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Low-dose CT has a place in spondyloarthritis imaging toolbox
MADISON, WISC. – said Robert Lambert, MD, speaking at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
“Low-dose CT of the SI [sacroiliac] joints is probably underutilized,” said Dr. Lambert, chair of the department of radiology and diagnostic imaging at the University of Alberta, Edmonton. “Subtle bony changes are demonstrated very well, and it can be an excellent test for resolving equivocal findings on x-ray or MRI.”
An important first step in making imaging decisions is to put concerns about radiation exposure in context, said Dr. Lambert. “Today, almost all CT effective exposure doses are considered low risk.”
Older studies have shown that a conventional two-view chest radiograph delivers a dose of 0.1 mSv – the equivalent of 10 days of background radiation – whereas the highest radiation dose is delivered by a CT scan of the abdomen and pelvis with and without contrast. This examination delivers an effective dose of 20 mSv, the equivalent of 7 years of background radiation. Dr. Lambert pointed out what the “moderate” additional lifetime risk of malignancy – 1:500 – associated with this scan looks like in real-world numbers: “So the lifetime risk of cancer would increase from 20% to 20.2%.”
Recently, measurements of effective doses delivered in low-dose CT (ldCT) have shown that “most doses are significantly lower than previously quoted,” said Dr. Lambert. For example, ldCT of the SI joints delivers just 0.42 mSv, a radiation dose that’s in the same minimal risk category as a chest radiograph. In fact, for patients with high body mass, the radiation dose from ldCT of the SI joints can be less than that from a conventional radiograph.
“Could low-dose CT of the spine better detect new bone formation, compared to x-ray?” Dr. Lambert asked. A recent study attempted to answer the question, looking at 40 patients with ankylosing spondylitis who received ldCT at baseline and 2 years later (Ann Rheum Dis. 2018;77:371-7). In developing a CT syndesmophyte score (CTSS), two independent readers, blinded to the time order in which images were obtained, assessed vertebral syndesmophytes in the coronal and sagittal planes for each patient. The conclusion was that “new bone formation in the spine of patients with ankylosing spondylitis can be assessed reliably,” Dr. Lambert said.
A related study directly compared the new CTSS system with the modified Stoke Ankylosing Spondylitis Spine Score, used for conventional radiographs. Both studies used data from the Sensitive Imaging in Ankylosing Spondylitis cohort.
In this latter study, whole spine ldCT tracked progression better than conventional radiographs because it detected more new and growing syndesmophytes, Dr. Lambert said. One important reason for this was that conventional radiography only has utility in the cervical and lumbar spine and the pelvis, while most progression was seen in the thoracic spine with ldCT (Ann Rheum Dis. 2018;77:293-9).
The radiation dose for ldCT of the spine – approximately 4 mSv – is about 10 times that for ldCT of the SI joints, but still one-half to three-quarters of the dose for a whole-spine CT, Dr. Lambert said. Put another way, the ldCT whole-spine dose is nearly equivalent to the dose for the three radiographic studies required to image the cervical, thoracic, and lumbar spine.
Another imaging approach using CT zooms in on the thoracolumbar spine, imaging vertebrae T10-L4. Through sophisticated computational reconstruction techniques, the researchers were able to quantify syndesmophyte height circumferentially around each vertebra (J Rheumatol. 2015;42[3]:472-8).
The study, which imaged 33 patients at baseline and then at year 1 and year 2, found that the circumferential syndesmophyte height correlated well with spinal flexibility. Variation was low between two scans performed on the same day, at 0.893% per patient. Despite these advantages of high reliability and good sensitivity to change, one consideration for clinical consideration is the radiation dose, estimated about 8 mSv, Dr. Lambert noted.
Though MRI is a keystone for diagnosis and management of spondyloarthritis, Dr. Lambert pointed out that it’s more expensive than CT and still not routinely available everywhere. He also noted that reimbursement and prior authorizations may be easier to obtain for CT.
“Low-dose CT has tremendous research potential, especially in the thoracic spine,” said Dr. Lambert. “But it’s not ready for routine clinical use. First, the dose is not trivial, at about 4 mSv.” Also, it’s time consuming to interpret and not all CT scanners are compatible with ldCT techniques. “Lower dose can mean lower imaging quality,” and syndesmophytes can be harder to detect in larger individuals.
Dr. Lambert reported no relevant conflicts of interest.
MADISON, WISC. – said Robert Lambert, MD, speaking at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
“Low-dose CT of the SI [sacroiliac] joints is probably underutilized,” said Dr. Lambert, chair of the department of radiology and diagnostic imaging at the University of Alberta, Edmonton. “Subtle bony changes are demonstrated very well, and it can be an excellent test for resolving equivocal findings on x-ray or MRI.”
An important first step in making imaging decisions is to put concerns about radiation exposure in context, said Dr. Lambert. “Today, almost all CT effective exposure doses are considered low risk.”
Older studies have shown that a conventional two-view chest radiograph delivers a dose of 0.1 mSv – the equivalent of 10 days of background radiation – whereas the highest radiation dose is delivered by a CT scan of the abdomen and pelvis with and without contrast. This examination delivers an effective dose of 20 mSv, the equivalent of 7 years of background radiation. Dr. Lambert pointed out what the “moderate” additional lifetime risk of malignancy – 1:500 – associated with this scan looks like in real-world numbers: “So the lifetime risk of cancer would increase from 20% to 20.2%.”
Recently, measurements of effective doses delivered in low-dose CT (ldCT) have shown that “most doses are significantly lower than previously quoted,” said Dr. Lambert. For example, ldCT of the SI joints delivers just 0.42 mSv, a radiation dose that’s in the same minimal risk category as a chest radiograph. In fact, for patients with high body mass, the radiation dose from ldCT of the SI joints can be less than that from a conventional radiograph.
“Could low-dose CT of the spine better detect new bone formation, compared to x-ray?” Dr. Lambert asked. A recent study attempted to answer the question, looking at 40 patients with ankylosing spondylitis who received ldCT at baseline and 2 years later (Ann Rheum Dis. 2018;77:371-7). In developing a CT syndesmophyte score (CTSS), two independent readers, blinded to the time order in which images were obtained, assessed vertebral syndesmophytes in the coronal and sagittal planes for each patient. The conclusion was that “new bone formation in the spine of patients with ankylosing spondylitis can be assessed reliably,” Dr. Lambert said.
A related study directly compared the new CTSS system with the modified Stoke Ankylosing Spondylitis Spine Score, used for conventional radiographs. Both studies used data from the Sensitive Imaging in Ankylosing Spondylitis cohort.
In this latter study, whole spine ldCT tracked progression better than conventional radiographs because it detected more new and growing syndesmophytes, Dr. Lambert said. One important reason for this was that conventional radiography only has utility in the cervical and lumbar spine and the pelvis, while most progression was seen in the thoracic spine with ldCT (Ann Rheum Dis. 2018;77:293-9).
The radiation dose for ldCT of the spine – approximately 4 mSv – is about 10 times that for ldCT of the SI joints, but still one-half to three-quarters of the dose for a whole-spine CT, Dr. Lambert said. Put another way, the ldCT whole-spine dose is nearly equivalent to the dose for the three radiographic studies required to image the cervical, thoracic, and lumbar spine.
Another imaging approach using CT zooms in on the thoracolumbar spine, imaging vertebrae T10-L4. Through sophisticated computational reconstruction techniques, the researchers were able to quantify syndesmophyte height circumferentially around each vertebra (J Rheumatol. 2015;42[3]:472-8).
The study, which imaged 33 patients at baseline and then at year 1 and year 2, found that the circumferential syndesmophyte height correlated well with spinal flexibility. Variation was low between two scans performed on the same day, at 0.893% per patient. Despite these advantages of high reliability and good sensitivity to change, one consideration for clinical consideration is the radiation dose, estimated about 8 mSv, Dr. Lambert noted.
Though MRI is a keystone for diagnosis and management of spondyloarthritis, Dr. Lambert pointed out that it’s more expensive than CT and still not routinely available everywhere. He also noted that reimbursement and prior authorizations may be easier to obtain for CT.
“Low-dose CT has tremendous research potential, especially in the thoracic spine,” said Dr. Lambert. “But it’s not ready for routine clinical use. First, the dose is not trivial, at about 4 mSv.” Also, it’s time consuming to interpret and not all CT scanners are compatible with ldCT techniques. “Lower dose can mean lower imaging quality,” and syndesmophytes can be harder to detect in larger individuals.
Dr. Lambert reported no relevant conflicts of interest.
MADISON, WISC. – said Robert Lambert, MD, speaking at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).
“Low-dose CT of the SI [sacroiliac] joints is probably underutilized,” said Dr. Lambert, chair of the department of radiology and diagnostic imaging at the University of Alberta, Edmonton. “Subtle bony changes are demonstrated very well, and it can be an excellent test for resolving equivocal findings on x-ray or MRI.”
An important first step in making imaging decisions is to put concerns about radiation exposure in context, said Dr. Lambert. “Today, almost all CT effective exposure doses are considered low risk.”
Older studies have shown that a conventional two-view chest radiograph delivers a dose of 0.1 mSv – the equivalent of 10 days of background radiation – whereas the highest radiation dose is delivered by a CT scan of the abdomen and pelvis with and without contrast. This examination delivers an effective dose of 20 mSv, the equivalent of 7 years of background radiation. Dr. Lambert pointed out what the “moderate” additional lifetime risk of malignancy – 1:500 – associated with this scan looks like in real-world numbers: “So the lifetime risk of cancer would increase from 20% to 20.2%.”
Recently, measurements of effective doses delivered in low-dose CT (ldCT) have shown that “most doses are significantly lower than previously quoted,” said Dr. Lambert. For example, ldCT of the SI joints delivers just 0.42 mSv, a radiation dose that’s in the same minimal risk category as a chest radiograph. In fact, for patients with high body mass, the radiation dose from ldCT of the SI joints can be less than that from a conventional radiograph.
“Could low-dose CT of the spine better detect new bone formation, compared to x-ray?” Dr. Lambert asked. A recent study attempted to answer the question, looking at 40 patients with ankylosing spondylitis who received ldCT at baseline and 2 years later (Ann Rheum Dis. 2018;77:371-7). In developing a CT syndesmophyte score (CTSS), two independent readers, blinded to the time order in which images were obtained, assessed vertebral syndesmophytes in the coronal and sagittal planes for each patient. The conclusion was that “new bone formation in the spine of patients with ankylosing spondylitis can be assessed reliably,” Dr. Lambert said.
A related study directly compared the new CTSS system with the modified Stoke Ankylosing Spondylitis Spine Score, used for conventional radiographs. Both studies used data from the Sensitive Imaging in Ankylosing Spondylitis cohort.
In this latter study, whole spine ldCT tracked progression better than conventional radiographs because it detected more new and growing syndesmophytes, Dr. Lambert said. One important reason for this was that conventional radiography only has utility in the cervical and lumbar spine and the pelvis, while most progression was seen in the thoracic spine with ldCT (Ann Rheum Dis. 2018;77:293-9).
The radiation dose for ldCT of the spine – approximately 4 mSv – is about 10 times that for ldCT of the SI joints, but still one-half to three-quarters of the dose for a whole-spine CT, Dr. Lambert said. Put another way, the ldCT whole-spine dose is nearly equivalent to the dose for the three radiographic studies required to image the cervical, thoracic, and lumbar spine.
Another imaging approach using CT zooms in on the thoracolumbar spine, imaging vertebrae T10-L4. Through sophisticated computational reconstruction techniques, the researchers were able to quantify syndesmophyte height circumferentially around each vertebra (J Rheumatol. 2015;42[3]:472-8).
The study, which imaged 33 patients at baseline and then at year 1 and year 2, found that the circumferential syndesmophyte height correlated well with spinal flexibility. Variation was low between two scans performed on the same day, at 0.893% per patient. Despite these advantages of high reliability and good sensitivity to change, one consideration for clinical consideration is the radiation dose, estimated about 8 mSv, Dr. Lambert noted.
Though MRI is a keystone for diagnosis and management of spondyloarthritis, Dr. Lambert pointed out that it’s more expensive than CT and still not routinely available everywhere. He also noted that reimbursement and prior authorizations may be easier to obtain for CT.
“Low-dose CT has tremendous research potential, especially in the thoracic spine,” said Dr. Lambert. “But it’s not ready for routine clinical use. First, the dose is not trivial, at about 4 mSv.” Also, it’s time consuming to interpret and not all CT scanners are compatible with ldCT techniques. “Lower dose can mean lower imaging quality,” and syndesmophytes can be harder to detect in larger individuals.
Dr. Lambert reported no relevant conflicts of interest.
EXPERT ANALYSIS FROM SPARTAN 2019
Upcoming OA management guidelines reveal dearth of effective therapies
TORONTO – Draft guidelines for the management of OA developed by the Osteoarthritis Research Society International expose an inconvenient truth: Although a tremendous number of interventions are available for the treatment of OA, the cupboard is nearly bare when it comes to strongly recommended, evidence-based therapies.
Indeed, the sole strong, level Ia recommendation for pharmacotherapy of knee OA contained in the 2019 guidelines is for topical NSAIDs. The proposed guidelines contain no level Ia recommendations at all for nonpharmacologic treatment of knee OA. And for hip OA and polyarticular OA – the other two expressions of the disease addressed in the guidelines – there are no level Ia recommendations, pharmacologic or nonpharmacologic. The treatment recommendations for hip OA and polyarticular OA start at level Ib and drop-off in strength from there, Raveendhara R. Bannuru, MD, said at the OARSI 2019 World Congress. He and his fellow OARSI guideline panelists reviewed roughly 12,500 published abstracts before winnowing down the literature to 407 articles for data extraction. The voting panel was comprised of orthopedic surgeons, physical therapists, rheumatologists, primary care physicians, and sports medicine specialists from 10 countries. Panelists employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, resulting in guidelines which were categorized as either “strong,” that is, first-line, level Ia, a designation that required endorsement by at least 75% of panelists, or weaker “conditional” recommendations. Voting was conducted anonymously, Dr. Bannuru said in presenting highlights of the draft guidelines at the meeting sponsored by the Osteoarthritis Research Society International.
A challenge in coming up with evidence-based guidelines for OA management is that most of the existing research is focused on patients with knee OA and no comorbid conditions, he explained. The panelists wanted to create patient-centric guidelines, so they tackled hip OA and polyarticular OA as well, despite the paucity of good-quality data. And the guidelines separately address five common comorbidity scenarios for each of the three forms of OA: GI or cardiovascular comorbidity, frailty, comorbid widespread pain disorder/depression, and OA with no major comorbid conditions.
The draft guidelines feature one category of recommendations, known as the core recommendations, which are even stronger than the level Ia recommendations. The core recommendations are defined as key treatments deemed appropriate for nearly any OA patient at all points in treatment. The core recommendations are considered standard of care – the first interventions to utilize – to be supplemented by level Ia and Ib interventions added on as needed, with lower-level recommendations available when core plus levels Ia and Ib interventions don’t achieve the desired results.
The core recommendations include arthritis education, dietary weight management, and a structured, land-based exercise program involving strengthening and/or cardiovascular exercise and/or balance training. In a major departure from previous guidelines, mind-body exercise is categorized as a core recommendation, although just for patients with knee OA.
“Mind-body exercise is comprised of tai chi and yoga only. We do not recommend other things,” according to Dr. Bannuru, director of the Center for Treatment Comparison and Integrative Analysis at Tufts Medical Center, Boston.
For hip OA, mind-body exercise gets demoted to a level Ib nonpharmacologic recommendation across all five comorbidity categories, along with aquatic exercise, gait aids, and self-management programs.
Dr. Bannuru pointed out other highlights of the proposed guidelines: Opioids and acetaminophen are not recommended, duloxetine (Cymbalta) gets a conditional recommendation in OA patients with comorbid depression, and nonspecific NSAIDs are not recommended in OA patients with comorbid cardiovascular disease or frailty. When nonspecific NSAIDs are used, it should be at the lowest possible dose, for only 1-4 weeks, and in conjunction with a proton pump inhibitor, according to the draft guidelines.
Patient representatives asked the guideline panelists specifically about a number of interventions for OA popular in some circles but which the panel members are strongly opposed to because of unfavorable efficacy and safety profiles. The resulting “forget-about-it” list included colchicine, collagen, diacerein, doxycycline, dextrose prolotherapy, electrical stimulation, and electroacupuncture, with explanations provided as to why they deserve to be rejected.
The OA guidelines project was funded by the Arthritis Foundation, Versus Arthritis, and ReumaNederlands, with no industry funding.
TORONTO – Draft guidelines for the management of OA developed by the Osteoarthritis Research Society International expose an inconvenient truth: Although a tremendous number of interventions are available for the treatment of OA, the cupboard is nearly bare when it comes to strongly recommended, evidence-based therapies.
Indeed, the sole strong, level Ia recommendation for pharmacotherapy of knee OA contained in the 2019 guidelines is for topical NSAIDs. The proposed guidelines contain no level Ia recommendations at all for nonpharmacologic treatment of knee OA. And for hip OA and polyarticular OA – the other two expressions of the disease addressed in the guidelines – there are no level Ia recommendations, pharmacologic or nonpharmacologic. The treatment recommendations for hip OA and polyarticular OA start at level Ib and drop-off in strength from there, Raveendhara R. Bannuru, MD, said at the OARSI 2019 World Congress. He and his fellow OARSI guideline panelists reviewed roughly 12,500 published abstracts before winnowing down the literature to 407 articles for data extraction. The voting panel was comprised of orthopedic surgeons, physical therapists, rheumatologists, primary care physicians, and sports medicine specialists from 10 countries. Panelists employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, resulting in guidelines which were categorized as either “strong,” that is, first-line, level Ia, a designation that required endorsement by at least 75% of panelists, or weaker “conditional” recommendations. Voting was conducted anonymously, Dr. Bannuru said in presenting highlights of the draft guidelines at the meeting sponsored by the Osteoarthritis Research Society International.
A challenge in coming up with evidence-based guidelines for OA management is that most of the existing research is focused on patients with knee OA and no comorbid conditions, he explained. The panelists wanted to create patient-centric guidelines, so they tackled hip OA and polyarticular OA as well, despite the paucity of good-quality data. And the guidelines separately address five common comorbidity scenarios for each of the three forms of OA: GI or cardiovascular comorbidity, frailty, comorbid widespread pain disorder/depression, and OA with no major comorbid conditions.
The draft guidelines feature one category of recommendations, known as the core recommendations, which are even stronger than the level Ia recommendations. The core recommendations are defined as key treatments deemed appropriate for nearly any OA patient at all points in treatment. The core recommendations are considered standard of care – the first interventions to utilize – to be supplemented by level Ia and Ib interventions added on as needed, with lower-level recommendations available when core plus levels Ia and Ib interventions don’t achieve the desired results.
The core recommendations include arthritis education, dietary weight management, and a structured, land-based exercise program involving strengthening and/or cardiovascular exercise and/or balance training. In a major departure from previous guidelines, mind-body exercise is categorized as a core recommendation, although just for patients with knee OA.
“Mind-body exercise is comprised of tai chi and yoga only. We do not recommend other things,” according to Dr. Bannuru, director of the Center for Treatment Comparison and Integrative Analysis at Tufts Medical Center, Boston.
For hip OA, mind-body exercise gets demoted to a level Ib nonpharmacologic recommendation across all five comorbidity categories, along with aquatic exercise, gait aids, and self-management programs.
Dr. Bannuru pointed out other highlights of the proposed guidelines: Opioids and acetaminophen are not recommended, duloxetine (Cymbalta) gets a conditional recommendation in OA patients with comorbid depression, and nonspecific NSAIDs are not recommended in OA patients with comorbid cardiovascular disease or frailty. When nonspecific NSAIDs are used, it should be at the lowest possible dose, for only 1-4 weeks, and in conjunction with a proton pump inhibitor, according to the draft guidelines.
Patient representatives asked the guideline panelists specifically about a number of interventions for OA popular in some circles but which the panel members are strongly opposed to because of unfavorable efficacy and safety profiles. The resulting “forget-about-it” list included colchicine, collagen, diacerein, doxycycline, dextrose prolotherapy, electrical stimulation, and electroacupuncture, with explanations provided as to why they deserve to be rejected.
The OA guidelines project was funded by the Arthritis Foundation, Versus Arthritis, and ReumaNederlands, with no industry funding.
TORONTO – Draft guidelines for the management of OA developed by the Osteoarthritis Research Society International expose an inconvenient truth: Although a tremendous number of interventions are available for the treatment of OA, the cupboard is nearly bare when it comes to strongly recommended, evidence-based therapies.
Indeed, the sole strong, level Ia recommendation for pharmacotherapy of knee OA contained in the 2019 guidelines is for topical NSAIDs. The proposed guidelines contain no level Ia recommendations at all for nonpharmacologic treatment of knee OA. And for hip OA and polyarticular OA – the other two expressions of the disease addressed in the guidelines – there are no level Ia recommendations, pharmacologic or nonpharmacologic. The treatment recommendations for hip OA and polyarticular OA start at level Ib and drop-off in strength from there, Raveendhara R. Bannuru, MD, said at the OARSI 2019 World Congress. He and his fellow OARSI guideline panelists reviewed roughly 12,500 published abstracts before winnowing down the literature to 407 articles for data extraction. The voting panel was comprised of orthopedic surgeons, physical therapists, rheumatologists, primary care physicians, and sports medicine specialists from 10 countries. Panelists employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, resulting in guidelines which were categorized as either “strong,” that is, first-line, level Ia, a designation that required endorsement by at least 75% of panelists, or weaker “conditional” recommendations. Voting was conducted anonymously, Dr. Bannuru said in presenting highlights of the draft guidelines at the meeting sponsored by the Osteoarthritis Research Society International.
A challenge in coming up with evidence-based guidelines for OA management is that most of the existing research is focused on patients with knee OA and no comorbid conditions, he explained. The panelists wanted to create patient-centric guidelines, so they tackled hip OA and polyarticular OA as well, despite the paucity of good-quality data. And the guidelines separately address five common comorbidity scenarios for each of the three forms of OA: GI or cardiovascular comorbidity, frailty, comorbid widespread pain disorder/depression, and OA with no major comorbid conditions.
The draft guidelines feature one category of recommendations, known as the core recommendations, which are even stronger than the level Ia recommendations. The core recommendations are defined as key treatments deemed appropriate for nearly any OA patient at all points in treatment. The core recommendations are considered standard of care – the first interventions to utilize – to be supplemented by level Ia and Ib interventions added on as needed, with lower-level recommendations available when core plus levels Ia and Ib interventions don’t achieve the desired results.
The core recommendations include arthritis education, dietary weight management, and a structured, land-based exercise program involving strengthening and/or cardiovascular exercise and/or balance training. In a major departure from previous guidelines, mind-body exercise is categorized as a core recommendation, although just for patients with knee OA.
“Mind-body exercise is comprised of tai chi and yoga only. We do not recommend other things,” according to Dr. Bannuru, director of the Center for Treatment Comparison and Integrative Analysis at Tufts Medical Center, Boston.
For hip OA, mind-body exercise gets demoted to a level Ib nonpharmacologic recommendation across all five comorbidity categories, along with aquatic exercise, gait aids, and self-management programs.
Dr. Bannuru pointed out other highlights of the proposed guidelines: Opioids and acetaminophen are not recommended, duloxetine (Cymbalta) gets a conditional recommendation in OA patients with comorbid depression, and nonspecific NSAIDs are not recommended in OA patients with comorbid cardiovascular disease or frailty. When nonspecific NSAIDs are used, it should be at the lowest possible dose, for only 1-4 weeks, and in conjunction with a proton pump inhibitor, according to the draft guidelines.
Patient representatives asked the guideline panelists specifically about a number of interventions for OA popular in some circles but which the panel members are strongly opposed to because of unfavorable efficacy and safety profiles. The resulting “forget-about-it” list included colchicine, collagen, diacerein, doxycycline, dextrose prolotherapy, electrical stimulation, and electroacupuncture, with explanations provided as to why they deserve to be rejected.
The OA guidelines project was funded by the Arthritis Foundation, Versus Arthritis, and ReumaNederlands, with no industry funding.
REPORTING FROM OARSI 2019
Patients rate burden of OA equal to RA
TORONTO – The disease burden of osteoarthritis at the time of the first visit to a rheumatologist is similar to that of a new rheumatoid arthritis patient; the big difference between the two diseases is that a year later the disease burden of RA is significantly diminished, while it remains unchanged over time in OA patients, Theodore Pincus, MD, reported at the OARSI 2019 World Congress.
These divergent trajectories of disease burden, as measured using a validated patient self-assessment instrument, reflect the far superior and more numerous therapies available for treatment of RA. It’s an unfortunate disparity, especially given that OA is more than 20 times as prevalent as RA.
But the side-by-side, patient self-reported disease burden data presented by Dr. Pincus also underscored another point: “The severity of disease burden in OA to the patient appears to be underrated by the medical community, general public, and even patients,” he said at the meeting sponsored by the Osteoarthritis Research Society International.
Dr. Pincus, a pioneer in outcomes assessment in rheumatology, is credited with codeveloping the RAPID 3 (Routine Assessment of Patient Index Data 3) score, widely utilized by rheumatologists as part of routine care in clinical practice (Bull NYU Hosp Jt Dis. 2009;67[2]:211-25).
At OARSI 2019, he presented results of a longitudinal study of disease burden over the course of 2 years in 101 patients with OA and 175 with RA who completed the Multidimensional Health Assessment Questionnaire (MDHAQ) and RAPID 3 in the waiting room before their first and all subsequent office visits with a rheumatologist. The MDHAQ, another self-assessment tool codeveloped by Dr. Pincus, is a two-page questionnaire that includes scores for pain, physical function in 10 activities, fatigue, and a self-reported painful joint count.
At the first visit with a rheumatologist, the mean MDHAQ/RAPID 3 score on a 0-30 scale was 11.9 in the OA group and 13.7 in the RA patients, a difference small enough that Dr. Pincus dismissed it as not clinically significant. After 1 year, the mean score was 11.5 in the OA group, and 2 years later it was 11.9, identical to the OA patients’ score back at their first visit. Meanwhile, the RA patients improved from 13.7 at baseline to 10.9 at 1 year and 9.0 at 2 years, according to Dr. Pincus, professor of rheumatology at Rush Medical College, Chicago.
The between-group differences over time in pain and physical function were particularly telling. Pain on a 0-10 scale stuttered from 5.0 at first visit in the OA group to 4.9 at 1 year and 4.7 at 2 years, while the RA group registered much greater improvement, going from a mean of 5.5 at first visit to 4.3 at 1 year and 3.6 at 2 years. Meanwhile, physical function worsened over time in the OA group while improving in the RA group from 0.78 at first visit to 0.66 at 1 year and 0.53 at 2 years, he noted.
Dr. Pincus reported having no financial conflicts regarding this study.
TORONTO – The disease burden of osteoarthritis at the time of the first visit to a rheumatologist is similar to that of a new rheumatoid arthritis patient; the big difference between the two diseases is that a year later the disease burden of RA is significantly diminished, while it remains unchanged over time in OA patients, Theodore Pincus, MD, reported at the OARSI 2019 World Congress.
These divergent trajectories of disease burden, as measured using a validated patient self-assessment instrument, reflect the far superior and more numerous therapies available for treatment of RA. It’s an unfortunate disparity, especially given that OA is more than 20 times as prevalent as RA.
But the side-by-side, patient self-reported disease burden data presented by Dr. Pincus also underscored another point: “The severity of disease burden in OA to the patient appears to be underrated by the medical community, general public, and even patients,” he said at the meeting sponsored by the Osteoarthritis Research Society International.
Dr. Pincus, a pioneer in outcomes assessment in rheumatology, is credited with codeveloping the RAPID 3 (Routine Assessment of Patient Index Data 3) score, widely utilized by rheumatologists as part of routine care in clinical practice (Bull NYU Hosp Jt Dis. 2009;67[2]:211-25).
At OARSI 2019, he presented results of a longitudinal study of disease burden over the course of 2 years in 101 patients with OA and 175 with RA who completed the Multidimensional Health Assessment Questionnaire (MDHAQ) and RAPID 3 in the waiting room before their first and all subsequent office visits with a rheumatologist. The MDHAQ, another self-assessment tool codeveloped by Dr. Pincus, is a two-page questionnaire that includes scores for pain, physical function in 10 activities, fatigue, and a self-reported painful joint count.
At the first visit with a rheumatologist, the mean MDHAQ/RAPID 3 score on a 0-30 scale was 11.9 in the OA group and 13.7 in the RA patients, a difference small enough that Dr. Pincus dismissed it as not clinically significant. After 1 year, the mean score was 11.5 in the OA group, and 2 years later it was 11.9, identical to the OA patients’ score back at their first visit. Meanwhile, the RA patients improved from 13.7 at baseline to 10.9 at 1 year and 9.0 at 2 years, according to Dr. Pincus, professor of rheumatology at Rush Medical College, Chicago.
The between-group differences over time in pain and physical function were particularly telling. Pain on a 0-10 scale stuttered from 5.0 at first visit in the OA group to 4.9 at 1 year and 4.7 at 2 years, while the RA group registered much greater improvement, going from a mean of 5.5 at first visit to 4.3 at 1 year and 3.6 at 2 years. Meanwhile, physical function worsened over time in the OA group while improving in the RA group from 0.78 at first visit to 0.66 at 1 year and 0.53 at 2 years, he noted.
Dr. Pincus reported having no financial conflicts regarding this study.
TORONTO – The disease burden of osteoarthritis at the time of the first visit to a rheumatologist is similar to that of a new rheumatoid arthritis patient; the big difference between the two diseases is that a year later the disease burden of RA is significantly diminished, while it remains unchanged over time in OA patients, Theodore Pincus, MD, reported at the OARSI 2019 World Congress.
These divergent trajectories of disease burden, as measured using a validated patient self-assessment instrument, reflect the far superior and more numerous therapies available for treatment of RA. It’s an unfortunate disparity, especially given that OA is more than 20 times as prevalent as RA.
But the side-by-side, patient self-reported disease burden data presented by Dr. Pincus also underscored another point: “The severity of disease burden in OA to the patient appears to be underrated by the medical community, general public, and even patients,” he said at the meeting sponsored by the Osteoarthritis Research Society International.
Dr. Pincus, a pioneer in outcomes assessment in rheumatology, is credited with codeveloping the RAPID 3 (Routine Assessment of Patient Index Data 3) score, widely utilized by rheumatologists as part of routine care in clinical practice (Bull NYU Hosp Jt Dis. 2009;67[2]:211-25).
At OARSI 2019, he presented results of a longitudinal study of disease burden over the course of 2 years in 101 patients with OA and 175 with RA who completed the Multidimensional Health Assessment Questionnaire (MDHAQ) and RAPID 3 in the waiting room before their first and all subsequent office visits with a rheumatologist. The MDHAQ, another self-assessment tool codeveloped by Dr. Pincus, is a two-page questionnaire that includes scores for pain, physical function in 10 activities, fatigue, and a self-reported painful joint count.
At the first visit with a rheumatologist, the mean MDHAQ/RAPID 3 score on a 0-30 scale was 11.9 in the OA group and 13.7 in the RA patients, a difference small enough that Dr. Pincus dismissed it as not clinically significant. After 1 year, the mean score was 11.5 in the OA group, and 2 years later it was 11.9, identical to the OA patients’ score back at their first visit. Meanwhile, the RA patients improved from 13.7 at baseline to 10.9 at 1 year and 9.0 at 2 years, according to Dr. Pincus, professor of rheumatology at Rush Medical College, Chicago.
The between-group differences over time in pain and physical function were particularly telling. Pain on a 0-10 scale stuttered from 5.0 at first visit in the OA group to 4.9 at 1 year and 4.7 at 2 years, while the RA group registered much greater improvement, going from a mean of 5.5 at first visit to 4.3 at 1 year and 3.6 at 2 years. Meanwhile, physical function worsened over time in the OA group while improving in the RA group from 0.78 at first visit to 0.66 at 1 year and 0.53 at 2 years, he noted.
Dr. Pincus reported having no financial conflicts regarding this study.
REPORTING FROM OARSI 2019
Prepare for deluge of JAK inhibitors for RA
MAUI, HAWAII – As it grows increasingly likely that oral Janus kinase inhibitors will constitute a major development in the treatment of rheumatoid arthritis, with a bevy of these agents becoming available for that indication, rheumatologists are asking questions about the coming revolution. Like, when should these agents be used? What are the major safety and efficacy differences, if any, within the class? How clinically relevant is JAK selectivity? And which JAK inhibitor is the best choice?
on these and other related questions at the 2019 Rheumatology Winter Clinical Symposium.
These issues take on growing relevance for clinicians and their RA patients because two oral small molecule JAK inhibitors – tofacitinib (Xeljanz) and baricitinib (Olumiant) – are already approved for RA, and three more – upadacitinib, filgotinib, and peficitinib – are on the horizon. Indeed, AbbVie has already filed for marketing approval of once-daily upadacitinib for RA on the basis of an impressive development program featuring six phase 3 trials, with a priority review decision from the Food and Drug Administration anticipated this fall. Filgotinib is the focus of three phase 3 studies, one of which is viewed as a home run, with the other two yet to report results. Peficitinib is backed by two positive phase 3 trials, although its manufacturer will at least initially seek marketing approval only in Japan and South Korea. And numerous other JAK inhibitors are in development for a variety of indications.
When should a JAK inhibitor be used?
That’s easy, according to Roy M. Fleischmann, MD: If the cost proves comparable, it makes sense to turn to a JAK inhibitor ahead of a tumor necrosis factor inhibitor or other biologic.
He noted that in the double-blind, phase 3 SELECT-COMPARE head-to-head comparison of upadacitinib at 15 mg/day, adalimumab (Humira) at 40 mg every other week, versus placebo, all on top of background methotrexate, upadacitinib proved superior to the market-leading tumor necrosis factor inhibitor in terms of both the American College of Rheumatology–defined 20% level of response (ACR 20) and 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP).
“The results were very dramatic,” noted Dr. Fleischmann, who presented the SELECT-COMPARE findings at the 2018 annual meeting of the American College of Rheumatology.
Moreover, other major trials have shown that baricitinib at 4 mg/day was superior in efficacy to adalimumab, and tofacitinib and peficitinib were “at least equal” to anti-TNF therapy, he added.
“These numbers are clinically meaningful – not so much for the difference in ACR 20, but in the depth of response: the ACR 50 and 70, the CDAI. I think these drugs are better than adalimumab,” declared Dr. Fleischmann, codirector of the division of rheumatology at Texas Health Presbyterian Medical Center, Dallas.
Mark Genovese, MD, concurred.
“I think that for most patients who don’t have a lot of other comorbidities, they would certainly prefer to take a pill over a shot. And if you have a drug that’s more effective than the standard of care and it comes at a reasonable price point – and ‘reasonable’ is in the eye of the beholder – but if I can get access to it on the formulary, I’d have no qualms about putting them on a JAK inhibitor before I’d move to a TNF inhibitor,” said Dr. Genovese, professor of medicine and director of the rheumatology clinic at Stanford (Calif.) University.
Upadacitinib elicited a better response at 30 mg than at 15 mg once daily in the phase 3 program; however, both speakers indicated they’d be happy with access to the 15-mg dose, should the FDA go that route, since it has a better safety profile.
Dr. Genovese was principal investigator in the previously reported multicenter FINCH2 trial of filgotinib at 100 or 200 mg/day in RA patients with a prior inadequate response to one or more biologic disease-modifying antirheumatic drugs.
“Impressive results in a refractory population,” he said. “I don’t see a big difference in safety between 100 and 200 mg, so I’d opt for the 200 because it worked really well in patients who had refractory disease.”
Other advantages of JAK inhibitors
Speed of onset is another advantage in addition to oral administration and efficacy greater than or equivalent to anti-TNF therapy, according to Dr. Genovese.
“As a class, JAK inhibitors have a faster onset than methotrexate in terms of improvement in disease activity and pain. So in a few weeks you can have a sense of whether folks are going to be responders,” the rheumatologist said.
Does JAK isoform selectivity really make a difference in terms of efficacy and safety?
It’s doubtful, the rheumatologists agreed. All of these oral small molecules target JAK1, and that’s what’s key.
Tofacitinib is relatively selective for JAK1 and JAK3, baricitinib for JAK1 and JAK2, upadacitinib and fibotinib for JAK1, and peficitinib is a pan-JAK inhibitor.
What are the safety concerns with this class of medications?
The risk of herpes zoster is higher than with TNF inhibitors, reinforcing the importance of varicella vaccination in JAK inhibitor candidates. Anemia occurs in a small percentage of patients. As for the risk of venous thromboembolism as a potential side effect of JAK inhibitors, a topic of great concern to the FDA, Dr. Fleischmann dismissed it as vastly overblown.
“I think VTEs are an RA effect. You see it with all the drugs, including methotrexate,” he said.
Idiosyncratic self-limited increases in creatine kinase have been seen in 2%-4% of patients on JAK inhibitors in pretty much all of the clinical trials. “I’m not aware of any cases of myositis, though,” Dr. Fleischmann noted.
As for the teratogenicity potential of JAK inhibitors, Dr. Genovese said that, as is true for most medications, it hasn’t been well studied.
“We don’t know. But I would not choose to use a JAK inhibitor in a woman who is going to conceive, has conceived, or is breastfeeding. I just don’t think that would be a good decision,” according to the rheumatologist.
Which JAK inhibitor is the best choice for treatment of RA?
It’s impossible to say because of the hazards in trying to draw meaningful conclusions from cross-study comparisons, the experts agreed.
“It’s a challenge. I think at the end of the day there will probably be one agent that looks like it might be best in class predicated on having the most number of indications, and that will probably become a preferred agent. The question is, does that happen before tofacitinib goes generic? And I don’t know the answer to that,” Dr. Genovese said.
Notably, upadacitinib is the subject of a plethora of ongoing phase 3 trials in atopic dermatitis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. It is also in earlier-phase investigation for the treatment of ankylosing spondylitis.
Do we really need all these JAK inhibitors?
“How many TNF inhibitors do you need?” Dr. Genovese retorted. “I think the reality is there’s probably a finite number and additional members add to the class, but there probably will always be one or two that are going to be best in class.”
Both rheumatologists indicated they serve as consultants to more than a dozen pharmaceutical companies and receive research grants from numerous firms.
MAUI, HAWAII – As it grows increasingly likely that oral Janus kinase inhibitors will constitute a major development in the treatment of rheumatoid arthritis, with a bevy of these agents becoming available for that indication, rheumatologists are asking questions about the coming revolution. Like, when should these agents be used? What are the major safety and efficacy differences, if any, within the class? How clinically relevant is JAK selectivity? And which JAK inhibitor is the best choice?
on these and other related questions at the 2019 Rheumatology Winter Clinical Symposium.
These issues take on growing relevance for clinicians and their RA patients because two oral small molecule JAK inhibitors – tofacitinib (Xeljanz) and baricitinib (Olumiant) – are already approved for RA, and three more – upadacitinib, filgotinib, and peficitinib – are on the horizon. Indeed, AbbVie has already filed for marketing approval of once-daily upadacitinib for RA on the basis of an impressive development program featuring six phase 3 trials, with a priority review decision from the Food and Drug Administration anticipated this fall. Filgotinib is the focus of three phase 3 studies, one of which is viewed as a home run, with the other two yet to report results. Peficitinib is backed by two positive phase 3 trials, although its manufacturer will at least initially seek marketing approval only in Japan and South Korea. And numerous other JAK inhibitors are in development for a variety of indications.
When should a JAK inhibitor be used?
That’s easy, according to Roy M. Fleischmann, MD: If the cost proves comparable, it makes sense to turn to a JAK inhibitor ahead of a tumor necrosis factor inhibitor or other biologic.
He noted that in the double-blind, phase 3 SELECT-COMPARE head-to-head comparison of upadacitinib at 15 mg/day, adalimumab (Humira) at 40 mg every other week, versus placebo, all on top of background methotrexate, upadacitinib proved superior to the market-leading tumor necrosis factor inhibitor in terms of both the American College of Rheumatology–defined 20% level of response (ACR 20) and 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP).
“The results were very dramatic,” noted Dr. Fleischmann, who presented the SELECT-COMPARE findings at the 2018 annual meeting of the American College of Rheumatology.
Moreover, other major trials have shown that baricitinib at 4 mg/day was superior in efficacy to adalimumab, and tofacitinib and peficitinib were “at least equal” to anti-TNF therapy, he added.
“These numbers are clinically meaningful – not so much for the difference in ACR 20, but in the depth of response: the ACR 50 and 70, the CDAI. I think these drugs are better than adalimumab,” declared Dr. Fleischmann, codirector of the division of rheumatology at Texas Health Presbyterian Medical Center, Dallas.
Mark Genovese, MD, concurred.
“I think that for most patients who don’t have a lot of other comorbidities, they would certainly prefer to take a pill over a shot. And if you have a drug that’s more effective than the standard of care and it comes at a reasonable price point – and ‘reasonable’ is in the eye of the beholder – but if I can get access to it on the formulary, I’d have no qualms about putting them on a JAK inhibitor before I’d move to a TNF inhibitor,” said Dr. Genovese, professor of medicine and director of the rheumatology clinic at Stanford (Calif.) University.
Upadacitinib elicited a better response at 30 mg than at 15 mg once daily in the phase 3 program; however, both speakers indicated they’d be happy with access to the 15-mg dose, should the FDA go that route, since it has a better safety profile.
Dr. Genovese was principal investigator in the previously reported multicenter FINCH2 trial of filgotinib at 100 or 200 mg/day in RA patients with a prior inadequate response to one or more biologic disease-modifying antirheumatic drugs.
“Impressive results in a refractory population,” he said. “I don’t see a big difference in safety between 100 and 200 mg, so I’d opt for the 200 because it worked really well in patients who had refractory disease.”
Other advantages of JAK inhibitors
Speed of onset is another advantage in addition to oral administration and efficacy greater than or equivalent to anti-TNF therapy, according to Dr. Genovese.
“As a class, JAK inhibitors have a faster onset than methotrexate in terms of improvement in disease activity and pain. So in a few weeks you can have a sense of whether folks are going to be responders,” the rheumatologist said.
Does JAK isoform selectivity really make a difference in terms of efficacy and safety?
It’s doubtful, the rheumatologists agreed. All of these oral small molecules target JAK1, and that’s what’s key.
Tofacitinib is relatively selective for JAK1 and JAK3, baricitinib for JAK1 and JAK2, upadacitinib and fibotinib for JAK1, and peficitinib is a pan-JAK inhibitor.
What are the safety concerns with this class of medications?
The risk of herpes zoster is higher than with TNF inhibitors, reinforcing the importance of varicella vaccination in JAK inhibitor candidates. Anemia occurs in a small percentage of patients. As for the risk of venous thromboembolism as a potential side effect of JAK inhibitors, a topic of great concern to the FDA, Dr. Fleischmann dismissed it as vastly overblown.
“I think VTEs are an RA effect. You see it with all the drugs, including methotrexate,” he said.
Idiosyncratic self-limited increases in creatine kinase have been seen in 2%-4% of patients on JAK inhibitors in pretty much all of the clinical trials. “I’m not aware of any cases of myositis, though,” Dr. Fleischmann noted.
As for the teratogenicity potential of JAK inhibitors, Dr. Genovese said that, as is true for most medications, it hasn’t been well studied.
“We don’t know. But I would not choose to use a JAK inhibitor in a woman who is going to conceive, has conceived, or is breastfeeding. I just don’t think that would be a good decision,” according to the rheumatologist.
Which JAK inhibitor is the best choice for treatment of RA?
It’s impossible to say because of the hazards in trying to draw meaningful conclusions from cross-study comparisons, the experts agreed.
“It’s a challenge. I think at the end of the day there will probably be one agent that looks like it might be best in class predicated on having the most number of indications, and that will probably become a preferred agent. The question is, does that happen before tofacitinib goes generic? And I don’t know the answer to that,” Dr. Genovese said.
Notably, upadacitinib is the subject of a plethora of ongoing phase 3 trials in atopic dermatitis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. It is also in earlier-phase investigation for the treatment of ankylosing spondylitis.
Do we really need all these JAK inhibitors?
“How many TNF inhibitors do you need?” Dr. Genovese retorted. “I think the reality is there’s probably a finite number and additional members add to the class, but there probably will always be one or two that are going to be best in class.”
Both rheumatologists indicated they serve as consultants to more than a dozen pharmaceutical companies and receive research grants from numerous firms.
MAUI, HAWAII – As it grows increasingly likely that oral Janus kinase inhibitors will constitute a major development in the treatment of rheumatoid arthritis, with a bevy of these agents becoming available for that indication, rheumatologists are asking questions about the coming revolution. Like, when should these agents be used? What are the major safety and efficacy differences, if any, within the class? How clinically relevant is JAK selectivity? And which JAK inhibitor is the best choice?
on these and other related questions at the 2019 Rheumatology Winter Clinical Symposium.
These issues take on growing relevance for clinicians and their RA patients because two oral small molecule JAK inhibitors – tofacitinib (Xeljanz) and baricitinib (Olumiant) – are already approved for RA, and three more – upadacitinib, filgotinib, and peficitinib – are on the horizon. Indeed, AbbVie has already filed for marketing approval of once-daily upadacitinib for RA on the basis of an impressive development program featuring six phase 3 trials, with a priority review decision from the Food and Drug Administration anticipated this fall. Filgotinib is the focus of three phase 3 studies, one of which is viewed as a home run, with the other two yet to report results. Peficitinib is backed by two positive phase 3 trials, although its manufacturer will at least initially seek marketing approval only in Japan and South Korea. And numerous other JAK inhibitors are in development for a variety of indications.
When should a JAK inhibitor be used?
That’s easy, according to Roy M. Fleischmann, MD: If the cost proves comparable, it makes sense to turn to a JAK inhibitor ahead of a tumor necrosis factor inhibitor or other biologic.
He noted that in the double-blind, phase 3 SELECT-COMPARE head-to-head comparison of upadacitinib at 15 mg/day, adalimumab (Humira) at 40 mg every other week, versus placebo, all on top of background methotrexate, upadacitinib proved superior to the market-leading tumor necrosis factor inhibitor in terms of both the American College of Rheumatology–defined 20% level of response (ACR 20) and 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP).
“The results were very dramatic,” noted Dr. Fleischmann, who presented the SELECT-COMPARE findings at the 2018 annual meeting of the American College of Rheumatology.
Moreover, other major trials have shown that baricitinib at 4 mg/day was superior in efficacy to adalimumab, and tofacitinib and peficitinib were “at least equal” to anti-TNF therapy, he added.
“These numbers are clinically meaningful – not so much for the difference in ACR 20, but in the depth of response: the ACR 50 and 70, the CDAI. I think these drugs are better than adalimumab,” declared Dr. Fleischmann, codirector of the division of rheumatology at Texas Health Presbyterian Medical Center, Dallas.
Mark Genovese, MD, concurred.
“I think that for most patients who don’t have a lot of other comorbidities, they would certainly prefer to take a pill over a shot. And if you have a drug that’s more effective than the standard of care and it comes at a reasonable price point – and ‘reasonable’ is in the eye of the beholder – but if I can get access to it on the formulary, I’d have no qualms about putting them on a JAK inhibitor before I’d move to a TNF inhibitor,” said Dr. Genovese, professor of medicine and director of the rheumatology clinic at Stanford (Calif.) University.
Upadacitinib elicited a better response at 30 mg than at 15 mg once daily in the phase 3 program; however, both speakers indicated they’d be happy with access to the 15-mg dose, should the FDA go that route, since it has a better safety profile.
Dr. Genovese was principal investigator in the previously reported multicenter FINCH2 trial of filgotinib at 100 or 200 mg/day in RA patients with a prior inadequate response to one or more biologic disease-modifying antirheumatic drugs.
“Impressive results in a refractory population,” he said. “I don’t see a big difference in safety between 100 and 200 mg, so I’d opt for the 200 because it worked really well in patients who had refractory disease.”
Other advantages of JAK inhibitors
Speed of onset is another advantage in addition to oral administration and efficacy greater than or equivalent to anti-TNF therapy, according to Dr. Genovese.
“As a class, JAK inhibitors have a faster onset than methotrexate in terms of improvement in disease activity and pain. So in a few weeks you can have a sense of whether folks are going to be responders,” the rheumatologist said.
Does JAK isoform selectivity really make a difference in terms of efficacy and safety?
It’s doubtful, the rheumatologists agreed. All of these oral small molecules target JAK1, and that’s what’s key.
Tofacitinib is relatively selective for JAK1 and JAK3, baricitinib for JAK1 and JAK2, upadacitinib and fibotinib for JAK1, and peficitinib is a pan-JAK inhibitor.
What are the safety concerns with this class of medications?
The risk of herpes zoster is higher than with TNF inhibitors, reinforcing the importance of varicella vaccination in JAK inhibitor candidates. Anemia occurs in a small percentage of patients. As for the risk of venous thromboembolism as a potential side effect of JAK inhibitors, a topic of great concern to the FDA, Dr. Fleischmann dismissed it as vastly overblown.
“I think VTEs are an RA effect. You see it with all the drugs, including methotrexate,” he said.
Idiosyncratic self-limited increases in creatine kinase have been seen in 2%-4% of patients on JAK inhibitors in pretty much all of the clinical trials. “I’m not aware of any cases of myositis, though,” Dr. Fleischmann noted.
As for the teratogenicity potential of JAK inhibitors, Dr. Genovese said that, as is true for most medications, it hasn’t been well studied.
“We don’t know. But I would not choose to use a JAK inhibitor in a woman who is going to conceive, has conceived, or is breastfeeding. I just don’t think that would be a good decision,” according to the rheumatologist.
Which JAK inhibitor is the best choice for treatment of RA?
It’s impossible to say because of the hazards in trying to draw meaningful conclusions from cross-study comparisons, the experts agreed.
“It’s a challenge. I think at the end of the day there will probably be one agent that looks like it might be best in class predicated on having the most number of indications, and that will probably become a preferred agent. The question is, does that happen before tofacitinib goes generic? And I don’t know the answer to that,” Dr. Genovese said.
Notably, upadacitinib is the subject of a plethora of ongoing phase 3 trials in atopic dermatitis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. It is also in earlier-phase investigation for the treatment of ankylosing spondylitis.
Do we really need all these JAK inhibitors?
“How many TNF inhibitors do you need?” Dr. Genovese retorted. “I think the reality is there’s probably a finite number and additional members add to the class, but there probably will always be one or two that are going to be best in class.”
Both rheumatologists indicated they serve as consultants to more than a dozen pharmaceutical companies and receive research grants from numerous firms.
REPORTING FROM RWCS 2019
Nintedanib cut lung function decline in interstitial lung disease with systemic sclerosis
DALLAS – Nintedanib, a tyrosine kinase inhibitor, decreased by 44% the annual rate of lung function decline among patients with interstitial lung disease associated with systemic sclerosis, a year-long study has found.
In a placebo-controlled 52-week trial, forced vital capacity (FVC) in patients who took nintedanib (Ofev) declined by a mean of 52 mL – significantly less than the mean 93 mL decline seen among those who were given placebo, Oliver Distler, MD, said at the annual meeting of the American Thoracic Society.
“These are people in their mid-40s and -50s,” said Dr. Distler of the University of Zürich. “They have a long time to go. If there is an annual preservation of lung function by 40%, if you have that every year, it becomes very surely clinically significant. A decline in FVC is also a good surrogate marker of mortality in interstitial lung disease associated with systemic sclerosis. Assuming the effects are ongoing above the 1 year we looked at, then indeed these results are clinically important.”
The study was simultaneously published in the New England Journal of Medicine. Nintedanib is already approved for idiopathic pulmonary fibrosis. But some data suggest that it also exerts antifibrotic and anti-inflammatory effects in animal models of systemic sclerosis and inflammatory lung disease (ILD). SENSCIS (the Safety and Efficacy of Nintedanib in Systemic Sclerosis trial) investigated the molecule’s use in patients with ILD associated with systemic sclerosis.
Conducted in 32 countries, SENSCIS comprised 576 patients with the disorder, whose sclerosis affected at least 10% of their lungs. They were assigned to 52 weeks of either placebo or 150 mg nintedanib twice weekly. However, patients stayed on their blinded treatment until the last patient enrolled had finished the year of treatment; some patients took the drug for 100 weeks, Dr. Distler said. The primary endpoint was annual rate of decline in the forced vital capacity (FEV). Secondary endpoints included changes of the modified Rodnan skin score and in the total score on the St. George’s Respiratory Questionnaire.
Patients were a mean of 54 years old, with a mean disease duration of about 3 years. About half had diffuse cutaneous systemic sclerosis; the sclerosis was limited in the remainder. The mean extent of lung fibrosis was about 36%. Half were taking mycophenolate at baseline, which was allowed as background treatment, along with up to 10 mg/day of prednisone. Any patient who experienced clinically significant lung function deterioration could receive additional therapy at the investigator’s discretion.
The mean baseline FEV for these patients was 72.5% of predicted value. The mean diffusing capacity of the lungs for carbon monoxide was 53% of expected capacity.
Most patients completed the study (80% of the active group and 89% of the placebo group). The mean drug exposure duration was 10 months in the active group and 11 in the placebo group.
Improvement began early in treatment, with the efficacy curves separating by week 12 and continuing to diverge. After 52 weeks of therapy, the annual rate of change was 41 mL less in the active group than in the placebo group (–54.4 mL vs. –93.3 mL). The mean adjusted absolute change from baseline was –54.6 mL in the active group and –101 mL in the placebo at week 52. Significantly fewer patients taking nintedanib also lost more than 10% of FVC by week 52 (16.7% vs. 18%).
The St. George’s Respiratory Questionnaire score improved about one point in the active group and declined about one point in the placebo group.
Nintedanib was equally effective across a number of subgroups, including those divided by sex, age, and race. Antitopoisomerase antibodies and so-called antitopoisomerase I antibody status did not affect nintedanib’s action. Nintedanib also significantly improved scores on the Health Assessment Questionnaire without Disability Index and dyspnea.
More patients in the active group than in on placebo discontinued treatment because of a serious adverse event (16% vs. 8.7%). The most common of these were diarrhea (75.7% vs. 31%), nausea (31.6% vs. 13.5%), and vomiting (24.7% vs.10.4%). Skin ulcers occurred in about 18% of each group. Patients in the active group were significantly more likely to develop elevated alanine and aspartate aminotransferase of up to three times normal levels (4.9% vs. 0.7%).
Treatment did not significantly affect mortality rates, however. Over the treatment period, 10 patients in the nintedanib group and 9 in the placebo group died (3.5% vs. 3.1%).
The study was sponsored by Boehringer Ingelheim. Dr. Distler was the primary investigator on the trial.
SOURCE: Distler O et al. ATS 2019, Abstract A7360.
DALLAS – Nintedanib, a tyrosine kinase inhibitor, decreased by 44% the annual rate of lung function decline among patients with interstitial lung disease associated with systemic sclerosis, a year-long study has found.
In a placebo-controlled 52-week trial, forced vital capacity (FVC) in patients who took nintedanib (Ofev) declined by a mean of 52 mL – significantly less than the mean 93 mL decline seen among those who were given placebo, Oliver Distler, MD, said at the annual meeting of the American Thoracic Society.
“These are people in their mid-40s and -50s,” said Dr. Distler of the University of Zürich. “They have a long time to go. If there is an annual preservation of lung function by 40%, if you have that every year, it becomes very surely clinically significant. A decline in FVC is also a good surrogate marker of mortality in interstitial lung disease associated with systemic sclerosis. Assuming the effects are ongoing above the 1 year we looked at, then indeed these results are clinically important.”
The study was simultaneously published in the New England Journal of Medicine. Nintedanib is already approved for idiopathic pulmonary fibrosis. But some data suggest that it also exerts antifibrotic and anti-inflammatory effects in animal models of systemic sclerosis and inflammatory lung disease (ILD). SENSCIS (the Safety and Efficacy of Nintedanib in Systemic Sclerosis trial) investigated the molecule’s use in patients with ILD associated with systemic sclerosis.
Conducted in 32 countries, SENSCIS comprised 576 patients with the disorder, whose sclerosis affected at least 10% of their lungs. They were assigned to 52 weeks of either placebo or 150 mg nintedanib twice weekly. However, patients stayed on their blinded treatment until the last patient enrolled had finished the year of treatment; some patients took the drug for 100 weeks, Dr. Distler said. The primary endpoint was annual rate of decline in the forced vital capacity (FEV). Secondary endpoints included changes of the modified Rodnan skin score and in the total score on the St. George’s Respiratory Questionnaire.
Patients were a mean of 54 years old, with a mean disease duration of about 3 years. About half had diffuse cutaneous systemic sclerosis; the sclerosis was limited in the remainder. The mean extent of lung fibrosis was about 36%. Half were taking mycophenolate at baseline, which was allowed as background treatment, along with up to 10 mg/day of prednisone. Any patient who experienced clinically significant lung function deterioration could receive additional therapy at the investigator’s discretion.
The mean baseline FEV for these patients was 72.5% of predicted value. The mean diffusing capacity of the lungs for carbon monoxide was 53% of expected capacity.
Most patients completed the study (80% of the active group and 89% of the placebo group). The mean drug exposure duration was 10 months in the active group and 11 in the placebo group.
Improvement began early in treatment, with the efficacy curves separating by week 12 and continuing to diverge. After 52 weeks of therapy, the annual rate of change was 41 mL less in the active group than in the placebo group (–54.4 mL vs. –93.3 mL). The mean adjusted absolute change from baseline was –54.6 mL in the active group and –101 mL in the placebo at week 52. Significantly fewer patients taking nintedanib also lost more than 10% of FVC by week 52 (16.7% vs. 18%).
The St. George’s Respiratory Questionnaire score improved about one point in the active group and declined about one point in the placebo group.
Nintedanib was equally effective across a number of subgroups, including those divided by sex, age, and race. Antitopoisomerase antibodies and so-called antitopoisomerase I antibody status did not affect nintedanib’s action. Nintedanib also significantly improved scores on the Health Assessment Questionnaire without Disability Index and dyspnea.
More patients in the active group than in on placebo discontinued treatment because of a serious adverse event (16% vs. 8.7%). The most common of these were diarrhea (75.7% vs. 31%), nausea (31.6% vs. 13.5%), and vomiting (24.7% vs.10.4%). Skin ulcers occurred in about 18% of each group. Patients in the active group were significantly more likely to develop elevated alanine and aspartate aminotransferase of up to three times normal levels (4.9% vs. 0.7%).
Treatment did not significantly affect mortality rates, however. Over the treatment period, 10 patients in the nintedanib group and 9 in the placebo group died (3.5% vs. 3.1%).
The study was sponsored by Boehringer Ingelheim. Dr. Distler was the primary investigator on the trial.
SOURCE: Distler O et al. ATS 2019, Abstract A7360.
DALLAS – Nintedanib, a tyrosine kinase inhibitor, decreased by 44% the annual rate of lung function decline among patients with interstitial lung disease associated with systemic sclerosis, a year-long study has found.
In a placebo-controlled 52-week trial, forced vital capacity (FVC) in patients who took nintedanib (Ofev) declined by a mean of 52 mL – significantly less than the mean 93 mL decline seen among those who were given placebo, Oliver Distler, MD, said at the annual meeting of the American Thoracic Society.
“These are people in their mid-40s and -50s,” said Dr. Distler of the University of Zürich. “They have a long time to go. If there is an annual preservation of lung function by 40%, if you have that every year, it becomes very surely clinically significant. A decline in FVC is also a good surrogate marker of mortality in interstitial lung disease associated with systemic sclerosis. Assuming the effects are ongoing above the 1 year we looked at, then indeed these results are clinically important.”
The study was simultaneously published in the New England Journal of Medicine. Nintedanib is already approved for idiopathic pulmonary fibrosis. But some data suggest that it also exerts antifibrotic and anti-inflammatory effects in animal models of systemic sclerosis and inflammatory lung disease (ILD). SENSCIS (the Safety and Efficacy of Nintedanib in Systemic Sclerosis trial) investigated the molecule’s use in patients with ILD associated with systemic sclerosis.
Conducted in 32 countries, SENSCIS comprised 576 patients with the disorder, whose sclerosis affected at least 10% of their lungs. They were assigned to 52 weeks of either placebo or 150 mg nintedanib twice weekly. However, patients stayed on their blinded treatment until the last patient enrolled had finished the year of treatment; some patients took the drug for 100 weeks, Dr. Distler said. The primary endpoint was annual rate of decline in the forced vital capacity (FEV). Secondary endpoints included changes of the modified Rodnan skin score and in the total score on the St. George’s Respiratory Questionnaire.
Patients were a mean of 54 years old, with a mean disease duration of about 3 years. About half had diffuse cutaneous systemic sclerosis; the sclerosis was limited in the remainder. The mean extent of lung fibrosis was about 36%. Half were taking mycophenolate at baseline, which was allowed as background treatment, along with up to 10 mg/day of prednisone. Any patient who experienced clinically significant lung function deterioration could receive additional therapy at the investigator’s discretion.
The mean baseline FEV for these patients was 72.5% of predicted value. The mean diffusing capacity of the lungs for carbon monoxide was 53% of expected capacity.
Most patients completed the study (80% of the active group and 89% of the placebo group). The mean drug exposure duration was 10 months in the active group and 11 in the placebo group.
Improvement began early in treatment, with the efficacy curves separating by week 12 and continuing to diverge. After 52 weeks of therapy, the annual rate of change was 41 mL less in the active group than in the placebo group (–54.4 mL vs. –93.3 mL). The mean adjusted absolute change from baseline was –54.6 mL in the active group and –101 mL in the placebo at week 52. Significantly fewer patients taking nintedanib also lost more than 10% of FVC by week 52 (16.7% vs. 18%).
The St. George’s Respiratory Questionnaire score improved about one point in the active group and declined about one point in the placebo group.
Nintedanib was equally effective across a number of subgroups, including those divided by sex, age, and race. Antitopoisomerase antibodies and so-called antitopoisomerase I antibody status did not affect nintedanib’s action. Nintedanib also significantly improved scores on the Health Assessment Questionnaire without Disability Index and dyspnea.
More patients in the active group than in on placebo discontinued treatment because of a serious adverse event (16% vs. 8.7%). The most common of these were diarrhea (75.7% vs. 31%), nausea (31.6% vs. 13.5%), and vomiting (24.7% vs.10.4%). Skin ulcers occurred in about 18% of each group. Patients in the active group were significantly more likely to develop elevated alanine and aspartate aminotransferase of up to three times normal levels (4.9% vs. 0.7%).
Treatment did not significantly affect mortality rates, however. Over the treatment period, 10 patients in the nintedanib group and 9 in the placebo group died (3.5% vs. 3.1%).
The study was sponsored by Boehringer Ingelheim. Dr. Distler was the primary investigator on the trial.
SOURCE: Distler O et al. ATS 2019, Abstract A7360.
AT ATS 2019
Key clinical point: The tyrosine kinase inhibitor nintedanib may be a useful treatment for interstitial lung disease associated with systemic sclerosis (SS-ILD).
Major finding: Nintedanib decreased the annual rate of lung function decline by 44% among patients with SS-ILD.
Study details: The randomized, placebo-controlled study comprised 576 patients.
Disclosures: The trial was sponsored by Boehringer Ingelheim. Dr. Distler is the primary investigator.
Source: Distler O et al. ATS 2019, Abstract A7360.
Rheumatoid arthritis treatment less aggressive, not less favorable in older adults
BIRMINGHAM, ENGLAND – Being diagnosed with rheumatoid arthritis at age 75 years or older made it less likely that patients would receive intensive therapy than their younger counterparts, but that did not mean that they were treated any less favorably overall, according to findings derived from the Early RA Network cohort.
“The claim that the elderly are treated less aggressively isn’t completely true throughout the whole treat-to-target strategy,” said Simone Howard of King’s College London at the British Society for Rheumatology annual conference. While older patients were less likely to receive intensive treatment up to 2 years after their diagnosis, there was a shorter delay between the onset of symptoms and the first outpatient visit to a rheumatology clinic.
When compared against patients who were younger than 65 years, those aged 65-74 years and 75 years and older were 11% (P = .02) and 15% (P = .02) more likely to have their first outpatient visit within 10 months.
Furthermore, no significant differences were seen between any age groups in the time to first initiation of a conventional synthetic disease-modifying antirheumatic drug (csDMARD), which averaged nearly 3 months after symptoms appeared.
Ms. Howard, who has previously worked at the European Medicines Agency, noted that, during her time at the EMA, “there was a real push to incorporate the elderly into the regulatory framework more. In parallel, there were also reports of the elderly being treated less aggressively. So the question was, where was that coming from?”
Similar therapeutic approaches are advocated for older and younger RA patients, and to look for any disparities, Ms. Howard and associates turned to the Early RA Network (ERAN) to “investigate potential treatment bias against the elderly.”
ERAN is a hospital-based inception cohort of 1,236 patients with early RA who were recruited across 23 centers in the United Kingdom and Ireland between 2002 and 2014.
Of 1,131 patients used in the analyses, 9.7% (n = 110) were 75 years or older, 21.5% (n = 243) were aged 65-74 years, and 68.8% (n = 778) were 65 years or younger. The majority (67.7%) of patients were female.
Patients aged 75 years and older were more likely to present with comorbidities than the youngest group, and they had higher health assessment questionnaire scores at baseline. However, they were no more likely to have high disease activity at the first visit, which was defined as a disease activity score in 28 joints of more than 5, and the older patients were 27% less likely to be seropositive (P = .004).
“It’s when we come to pharmacological aspects of care that we are seeing treatment biases,” Ms. Howard noted. Patients over 75 years were significantly more likely than the youngest age group to be treated with glucocorticoids or csDMARD monotherapy at 1 year, and 23% more likely to be on less aggressive therapy (P equal to or less than .0001). Aggressive therapy was defined as the use of a combination of csDMARDs or the use of biologic drugs.
At 2 years, the oldest patients were 46% more likely than those under 65 years to be on less-intensive therapies (P equal to or less than .0001), with those aged 65-74 years 19% more likely to be on glucocorticoid or csDMARD therapy (P = .005).
Factors such as patient choice and tolerance were not considered in the analyses and could be important, Ms. Howard conceded in response to a question after her presentation.
Another point raised was that perhaps the prescribing of aggressive therapy would rationally be different in someone diagnosed with RA at age 85 versus 65 because the duration of time that would be likely to be lived with accumulating joint damage would be shorter at the older age and that would be balanced against the other effects of the therapy. So, there may be important reasons in shared decision making that influenced the treatment choices other than the age of patients.
Ms. Howard agreed, noting that this demonstrated the need to be careful around the language used for defining what constituted aggressive or intensive therapy.
She and her coauthors reported no conflicts of interest.
SOURCE: Howard S et al. Rheumatology. 2019;58(suppl 3), Abstract 011.
BIRMINGHAM, ENGLAND – Being diagnosed with rheumatoid arthritis at age 75 years or older made it less likely that patients would receive intensive therapy than their younger counterparts, but that did not mean that they were treated any less favorably overall, according to findings derived from the Early RA Network cohort.
“The claim that the elderly are treated less aggressively isn’t completely true throughout the whole treat-to-target strategy,” said Simone Howard of King’s College London at the British Society for Rheumatology annual conference. While older patients were less likely to receive intensive treatment up to 2 years after their diagnosis, there was a shorter delay between the onset of symptoms and the first outpatient visit to a rheumatology clinic.
When compared against patients who were younger than 65 years, those aged 65-74 years and 75 years and older were 11% (P = .02) and 15% (P = .02) more likely to have their first outpatient visit within 10 months.
Furthermore, no significant differences were seen between any age groups in the time to first initiation of a conventional synthetic disease-modifying antirheumatic drug (csDMARD), which averaged nearly 3 months after symptoms appeared.
Ms. Howard, who has previously worked at the European Medicines Agency, noted that, during her time at the EMA, “there was a real push to incorporate the elderly into the regulatory framework more. In parallel, there were also reports of the elderly being treated less aggressively. So the question was, where was that coming from?”
Similar therapeutic approaches are advocated for older and younger RA patients, and to look for any disparities, Ms. Howard and associates turned to the Early RA Network (ERAN) to “investigate potential treatment bias against the elderly.”
ERAN is a hospital-based inception cohort of 1,236 patients with early RA who were recruited across 23 centers in the United Kingdom and Ireland between 2002 and 2014.
Of 1,131 patients used in the analyses, 9.7% (n = 110) were 75 years or older, 21.5% (n = 243) were aged 65-74 years, and 68.8% (n = 778) were 65 years or younger. The majority (67.7%) of patients were female.
Patients aged 75 years and older were more likely to present with comorbidities than the youngest group, and they had higher health assessment questionnaire scores at baseline. However, they were no more likely to have high disease activity at the first visit, which was defined as a disease activity score in 28 joints of more than 5, and the older patients were 27% less likely to be seropositive (P = .004).
“It’s when we come to pharmacological aspects of care that we are seeing treatment biases,” Ms. Howard noted. Patients over 75 years were significantly more likely than the youngest age group to be treated with glucocorticoids or csDMARD monotherapy at 1 year, and 23% more likely to be on less aggressive therapy (P equal to or less than .0001). Aggressive therapy was defined as the use of a combination of csDMARDs or the use of biologic drugs.
At 2 years, the oldest patients were 46% more likely than those under 65 years to be on less-intensive therapies (P equal to or less than .0001), with those aged 65-74 years 19% more likely to be on glucocorticoid or csDMARD therapy (P = .005).
Factors such as patient choice and tolerance were not considered in the analyses and could be important, Ms. Howard conceded in response to a question after her presentation.
Another point raised was that perhaps the prescribing of aggressive therapy would rationally be different in someone diagnosed with RA at age 85 versus 65 because the duration of time that would be likely to be lived with accumulating joint damage would be shorter at the older age and that would be balanced against the other effects of the therapy. So, there may be important reasons in shared decision making that influenced the treatment choices other than the age of patients.
Ms. Howard agreed, noting that this demonstrated the need to be careful around the language used for defining what constituted aggressive or intensive therapy.
She and her coauthors reported no conflicts of interest.
SOURCE: Howard S et al. Rheumatology. 2019;58(suppl 3), Abstract 011.
BIRMINGHAM, ENGLAND – Being diagnosed with rheumatoid arthritis at age 75 years or older made it less likely that patients would receive intensive therapy than their younger counterparts, but that did not mean that they were treated any less favorably overall, according to findings derived from the Early RA Network cohort.
“The claim that the elderly are treated less aggressively isn’t completely true throughout the whole treat-to-target strategy,” said Simone Howard of King’s College London at the British Society for Rheumatology annual conference. While older patients were less likely to receive intensive treatment up to 2 years after their diagnosis, there was a shorter delay between the onset of symptoms and the first outpatient visit to a rheumatology clinic.
When compared against patients who were younger than 65 years, those aged 65-74 years and 75 years and older were 11% (P = .02) and 15% (P = .02) more likely to have their first outpatient visit within 10 months.
Furthermore, no significant differences were seen between any age groups in the time to first initiation of a conventional synthetic disease-modifying antirheumatic drug (csDMARD), which averaged nearly 3 months after symptoms appeared.
Ms. Howard, who has previously worked at the European Medicines Agency, noted that, during her time at the EMA, “there was a real push to incorporate the elderly into the regulatory framework more. In parallel, there were also reports of the elderly being treated less aggressively. So the question was, where was that coming from?”
Similar therapeutic approaches are advocated for older and younger RA patients, and to look for any disparities, Ms. Howard and associates turned to the Early RA Network (ERAN) to “investigate potential treatment bias against the elderly.”
ERAN is a hospital-based inception cohort of 1,236 patients with early RA who were recruited across 23 centers in the United Kingdom and Ireland between 2002 and 2014.
Of 1,131 patients used in the analyses, 9.7% (n = 110) were 75 years or older, 21.5% (n = 243) were aged 65-74 years, and 68.8% (n = 778) were 65 years or younger. The majority (67.7%) of patients were female.
Patients aged 75 years and older were more likely to present with comorbidities than the youngest group, and they had higher health assessment questionnaire scores at baseline. However, they were no more likely to have high disease activity at the first visit, which was defined as a disease activity score in 28 joints of more than 5, and the older patients were 27% less likely to be seropositive (P = .004).
“It’s when we come to pharmacological aspects of care that we are seeing treatment biases,” Ms. Howard noted. Patients over 75 years were significantly more likely than the youngest age group to be treated with glucocorticoids or csDMARD monotherapy at 1 year, and 23% more likely to be on less aggressive therapy (P equal to or less than .0001). Aggressive therapy was defined as the use of a combination of csDMARDs or the use of biologic drugs.
At 2 years, the oldest patients were 46% more likely than those under 65 years to be on less-intensive therapies (P equal to or less than .0001), with those aged 65-74 years 19% more likely to be on glucocorticoid or csDMARD therapy (P = .005).
Factors such as patient choice and tolerance were not considered in the analyses and could be important, Ms. Howard conceded in response to a question after her presentation.
Another point raised was that perhaps the prescribing of aggressive therapy would rationally be different in someone diagnosed with RA at age 85 versus 65 because the duration of time that would be likely to be lived with accumulating joint damage would be shorter at the older age and that would be balanced against the other effects of the therapy. So, there may be important reasons in shared decision making that influenced the treatment choices other than the age of patients.
Ms. Howard agreed, noting that this demonstrated the need to be careful around the language used for defining what constituted aggressive or intensive therapy.
She and her coauthors reported no conflicts of interest.
SOURCE: Howard S et al. Rheumatology. 2019;58(suppl 3), Abstract 011.
REPORTING FROM BSR 2019
Significant increase in low-attenuation coronary plaques found in lupus
SAN FRANCISCO – according to an investigation from Johns Hopkins University, Baltimore.
All of the 102 lupus patients in the coronary artery CT angiography study also had positive plaque remodeling, meaning that at least one low-attenuation plaque was growing into the lumen wall, not the lumen itself, which makes them difficult to detect on standard imaging. Low-attenuation plaques were defined in the study as a plaque larger than 1 mm2 with a radiodensity below 30 Hounsfield units.
Low-attenuation plaques are inherently unstable; they’re fatty, necrotic, and have a high risk of rupturing; their presence in the lumen wall is especially worrisome. In the general population, they sometimes regress, scarring down over time and no longer posing a threat. That didn’t happen in the 30 lupus patients who had follow-up CT angiographies, some 9 years after their first.
The team conducted the study to help understand why cardiovascular disease is so common in lupus, and the leading cause of death. Hopkins investigators have shown previously that statins have no effect on the risk or plaque occurrence and progression, and the cardiovascular risk doesn’t always seem to correlate with disease control. For those and other reasons, the current thinking at Hopkins is that cardiovascular disease in lupus is somehow different than in the general population, said George Stojan, MD, an assistant professor of rheumatology at the school and codirector of the Hopkins Lupus Center.
The goal is “to figure out exactly what to look for when we assess the risk; I don’t think we understand that at this point. We assume patients with lupus behave exactly like patients who don’t have lupus, but they obviously don’t. They do not respond to statins. They have a higher risk no matter what you do for them, even when their disease activity is low, and how much plaque they have over time doesn’t really correlate with disease activity,” he said at an international conference on systemic lupus erythematosus.
“Once we understand” the mechanism, “then we can try to [alter] it. Maybe we can look at new drugs, like the PCSK9 inhibitors which have shown a lot of promise in the general population.” At this point, however, “we don’t really know how to intervene,” Dr. Stojan said.
In the meantime, positive remodeling and low-attenuation, noncalcified plaques (LANCPs) might be something to look for when assessing systemic lupus erythematosus cardiovascular risk. “A simple coronary calcium score, something that all doctors do,” is not enough in lupus, nor is simply checking for lumen obstruction. Also, it’s important not to be misled by an overall reduction in noncalcified plaques. “Low-attenuation, noncalcified plaques don’t [regress] over time in lupus, and they are the ones that lead to cardiovascular events,” he said.
The CT angiography findings were compared with findings in 100 healthy controls who had two CT angiograms in a University of California, Los Angeles, cohort. Overall, there was a mean of 458 LANCPs among lupus patients, versus 42 among controls, a more than 900% difference (P less than .001).
Women with lupus aged under 44 years had a mean of 63 LANCPs; none were detected in healthy women under 44 years. Among women aged 45-59 years, there was a mean of 451 LANCPs in the lupus group versus 53 in the control arm. The findings were highly statistically significant, and almost statistically significant for women 60 years or older, 695 lesions among lupus patients versus 22 (P = .0576).
There were only nine men with lupus in the study, but the findings were similar versus male controls.
While mean LANCP volume regressed over time in the control group (mean, –6.90 mm3; P = .0002), a mean regression of –13.56 mm3 in the lupus group was not statistically significant (P = .4570).
Both controls and lupus patients had a positive remodeling index. It progressed in the lupus group over time, and regressed in controls, but the findings were not statistically significant.
“Statins did nothing for the lupus patients. They didn’t affect progress of coronary plaques at all. We still treat patients because theoretically we don’t have anything better, but we know that they don’t really work in this population,” Dr. Stojan said
The work is funded by the National Institutes of Health. Dr. Stojan didn’t report any relevant disclosures.
SOURCE: Stojan G et al. Lupus Sci Med. 2019;6[suppl 1]:A200, Abstract 274.
SAN FRANCISCO – according to an investigation from Johns Hopkins University, Baltimore.
All of the 102 lupus patients in the coronary artery CT angiography study also had positive plaque remodeling, meaning that at least one low-attenuation plaque was growing into the lumen wall, not the lumen itself, which makes them difficult to detect on standard imaging. Low-attenuation plaques were defined in the study as a plaque larger than 1 mm2 with a radiodensity below 30 Hounsfield units.
Low-attenuation plaques are inherently unstable; they’re fatty, necrotic, and have a high risk of rupturing; their presence in the lumen wall is especially worrisome. In the general population, they sometimes regress, scarring down over time and no longer posing a threat. That didn’t happen in the 30 lupus patients who had follow-up CT angiographies, some 9 years after their first.
The team conducted the study to help understand why cardiovascular disease is so common in lupus, and the leading cause of death. Hopkins investigators have shown previously that statins have no effect on the risk or plaque occurrence and progression, and the cardiovascular risk doesn’t always seem to correlate with disease control. For those and other reasons, the current thinking at Hopkins is that cardiovascular disease in lupus is somehow different than in the general population, said George Stojan, MD, an assistant professor of rheumatology at the school and codirector of the Hopkins Lupus Center.
The goal is “to figure out exactly what to look for when we assess the risk; I don’t think we understand that at this point. We assume patients with lupus behave exactly like patients who don’t have lupus, but they obviously don’t. They do not respond to statins. They have a higher risk no matter what you do for them, even when their disease activity is low, and how much plaque they have over time doesn’t really correlate with disease activity,” he said at an international conference on systemic lupus erythematosus.
“Once we understand” the mechanism, “then we can try to [alter] it. Maybe we can look at new drugs, like the PCSK9 inhibitors which have shown a lot of promise in the general population.” At this point, however, “we don’t really know how to intervene,” Dr. Stojan said.
In the meantime, positive remodeling and low-attenuation, noncalcified plaques (LANCPs) might be something to look for when assessing systemic lupus erythematosus cardiovascular risk. “A simple coronary calcium score, something that all doctors do,” is not enough in lupus, nor is simply checking for lumen obstruction. Also, it’s important not to be misled by an overall reduction in noncalcified plaques. “Low-attenuation, noncalcified plaques don’t [regress] over time in lupus, and they are the ones that lead to cardiovascular events,” he said.
The CT angiography findings were compared with findings in 100 healthy controls who had two CT angiograms in a University of California, Los Angeles, cohort. Overall, there was a mean of 458 LANCPs among lupus patients, versus 42 among controls, a more than 900% difference (P less than .001).
Women with lupus aged under 44 years had a mean of 63 LANCPs; none were detected in healthy women under 44 years. Among women aged 45-59 years, there was a mean of 451 LANCPs in the lupus group versus 53 in the control arm. The findings were highly statistically significant, and almost statistically significant for women 60 years or older, 695 lesions among lupus patients versus 22 (P = .0576).
There were only nine men with lupus in the study, but the findings were similar versus male controls.
While mean LANCP volume regressed over time in the control group (mean, –6.90 mm3; P = .0002), a mean regression of –13.56 mm3 in the lupus group was not statistically significant (P = .4570).
Both controls and lupus patients had a positive remodeling index. It progressed in the lupus group over time, and regressed in controls, but the findings were not statistically significant.
“Statins did nothing for the lupus patients. They didn’t affect progress of coronary plaques at all. We still treat patients because theoretically we don’t have anything better, but we know that they don’t really work in this population,” Dr. Stojan said
The work is funded by the National Institutes of Health. Dr. Stojan didn’t report any relevant disclosures.
SOURCE: Stojan G et al. Lupus Sci Med. 2019;6[suppl 1]:A200, Abstract 274.
SAN FRANCISCO – according to an investigation from Johns Hopkins University, Baltimore.
All of the 102 lupus patients in the coronary artery CT angiography study also had positive plaque remodeling, meaning that at least one low-attenuation plaque was growing into the lumen wall, not the lumen itself, which makes them difficult to detect on standard imaging. Low-attenuation plaques were defined in the study as a plaque larger than 1 mm2 with a radiodensity below 30 Hounsfield units.
Low-attenuation plaques are inherently unstable; they’re fatty, necrotic, and have a high risk of rupturing; their presence in the lumen wall is especially worrisome. In the general population, they sometimes regress, scarring down over time and no longer posing a threat. That didn’t happen in the 30 lupus patients who had follow-up CT angiographies, some 9 years after their first.
The team conducted the study to help understand why cardiovascular disease is so common in lupus, and the leading cause of death. Hopkins investigators have shown previously that statins have no effect on the risk or plaque occurrence and progression, and the cardiovascular risk doesn’t always seem to correlate with disease control. For those and other reasons, the current thinking at Hopkins is that cardiovascular disease in lupus is somehow different than in the general population, said George Stojan, MD, an assistant professor of rheumatology at the school and codirector of the Hopkins Lupus Center.
The goal is “to figure out exactly what to look for when we assess the risk; I don’t think we understand that at this point. We assume patients with lupus behave exactly like patients who don’t have lupus, but they obviously don’t. They do not respond to statins. They have a higher risk no matter what you do for them, even when their disease activity is low, and how much plaque they have over time doesn’t really correlate with disease activity,” he said at an international conference on systemic lupus erythematosus.
“Once we understand” the mechanism, “then we can try to [alter] it. Maybe we can look at new drugs, like the PCSK9 inhibitors which have shown a lot of promise in the general population.” At this point, however, “we don’t really know how to intervene,” Dr. Stojan said.
In the meantime, positive remodeling and low-attenuation, noncalcified plaques (LANCPs) might be something to look for when assessing systemic lupus erythematosus cardiovascular risk. “A simple coronary calcium score, something that all doctors do,” is not enough in lupus, nor is simply checking for lumen obstruction. Also, it’s important not to be misled by an overall reduction in noncalcified plaques. “Low-attenuation, noncalcified plaques don’t [regress] over time in lupus, and they are the ones that lead to cardiovascular events,” he said.
The CT angiography findings were compared with findings in 100 healthy controls who had two CT angiograms in a University of California, Los Angeles, cohort. Overall, there was a mean of 458 LANCPs among lupus patients, versus 42 among controls, a more than 900% difference (P less than .001).
Women with lupus aged under 44 years had a mean of 63 LANCPs; none were detected in healthy women under 44 years. Among women aged 45-59 years, there was a mean of 451 LANCPs in the lupus group versus 53 in the control arm. The findings were highly statistically significant, and almost statistically significant for women 60 years or older, 695 lesions among lupus patients versus 22 (P = .0576).
There were only nine men with lupus in the study, but the findings were similar versus male controls.
While mean LANCP volume regressed over time in the control group (mean, –6.90 mm3; P = .0002), a mean regression of –13.56 mm3 in the lupus group was not statistically significant (P = .4570).
Both controls and lupus patients had a positive remodeling index. It progressed in the lupus group over time, and regressed in controls, but the findings were not statistically significant.
“Statins did nothing for the lupus patients. They didn’t affect progress of coronary plaques at all. We still treat patients because theoretically we don’t have anything better, but we know that they don’t really work in this population,” Dr. Stojan said
The work is funded by the National Institutes of Health. Dr. Stojan didn’t report any relevant disclosures.
SOURCE: Stojan G et al. Lupus Sci Med. 2019;6[suppl 1]:A200, Abstract 274.
REPORTING FROM LUPUS 2019
Key clinical point: Positive remodeling and low-attenuation, noncalcified plaques might be something to look for when assessing systemic lupus erythematosus cardiovascular risk.
Major finding: There was a mean of 458 low-attenuation, noncalcified plaques among lupus patients versus 42 among controls, a more than 900% difference (P less than .001)
Study details: Coronary CT angiography in 102 lupus patients and 100 healthy controls
Disclosures: The National Institutes of Health funded the work. The lead investigator didn’t report any relevant disclosures.
Source: Stojan G et al. Lupus Sci Med. 2019;6[suppl 1]:A200, Abstract 274.
Methotrexate does not cause rheumatoid interstitial lung disease
BIRMINGHAM, ENGLAND – Data from two early RA inception cohorts provide reassurance that methotrexate does not cause interstitial lung disease and suggest that treatment with methotrexate might even be protective.
In the Early RA Study (ERAS) and Early RA Network (ERAN), which together include 2,701 patients with RA, 101 (3.7%) had interstitial lung disease (ILD). There were 92 patients with RA-ILD who had information available on exposure to any conventional synthetic disease-modifying antirheumatic drug (csDMARD); of these, 39 (2.5%) had been exposed to methotrexate (n = 1,578) and 53 (4.8%) to other csDMARDs (n = 1,114).
Multivariate analysis showed that methotrexate exposure was associated with a reduced risk of developing ILD, with an odds ratio of 0.48 (P = .004). In a separate analysis that excluded 25 patients who had ILD before they received any csDMARD therapy (n = 67), there was no association between methotrexate use and ILD (OR, 0.85; P = .578). In fact, there was a nonsignificant trend for a delayed onset of ILD in patients who had been treated with methotrexate (OR, 0.54; P = .072).
Methotrexate use is associated with an acute hypersensitivity pneumonitis in patients with RA, explained Patrick Kiely, MBBS, PhD, of St. George’s University Hospitals NHS Foundation Trust in London at the British Society for Rheumatology annual conference. “This is well recognized, it’s very rare [0.43%-1.00%], it’s easy to spot, and usually goes away if you stop methotrexate,” said Dr. Kiely, adding that “it’s not benign, and severe cases can be life threatening.”
Because of the association between methotrexate and pneumonitis, there has been concern that methotrexate may exacerbate or even cause ILD in RA but there are sparse data available to confirm this. The bottom line is that you should not start someone on methotrexate if you think their existing lung capacity is not up to treatment with methotrexate, Dr. Kiely said.
ILD is not always symptomatic in RA, but when it is, it is associated with very poor survival. The lung disease can be present before joint symptoms, Dr. Kiely said. Although less than 10% of cases may be symptomatic, this “is a big deal, because it has a high mortality, with death within 5 years. It’s the second-commonest cause of excess mortality in RA after cardiovascular disease.”
To look at the association between incident RA-ILD and the use of methotrexate, Dr. Kiely and associates analyzed data from ERAS (1986-2001) and ERAN (2002-2013), that together have more than 25 years of follow-up data on patients who were recruited at the first sign of RA symptoms. Patients within these cohorts have been treated according to best practice, and a range of outcomes – including RA-ILD – have been assessed at annual intervals.
In the patients who developed ILD after any csDMARD exposure, older age at RA onset (OR, 1.04; P less than .001) and having ever smoked (OR, 1.91; P = .016) were associated with the development of the lung disease. Incident ILD was also associated with being positive for rheumatoid factor (OR, 2.02; P = .029) at baseline. Being male was also associated with a higher risk for developing ILD, Dr. Kiely reported, as was a longer duration of time between the onset of first RA symptoms and the first secondary care visit. Conversely, the presence of nonrespiratory, major comorbidities at baseline appeared to be protective (OR, 0.62; P = .027).
“We found no association between methotrexate treatment and incident RA-ILD and a possibility that it may be protective,” Dr. Kiely concluded, noting that these data were now published in BMJ Open (2019;9:e028466. doi: 10.1136/bmjopen-2018-028466).
Following Dr. Kiely’s presentation, an audience member asked if the protective effect seen with methotrexate could have been caused by better disease control overall.
Dr. Kiely answered that, up until 2001, the time when ERAS was ongoing, standard practice in the United Kingdom was to use sulfasalazine, but then methotrexate started to be used in higher and higher doses, as seen in ERAN.
The interesting thing is that in ERAN more methotrexate was used in higher doses, but less RA-ILD was seen, Dr. Kiely observed. The overall prevalence of RA-ILD in the later early RA cohort was 3.2% and the median dose of methotrexate used was 20 mg. In ERAS, the prevalence was 4.2% and the median dose of methotrexate used was 10 mg.
There was a suggestion that disease control was slightly better in ERAN than ERAS, but that wasn’t statistically significant, Dr. Kiely said.
So, should a patient with RA and ILD be given methotrexate? There’s no reason not to, Dr. Kiely suggested, based on the evidence shown. Part of the challenge will now be convincing chest physician colleagues that methotrexate is not problematic in terms of causing ILD.
These findings are completely on board with the ILD group’s findings that methotrexate doesn’t cause pulmonary fibrosis in patients with RA, commented Julie Dawson, MD, of St. Helens and Knowsley Teaching Hospitals NHS Trust, St. Helens, England. Her own research, which includes a 10-year follow-up of patients with inflammatory arthritis, has shown that methotrexate does not appear to increase the risk of pulmonary fibrosis.
The study had no specific outside funding. Dr. Kiely reported having no conflicts of interest.
SOURCE: Kiely P et al. Rheumatology. 2019;58(suppl 3), Abstract 009.
BIRMINGHAM, ENGLAND – Data from two early RA inception cohorts provide reassurance that methotrexate does not cause interstitial lung disease and suggest that treatment with methotrexate might even be protective.
In the Early RA Study (ERAS) and Early RA Network (ERAN), which together include 2,701 patients with RA, 101 (3.7%) had interstitial lung disease (ILD). There were 92 patients with RA-ILD who had information available on exposure to any conventional synthetic disease-modifying antirheumatic drug (csDMARD); of these, 39 (2.5%) had been exposed to methotrexate (n = 1,578) and 53 (4.8%) to other csDMARDs (n = 1,114).
Multivariate analysis showed that methotrexate exposure was associated with a reduced risk of developing ILD, with an odds ratio of 0.48 (P = .004). In a separate analysis that excluded 25 patients who had ILD before they received any csDMARD therapy (n = 67), there was no association between methotrexate use and ILD (OR, 0.85; P = .578). In fact, there was a nonsignificant trend for a delayed onset of ILD in patients who had been treated with methotrexate (OR, 0.54; P = .072).
Methotrexate use is associated with an acute hypersensitivity pneumonitis in patients with RA, explained Patrick Kiely, MBBS, PhD, of St. George’s University Hospitals NHS Foundation Trust in London at the British Society for Rheumatology annual conference. “This is well recognized, it’s very rare [0.43%-1.00%], it’s easy to spot, and usually goes away if you stop methotrexate,” said Dr. Kiely, adding that “it’s not benign, and severe cases can be life threatening.”
Because of the association between methotrexate and pneumonitis, there has been concern that methotrexate may exacerbate or even cause ILD in RA but there are sparse data available to confirm this. The bottom line is that you should not start someone on methotrexate if you think their existing lung capacity is not up to treatment with methotrexate, Dr. Kiely said.
ILD is not always symptomatic in RA, but when it is, it is associated with very poor survival. The lung disease can be present before joint symptoms, Dr. Kiely said. Although less than 10% of cases may be symptomatic, this “is a big deal, because it has a high mortality, with death within 5 years. It’s the second-commonest cause of excess mortality in RA after cardiovascular disease.”
To look at the association between incident RA-ILD and the use of methotrexate, Dr. Kiely and associates analyzed data from ERAS (1986-2001) and ERAN (2002-2013), that together have more than 25 years of follow-up data on patients who were recruited at the first sign of RA symptoms. Patients within these cohorts have been treated according to best practice, and a range of outcomes – including RA-ILD – have been assessed at annual intervals.
In the patients who developed ILD after any csDMARD exposure, older age at RA onset (OR, 1.04; P less than .001) and having ever smoked (OR, 1.91; P = .016) were associated with the development of the lung disease. Incident ILD was also associated with being positive for rheumatoid factor (OR, 2.02; P = .029) at baseline. Being male was also associated with a higher risk for developing ILD, Dr. Kiely reported, as was a longer duration of time between the onset of first RA symptoms and the first secondary care visit. Conversely, the presence of nonrespiratory, major comorbidities at baseline appeared to be protective (OR, 0.62; P = .027).
“We found no association between methotrexate treatment and incident RA-ILD and a possibility that it may be protective,” Dr. Kiely concluded, noting that these data were now published in BMJ Open (2019;9:e028466. doi: 10.1136/bmjopen-2018-028466).
Following Dr. Kiely’s presentation, an audience member asked if the protective effect seen with methotrexate could have been caused by better disease control overall.
Dr. Kiely answered that, up until 2001, the time when ERAS was ongoing, standard practice in the United Kingdom was to use sulfasalazine, but then methotrexate started to be used in higher and higher doses, as seen in ERAN.
The interesting thing is that in ERAN more methotrexate was used in higher doses, but less RA-ILD was seen, Dr. Kiely observed. The overall prevalence of RA-ILD in the later early RA cohort was 3.2% and the median dose of methotrexate used was 20 mg. In ERAS, the prevalence was 4.2% and the median dose of methotrexate used was 10 mg.
There was a suggestion that disease control was slightly better in ERAN than ERAS, but that wasn’t statistically significant, Dr. Kiely said.
So, should a patient with RA and ILD be given methotrexate? There’s no reason not to, Dr. Kiely suggested, based on the evidence shown. Part of the challenge will now be convincing chest physician colleagues that methotrexate is not problematic in terms of causing ILD.
These findings are completely on board with the ILD group’s findings that methotrexate doesn’t cause pulmonary fibrosis in patients with RA, commented Julie Dawson, MD, of St. Helens and Knowsley Teaching Hospitals NHS Trust, St. Helens, England. Her own research, which includes a 10-year follow-up of patients with inflammatory arthritis, has shown that methotrexate does not appear to increase the risk of pulmonary fibrosis.
The study had no specific outside funding. Dr. Kiely reported having no conflicts of interest.
SOURCE: Kiely P et al. Rheumatology. 2019;58(suppl 3), Abstract 009.
BIRMINGHAM, ENGLAND – Data from two early RA inception cohorts provide reassurance that methotrexate does not cause interstitial lung disease and suggest that treatment with methotrexate might even be protective.
In the Early RA Study (ERAS) and Early RA Network (ERAN), which together include 2,701 patients with RA, 101 (3.7%) had interstitial lung disease (ILD). There were 92 patients with RA-ILD who had information available on exposure to any conventional synthetic disease-modifying antirheumatic drug (csDMARD); of these, 39 (2.5%) had been exposed to methotrexate (n = 1,578) and 53 (4.8%) to other csDMARDs (n = 1,114).
Multivariate analysis showed that methotrexate exposure was associated with a reduced risk of developing ILD, with an odds ratio of 0.48 (P = .004). In a separate analysis that excluded 25 patients who had ILD before they received any csDMARD therapy (n = 67), there was no association between methotrexate use and ILD (OR, 0.85; P = .578). In fact, there was a nonsignificant trend for a delayed onset of ILD in patients who had been treated with methotrexate (OR, 0.54; P = .072).
Methotrexate use is associated with an acute hypersensitivity pneumonitis in patients with RA, explained Patrick Kiely, MBBS, PhD, of St. George’s University Hospitals NHS Foundation Trust in London at the British Society for Rheumatology annual conference. “This is well recognized, it’s very rare [0.43%-1.00%], it’s easy to spot, and usually goes away if you stop methotrexate,” said Dr. Kiely, adding that “it’s not benign, and severe cases can be life threatening.”
Because of the association between methotrexate and pneumonitis, there has been concern that methotrexate may exacerbate or even cause ILD in RA but there are sparse data available to confirm this. The bottom line is that you should not start someone on methotrexate if you think their existing lung capacity is not up to treatment with methotrexate, Dr. Kiely said.
ILD is not always symptomatic in RA, but when it is, it is associated with very poor survival. The lung disease can be present before joint symptoms, Dr. Kiely said. Although less than 10% of cases may be symptomatic, this “is a big deal, because it has a high mortality, with death within 5 years. It’s the second-commonest cause of excess mortality in RA after cardiovascular disease.”
To look at the association between incident RA-ILD and the use of methotrexate, Dr. Kiely and associates analyzed data from ERAS (1986-2001) and ERAN (2002-2013), that together have more than 25 years of follow-up data on patients who were recruited at the first sign of RA symptoms. Patients within these cohorts have been treated according to best practice, and a range of outcomes – including RA-ILD – have been assessed at annual intervals.
In the patients who developed ILD after any csDMARD exposure, older age at RA onset (OR, 1.04; P less than .001) and having ever smoked (OR, 1.91; P = .016) were associated with the development of the lung disease. Incident ILD was also associated with being positive for rheumatoid factor (OR, 2.02; P = .029) at baseline. Being male was also associated with a higher risk for developing ILD, Dr. Kiely reported, as was a longer duration of time between the onset of first RA symptoms and the first secondary care visit. Conversely, the presence of nonrespiratory, major comorbidities at baseline appeared to be protective (OR, 0.62; P = .027).
“We found no association between methotrexate treatment and incident RA-ILD and a possibility that it may be protective,” Dr. Kiely concluded, noting that these data were now published in BMJ Open (2019;9:e028466. doi: 10.1136/bmjopen-2018-028466).
Following Dr. Kiely’s presentation, an audience member asked if the protective effect seen with methotrexate could have been caused by better disease control overall.
Dr. Kiely answered that, up until 2001, the time when ERAS was ongoing, standard practice in the United Kingdom was to use sulfasalazine, but then methotrexate started to be used in higher and higher doses, as seen in ERAN.
The interesting thing is that in ERAN more methotrexate was used in higher doses, but less RA-ILD was seen, Dr. Kiely observed. The overall prevalence of RA-ILD in the later early RA cohort was 3.2% and the median dose of methotrexate used was 20 mg. In ERAS, the prevalence was 4.2% and the median dose of methotrexate used was 10 mg.
There was a suggestion that disease control was slightly better in ERAN than ERAS, but that wasn’t statistically significant, Dr. Kiely said.
So, should a patient with RA and ILD be given methotrexate? There’s no reason not to, Dr. Kiely suggested, based on the evidence shown. Part of the challenge will now be convincing chest physician colleagues that methotrexate is not problematic in terms of causing ILD.
These findings are completely on board with the ILD group’s findings that methotrexate doesn’t cause pulmonary fibrosis in patients with RA, commented Julie Dawson, MD, of St. Helens and Knowsley Teaching Hospitals NHS Trust, St. Helens, England. Her own research, which includes a 10-year follow-up of patients with inflammatory arthritis, has shown that methotrexate does not appear to increase the risk of pulmonary fibrosis.
The study had no specific outside funding. Dr. Kiely reported having no conflicts of interest.
SOURCE: Kiely P et al. Rheumatology. 2019;58(suppl 3), Abstract 009.
REPORTING FROM BSR 2019
EMA: Stop high-dose Xeljanz in certain patients
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency has recommended that patients at high risk of blood clots in the lungs should not be prescribed the 10-mg, twice-daily dose of tofacitinib (Xeljanz).
The PRAC recommendation is based on results from an ongoing study of patients with rheumatoid arthritis (RA), which has shown that patients receiving the 10-mg, twice-daily dose – twice the approved dose for RA – are at an increased risk of blood clots in the lungs and death.
Patients at risk include those with heart failure, cancer, inherited blood clotting disorders, or a history of blood clots, as well as patients who take combined hormonal contraceptives, are receiving hormone replacement therapy, or are undergoing major surgery. In addition, age, obesity, smoking, or immobilization should also be considered as risk factors.
In Europe, tofacitinib is indicated for the treatment of RA, psoriatic arthritis, and severe ulcerative colitis. Because the 10-mg dose is the only indicated treatment for ulcerative colitis, patients with the disease and who are at high risk should not be started on tofacitinib, and patients who are already taking the drug should be switched to a different treatment.
“The new recommendations are temporary and follow previous PRAC advice not to exceed the recommended 5-mg, twice-daily dose when treating rheumatoid arthritis. The PRAC will now carry out a review of all available evidence, and updated guidance will be provided to patients and healthcare professionals once the review is concluded,” according to the European Medicines Agency.
Find the full press release on the European Medicines Agency website.
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency has recommended that patients at high risk of blood clots in the lungs should not be prescribed the 10-mg, twice-daily dose of tofacitinib (Xeljanz).
The PRAC recommendation is based on results from an ongoing study of patients with rheumatoid arthritis (RA), which has shown that patients receiving the 10-mg, twice-daily dose – twice the approved dose for RA – are at an increased risk of blood clots in the lungs and death.
Patients at risk include those with heart failure, cancer, inherited blood clotting disorders, or a history of blood clots, as well as patients who take combined hormonal contraceptives, are receiving hormone replacement therapy, or are undergoing major surgery. In addition, age, obesity, smoking, or immobilization should also be considered as risk factors.
In Europe, tofacitinib is indicated for the treatment of RA, psoriatic arthritis, and severe ulcerative colitis. Because the 10-mg dose is the only indicated treatment for ulcerative colitis, patients with the disease and who are at high risk should not be started on tofacitinib, and patients who are already taking the drug should be switched to a different treatment.
“The new recommendations are temporary and follow previous PRAC advice not to exceed the recommended 5-mg, twice-daily dose when treating rheumatoid arthritis. The PRAC will now carry out a review of all available evidence, and updated guidance will be provided to patients and healthcare professionals once the review is concluded,” according to the European Medicines Agency.
Find the full press release on the European Medicines Agency website.
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency has recommended that patients at high risk of blood clots in the lungs should not be prescribed the 10-mg, twice-daily dose of tofacitinib (Xeljanz).
The PRAC recommendation is based on results from an ongoing study of patients with rheumatoid arthritis (RA), which has shown that patients receiving the 10-mg, twice-daily dose – twice the approved dose for RA – are at an increased risk of blood clots in the lungs and death.
Patients at risk include those with heart failure, cancer, inherited blood clotting disorders, or a history of blood clots, as well as patients who take combined hormonal contraceptives, are receiving hormone replacement therapy, or are undergoing major surgery. In addition, age, obesity, smoking, or immobilization should also be considered as risk factors.
In Europe, tofacitinib is indicated for the treatment of RA, psoriatic arthritis, and severe ulcerative colitis. Because the 10-mg dose is the only indicated treatment for ulcerative colitis, patients with the disease and who are at high risk should not be started on tofacitinib, and patients who are already taking the drug should be switched to a different treatment.
“The new recommendations are temporary and follow previous PRAC advice not to exceed the recommended 5-mg, twice-daily dose when treating rheumatoid arthritis. The PRAC will now carry out a review of all available evidence, and updated guidance will be provided to patients and healthcare professionals once the review is concluded,” according to the European Medicines Agency.
Find the full press release on the European Medicines Agency website.
PT beats steroid injections for knee OA
TORONTO – Eight physical therapy sessions spread over 4-6 weeks in patients with knee osteoarthritis provided significantly greater and longer-lasting improvements in both pain and function than an intra-articular corticosteroid injection in a randomized, multicenter trial with 12 months of prospective, blinded follow-up, Daniel I. Rhon, DPT, DSc, reported at the OARSI 2019 World Congress.
“Considering the very low utilization rate of physical therapy prior to arthroplasty, perhaps we should more often give it a try before declaring that conservative care has failed and moving on to surgical management,” concluded Dr. Rhon, director of the primary care musculoskeletal research center at Brooke Army Medical Center in San Antonio.
Various studies have shown that close to 50% of patients with knee OA receive one or more intra-articular corticosteroid injections within 5 years prior to undergoing total knee arthroplasty, compared with physical therapy in only about 10% of patients, even though most guidelines rate both as first-line therapies, he noted at the meeting sponsored by the Osteoarthritis Research Society International.
He presented a randomized trial of 156 patients who sought treatment for pain caused by knee OA at army medical center primary care clinics. To his knowledge, this was the first-ever randomized, head-to-head comparison of the effectiveness of a physical therapy regimen versus corticosteroid injections for knee OA. Because he and his coinvestigators wanted a pragmatic study giving each treatment strategy its due, booster therapy was available to patients who requested it. Patients in the corticosteroid arm were able to receive up to two additional spaced intra-articular injections as needed, while those assigned to the individualized manual physical therapy intervention, which utilized exercises targeting the typical strength and movement deficits found in patients with knee OA, could have up to three additional sessions. At the outset, all participants received education about the benefits of regular low-impact physical activity, weight reduction, and strength and flexibility exercises.
The two treatment groups were comparable except that the physical therapy group had a longer disease duration – a mean of 123 months as compared with 89 in the corticosteroid group – and more radiographically severe disease. Indeed, 60% of patients randomized to physical therapy were Kellgren-Lawrence scale grade III-IV, versus 45% of those assigned to intra-articular corticosteroid injection.
The primary outcome in the study was change in Western Ontario & McMaster Universities Arthritis Index (WOMAC) score at 12 months. As early as 4 weeks into the study, the physical therapy group showed significantly greater improvement than in the comparison arm: from a mean baseline WOMAC score of 115 to 42.9 at 4 weeks, 42.5 at 6 months, and 38.4 at 1 year. The comparable figures in the intra-articular corticosteroid group were 113.3 at baseline, 53.3 at 4 weeks, 57.9 at 6 months, and 53.8 at 1 year.
“Physical therapy provided clinically important benefit that was superior to corticosteroid injection out to 1 year, while also providing the short-term benefit typically sought from corticosteroid injection,” Dr. Rhon observed.
The median improvement in WOMAC score at 1 year was 52% in the corticosteroid group and 71% in the physical therapy arm. About 59% of the physical therapy group experienced at least a 50% reduction in WOMAC score at 12 months, as did 38% of intra-articular injection recipients. The number needed to treat with physical therapy instead of intra-articular corticosteroids in order for one additional patient to achieve at least a 50% improvement in WOMAC score through 1 year of follow-up was four.
“We were a little bit surprised that there was such a large effect size in the study. The effect size in the injection group was bigger than reported in some other trials,” according to Dr. Rhon.
In terms of downstream utilization of health care, there were two knee arthroplasties and one arthroscopy in the study population, all in the intra-articular corticosteroid group. Seven patients in the intra-articular steroid group received more than three injections, including one patient with nine. And 13 patients in the physical therapy arm went outside the study in order to receive at least one corticosteroid injection.
One audience member pointed out that the physical therapy approach offers an important side benefit: In addition to improving pain and function, the exercise regimen has a favorable effect on comorbid metabolic diseases commonly associated with knee OA.
“An injection doesn’t achieve that,” he noted.
Dr. Rhon reported having no financial conflicts of interest regarding the randomized trial, sponsored by Madigan Army Medical Center. He receives research funding from the National Institutes of Health and the Congressionally Directed Medical Research Programs.
SOURCE: Rhon DI et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S32, Abstract 13
TORONTO – Eight physical therapy sessions spread over 4-6 weeks in patients with knee osteoarthritis provided significantly greater and longer-lasting improvements in both pain and function than an intra-articular corticosteroid injection in a randomized, multicenter trial with 12 months of prospective, blinded follow-up, Daniel I. Rhon, DPT, DSc, reported at the OARSI 2019 World Congress.
“Considering the very low utilization rate of physical therapy prior to arthroplasty, perhaps we should more often give it a try before declaring that conservative care has failed and moving on to surgical management,” concluded Dr. Rhon, director of the primary care musculoskeletal research center at Brooke Army Medical Center in San Antonio.
Various studies have shown that close to 50% of patients with knee OA receive one or more intra-articular corticosteroid injections within 5 years prior to undergoing total knee arthroplasty, compared with physical therapy in only about 10% of patients, even though most guidelines rate both as first-line therapies, he noted at the meeting sponsored by the Osteoarthritis Research Society International.
He presented a randomized trial of 156 patients who sought treatment for pain caused by knee OA at army medical center primary care clinics. To his knowledge, this was the first-ever randomized, head-to-head comparison of the effectiveness of a physical therapy regimen versus corticosteroid injections for knee OA. Because he and his coinvestigators wanted a pragmatic study giving each treatment strategy its due, booster therapy was available to patients who requested it. Patients in the corticosteroid arm were able to receive up to two additional spaced intra-articular injections as needed, while those assigned to the individualized manual physical therapy intervention, which utilized exercises targeting the typical strength and movement deficits found in patients with knee OA, could have up to three additional sessions. At the outset, all participants received education about the benefits of regular low-impact physical activity, weight reduction, and strength and flexibility exercises.
The two treatment groups were comparable except that the physical therapy group had a longer disease duration – a mean of 123 months as compared with 89 in the corticosteroid group – and more radiographically severe disease. Indeed, 60% of patients randomized to physical therapy were Kellgren-Lawrence scale grade III-IV, versus 45% of those assigned to intra-articular corticosteroid injection.
The primary outcome in the study was change in Western Ontario & McMaster Universities Arthritis Index (WOMAC) score at 12 months. As early as 4 weeks into the study, the physical therapy group showed significantly greater improvement than in the comparison arm: from a mean baseline WOMAC score of 115 to 42.9 at 4 weeks, 42.5 at 6 months, and 38.4 at 1 year. The comparable figures in the intra-articular corticosteroid group were 113.3 at baseline, 53.3 at 4 weeks, 57.9 at 6 months, and 53.8 at 1 year.
“Physical therapy provided clinically important benefit that was superior to corticosteroid injection out to 1 year, while also providing the short-term benefit typically sought from corticosteroid injection,” Dr. Rhon observed.
The median improvement in WOMAC score at 1 year was 52% in the corticosteroid group and 71% in the physical therapy arm. About 59% of the physical therapy group experienced at least a 50% reduction in WOMAC score at 12 months, as did 38% of intra-articular injection recipients. The number needed to treat with physical therapy instead of intra-articular corticosteroids in order for one additional patient to achieve at least a 50% improvement in WOMAC score through 1 year of follow-up was four.
“We were a little bit surprised that there was such a large effect size in the study. The effect size in the injection group was bigger than reported in some other trials,” according to Dr. Rhon.
In terms of downstream utilization of health care, there were two knee arthroplasties and one arthroscopy in the study population, all in the intra-articular corticosteroid group. Seven patients in the intra-articular steroid group received more than three injections, including one patient with nine. And 13 patients in the physical therapy arm went outside the study in order to receive at least one corticosteroid injection.
One audience member pointed out that the physical therapy approach offers an important side benefit: In addition to improving pain and function, the exercise regimen has a favorable effect on comorbid metabolic diseases commonly associated with knee OA.
“An injection doesn’t achieve that,” he noted.
Dr. Rhon reported having no financial conflicts of interest regarding the randomized trial, sponsored by Madigan Army Medical Center. He receives research funding from the National Institutes of Health and the Congressionally Directed Medical Research Programs.
SOURCE: Rhon DI et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S32, Abstract 13
TORONTO – Eight physical therapy sessions spread over 4-6 weeks in patients with knee osteoarthritis provided significantly greater and longer-lasting improvements in both pain and function than an intra-articular corticosteroid injection in a randomized, multicenter trial with 12 months of prospective, blinded follow-up, Daniel I. Rhon, DPT, DSc, reported at the OARSI 2019 World Congress.
“Considering the very low utilization rate of physical therapy prior to arthroplasty, perhaps we should more often give it a try before declaring that conservative care has failed and moving on to surgical management,” concluded Dr. Rhon, director of the primary care musculoskeletal research center at Brooke Army Medical Center in San Antonio.
Various studies have shown that close to 50% of patients with knee OA receive one or more intra-articular corticosteroid injections within 5 years prior to undergoing total knee arthroplasty, compared with physical therapy in only about 10% of patients, even though most guidelines rate both as first-line therapies, he noted at the meeting sponsored by the Osteoarthritis Research Society International.
He presented a randomized trial of 156 patients who sought treatment for pain caused by knee OA at army medical center primary care clinics. To his knowledge, this was the first-ever randomized, head-to-head comparison of the effectiveness of a physical therapy regimen versus corticosteroid injections for knee OA. Because he and his coinvestigators wanted a pragmatic study giving each treatment strategy its due, booster therapy was available to patients who requested it. Patients in the corticosteroid arm were able to receive up to two additional spaced intra-articular injections as needed, while those assigned to the individualized manual physical therapy intervention, which utilized exercises targeting the typical strength and movement deficits found in patients with knee OA, could have up to three additional sessions. At the outset, all participants received education about the benefits of regular low-impact physical activity, weight reduction, and strength and flexibility exercises.
The two treatment groups were comparable except that the physical therapy group had a longer disease duration – a mean of 123 months as compared with 89 in the corticosteroid group – and more radiographically severe disease. Indeed, 60% of patients randomized to physical therapy were Kellgren-Lawrence scale grade III-IV, versus 45% of those assigned to intra-articular corticosteroid injection.
The primary outcome in the study was change in Western Ontario & McMaster Universities Arthritis Index (WOMAC) score at 12 months. As early as 4 weeks into the study, the physical therapy group showed significantly greater improvement than in the comparison arm: from a mean baseline WOMAC score of 115 to 42.9 at 4 weeks, 42.5 at 6 months, and 38.4 at 1 year. The comparable figures in the intra-articular corticosteroid group were 113.3 at baseline, 53.3 at 4 weeks, 57.9 at 6 months, and 53.8 at 1 year.
“Physical therapy provided clinically important benefit that was superior to corticosteroid injection out to 1 year, while also providing the short-term benefit typically sought from corticosteroid injection,” Dr. Rhon observed.
The median improvement in WOMAC score at 1 year was 52% in the corticosteroid group and 71% in the physical therapy arm. About 59% of the physical therapy group experienced at least a 50% reduction in WOMAC score at 12 months, as did 38% of intra-articular injection recipients. The number needed to treat with physical therapy instead of intra-articular corticosteroids in order for one additional patient to achieve at least a 50% improvement in WOMAC score through 1 year of follow-up was four.
“We were a little bit surprised that there was such a large effect size in the study. The effect size in the injection group was bigger than reported in some other trials,” according to Dr. Rhon.
In terms of downstream utilization of health care, there were two knee arthroplasties and one arthroscopy in the study population, all in the intra-articular corticosteroid group. Seven patients in the intra-articular steroid group received more than three injections, including one patient with nine. And 13 patients in the physical therapy arm went outside the study in order to receive at least one corticosteroid injection.
One audience member pointed out that the physical therapy approach offers an important side benefit: In addition to improving pain and function, the exercise regimen has a favorable effect on comorbid metabolic diseases commonly associated with knee OA.
“An injection doesn’t achieve that,” he noted.
Dr. Rhon reported having no financial conflicts of interest regarding the randomized trial, sponsored by Madigan Army Medical Center. He receives research funding from the National Institutes of Health and the Congressionally Directed Medical Research Programs.
SOURCE: Rhon DI et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S32, Abstract 13
REPORTING FROM OARSI 2019