASAS) criteria3 that assist in identifying patients at risk for axSpA; and
- know when to refer moderate- to high-risk patients to rheumatologists for assistance with the diagnosis.
FPs should have a high index of suspicion in any patient who has chronic back pain (> 3 months) with other features of SpA, and should pay special attention to young adult patients (< 45 years) who have IBP features.
Continue to: Definitive data to show...
Definitive data to show what percentage of patients with nr-axSpA progress to AS are lacking. However, early identification of AS is important, as those who go undiagnosed have increased back pain, stiffness, progressive loss of mobility, and decreased quality of life. In addition, patients diagnosed after significant sacroiliitis is visible are less responsive to treatment.4
What follows is a review of what you’ll see and the tools that will help with diagnosis and referral.
The diagnosis dilemma
In the past, the modified New York criteria have been used to define AS, but they require the presence of both clinical symptoms and radiographic findings indicative of sacroiliitis for an AS designation.5,6 Because radiographic sacroiliitis can be a late finding in axSpA and nonexistent in nr-asSpA, these criteria are of limited clinical utility.
To assist in early identification, the ASAS published criteria to classify patients with early axSpA prior to radiographic manifestations.3 While not strictly diagnostic, these criteria combine patient history that includes evidence of IBP, human leukocyte antigen (HLA)-B27 positivity, and radiography to assist health care providers in identifying patients who may have axSpA and need prompt referral to a rheumatologist.
Easy to miss, even with evidence. It takes an average of 5 to 7 years for patients with radiographic evidence of AS to receive the proper diagnosis.7 There are several reasons for this. First, the axSpA spectrum encompasses a small percentage of patients who present to health care providers with back pain. In addition, many providers overlook the signs and symptoms of IBP, which are a hallmark of the condition. And finally, as stated earlier, true criteria for the diagnosis of axSpA do not exist.
Continue to: In addition...
In addition, AS predominantly affects people in the third and fourth decades of life, but as many as 5% of patients of all ages with chronic back pain (> 3 months) can be classified as having AS.8 In patients who have IBP features, 14% can be classified as having axSpA.9 Therefore, it is important to recognize the features of IBP (TABLE 110). The presence of 4 of the 5 of IBP features has a sensitivity of 77% and a specificity of 91.7% for IBP.10
A different kind of back pain. The vast majority of patients presenting with low back pain will have features of mechanical back pain, which include improvement with rest, mild and short-lived morning stiffness and/or pain upon waking, and the absence of inflammatory markers. Those with axSpA, on the other hand, are more likely to report improvement of pain with exercise, no improvement with rest, and pain at night with improvement upon rising. While the presence of IBP features alone isn’t diagnostic for nr-axSpA or AS, such features should increase your suspicion, especially when such features are present in younger patients.
Physical exam findings
Physical exam findings are neither sensitive nor specific for the diagnosis of an axSpA disorder, but can help build a case for one. The physical exam can also assist in identifying comorbid conditions including uveitis, psoriasis, dactylitis, and enthesitis. Experts do not recommend using serial measurements of axial range of motion because they are time-consuming, and normative values are highly variable.
On examination of the peripheral joints and feet, note any swollen, tender, or deformed joints, as well as any dactylitis. Although any enthesis can be affected in axSpA, the insertional points of the Achilles and the plantar fascia are the most typical,1 so pay particular attention to these areas. On skin exam, note any evidence of psoriatic manifestations. Refer all patients with suspected uveitis to an ophthalmologist for confirmation of the diagnosis.
Lab studies: Not definitive, but helpful
No laboratory studies confirm a diagnosis of nr-axSpA or AS; however, 2 studies—C-reactive protein (CRP) and HLA-B27—are important, as levels are listed as part of ASAS’s axSpA features (TABLE 23) and are factors that should be considered when deciding whether a referral is needed (TABLE 311). As such, HLA-B27 and CRP testing should be performed in all patients suspected of having an axSpA spectrum disorder.
Continue to: HLA-B27 is...
HLA-B27 is positive in 70% to 95% of patients with axSpA and can help build a case for the disorder.6,12 CRP is useful too, as an elevated CRP has important treatment implications (more on that in a bit).6
Other diagnoses in the differential include: degenerative disc disease, lumbar spondylosis, congenital vertebral anomalies, and osteoarthritis of the SI joint, bone metastasis, or primary bone tumors.1
Start with plain x-rays. The American College of Radiology (ACR) published appropriateness criteria for obtaining x-rays in patients suspected of having axSpA.13 Plain x-rays of the spine and SI joint are recommended for the initial evaluation. Magnetic resonance imaging (MRI) of the SI joint and/or spine should be obtained if the initial x-rays are negative or equivocal. Patient symptomology and/or exam findings determine whether to include the SI joint and/or spine. If the patient has subjective and objective findings concerning for pathology of both, then an MRI of the spine and SI joint is warranted.
Alternatively, computed tomography (CT) can be substituted if MRI is unavailable. In patients with known axSpA, surveillance radiography should not occur more often than every 2 years.6
Timely referral is essential
Timely referral to a rheumatologist is an essential part of early diagnosis and treatment. Advances in treatment options for axSpA have become available in recent years and offer new hope for patients.
Continue to: As the presence of IBP...
As the presence of IBP features portends a 3-fold increase in the risk for axSpA,8 we propose an approach to the referral of patients with IBP features that deviates slightly from the ASAS algorithm. We believe it is within the scope of FPs to recognize IBP features, order appropriate ancillary studies, start a trial of nonsteroidal anti-inflammatory drugs (NSAIDs), and follow-up with patients in 2 to 4 weeks to review results and evaluate treatment response. As such, all patients < 45 years old with IBP symptoms (TABLE 110) for 3 months or longer should be sent for laboratory workup (HLA-B27, CRP) and plain radiographs of the sacroiliac joints and lumbar spine.
Older patients, patients with IBP features for < 3 months, or patients < 45 years with IBP that have negative lab testing and negative radiographs should start an exercise program, be treated with an NSAID, and be assessed for ASAS spondyloarthritis features (TABLE 23).
Any patient with positive lab testing, positive radiographs, or ≥ 1 ASAS axSpA features should be referred to Rheumatology (TABLE 311). Patients with a negative radiograph should be evaluated with an MRI of the SI joints or spine (driven by pain location) and referred to Rheumatology if positive.
Keep in mind that not all patients fit neatly into an algorithm or a classification system. Therefore, we recommend that any patient with IBP features who fails to improve after 3 months of an exercise program, for whom you have a high index of suspicion for possible axSpA spectrum disease, receive appropriate ancillary studies and referral for expert consultation.
Exercise and NSAIDs form the basis of treatment
The purpose of treating patients with a suspected axSpA spectrum disorder is to decrease pain and stiffness, improve function and quality of life, and, ideally, halt or slow progression of disease. The only modifiable predictor of progression to axSpA is smoking; as such, encourage tobacco cessation if appropriate.14
Continue to: Nonpharmacologic treatment...
Nonpharmacologic treatment, such as regular aerobic exercise and strength training, should be prescribed for all patients with axSpA.6 Regular exercise is helpful in improving lower back pain, function, and spinal mobility. Combination endurance and strength-training programs are associated with the greatest benefits, and aquatic therapy is better than land-based therapy for pain.15 That said, recommend land-based exercises over no exercise when pool-based therapy is unavailable.
NSAIDs (eg, ibuprofen 200-800 mg at variable frequency, up to a maximum dose of 2400 mg/d; naproxen 250-500 mg bid) are the core treatment for patients with axSpA, as they improve pain, function, and quality of life.6 Both traditional NSAIDs and cyclooxygenase II (COX-II) inhibitors are effective; no differences in efficacy exist between the classes.6,15,16
NSAIDs have been shown to be as safe as placebo for up to 12 weeks of continuous use in patients without gastritis or renal disease.16 In patients with a gastrointestinal comorbidity, use NSAIDs cautiously.17
If adequate pain relief is not obtained after 2 to 4 weeks of NSAID use, try a different NSAID prior to escalating treatment.6 More research is needed to evaluate the effect of NSAIDs on spinal radiographic progression of disease because of conflicting results of existing studies.16
Unlike with other rheumatologic disorders, oral glucocorticoids and traditional disease-modifying anti-rheumatic drugs (DMARDs) are not effective in axSpA and should not be prescribed.18
Continue to: Other agents
Other agents. In patients who continue to have symptoms, or cannot tolerate 12 weeks of NSAIDs, newer biologic DMARDs may be considered. Tumor necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i) have shown the best efficacy.18,19 In patients with AS, these medications improve pain and function, increase the chance of achieving partial remission of symptoms, and reduce CRP levels and MRI-detectable inflammation of the SI joint and/or spine.1,19 At this time, these medications are reserved for use in patients with clinical symptoms consistent with, and radiographic evidence of, axSpA, or in patients with nr-axSpA who have elevated CRP levels.18
For patients diagnosed with axSpA, an elevated CRP, short symptom duration (or young age), and inflammation noted on MRI seem to be the best predictors of a good response to TNFi.20 All patients in whom biologic DMARDS are considered should be referred to a rheumatologist because of cost, potential adverse effects, and stringent indications for use.
Surveil disease progression to prevent complications
We don’t yet know if progression of axSpA is linear or if the process can be slowed or halted with timely treatment. We do know that the natural history of structural progression is low in patients with early nr-axSpA.
Examples of validated online tools that can assist in measuring patient response to treatment and/or progression of disease follow.21 They can be used alone or in combination to help monitor treatment and progression of disease.
- The Ankylosing Spondylitis Disease Activity Score (ASDAS) (https://www.asas-group.org/clinical-instruments/asdas-calculator/). This measure of disease activity uses a 5-item patient assessment and CRP level measurement.
- The Bath Ankylosing Spondylitis Functional Index (BASFI) (http://basdai.com/BASFI.php). The BASFI consists of 8 items pertaining to everyday function and 2 items assessing the ability of patients to cope with everyday life.
- The Ankylosing Spondylitis Quality of Life Scale (ASQoL; http://oml.eular.org/sysModules/obxOml/docs/ID_32/ASQoL%20Questionnaire%20English.pdf).The ASQoL is an 18-item questionnaire related to the impact of disease on sleep, mood, motivation, and activities of daily living, among others.
Comorbidities. Patients with axSpA have an increased lifetime risk for cardiovascular disease, osteoporosis, fracture, inflammatory bowel disease, and iritis.6 Acute back pain in a patient with axSpA should be evaluated for a fracture and not automatically deemed an axSpA flare.13 Obtain a CT scan of the spine for all patients with known spine ankyloses who are suspected of having a fracture (because of the low sensitivity of plain radiography).13
Continue to: Prognosis
Prognosis. AS is a progressive long-term medical condition. Patients may experience progressive spinal deformity, hip joint or sacroiliac arthroses, or neurologic compromise after trauma. Reserve surgical referral for patients with spinal deformity that significantly affects quality of life and is severe or progressing despite nonpharmacologic and pharmacologic measures. Refer patients with an unstable spinal fracture for surgical intervention.6
Advise patients of available local, national, and international support groups. The National Ankylosis Spondylitis Society (NASS) based in the United Kingdom and the Spondylitis Association of America (SAA) are patient-friendly, nonprofit organizations that provide resources and information to people to help them learn about and cope with their condition.
CASE
You diagnose IBP in this patient and proceed with a work-up. You order x-rays of the back and SI joint, a CRP level, and an HLA-B27 test. X-rays and laboratory studies are negative. The patient is encouraged by your recommendation to start an aerobic and strength training home exercise program. In addition, you prescribe naproxen 500 mg bid and ask the patient to return in 1 month.
On follow-up he states that the naproxen is working well to control his pain. Upon further chart review and questioning, the patient confirms a history of chronic plantar fasciosis and psoriasis that he has controlled with intermittent topical steroids. He denies visual disturbances or gastrointestinal complaints. You refer him to a rheumatologist, where biologic agents are discussed but not prescribed at this time.
CORRESPONDENCE
Carlton J Covey, MD, FAAFP, Nellis Family Medicine Residency Program, 4700 Las Vegas Blvd. North, Nellis AFB, NV 89191; carlton.j.covey.mil@mail.mil
CASE
A 38-year-old man presents to your primary care clinic with chronic low back stiffness and pain. You have evaluated and treated this patient for this complaint for more than a year. His symptoms are worse in the morning upon wakening and improve with activity and anti-inflammatory medications. He denies any trauma or change in his activity level. His medical history includes chronic insertional Achilles pain and plantar fasciopathy, both for approximately 2 years. The patient reports no systemic or constitutional symptoms, and no pertinent family history.
How would you proceed with his work-up?
Ankylosing spondylitis (AS) is a form of arthritis that primarily affects the spine and sacroiliac joints. It is the most common spondyloarthropathy (SpA)—a family of disorders that also includes psoriatic arthritis; arthritis associated with inflammatory bowel disease; reactive arthritis; and juvenile SpA.1 AS is most prevalent in Caucasians and may affect 0.1% to 1.4% of the population.2
Historically, a diagnosis of AS required radiographic evidence of inflammation of the axial spine or sacrum that manifested as chronic stiffness and back pain. However, the disease can also be mild or take time for radiographic evidence to appear. So an umbrella term emerged—axial spondyloarthritis (axSpA)—that includes both AS and the less severe form, called nonradiographic axSpA (nr-axSpA). While patients with AS exhibit radiographic abnormalities consistent with sacroiliitis, patients with early, or nr-axSpA, do not have radiographic abnormalities of the sacroiliac (SI) joint or axial spine.
In clinical practice, the distinction between AS and nr-axSpA has limited impact on the management of individual patients. However, early recognition, intervention, and treatment in patients who do not meet radiographic criteria for AS can improve patient-oriented outcomes.
The family physician (FP)’s role. It is not necessary that FPs be able to make a definitive diagnosis, but FPs should:
- be able to recognize the symptoms of inflammatory back pain (IBP);
- know which radiographic and laboratory studies to obtain and when;
- know the Assessment of SpondyloArthritis international Society (ASAS) criteria3 that assist in identifying patients at risk for axSpA; and
- know when to refer moderate- to high-risk patients to rheumatologists for assistance with the diagnosis.
FPs should have a high index of suspicion in any patient who has chronic back pain (> 3 months) with other features of SpA, and should pay special attention to young adult patients (< 45 years) who have IBP features.
Continue to: Definitive data to show...
Definitive data to show what percentage of patients with nr-axSpA progress to AS are lacking. However, early identification of AS is important, as those who go undiagnosed have increased back pain, stiffness, progressive loss of mobility, and decreased quality of life. In addition, patients diagnosed after significant sacroiliitis is visible are less responsive to treatment.4
What follows is a review of what you’ll see and the tools that will help with diagnosis and referral.
The diagnosis dilemma
In the past, the modified New York criteria have been used to define AS, but they require the presence of both clinical symptoms and radiographic findings indicative of sacroiliitis for an AS designation.5,6 Because radiographic sacroiliitis can be a late finding in axSpA and nonexistent in nr-asSpA, these criteria are of limited clinical utility.
To assist in early identification, the ASAS published criteria to classify patients with early axSpA prior to radiographic manifestations.3 While not strictly diagnostic, these criteria combine patient history that includes evidence of IBP, human leukocyte antigen (HLA)-B27 positivity, and radiography to assist health care providers in identifying patients who may have axSpA and need prompt referral to a rheumatologist.
Easy to miss, even with evidence. It takes an average of 5 to 7 years for patients with radiographic evidence of AS to receive the proper diagnosis.7 There are several reasons for this. First, the axSpA spectrum encompasses a small percentage of patients who present to health care providers with back pain. In addition, many providers overlook the signs and symptoms of IBP, which are a hallmark of the condition. And finally, as stated earlier, true criteria for the diagnosis of axSpA do not exist.
Continue to: In addition...
In addition, AS predominantly affects people in the third and fourth decades of life, but as many as 5% of patients of all ages with chronic back pain (> 3 months) can be classified as having AS.8 In patients who have IBP features, 14% can be classified as having axSpA.9 Therefore, it is important to recognize the features of IBP (TABLE 110). The presence of 4 of the 5 of IBP features has a sensitivity of 77% and a specificity of 91.7% for IBP.10
A different kind of back pain. The vast majority of patients presenting with low back pain will have features of mechanical back pain, which include improvement with rest, mild and short-lived morning stiffness and/or pain upon waking, and the absence of inflammatory markers. Those with axSpA, on the other hand, are more likely to report improvement of pain with exercise, no improvement with rest, and pain at night with improvement upon rising. While the presence of IBP features alone isn’t diagnostic for nr-axSpA or AS, such features should increase your suspicion, especially when such features are present in younger patients.
Physical exam findings
Physical exam findings are neither sensitive nor specific for the diagnosis of an axSpA disorder, but can help build a case for one. The physical exam can also assist in identifying comorbid conditions including uveitis, psoriasis, dactylitis, and enthesitis. Experts do not recommend using serial measurements of axial range of motion because they are time-consuming, and normative values are highly variable.
On examination of the peripheral joints and feet, note any swollen, tender, or deformed joints, as well as any dactylitis. Although any enthesis can be affected in axSpA, the insertional points of the Achilles and the plantar fascia are the most typical,1 so pay particular attention to these areas. On skin exam, note any evidence of psoriatic manifestations. Refer all patients with suspected uveitis to an ophthalmologist for confirmation of the diagnosis.
Lab studies: Not definitive, but helpful
No laboratory studies confirm a diagnosis of nr-axSpA or AS; however, 2 studies—C-reactive protein (CRP) and HLA-B27—are important, as levels are listed as part of ASAS’s axSpA features (TABLE 23) and are factors that should be considered when deciding whether a referral is needed (TABLE 311). As such, HLA-B27 and CRP testing should be performed in all patients suspected of having an axSpA spectrum disorder.
Continue to: HLA-B27 is...
HLA-B27 is positive in 70% to 95% of patients with axSpA and can help build a case for the disorder.6,12 CRP is useful too, as an elevated CRP has important treatment implications (more on that in a bit).6
Other diagnoses in the differential include: degenerative disc disease, lumbar spondylosis, congenital vertebral anomalies, and osteoarthritis of the SI joint, bone metastasis, or primary bone tumors.1
Start with plain x-rays. The American College of Radiology (ACR) published appropriateness criteria for obtaining x-rays in patients suspected of having axSpA.13 Plain x-rays of the spine and SI joint are recommended for the initial evaluation. Magnetic resonance imaging (MRI) of the SI joint and/or spine should be obtained if the initial x-rays are negative or equivocal. Patient symptomology and/or exam findings determine whether to include the SI joint and/or spine. If the patient has subjective and objective findings concerning for pathology of both, then an MRI of the spine and SI joint is warranted.
Alternatively, computed tomography (CT) can be substituted if MRI is unavailable. In patients with known axSpA, surveillance radiography should not occur more often than every 2 years.6
Timely referral is essential
Timely referral to a rheumatologist is an essential part of early diagnosis and treatment. Advances in treatment options for axSpA have become available in recent years and offer new hope for patients.
Continue to: As the presence of IBP...
As the presence of IBP features portends a 3-fold increase in the risk for axSpA,8 we propose an approach to the referral of patients with IBP features that deviates slightly from the ASAS algorithm. We believe it is within the scope of FPs to recognize IBP features, order appropriate ancillary studies, start a trial of nonsteroidal anti-inflammatory drugs (NSAIDs), and follow-up with patients in 2 to 4 weeks to review results and evaluate treatment response. As such, all patients < 45 years old with IBP symptoms (TABLE 110) for 3 months or longer should be sent for laboratory workup (HLA-B27, CRP) and plain radiographs of the sacroiliac joints and lumbar spine.
Older patients, patients with IBP features for < 3 months, or patients < 45 years with IBP that have negative lab testing and negative radiographs should start an exercise program, be treated with an NSAID, and be assessed for ASAS spondyloarthritis features (TABLE 23).
Any patient with positive lab testing, positive radiographs, or ≥ 1 ASAS axSpA features should be referred to Rheumatology (TABLE 311). Patients with a negative radiograph should be evaluated with an MRI of the SI joints or spine (driven by pain location) and referred to Rheumatology if positive.
Keep in mind that not all patients fit neatly into an algorithm or a classification system. Therefore, we recommend that any patient with IBP features who fails to improve after 3 months of an exercise program, for whom you have a high index of suspicion for possible axSpA spectrum disease, receive appropriate ancillary studies and referral for expert consultation.
Exercise and NSAIDs form the basis of treatment
The purpose of treating patients with a suspected axSpA spectrum disorder is to decrease pain and stiffness, improve function and quality of life, and, ideally, halt or slow progression of disease. The only modifiable predictor of progression to axSpA is smoking; as such, encourage tobacco cessation if appropriate.14
Continue to: Nonpharmacologic treatment...
Nonpharmacologic treatment, such as regular aerobic exercise and strength training, should be prescribed for all patients with axSpA.6 Regular exercise is helpful in improving lower back pain, function, and spinal mobility. Combination endurance and strength-training programs are associated with the greatest benefits, and aquatic therapy is better than land-based therapy for pain.15 That said, recommend land-based exercises over no exercise when pool-based therapy is unavailable.
NSAIDs (eg, ibuprofen 200-800 mg at variable frequency, up to a maximum dose of 2400 mg/d; naproxen 250-500 mg bid) are the core treatment for patients with axSpA, as they improve pain, function, and quality of life.6 Both traditional NSAIDs and cyclooxygenase II (COX-II) inhibitors are effective; no differences in efficacy exist between the classes.6,15,16
NSAIDs have been shown to be as safe as placebo for up to 12 weeks of continuous use in patients without gastritis or renal disease.16 In patients with a gastrointestinal comorbidity, use NSAIDs cautiously.17
If adequate pain relief is not obtained after 2 to 4 weeks of NSAID use, try a different NSAID prior to escalating treatment.6 More research is needed to evaluate the effect of NSAIDs on spinal radiographic progression of disease because of conflicting results of existing studies.16
Unlike with other rheumatologic disorders, oral glucocorticoids and traditional disease-modifying anti-rheumatic drugs (DMARDs) are not effective in axSpA and should not be prescribed.18
Continue to: Other agents
Other agents. In patients who continue to have symptoms, or cannot tolerate 12 weeks of NSAIDs, newer biologic DMARDs may be considered. Tumor necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i) have shown the best efficacy.18,19 In patients with AS, these medications improve pain and function, increase the chance of achieving partial remission of symptoms, and reduce CRP levels and MRI-detectable inflammation of the SI joint and/or spine.1,19 At this time, these medications are reserved for use in patients with clinical symptoms consistent with, and radiographic evidence of, axSpA, or in patients with nr-axSpA who have elevated CRP levels.18
For patients diagnosed with axSpA, an elevated CRP, short symptom duration (or young age), and inflammation noted on MRI seem to be the best predictors of a good response to TNFi.20 All patients in whom biologic DMARDS are considered should be referred to a rheumatologist because of cost, potential adverse effects, and stringent indications for use.
Surveil disease progression to prevent complications
We don’t yet know if progression of axSpA is linear or if the process can be slowed or halted with timely treatment. We do know that the natural history of structural progression is low in patients with early nr-axSpA.
Examples of validated online tools that can assist in measuring patient response to treatment and/or progression of disease follow.21 They can be used alone or in combination to help monitor treatment and progression of disease.
- The Ankylosing Spondylitis Disease Activity Score (ASDAS) (https://www.asas-group.org/clinical-instruments/asdas-calculator/). This measure of disease activity uses a 5-item patient assessment and CRP level measurement.
- The Bath Ankylosing Spondylitis Functional Index (BASFI) (http://basdai.com/BASFI.php). The BASFI consists of 8 items pertaining to everyday function and 2 items assessing the ability of patients to cope with everyday life.
- The Ankylosing Spondylitis Quality of Life Scale (ASQoL; http://oml.eular.org/sysModules/obxOml/docs/ID_32/ASQoL%20Questionnaire%20English.pdf).The ASQoL is an 18-item questionnaire related to the impact of disease on sleep, mood, motivation, and activities of daily living, among others.
Comorbidities. Patients with axSpA have an increased lifetime risk for cardiovascular disease, osteoporosis, fracture, inflammatory bowel disease, and iritis.6 Acute back pain in a patient with axSpA should be evaluated for a fracture and not automatically deemed an axSpA flare.13 Obtain a CT scan of the spine for all patients with known spine ankyloses who are suspected of having a fracture (because of the low sensitivity of plain radiography).13
Continue to: Prognosis
Prognosis. AS is a progressive long-term medical condition. Patients may experience progressive spinal deformity, hip joint or sacroiliac arthroses, or neurologic compromise after trauma. Reserve surgical referral for patients with spinal deformity that significantly affects quality of life and is severe or progressing despite nonpharmacologic and pharmacologic measures. Refer patients with an unstable spinal fracture for surgical intervention.6
Advise patients of available local, national, and international support groups. The National Ankylosis Spondylitis Society (NASS) based in the United Kingdom and the Spondylitis Association of America (SAA) are patient-friendly, nonprofit organizations that provide resources and information to people to help them learn about and cope with their condition.
CASE
You diagnose IBP in this patient and proceed with a work-up. You order x-rays of the back and SI joint, a CRP level, and an HLA-B27 test. X-rays and laboratory studies are negative. The patient is encouraged by your recommendation to start an aerobic and strength training home exercise program. In addition, you prescribe naproxen 500 mg bid and ask the patient to return in 1 month.
On follow-up he states that the naproxen is working well to control his pain. Upon further chart review and questioning, the patient confirms a history of chronic plantar fasciosis and psoriasis that he has controlled with intermittent topical steroids. He denies visual disturbances or gastrointestinal complaints. You refer him to a rheumatologist, where biologic agents are discussed but not prescribed at this time.
CORRESPONDENCE
Carlton J Covey, MD, FAAFP, Nellis Family Medicine Residency Program, 4700 Las Vegas Blvd. North, Nellis AFB, NV 89191; carlton.j.covey.mil@mail.mil
1. Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet. 2017;390:73-84.
2. Lawrence R, Helmick C, Arnett F, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 1998;41:778-799.
3. Rudwaleit M, van der Heijde D, Landewe R, et al. The development of assessment of spondyloarthritis international society classification criteria for axial spondyloarthritis (part II); validation and final selection. Ann Rheum Dis. 2009;68:777-783.
4. Seo MR, Baek HL, Yoon HH, et al. Delayed diagnosis is linked to worse outcomes and unfavorable treatment responses in patients with axial spondyloarthritis. Clin Rheumatol. 2015;34:1397-1405.
5. van der Linden SM, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27:361-68.
6. National Institute for Health and Care Excellence. NICE Guideline, No. 65. Spondyloarthritis in over 16s: diagnosis and management. February 2017. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0091652/. Accessed April 24, 2019.
7. Dincer U, Cakar E, Kiralp MZ, et al. Diagnosis delay in patients with ankylosing spondylitis: possible reasons and proposals for new diagnostic criteria. Clin Rheumatol. 2008:27:457-462.
8. Underwood MR, Dawes P. Inflammatory back pain in primary care. Br J Rheumatol. 1995;34:1074-1077.
9. Strand V, Singh J. Evaluation and management of the patient with suspected inflammatory spine disease. Mayo Clin Proc. 2017;92:555-564.
10. Sieper J, van der Heijde D, Landewe R, et al. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS). Ann Rheum Dis. 2009;68:784-788.
11. Poddubnyy D, van Tubergen A, Landewe R, et al. Development of ASAS-endorsed recommendation for the early referral of patients with a suspicion of axial spondyloarthritis. Ann Rheum Dis. 2015;74:1483-1487.
12. Rostom S, Dougados M, Gossec L. New tools for diagnosing spondyloarthropathy. Joint Bone Spine. 2010;77:108-114.
13. Bernard SA, Kransdorf MJ, Beaman FD, et al. ACR appropriateness criteria chronic back pain suspected sacroiliitis-spondyloarthropathy. J Am Coll Radiol. 2017;14:S62-S70.
14. Dougados M, Demattei C, van den Berg R, et al. Rate and predisposing factors for sacroiliac joint radiographic progression after a two-year follow-up period in recent-onset spondyloarthritis. Arthritis Rheumatol. 2016;68:1904-1913.
15. Regel A, Sepriano A, Baraliakos X, et al. Efficacy and safety of non-pharmacological treatment: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis. RMD Open. 2017;3:e000397.
16. Kroon FPB, van der Burg LRA, Ramiro S, et al. Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis). Cochrane Database Syst Rev. 2015;7:CD010952.
17. Radner H, Ramiro S, Buchbinder R, et al. Pain management for inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and other spondyloarthritis) and gastrointestinal or liver comorbidity. Cochrane Database Syst Rev. 2012;1:CD008951.
18. van der Heijde D, Ramiro S, Landewe R, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017;76:978-991.
19. Maxwell LJ, Zochling J, Boonen A, et al. TNF-alpha inhibitors for ankylosing spondylitis. Cochrane Database Syst Rev. 2015;4:CN005468.
20. Sieper J, Poddubnyy D. New evidence on the management of spondyloarthritis. Nat Rev Rheumatol. 2016;12:282-295.
21. Zochling J. Measures of symptoms and disease status in ankylosing spondylitis. Arthritis Care Res. 2011;63:S47-S58.
1. Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet. 2017;390:73-84.
2. Lawrence R, Helmick C, Arnett F, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 1998;41:778-799.
3. Rudwaleit M, van der Heijde D, Landewe R, et al. The development of assessment of spondyloarthritis international society classification criteria for axial spondyloarthritis (part II); validation and final selection. Ann Rheum Dis. 2009;68:777-783.
4. Seo MR, Baek HL, Yoon HH, et al. Delayed diagnosis is linked to worse outcomes and unfavorable treatment responses in patients with axial spondyloarthritis. Clin Rheumatol. 2015;34:1397-1405.
5. van der Linden SM, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27:361-68.
6. National Institute for Health and Care Excellence. NICE Guideline, No. 65. Spondyloarthritis in over 16s: diagnosis and management. February 2017. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0091652/. Accessed April 24, 2019.
7. Dincer U, Cakar E, Kiralp MZ, et al. Diagnosis delay in patients with ankylosing spondylitis: possible reasons and proposals for new diagnostic criteria. Clin Rheumatol. 2008:27:457-462.
8. Underwood MR, Dawes P. Inflammatory back pain in primary care. Br J Rheumatol. 1995;34:1074-1077.
9. Strand V, Singh J. Evaluation and management of the patient with suspected inflammatory spine disease. Mayo Clin Proc. 2017;92:555-564.
10. Sieper J, van der Heijde D, Landewe R, et al. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS). Ann Rheum Dis. 2009;68:784-788.
11. Poddubnyy D, van Tubergen A, Landewe R, et al. Development of ASAS-endorsed recommendation for the early referral of patients with a suspicion of axial spondyloarthritis. Ann Rheum Dis. 2015;74:1483-1487.
12. Rostom S, Dougados M, Gossec L. New tools for diagnosing spondyloarthropathy. Joint Bone Spine. 2010;77:108-114.
13. Bernard SA, Kransdorf MJ, Beaman FD, et al. ACR appropriateness criteria chronic back pain suspected sacroiliitis-spondyloarthropathy. J Am Coll Radiol. 2017;14:S62-S70.
14. Dougados M, Demattei C, van den Berg R, et al. Rate and predisposing factors for sacroiliac joint radiographic progression after a two-year follow-up period in recent-onset spondyloarthritis. Arthritis Rheumatol. 2016;68:1904-1913.
15. Regel A, Sepriano A, Baraliakos X, et al. Efficacy and safety of non-pharmacological treatment: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis. RMD Open. 2017;3:e000397.
16. Kroon FPB, van der Burg LRA, Ramiro S, et al. Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis). Cochrane Database Syst Rev. 2015;7:CD010952.
17. Radner H, Ramiro S, Buchbinder R, et al. Pain management for inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and other spondyloarthritis) and gastrointestinal or liver comorbidity. Cochrane Database Syst Rev. 2012;1:CD008951.
18. van der Heijde D, Ramiro S, Landewe R, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017;76:978-991.
19. Maxwell LJ, Zochling J, Boonen A, et al. TNF-alpha inhibitors for ankylosing spondylitis. Cochrane Database Syst Rev. 2015;4:CN005468.
20. Sieper J, Poddubnyy D. New evidence on the management of spondyloarthritis. Nat Rev Rheumatol. 2016;12:282-295.
21. Zochling J. Measures of symptoms and disease status in ankylosing spondylitis. Arthritis Care Res. 2011;63:S47-S58.
PRACTICE RECOMMENDATIONS
› Evaluate all patients with back pain lasting > 3 months for inflammatory back pain features. C
› Treat all patients with confirmed or suspected axial spondyloarthritis with a trial of nonsteroidal anti-inflammatory drugs. A
› Recommend that all patients with back pain—including those with suspected axial spondyloarthritis—start an exercise program that includes both strength and aerobic activities. A
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
Higher infection risk in RA seen with high blood biologic levels
BIRMINGHAM, ENGLAND – Higher blood biologic drug levels in the first year of treatment for rheumatoid arthritis independently increased the risk of any infection by about 50% when compared against low or normal levels in a new observational cohort study, providing support for monitoring biologic drug levels to help to predict infection risk.
Data from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA) that were presented at the British Society for Rheumatology annual conference showed that the adjusted hazard ratio for any infection occurring within the first year among patients with high drug levels was 1.51, with a 95% confidence interval (CI) of 1.14 to 2.01. The adjustments took into account patients’ age, gender, disease activity score, and use of methotrexate.
There are more than 10 biologics now available for use in rheumatoid arthritis but deciding which to use in a particular patient remains very much “a trial and error approach,” first author Meghna Jani, MBChB, said at the conference.
“From a patient perspective, one of the most important concerns continues to be the risk of serious infections and adverse events,” added Dr. Jani, a National Institute for Health Research Academic Clinical Lecturer in Rheumatology at the University of Manchester (England).
The link between biologic agents and infections, including those that could result in hospitalization or other serious consequences, has been well studied in biologics registries. It is known, for example, that the risk of infections with tumor necrosis factor inhibitor treatment seems to be highest during the first 6-12 months of treatment.
According to Dr. Jani, conventional means of determining risk – such as patient age and the presence of comorbid factors – have limited benefit in terms of deciding which patients could be at heightened risk of infections. “Ideally, we need biomarkers in rheumatology that can be implemented in clinical practice and help us predict efficacy and safety, as well as help us use these medications much more cost-effectively,” she said.
Four years ago, a meta-analysis (Lancet. 2015;386:258-65) suggested that the risk of infection may be linked to using higher doses of anti–tumor necrosis factor drugs, which led the BSRBR-RA team to see if elevated levels of these drugs in the serum could be predictive of the infection risk and thus used as a possible biomarker. There was also prior evidence that serum drug concentrations of biologics were associated with long-term treatment response and that a certain level was needed to determine the likely treatment response.
In the current study, Dr. Jani and colleagues used data on 703 patients with rheumatoid arthritis starting biologic therapy who were simultaneously recruited into the BSRBR-RA, which has been running since 2001, and the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS). The BSRBR-RA did not collect biological samples, but in BRAGGSS serological samples were collected at 3-, 6-, and 12-month intervals after the start of a biologic treatment, along with other assessments. This is the first time two national, U.K.-based, rheumatoid arthritis cohorts have been linked in this way, Dr. Jani said.
Serum samples taken from the patients were assessed via enzyme-linked immunoassay to determine levels of the biologic agent used, with high drug levels defined as more than 4 mcg/mL for etanercept (n = 286), tocilizumab (n = 104), and infliximab (n = 14); more than 8 mcg/mL for adalimumab (n = 179), and 25 mcg/mL or more for certolizumab pegol (n = 120).
In the study, about three-quarters of the patients were women. The mean age was 58 years, and disease duration was just under 6 years. Most patients were starting their first biologic.
The crude rate of all infections at 1 year, including recurrent infections, was 464 per 1,000 patient-years in the high biologic drug level group versus 314 per 1,000 patient-years in the low biologic drug level group. When only the first infections were considered, the crude rate of all infections within the first year were a respective 300 and 229 per 1,000 patient-years, with an adjusted hazard ratio of 1.27, Dr. Jani reported.
As expected, lower respiratory tract infections were the most common type of infection, occurring in 34% of patients with high drug levels versus around 10% in the low drug level group. Upper respiratory tract, urinary tract, and skin infections including shingles were seen in a respective 16%, 15%, and 8% in the high drug level group, with rates less than 5% in the low drug level group.
Of note, there were certain types of infections present in the high but not low drug level groups: bacterial peritonitis, neutropenic sepsis, and herpes zoster.
Crude rates for serious infections at 1 year were 76 and 54 per 1,000 patient-years, respectively, for the high and low drug level groups. The crude rates for the first serious infection within the first year were 44 and 29 per 1,000 patient-years. The adjusted hazard ratio for the risk of serious infection at 1 year was 1.26. Serious infections were rare events, Dr. Jani emphasized, so the power was reduced, but “there was a slightly increased risk.”
Aside from the low statistical power to assess the rarer serious infections, another limitation was that drug levels were not measured at the time of the adverse event.
Concluding, Dr. Jani suggested that perhaps monitoring drug levels could be useful in predicting the risk of infection in patients being treated with biologics for rheumatoid arthritis.
Furthermore, “in patients with remission, dose-tapering guided by therapeutic drug monitoring may help lower infection risk and help us balance safety and efficacy.”
When asked to comment, Tore K. Kvien, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, supported this conclusion. “Therapeutic drug monitoring [TDM] is widely used among gastroenterologists when treating inflammatory bowel diseases with TNF inhibitors. In recent years, data from several research groups in rheumatology have indicated that TDM may help to optimize drug efficacy. The results from Dr. Jani and her colleagues also support that TDM may be important for safety. The importance of TDM as a ‘new’ hot topic in rheumatology is also supported by the recent establishment of a EULAR [European League Against Rheumatism] task force to further explore the value of TDM when treating patients with inflammatory joint diseases.”
The BSRBR-RA is funded through the BSR, which receives restricted income from several U.K. pharmaceutical companies. These currently include AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche, and in the past, Swedish Orphan Biovitrum and Merck. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Jani has no personal conflicts of interest to disclose.
SOURCE: Jani M et al. Rheumatology, 2019 April;58(Suppl 3):kez105.018.
In this study, the authors use the major British Society for Rheumatology Biologics Register – Rheumatoid Arthritis and examine infections and serious infections across biologics. They define “low/normal” blood levels versus “high” blood levels based on concentration-effect curves. Examining data censored at 1 year versus incidence during 1 year, the results are somewhat inconsistent. With larger numbers available for data censored at 1 year, there is some increased risk using hazard ratios for both all infections and serious infections. With smaller numbers for incident infections during the first year, this hazard ratio does not show an effect.
Daniel E. Furst, MD, is professor of medicine (emeritus) at the University of California, Los Angeles, an adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy). He is also practices part-time in Los Angeles and Seattle.
In this study, the authors use the major British Society for Rheumatology Biologics Register – Rheumatoid Arthritis and examine infections and serious infections across biologics. They define “low/normal” blood levels versus “high” blood levels based on concentration-effect curves. Examining data censored at 1 year versus incidence during 1 year, the results are somewhat inconsistent. With larger numbers available for data censored at 1 year, there is some increased risk using hazard ratios for both all infections and serious infections. With smaller numbers for incident infections during the first year, this hazard ratio does not show an effect.
Daniel E. Furst, MD, is professor of medicine (emeritus) at the University of California, Los Angeles, an adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy). He is also practices part-time in Los Angeles and Seattle.
In this study, the authors use the major British Society for Rheumatology Biologics Register – Rheumatoid Arthritis and examine infections and serious infections across biologics. They define “low/normal” blood levels versus “high” blood levels based on concentration-effect curves. Examining data censored at 1 year versus incidence during 1 year, the results are somewhat inconsistent. With larger numbers available for data censored at 1 year, there is some increased risk using hazard ratios for both all infections and serious infections. With smaller numbers for incident infections during the first year, this hazard ratio does not show an effect.
Daniel E. Furst, MD, is professor of medicine (emeritus) at the University of California, Los Angeles, an adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy). He is also practices part-time in Los Angeles and Seattle.
BIRMINGHAM, ENGLAND – Higher blood biologic drug levels in the first year of treatment for rheumatoid arthritis independently increased the risk of any infection by about 50% when compared against low or normal levels in a new observational cohort study, providing support for monitoring biologic drug levels to help to predict infection risk.
Data from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA) that were presented at the British Society for Rheumatology annual conference showed that the adjusted hazard ratio for any infection occurring within the first year among patients with high drug levels was 1.51, with a 95% confidence interval (CI) of 1.14 to 2.01. The adjustments took into account patients’ age, gender, disease activity score, and use of methotrexate.
There are more than 10 biologics now available for use in rheumatoid arthritis but deciding which to use in a particular patient remains very much “a trial and error approach,” first author Meghna Jani, MBChB, said at the conference.
“From a patient perspective, one of the most important concerns continues to be the risk of serious infections and adverse events,” added Dr. Jani, a National Institute for Health Research Academic Clinical Lecturer in Rheumatology at the University of Manchester (England).
The link between biologic agents and infections, including those that could result in hospitalization or other serious consequences, has been well studied in biologics registries. It is known, for example, that the risk of infections with tumor necrosis factor inhibitor treatment seems to be highest during the first 6-12 months of treatment.
According to Dr. Jani, conventional means of determining risk – such as patient age and the presence of comorbid factors – have limited benefit in terms of deciding which patients could be at heightened risk of infections. “Ideally, we need biomarkers in rheumatology that can be implemented in clinical practice and help us predict efficacy and safety, as well as help us use these medications much more cost-effectively,” she said.
Four years ago, a meta-analysis (Lancet. 2015;386:258-65) suggested that the risk of infection may be linked to using higher doses of anti–tumor necrosis factor drugs, which led the BSRBR-RA team to see if elevated levels of these drugs in the serum could be predictive of the infection risk and thus used as a possible biomarker. There was also prior evidence that serum drug concentrations of biologics were associated with long-term treatment response and that a certain level was needed to determine the likely treatment response.
In the current study, Dr. Jani and colleagues used data on 703 patients with rheumatoid arthritis starting biologic therapy who were simultaneously recruited into the BSRBR-RA, which has been running since 2001, and the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS). The BSRBR-RA did not collect biological samples, but in BRAGGSS serological samples were collected at 3-, 6-, and 12-month intervals after the start of a biologic treatment, along with other assessments. This is the first time two national, U.K.-based, rheumatoid arthritis cohorts have been linked in this way, Dr. Jani said.
Serum samples taken from the patients were assessed via enzyme-linked immunoassay to determine levels of the biologic agent used, with high drug levels defined as more than 4 mcg/mL for etanercept (n = 286), tocilizumab (n = 104), and infliximab (n = 14); more than 8 mcg/mL for adalimumab (n = 179), and 25 mcg/mL or more for certolizumab pegol (n = 120).
In the study, about three-quarters of the patients were women. The mean age was 58 years, and disease duration was just under 6 years. Most patients were starting their first biologic.
The crude rate of all infections at 1 year, including recurrent infections, was 464 per 1,000 patient-years in the high biologic drug level group versus 314 per 1,000 patient-years in the low biologic drug level group. When only the first infections were considered, the crude rate of all infections within the first year were a respective 300 and 229 per 1,000 patient-years, with an adjusted hazard ratio of 1.27, Dr. Jani reported.
As expected, lower respiratory tract infections were the most common type of infection, occurring in 34% of patients with high drug levels versus around 10% in the low drug level group. Upper respiratory tract, urinary tract, and skin infections including shingles were seen in a respective 16%, 15%, and 8% in the high drug level group, with rates less than 5% in the low drug level group.
Of note, there were certain types of infections present in the high but not low drug level groups: bacterial peritonitis, neutropenic sepsis, and herpes zoster.
Crude rates for serious infections at 1 year were 76 and 54 per 1,000 patient-years, respectively, for the high and low drug level groups. The crude rates for the first serious infection within the first year were 44 and 29 per 1,000 patient-years. The adjusted hazard ratio for the risk of serious infection at 1 year was 1.26. Serious infections were rare events, Dr. Jani emphasized, so the power was reduced, but “there was a slightly increased risk.”
Aside from the low statistical power to assess the rarer serious infections, another limitation was that drug levels were not measured at the time of the adverse event.
Concluding, Dr. Jani suggested that perhaps monitoring drug levels could be useful in predicting the risk of infection in patients being treated with biologics for rheumatoid arthritis.
Furthermore, “in patients with remission, dose-tapering guided by therapeutic drug monitoring may help lower infection risk and help us balance safety and efficacy.”
When asked to comment, Tore K. Kvien, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, supported this conclusion. “Therapeutic drug monitoring [TDM] is widely used among gastroenterologists when treating inflammatory bowel diseases with TNF inhibitors. In recent years, data from several research groups in rheumatology have indicated that TDM may help to optimize drug efficacy. The results from Dr. Jani and her colleagues also support that TDM may be important for safety. The importance of TDM as a ‘new’ hot topic in rheumatology is also supported by the recent establishment of a EULAR [European League Against Rheumatism] task force to further explore the value of TDM when treating patients with inflammatory joint diseases.”
The BSRBR-RA is funded through the BSR, which receives restricted income from several U.K. pharmaceutical companies. These currently include AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche, and in the past, Swedish Orphan Biovitrum and Merck. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Jani has no personal conflicts of interest to disclose.
SOURCE: Jani M et al. Rheumatology, 2019 April;58(Suppl 3):kez105.018.
BIRMINGHAM, ENGLAND – Higher blood biologic drug levels in the first year of treatment for rheumatoid arthritis independently increased the risk of any infection by about 50% when compared against low or normal levels in a new observational cohort study, providing support for monitoring biologic drug levels to help to predict infection risk.
Data from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA) that were presented at the British Society for Rheumatology annual conference showed that the adjusted hazard ratio for any infection occurring within the first year among patients with high drug levels was 1.51, with a 95% confidence interval (CI) of 1.14 to 2.01. The adjustments took into account patients’ age, gender, disease activity score, and use of methotrexate.
There are more than 10 biologics now available for use in rheumatoid arthritis but deciding which to use in a particular patient remains very much “a trial and error approach,” first author Meghna Jani, MBChB, said at the conference.
“From a patient perspective, one of the most important concerns continues to be the risk of serious infections and adverse events,” added Dr. Jani, a National Institute for Health Research Academic Clinical Lecturer in Rheumatology at the University of Manchester (England).
The link between biologic agents and infections, including those that could result in hospitalization or other serious consequences, has been well studied in biologics registries. It is known, for example, that the risk of infections with tumor necrosis factor inhibitor treatment seems to be highest during the first 6-12 months of treatment.
According to Dr. Jani, conventional means of determining risk – such as patient age and the presence of comorbid factors – have limited benefit in terms of deciding which patients could be at heightened risk of infections. “Ideally, we need biomarkers in rheumatology that can be implemented in clinical practice and help us predict efficacy and safety, as well as help us use these medications much more cost-effectively,” she said.
Four years ago, a meta-analysis (Lancet. 2015;386:258-65) suggested that the risk of infection may be linked to using higher doses of anti–tumor necrosis factor drugs, which led the BSRBR-RA team to see if elevated levels of these drugs in the serum could be predictive of the infection risk and thus used as a possible biomarker. There was also prior evidence that serum drug concentrations of biologics were associated with long-term treatment response and that a certain level was needed to determine the likely treatment response.
In the current study, Dr. Jani and colleagues used data on 703 patients with rheumatoid arthritis starting biologic therapy who were simultaneously recruited into the BSRBR-RA, which has been running since 2001, and the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS). The BSRBR-RA did not collect biological samples, but in BRAGGSS serological samples were collected at 3-, 6-, and 12-month intervals after the start of a biologic treatment, along with other assessments. This is the first time two national, U.K.-based, rheumatoid arthritis cohorts have been linked in this way, Dr. Jani said.
Serum samples taken from the patients were assessed via enzyme-linked immunoassay to determine levels of the biologic agent used, with high drug levels defined as more than 4 mcg/mL for etanercept (n = 286), tocilizumab (n = 104), and infliximab (n = 14); more than 8 mcg/mL for adalimumab (n = 179), and 25 mcg/mL or more for certolizumab pegol (n = 120).
In the study, about three-quarters of the patients were women. The mean age was 58 years, and disease duration was just under 6 years. Most patients were starting their first biologic.
The crude rate of all infections at 1 year, including recurrent infections, was 464 per 1,000 patient-years in the high biologic drug level group versus 314 per 1,000 patient-years in the low biologic drug level group. When only the first infections were considered, the crude rate of all infections within the first year were a respective 300 and 229 per 1,000 patient-years, with an adjusted hazard ratio of 1.27, Dr. Jani reported.
As expected, lower respiratory tract infections were the most common type of infection, occurring in 34% of patients with high drug levels versus around 10% in the low drug level group. Upper respiratory tract, urinary tract, and skin infections including shingles were seen in a respective 16%, 15%, and 8% in the high drug level group, with rates less than 5% in the low drug level group.
Of note, there were certain types of infections present in the high but not low drug level groups: bacterial peritonitis, neutropenic sepsis, and herpes zoster.
Crude rates for serious infections at 1 year were 76 and 54 per 1,000 patient-years, respectively, for the high and low drug level groups. The crude rates for the first serious infection within the first year were 44 and 29 per 1,000 patient-years. The adjusted hazard ratio for the risk of serious infection at 1 year was 1.26. Serious infections were rare events, Dr. Jani emphasized, so the power was reduced, but “there was a slightly increased risk.”
Aside from the low statistical power to assess the rarer serious infections, another limitation was that drug levels were not measured at the time of the adverse event.
Concluding, Dr. Jani suggested that perhaps monitoring drug levels could be useful in predicting the risk of infection in patients being treated with biologics for rheumatoid arthritis.
Furthermore, “in patients with remission, dose-tapering guided by therapeutic drug monitoring may help lower infection risk and help us balance safety and efficacy.”
When asked to comment, Tore K. Kvien, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, supported this conclusion. “Therapeutic drug monitoring [TDM] is widely used among gastroenterologists when treating inflammatory bowel diseases with TNF inhibitors. In recent years, data from several research groups in rheumatology have indicated that TDM may help to optimize drug efficacy. The results from Dr. Jani and her colleagues also support that TDM may be important for safety. The importance of TDM as a ‘new’ hot topic in rheumatology is also supported by the recent establishment of a EULAR [European League Against Rheumatism] task force to further explore the value of TDM when treating patients with inflammatory joint diseases.”
The BSRBR-RA is funded through the BSR, which receives restricted income from several U.K. pharmaceutical companies. These currently include AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche, and in the past, Swedish Orphan Biovitrum and Merck. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Jani has no personal conflicts of interest to disclose.
SOURCE: Jani M et al. Rheumatology, 2019 April;58(Suppl 3):kez105.018.
REPORTING FROM BSR 2019