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Emerging understanding of the increased incidence of cardiovascular disease in patients with rheumatoid arthritis is providing greater insight regarding mitigation of risk, according to Jon T. Giles, MD.
The mechanisms of increased cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) are multifactorial; in addition to traditional risk factors for CVD, chronically elevated levels of systemic inflammatory cytokines likely play a major role in atherogenesis and myocardial dysfunction in RA patients, and the interactions between those elevated cytokine levels and traditional risk factors also play a likely role, Dr. Giles, a rheumatologist, epidemiologist, and clinical researcher in the division of rheumatology at Columbia University, New York, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
In addition, the relationship between traditional fasting lipids and atherosclerosis is different in RA patients from that in non-RA patients, he said, noting that this has important implications for CVD screening and risk management. The phenotype of CVD in RA based on the current literature is also one involving more coronary atherosclerosis in which the atherosclerotic plaques are more inflamed.
“There’s more myocardial dysfunction,” Dr. Giles said, noting that this dysfunction may be partly mediated by more myocardial fibrosis and possibly active subclinical low-grade myocarditis.
It is possible that traditional CVD risk factors such as smoking and hypertension have a greater impact in RA patients, but it’s likely that most of the differences are related to RA-specific factors such as autoimmunity, inflammation, and genetics, as well as some nontraditional CVD risk factors such as stress, anxiety, and depression that may be increased in RA patients, he noted.
With respect to traditional CVD risk factors, a recent study of more than 5,600 RA patients without CVD who were followed for an average of almost 6 years at 13 centers in Europe and the United States showed that 389 experienced CVD events, and the most common CVD risk factors in those patients were smoking – particularly in men – and hypertension.
“But also, RA characteristics played a big role,” he said.
Disease activity was one of the major risk factors for CVD events in RA patients, and the traditional CVD risk factor of hyperlipidemia, and particularly elevated low-density lipoprotein (LDL) levels, had less influence in RA patients than in the general population. In men it was “a negative predictor” of CVD events, he said (Ann Rheum Dis. 2018;77:48-54).
Prior studies have also shown a “strange relationship” between lipids and CVD risk in RA patients. For example, RA patients with very low LDL cholesterol have been shown to have higher CVD event rates – a phenomenon known as the “lipid paradox” – and it may be related to inflammation, but the mechanism is unclear,” he said.
To further assess whether RA patients with abnormally low LDL cholesterol levels without the use of statin therapy had more atherosclerotic burden, Dr. Giles and his colleagues looked at more than 600 RA patients and more than 1,000 non-RA patients (Arthritis Rheumatol. 2015;67[suppl 10]:Abstract 2127). They found that RA patients did, indeed, have a greater atherosclerotic burden, which was “quite shocking,” he said.
The burden rivaled that seen in patients with LDL levels greater than 160 mg/dL, he noted.
“Interestingly, these patients did not have higher levels of inflammatory markers, and they did not have higher disease activity scores. They looked exactly the same as the rest of the RA patients,” he said, noting that investigation into why the LDL levels in these patients are so low is ongoing.
As for how atherogenic lipoproteins allow for atherosclerosis and atherogenesis to occur in the setting of low LDL in RA patients, it turns out it’s not just the amount, but also the characteristics of the lipoproteins, such as the size and oxidization of the LDL, which change in the context of systemic inflammation, he explained.
Further, during an acute-phase reaction, high-density lipoprotein (HDL) composition changes rapidly from antiatherogenic to proinflammatory.
Extensive evidence shows that endothelial function is diminished in RA, and that RA patients have these and other proatherogenic mechanisms, as well as other elements of immunity that are associated with atherogenesis, including aspects of both innate and adaptive immune function, he said.
Given the emerging understanding of CVD risk in RA, mitigation of that risk is an important consideration. In fact, the European League Against Rheumatism updated its CVD management guidelines in 2015/2016, including a statement that rheumatologists are responsible for CVD risk management in RA patients (Ann Rheum Dis. 2017;76:17-28).
The guidelines are intended for all inflammatory arthritis, and the recommendation with the strongest level of evidence relates to optimization of disease activity. Also recommended are:
- CVD screening every 5 years.
- Use of a 1.5 multiplier for risk scores.
- Secondary screening with imaging for select patients.
- Management of traditional risk factors according to local guidelines.
- Minimization of the use of NSAIDs and corticosteroids.
- Emphasis on lifestyle management.
Importantly, research has suggested that screening for hyperlipidemia is substandard in RA, and that standard risk stratification tools underperform in the setting of RA, he said.
“So my approach, and this is not evidence based yet ... comes down to what [a patient’s] apparent risk is. So if an RA patient is high risk based on your apparent risk prediction, then they are likely high risk and maybe even higher than estimated,” Dr. Giles said. These patients need optimization of their traditional risk factors and their inflammatory factors and should therefore receive a high-intensity statin regardless of lipid levels, he said.
That means atorvastatin at a dose of at least 40 mg or rosuvastatin at a dose of at least 20 mg, he said, adding that some studies have suggested that statins work as well in RA patients as in non-RA patients, and that RA patients with CVD risk do better with a statin than without.
He considers patients who have intermediate risk based on the risk calculation to actually be high risk in most cases, and they, too, need maximal optimization of traditional CVD risk factors and inflammatory factors.
“Consider one-time secondary imaging for all of these patients,” he advised, noting that a coronary calcium score from a chest CT scan is a good option that has low radiation, can be quantified, and is increasingly covered by insurance.
A coronary calcium score of 0 on chest CT is highly reassuring, and a score that is greater than what is expected for age, gender, and/or race can help define the intensity of intervention, he said.
For example, if a patient’s score is 300 but should be 50, that patient should be treated as if he or she has coronary artery disease. Patients with high scores in general – particularly those with scores over 300 – should also be maximally managed, he said.
Patients at low risk based on risk calculations usually are low risk, but some can be high risk, so again, maximal optimization of risk factors is recommended.
Secondary imaging can be considered in some of these patients, and while it’s not entirely clear which are at greatest risk, Dr. Giles said he recommends screening those with treatment-resistant active disease, those with high disease severity, and those with abnormally low LDL.
Dr. Giles is a consultant for Genentech, Lilly, Horizon, Bristol-Myers Squibb, and UCB, and he has received grant support from Pfizer.
Emerging understanding of the increased incidence of cardiovascular disease in patients with rheumatoid arthritis is providing greater insight regarding mitigation of risk, according to Jon T. Giles, MD.
The mechanisms of increased cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) are multifactorial; in addition to traditional risk factors for CVD, chronically elevated levels of systemic inflammatory cytokines likely play a major role in atherogenesis and myocardial dysfunction in RA patients, and the interactions between those elevated cytokine levels and traditional risk factors also play a likely role, Dr. Giles, a rheumatologist, epidemiologist, and clinical researcher in the division of rheumatology at Columbia University, New York, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
In addition, the relationship between traditional fasting lipids and atherosclerosis is different in RA patients from that in non-RA patients, he said, noting that this has important implications for CVD screening and risk management. The phenotype of CVD in RA based on the current literature is also one involving more coronary atherosclerosis in which the atherosclerotic plaques are more inflamed.
“There’s more myocardial dysfunction,” Dr. Giles said, noting that this dysfunction may be partly mediated by more myocardial fibrosis and possibly active subclinical low-grade myocarditis.
It is possible that traditional CVD risk factors such as smoking and hypertension have a greater impact in RA patients, but it’s likely that most of the differences are related to RA-specific factors such as autoimmunity, inflammation, and genetics, as well as some nontraditional CVD risk factors such as stress, anxiety, and depression that may be increased in RA patients, he noted.
With respect to traditional CVD risk factors, a recent study of more than 5,600 RA patients without CVD who were followed for an average of almost 6 years at 13 centers in Europe and the United States showed that 389 experienced CVD events, and the most common CVD risk factors in those patients were smoking – particularly in men – and hypertension.
“But also, RA characteristics played a big role,” he said.
Disease activity was one of the major risk factors for CVD events in RA patients, and the traditional CVD risk factor of hyperlipidemia, and particularly elevated low-density lipoprotein (LDL) levels, had less influence in RA patients than in the general population. In men it was “a negative predictor” of CVD events, he said (Ann Rheum Dis. 2018;77:48-54).
Prior studies have also shown a “strange relationship” between lipids and CVD risk in RA patients. For example, RA patients with very low LDL cholesterol have been shown to have higher CVD event rates – a phenomenon known as the “lipid paradox” – and it may be related to inflammation, but the mechanism is unclear,” he said.
To further assess whether RA patients with abnormally low LDL cholesterol levels without the use of statin therapy had more atherosclerotic burden, Dr. Giles and his colleagues looked at more than 600 RA patients and more than 1,000 non-RA patients (Arthritis Rheumatol. 2015;67[suppl 10]:Abstract 2127). They found that RA patients did, indeed, have a greater atherosclerotic burden, which was “quite shocking,” he said.
The burden rivaled that seen in patients with LDL levels greater than 160 mg/dL, he noted.
“Interestingly, these patients did not have higher levels of inflammatory markers, and they did not have higher disease activity scores. They looked exactly the same as the rest of the RA patients,” he said, noting that investigation into why the LDL levels in these patients are so low is ongoing.
As for how atherogenic lipoproteins allow for atherosclerosis and atherogenesis to occur in the setting of low LDL in RA patients, it turns out it’s not just the amount, but also the characteristics of the lipoproteins, such as the size and oxidization of the LDL, which change in the context of systemic inflammation, he explained.
Further, during an acute-phase reaction, high-density lipoprotein (HDL) composition changes rapidly from antiatherogenic to proinflammatory.
Extensive evidence shows that endothelial function is diminished in RA, and that RA patients have these and other proatherogenic mechanisms, as well as other elements of immunity that are associated with atherogenesis, including aspects of both innate and adaptive immune function, he said.
Given the emerging understanding of CVD risk in RA, mitigation of that risk is an important consideration. In fact, the European League Against Rheumatism updated its CVD management guidelines in 2015/2016, including a statement that rheumatologists are responsible for CVD risk management in RA patients (Ann Rheum Dis. 2017;76:17-28).
The guidelines are intended for all inflammatory arthritis, and the recommendation with the strongest level of evidence relates to optimization of disease activity. Also recommended are:
- CVD screening every 5 years.
- Use of a 1.5 multiplier for risk scores.
- Secondary screening with imaging for select patients.
- Management of traditional risk factors according to local guidelines.
- Minimization of the use of NSAIDs and corticosteroids.
- Emphasis on lifestyle management.
Importantly, research has suggested that screening for hyperlipidemia is substandard in RA, and that standard risk stratification tools underperform in the setting of RA, he said.
“So my approach, and this is not evidence based yet ... comes down to what [a patient’s] apparent risk is. So if an RA patient is high risk based on your apparent risk prediction, then they are likely high risk and maybe even higher than estimated,” Dr. Giles said. These patients need optimization of their traditional risk factors and their inflammatory factors and should therefore receive a high-intensity statin regardless of lipid levels, he said.
That means atorvastatin at a dose of at least 40 mg or rosuvastatin at a dose of at least 20 mg, he said, adding that some studies have suggested that statins work as well in RA patients as in non-RA patients, and that RA patients with CVD risk do better with a statin than without.
He considers patients who have intermediate risk based on the risk calculation to actually be high risk in most cases, and they, too, need maximal optimization of traditional CVD risk factors and inflammatory factors.
“Consider one-time secondary imaging for all of these patients,” he advised, noting that a coronary calcium score from a chest CT scan is a good option that has low radiation, can be quantified, and is increasingly covered by insurance.
A coronary calcium score of 0 on chest CT is highly reassuring, and a score that is greater than what is expected for age, gender, and/or race can help define the intensity of intervention, he said.
For example, if a patient’s score is 300 but should be 50, that patient should be treated as if he or she has coronary artery disease. Patients with high scores in general – particularly those with scores over 300 – should also be maximally managed, he said.
Patients at low risk based on risk calculations usually are low risk, but some can be high risk, so again, maximal optimization of risk factors is recommended.
Secondary imaging can be considered in some of these patients, and while it’s not entirely clear which are at greatest risk, Dr. Giles said he recommends screening those with treatment-resistant active disease, those with high disease severity, and those with abnormally low LDL.
Dr. Giles is a consultant for Genentech, Lilly, Horizon, Bristol-Myers Squibb, and UCB, and he has received grant support from Pfizer.
Emerging understanding of the increased incidence of cardiovascular disease in patients with rheumatoid arthritis is providing greater insight regarding mitigation of risk, according to Jon T. Giles, MD.
The mechanisms of increased cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) are multifactorial; in addition to traditional risk factors for CVD, chronically elevated levels of systemic inflammatory cytokines likely play a major role in atherogenesis and myocardial dysfunction in RA patients, and the interactions between those elevated cytokine levels and traditional risk factors also play a likely role, Dr. Giles, a rheumatologist, epidemiologist, and clinical researcher in the division of rheumatology at Columbia University, New York, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
In addition, the relationship between traditional fasting lipids and atherosclerosis is different in RA patients from that in non-RA patients, he said, noting that this has important implications for CVD screening and risk management. The phenotype of CVD in RA based on the current literature is also one involving more coronary atherosclerosis in which the atherosclerotic plaques are more inflamed.
“There’s more myocardial dysfunction,” Dr. Giles said, noting that this dysfunction may be partly mediated by more myocardial fibrosis and possibly active subclinical low-grade myocarditis.
It is possible that traditional CVD risk factors such as smoking and hypertension have a greater impact in RA patients, but it’s likely that most of the differences are related to RA-specific factors such as autoimmunity, inflammation, and genetics, as well as some nontraditional CVD risk factors such as stress, anxiety, and depression that may be increased in RA patients, he noted.
With respect to traditional CVD risk factors, a recent study of more than 5,600 RA patients without CVD who were followed for an average of almost 6 years at 13 centers in Europe and the United States showed that 389 experienced CVD events, and the most common CVD risk factors in those patients were smoking – particularly in men – and hypertension.
“But also, RA characteristics played a big role,” he said.
Disease activity was one of the major risk factors for CVD events in RA patients, and the traditional CVD risk factor of hyperlipidemia, and particularly elevated low-density lipoprotein (LDL) levels, had less influence in RA patients than in the general population. In men it was “a negative predictor” of CVD events, he said (Ann Rheum Dis. 2018;77:48-54).
Prior studies have also shown a “strange relationship” between lipids and CVD risk in RA patients. For example, RA patients with very low LDL cholesterol have been shown to have higher CVD event rates – a phenomenon known as the “lipid paradox” – and it may be related to inflammation, but the mechanism is unclear,” he said.
To further assess whether RA patients with abnormally low LDL cholesterol levels without the use of statin therapy had more atherosclerotic burden, Dr. Giles and his colleagues looked at more than 600 RA patients and more than 1,000 non-RA patients (Arthritis Rheumatol. 2015;67[suppl 10]:Abstract 2127). They found that RA patients did, indeed, have a greater atherosclerotic burden, which was “quite shocking,” he said.
The burden rivaled that seen in patients with LDL levels greater than 160 mg/dL, he noted.
“Interestingly, these patients did not have higher levels of inflammatory markers, and they did not have higher disease activity scores. They looked exactly the same as the rest of the RA patients,” he said, noting that investigation into why the LDL levels in these patients are so low is ongoing.
As for how atherogenic lipoproteins allow for atherosclerosis and atherogenesis to occur in the setting of low LDL in RA patients, it turns out it’s not just the amount, but also the characteristics of the lipoproteins, such as the size and oxidization of the LDL, which change in the context of systemic inflammation, he explained.
Further, during an acute-phase reaction, high-density lipoprotein (HDL) composition changes rapidly from antiatherogenic to proinflammatory.
Extensive evidence shows that endothelial function is diminished in RA, and that RA patients have these and other proatherogenic mechanisms, as well as other elements of immunity that are associated with atherogenesis, including aspects of both innate and adaptive immune function, he said.
Given the emerging understanding of CVD risk in RA, mitigation of that risk is an important consideration. In fact, the European League Against Rheumatism updated its CVD management guidelines in 2015/2016, including a statement that rheumatologists are responsible for CVD risk management in RA patients (Ann Rheum Dis. 2017;76:17-28).
The guidelines are intended for all inflammatory arthritis, and the recommendation with the strongest level of evidence relates to optimization of disease activity. Also recommended are:
- CVD screening every 5 years.
- Use of a 1.5 multiplier for risk scores.
- Secondary screening with imaging for select patients.
- Management of traditional risk factors according to local guidelines.
- Minimization of the use of NSAIDs and corticosteroids.
- Emphasis on lifestyle management.
Importantly, research has suggested that screening for hyperlipidemia is substandard in RA, and that standard risk stratification tools underperform in the setting of RA, he said.
“So my approach, and this is not evidence based yet ... comes down to what [a patient’s] apparent risk is. So if an RA patient is high risk based on your apparent risk prediction, then they are likely high risk and maybe even higher than estimated,” Dr. Giles said. These patients need optimization of their traditional risk factors and their inflammatory factors and should therefore receive a high-intensity statin regardless of lipid levels, he said.
That means atorvastatin at a dose of at least 40 mg or rosuvastatin at a dose of at least 20 mg, he said, adding that some studies have suggested that statins work as well in RA patients as in non-RA patients, and that RA patients with CVD risk do better with a statin than without.
He considers patients who have intermediate risk based on the risk calculation to actually be high risk in most cases, and they, too, need maximal optimization of traditional CVD risk factors and inflammatory factors.
“Consider one-time secondary imaging for all of these patients,” he advised, noting that a coronary calcium score from a chest CT scan is a good option that has low radiation, can be quantified, and is increasingly covered by insurance.
A coronary calcium score of 0 on chest CT is highly reassuring, and a score that is greater than what is expected for age, gender, and/or race can help define the intensity of intervention, he said.
For example, if a patient’s score is 300 but should be 50, that patient should be treated as if he or she has coronary artery disease. Patients with high scores in general – particularly those with scores over 300 – should also be maximally managed, he said.
Patients at low risk based on risk calculations usually are low risk, but some can be high risk, so again, maximal optimization of risk factors is recommended.
Secondary imaging can be considered in some of these patients, and while it’s not entirely clear which are at greatest risk, Dr. Giles said he recommends screening those with treatment-resistant active disease, those with high disease severity, and those with abnormally low LDL.
Dr. Giles is a consultant for Genentech, Lilly, Horizon, Bristol-Myers Squibb, and UCB, and he has received grant support from Pfizer.
EXPERT ANALYSIS FROM THE WINTER RHEUMATOLOGY SYMPOSIUM
Venous thromboembolism risk elevated in ankylosing spondylitis patients
Newly diagnosed ankylosing spondylitis (AS) patients are at increased risk for venous thromboembolism (VTE), especially during the first year after diagnosis, according to a population-based study of 7,190 cases.
In a study published in Annals of the Rheumatic Diseases, the researchers identified 7,190 incident cases of AS among adults using a health care database of residents of British Columbia and matched them for age, sex, and entry time into the cohort with 71,900 healthy individuals from the general population over a mean follow-up time of 6.2 years.
The incidence rate of VTE overall per 1,000 person-years was 1.56 among AS patients, compared with 0.77 in a control cohort from the general population. The incidence rates for DVT were 1.06 in AS patients and 0.50 in controls; incidence rates for PE were 0.79 in AS patients and 0.40 in controls.
The adjusted hazard ratios for VTE overall and DVT were similar and statistically significant in AS patients at 1.53 and 1.62, respectively, versus controls. But the adjusted hazard ratio of 1.36 for PE did not reach statistical significance. The adjusted risks of VTE overall, PE, and DVT were highest in the first year of diagnosis, reaching twofold greater risk for all, but none of the risks were statistically significant.
More research is needed to better identify subsets of AS patients at increased risk for VTE, and to assess whether treatment of inflammation can mitigate this risk, but in the meantime clinicians should be alert to the possibility of life-threatening complications from DVT and PE in their AS patients, especially soon after diagnosis, the researchers said.
The findings are supported by the study’s large sample size but are also limited by several factors, including the observational nature of the study and an inability to account for use of NSAIDs, the researchers noted.
“These results call for awareness of this complication, increased vigilance, and preventive intervention by controlling the inflammatory process or by anticoagulation in a high-risk AS population,” they concluded.
The study was supported in part by grants from the Canadian Arthritis Network, the Arthritis Society of Canada, the British Columbia Lupus Society, and the Canadian Institutes for Health Research. The researchers had no financial conflicts to disclose.
SOURCE: Aviña-Zubieta JA et al. Ann Rheum Dis. 2019 Feb 8. doi: 10.1136/annrheumdis-2018-214388.
Newly diagnosed ankylosing spondylitis (AS) patients are at increased risk for venous thromboembolism (VTE), especially during the first year after diagnosis, according to a population-based study of 7,190 cases.
In a study published in Annals of the Rheumatic Diseases, the researchers identified 7,190 incident cases of AS among adults using a health care database of residents of British Columbia and matched them for age, sex, and entry time into the cohort with 71,900 healthy individuals from the general population over a mean follow-up time of 6.2 years.
The incidence rate of VTE overall per 1,000 person-years was 1.56 among AS patients, compared with 0.77 in a control cohort from the general population. The incidence rates for DVT were 1.06 in AS patients and 0.50 in controls; incidence rates for PE were 0.79 in AS patients and 0.40 in controls.
The adjusted hazard ratios for VTE overall and DVT were similar and statistically significant in AS patients at 1.53 and 1.62, respectively, versus controls. But the adjusted hazard ratio of 1.36 for PE did not reach statistical significance. The adjusted risks of VTE overall, PE, and DVT were highest in the first year of diagnosis, reaching twofold greater risk for all, but none of the risks were statistically significant.
More research is needed to better identify subsets of AS patients at increased risk for VTE, and to assess whether treatment of inflammation can mitigate this risk, but in the meantime clinicians should be alert to the possibility of life-threatening complications from DVT and PE in their AS patients, especially soon after diagnosis, the researchers said.
The findings are supported by the study’s large sample size but are also limited by several factors, including the observational nature of the study and an inability to account for use of NSAIDs, the researchers noted.
“These results call for awareness of this complication, increased vigilance, and preventive intervention by controlling the inflammatory process or by anticoagulation in a high-risk AS population,” they concluded.
The study was supported in part by grants from the Canadian Arthritis Network, the Arthritis Society of Canada, the British Columbia Lupus Society, and the Canadian Institutes for Health Research. The researchers had no financial conflicts to disclose.
SOURCE: Aviña-Zubieta JA et al. Ann Rheum Dis. 2019 Feb 8. doi: 10.1136/annrheumdis-2018-214388.
Newly diagnosed ankylosing spondylitis (AS) patients are at increased risk for venous thromboembolism (VTE), especially during the first year after diagnosis, according to a population-based study of 7,190 cases.
In a study published in Annals of the Rheumatic Diseases, the researchers identified 7,190 incident cases of AS among adults using a health care database of residents of British Columbia and matched them for age, sex, and entry time into the cohort with 71,900 healthy individuals from the general population over a mean follow-up time of 6.2 years.
The incidence rate of VTE overall per 1,000 person-years was 1.56 among AS patients, compared with 0.77 in a control cohort from the general population. The incidence rates for DVT were 1.06 in AS patients and 0.50 in controls; incidence rates for PE were 0.79 in AS patients and 0.40 in controls.
The adjusted hazard ratios for VTE overall and DVT were similar and statistically significant in AS patients at 1.53 and 1.62, respectively, versus controls. But the adjusted hazard ratio of 1.36 for PE did not reach statistical significance. The adjusted risks of VTE overall, PE, and DVT were highest in the first year of diagnosis, reaching twofold greater risk for all, but none of the risks were statistically significant.
More research is needed to better identify subsets of AS patients at increased risk for VTE, and to assess whether treatment of inflammation can mitigate this risk, but in the meantime clinicians should be alert to the possibility of life-threatening complications from DVT and PE in their AS patients, especially soon after diagnosis, the researchers said.
The findings are supported by the study’s large sample size but are also limited by several factors, including the observational nature of the study and an inability to account for use of NSAIDs, the researchers noted.
“These results call for awareness of this complication, increased vigilance, and preventive intervention by controlling the inflammatory process or by anticoagulation in a high-risk AS population,” they concluded.
The study was supported in part by grants from the Canadian Arthritis Network, the Arthritis Society of Canada, the British Columbia Lupus Society, and the Canadian Institutes for Health Research. The researchers had no financial conflicts to disclose.
SOURCE: Aviña-Zubieta JA et al. Ann Rheum Dis. 2019 Feb 8. doi: 10.1136/annrheumdis-2018-214388.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point: Newly diagnosed AS patients demonstrated increased risk of venous thromboembolism, including deep vein thrombosis and pulmonary embolism, compared with controls.
Major finding: The relative risk for deep vein thrombosis was 63% higher for AS patients versus controls, but a 39% higher risk of pulmonary embolism did not reach statistical significance.
Study details: A population-based study including 7,190 incident AS cases and 71,900 matched controls from a health care database of residents of British Columbia.
Disclosures: The study was supported in part by grants from the Canadian Arthritis Network, the Arthritis Society of Canada, the British Columbia Lupus Society, and the Canadian Institutes for Health Research. The researchers had no financial conflicts to disclose.
Source: Aviña-Zubieta JA et al. Ann Rheum Dis. 2019 Feb 8. doi: 10.1136/annrheumdis-2018-214388.
New findings raise questions about the role of ANAs in SLE
Antinuclear antibodies (ANAs) have long been considered an important marker in rheumatologic conditions, particularly for the diagnosis and classification of patients with systemic lupus erythematosus, but recent findings are raising new questions about their role.
“We’ve measured ANAs for a long time – it’s a very important test in rheumatology,” David S. Pisetsky, MD, PhD, explained in an interview.
However, even though this test has been around for decades, “some interesting things have developed around it that have made a lot of people, including me, take a second look,” said Dr. Pisetsky, professor of medicine and immunology at Duke University, Durham, N.C.
He elaborated on those recent findings, which relate to the findings of ANA negativity in patients with an established diagnosis of systemic lupus erythematosus (SLE) and to variability among ANA test kit findings, during a presentation at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
“Screening of patients during clinical trials for new treatments of SLE suggest that a significant number of people with lupus – 20%-30%, in fact – are ANA negative despite disease activity at the time the test is done,” he said.
For example, unpublished (but recently submitted) data from a phase 2 trial looking at the efficacy and safety of an interleukin-6 monoclonal antibody for the treatment of SLE showed that 23.8% of baseline samples from 183 SLE patients with positive historical ANA and clinically active lupus prior to randomization were ANA negative.
A particular concern with respect to such findings is that ANA positivity is typically a criterion for entry into clinical trials of therapies for lupus and prescription of medications approved for active lupus, Dr. Pisetsky said.
“On the other hand, about 20% of otherwise healthy people – especially women – can be ANA positive, so it’s always been problematic as a screening test due to these false positives, but these new findings suggest that in lupus a real concern is false negatives,” he said. “It’s quite a surprise.”
The findings raise questions about whether ANA negativity in SLE reflects the natural history of the disease, an effect of treatments, or a problem with the assays.
It appears an important problem relates to test kit variability, he said.
“There are lots of different ANA test kits. Their performance characteristics are very different. The performance of ANA tests is much more variable than people realize,” he said, citing data from an analysis that he and his colleagues conducted using 103 samples from a cohort of patients with established SLE.
In that 2017 study, an ANA enzyme-linked immunosorbent assay showed an ANA-negativity rate of 11.7% with zero indeterminate tests, whereas three different test kits showed ANA-negativity rates of 22.3% (with 8.7% of samples reported as indeterminate), 9.7% (with another 9.7% indeterminate), and 4.9% (with another 1.9% indeterminate), respectively. Multiplex testing showed a 13.6% ANA-negativity rate and an indeterminate rate of 7.8% (Ann Rheum Dis. 2018;77:911-3).
Only one sample tested negative for ANA on all three test kits, and disagreement about ANA negativity occurred in one-third of the samples, he said.
Anti–double-stranded DNA assays
Recent findings also raise questions about the use of assays that specifically assess for anti–double-stranded DNA (anti-dsDNA) antibodies, which are highly associated with SLE and have been used as a biomarker for the disease, Dr. Pisetsky said.
For example, a comparison of two anti-dsDNA assays showed discordant results with respect to negativity for anti-dsDNA antibodies in 64 of 181 samples from SLE patients. One assay showed a 70.7% rate of anti-dsDNA negativity and the other showed a 37.6% rate.
The concern regarding test variability relates to the issue of ANA positivity and eligibility for study enrollment and certain treatments; test variability can affect the diagnosis of patients with SLE because ANA positivity is an important finding in routine clinical care, and for anti-dsDNA, test variability can affect assessment of disease activity, he explained.
Tests may differ in a number of ways, such as in their specificity, sensitivity, avidity, and range of epitopes detected. Unfortunately, not enough is known at this point to make specific recommendations regarding best test kits, and while there are alternative technologies that could be useful for ANA testing, none has been validated for particular use in the assessment of trial eligibility, Dr. Pisetsky said.
Nonetheless, awareness of the test variability is important, especially when it comes to assessing patients for trial eligibility and prescribing medications, he added. “For practical, real-world utilization, people need to know about this.”
Dr. Pisetsky reported receiving ANA-related research support from Pfizer, conducting collaborative research with Bio-Rad and EuroImmun, and serving as an adviser to ImmunArray.
Antinuclear antibodies (ANAs) have long been considered an important marker in rheumatologic conditions, particularly for the diagnosis and classification of patients with systemic lupus erythematosus, but recent findings are raising new questions about their role.
“We’ve measured ANAs for a long time – it’s a very important test in rheumatology,” David S. Pisetsky, MD, PhD, explained in an interview.
However, even though this test has been around for decades, “some interesting things have developed around it that have made a lot of people, including me, take a second look,” said Dr. Pisetsky, professor of medicine and immunology at Duke University, Durham, N.C.
He elaborated on those recent findings, which relate to the findings of ANA negativity in patients with an established diagnosis of systemic lupus erythematosus (SLE) and to variability among ANA test kit findings, during a presentation at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
“Screening of patients during clinical trials for new treatments of SLE suggest that a significant number of people with lupus – 20%-30%, in fact – are ANA negative despite disease activity at the time the test is done,” he said.
For example, unpublished (but recently submitted) data from a phase 2 trial looking at the efficacy and safety of an interleukin-6 monoclonal antibody for the treatment of SLE showed that 23.8% of baseline samples from 183 SLE patients with positive historical ANA and clinically active lupus prior to randomization were ANA negative.
A particular concern with respect to such findings is that ANA positivity is typically a criterion for entry into clinical trials of therapies for lupus and prescription of medications approved for active lupus, Dr. Pisetsky said.
“On the other hand, about 20% of otherwise healthy people – especially women – can be ANA positive, so it’s always been problematic as a screening test due to these false positives, but these new findings suggest that in lupus a real concern is false negatives,” he said. “It’s quite a surprise.”
The findings raise questions about whether ANA negativity in SLE reflects the natural history of the disease, an effect of treatments, or a problem with the assays.
It appears an important problem relates to test kit variability, he said.
“There are lots of different ANA test kits. Their performance characteristics are very different. The performance of ANA tests is much more variable than people realize,” he said, citing data from an analysis that he and his colleagues conducted using 103 samples from a cohort of patients with established SLE.
In that 2017 study, an ANA enzyme-linked immunosorbent assay showed an ANA-negativity rate of 11.7% with zero indeterminate tests, whereas three different test kits showed ANA-negativity rates of 22.3% (with 8.7% of samples reported as indeterminate), 9.7% (with another 9.7% indeterminate), and 4.9% (with another 1.9% indeterminate), respectively. Multiplex testing showed a 13.6% ANA-negativity rate and an indeterminate rate of 7.8% (Ann Rheum Dis. 2018;77:911-3).
Only one sample tested negative for ANA on all three test kits, and disagreement about ANA negativity occurred in one-third of the samples, he said.
Anti–double-stranded DNA assays
Recent findings also raise questions about the use of assays that specifically assess for anti–double-stranded DNA (anti-dsDNA) antibodies, which are highly associated with SLE and have been used as a biomarker for the disease, Dr. Pisetsky said.
For example, a comparison of two anti-dsDNA assays showed discordant results with respect to negativity for anti-dsDNA antibodies in 64 of 181 samples from SLE patients. One assay showed a 70.7% rate of anti-dsDNA negativity and the other showed a 37.6% rate.
The concern regarding test variability relates to the issue of ANA positivity and eligibility for study enrollment and certain treatments; test variability can affect the diagnosis of patients with SLE because ANA positivity is an important finding in routine clinical care, and for anti-dsDNA, test variability can affect assessment of disease activity, he explained.
Tests may differ in a number of ways, such as in their specificity, sensitivity, avidity, and range of epitopes detected. Unfortunately, not enough is known at this point to make specific recommendations regarding best test kits, and while there are alternative technologies that could be useful for ANA testing, none has been validated for particular use in the assessment of trial eligibility, Dr. Pisetsky said.
Nonetheless, awareness of the test variability is important, especially when it comes to assessing patients for trial eligibility and prescribing medications, he added. “For practical, real-world utilization, people need to know about this.”
Dr. Pisetsky reported receiving ANA-related research support from Pfizer, conducting collaborative research with Bio-Rad and EuroImmun, and serving as an adviser to ImmunArray.
Antinuclear antibodies (ANAs) have long been considered an important marker in rheumatologic conditions, particularly for the diagnosis and classification of patients with systemic lupus erythematosus, but recent findings are raising new questions about their role.
“We’ve measured ANAs for a long time – it’s a very important test in rheumatology,” David S. Pisetsky, MD, PhD, explained in an interview.
However, even though this test has been around for decades, “some interesting things have developed around it that have made a lot of people, including me, take a second look,” said Dr. Pisetsky, professor of medicine and immunology at Duke University, Durham, N.C.
He elaborated on those recent findings, which relate to the findings of ANA negativity in patients with an established diagnosis of systemic lupus erythematosus (SLE) and to variability among ANA test kit findings, during a presentation at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
“Screening of patients during clinical trials for new treatments of SLE suggest that a significant number of people with lupus – 20%-30%, in fact – are ANA negative despite disease activity at the time the test is done,” he said.
For example, unpublished (but recently submitted) data from a phase 2 trial looking at the efficacy and safety of an interleukin-6 monoclonal antibody for the treatment of SLE showed that 23.8% of baseline samples from 183 SLE patients with positive historical ANA and clinically active lupus prior to randomization were ANA negative.
A particular concern with respect to such findings is that ANA positivity is typically a criterion for entry into clinical trials of therapies for lupus and prescription of medications approved for active lupus, Dr. Pisetsky said.
“On the other hand, about 20% of otherwise healthy people – especially women – can be ANA positive, so it’s always been problematic as a screening test due to these false positives, but these new findings suggest that in lupus a real concern is false negatives,” he said. “It’s quite a surprise.”
The findings raise questions about whether ANA negativity in SLE reflects the natural history of the disease, an effect of treatments, or a problem with the assays.
It appears an important problem relates to test kit variability, he said.
“There are lots of different ANA test kits. Their performance characteristics are very different. The performance of ANA tests is much more variable than people realize,” he said, citing data from an analysis that he and his colleagues conducted using 103 samples from a cohort of patients with established SLE.
In that 2017 study, an ANA enzyme-linked immunosorbent assay showed an ANA-negativity rate of 11.7% with zero indeterminate tests, whereas three different test kits showed ANA-negativity rates of 22.3% (with 8.7% of samples reported as indeterminate), 9.7% (with another 9.7% indeterminate), and 4.9% (with another 1.9% indeterminate), respectively. Multiplex testing showed a 13.6% ANA-negativity rate and an indeterminate rate of 7.8% (Ann Rheum Dis. 2018;77:911-3).
Only one sample tested negative for ANA on all three test kits, and disagreement about ANA negativity occurred in one-third of the samples, he said.
Anti–double-stranded DNA assays
Recent findings also raise questions about the use of assays that specifically assess for anti–double-stranded DNA (anti-dsDNA) antibodies, which are highly associated with SLE and have been used as a biomarker for the disease, Dr. Pisetsky said.
For example, a comparison of two anti-dsDNA assays showed discordant results with respect to negativity for anti-dsDNA antibodies in 64 of 181 samples from SLE patients. One assay showed a 70.7% rate of anti-dsDNA negativity and the other showed a 37.6% rate.
The concern regarding test variability relates to the issue of ANA positivity and eligibility for study enrollment and certain treatments; test variability can affect the diagnosis of patients with SLE because ANA positivity is an important finding in routine clinical care, and for anti-dsDNA, test variability can affect assessment of disease activity, he explained.
Tests may differ in a number of ways, such as in their specificity, sensitivity, avidity, and range of epitopes detected. Unfortunately, not enough is known at this point to make specific recommendations regarding best test kits, and while there are alternative technologies that could be useful for ANA testing, none has been validated for particular use in the assessment of trial eligibility, Dr. Pisetsky said.
Nonetheless, awareness of the test variability is important, especially when it comes to assessing patients for trial eligibility and prescribing medications, he added. “For practical, real-world utilization, people need to know about this.”
Dr. Pisetsky reported receiving ANA-related research support from Pfizer, conducting collaborative research with Bio-Rad and EuroImmun, and serving as an adviser to ImmunArray.
EXPERT ANALYSIS FROM THE WINTER RHEUMATOLOGY SYMPOSIUM
Different disease features found with family history of psoriasis versus PsA
the results of a retrospective cohort study suggest.
A family history of psoriasis was associated with younger onset of psoriatic disease and the presence of enthesitis, while by contrast, a family history of psoriatic arthritis (PsA) was associated with lower risk of plaque psoriasis and higher risk of deformities, according to Dilek Solmaz, MD, of the University of Ottawa and her coauthors, who reported their findings in Arthritis Care & Research.
“The link between family history of psoriasis/psoriatic arthritis and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets,” the investigators wrote.
Most, if not all, previous studies evaluating family history have grouped psoriasis and PsA together, according to Dr. Solmaz and her colleagues, rather than looking at the individual effects of psoriasis or PsA family history that may lead to unique disease phenotypes, as was done in the present study.
The investigators based their retrospective analysis on patients recruited in a longitudinal, multicenter database in Turkey and Canada. The mean age of patients in the study was 48 years; nearly 65% were female.
Out of 1,393 patients in the database, 444 had a family history of psoriasis or PsA. That included 335 patients with a psoriasis-only family history and 74 with a family history of PsA; another 35 patients weren’t sure about having a family history of PsA or psoriasis and were left out of the analysis.
Plaque psoriasis was more common in individuals with a family history of only psoriasis, while pustular psoriasis was more common in those with a PsA family history, the investigators reported.
In multivariate analyses, having a family member with psoriasis was a risk factor for younger age of psoriasis onset (odds ratio, 0.976; 95% confidence interval, 0.964-0.989; P less than .001) as well as a higher risk for enthesitis (OR, 1.931; 95% CI, 1.276-2.922; P = .002) when compared against patients without a family history of psoriasis.
Patients with a family history of PsA were more likely to have deformities (OR, 2.557; 95% CI, 1.250-5.234; P less than .010) and lower risk of plaque-type psoriasis (OR, 0.417; 95% CI, 0.213-0.816; P less than .011) than patients without a family history of PsA.
Disease onset was earlier among patients with a family history of psoriasis at a mean of 28.1 years versus 31.9 years for those with a family history of PsA (P less than .001).
Dr. Solmaz and her colleagues reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.
SOURCE: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.
the results of a retrospective cohort study suggest.
A family history of psoriasis was associated with younger onset of psoriatic disease and the presence of enthesitis, while by contrast, a family history of psoriatic arthritis (PsA) was associated with lower risk of plaque psoriasis and higher risk of deformities, according to Dilek Solmaz, MD, of the University of Ottawa and her coauthors, who reported their findings in Arthritis Care & Research.
“The link between family history of psoriasis/psoriatic arthritis and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets,” the investigators wrote.
Most, if not all, previous studies evaluating family history have grouped psoriasis and PsA together, according to Dr. Solmaz and her colleagues, rather than looking at the individual effects of psoriasis or PsA family history that may lead to unique disease phenotypes, as was done in the present study.
The investigators based their retrospective analysis on patients recruited in a longitudinal, multicenter database in Turkey and Canada. The mean age of patients in the study was 48 years; nearly 65% were female.
Out of 1,393 patients in the database, 444 had a family history of psoriasis or PsA. That included 335 patients with a psoriasis-only family history and 74 with a family history of PsA; another 35 patients weren’t sure about having a family history of PsA or psoriasis and were left out of the analysis.
Plaque psoriasis was more common in individuals with a family history of only psoriasis, while pustular psoriasis was more common in those with a PsA family history, the investigators reported.
In multivariate analyses, having a family member with psoriasis was a risk factor for younger age of psoriasis onset (odds ratio, 0.976; 95% confidence interval, 0.964-0.989; P less than .001) as well as a higher risk for enthesitis (OR, 1.931; 95% CI, 1.276-2.922; P = .002) when compared against patients without a family history of psoriasis.
Patients with a family history of PsA were more likely to have deformities (OR, 2.557; 95% CI, 1.250-5.234; P less than .010) and lower risk of plaque-type psoriasis (OR, 0.417; 95% CI, 0.213-0.816; P less than .011) than patients without a family history of PsA.
Disease onset was earlier among patients with a family history of psoriasis at a mean of 28.1 years versus 31.9 years for those with a family history of PsA (P less than .001).
Dr. Solmaz and her colleagues reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.
SOURCE: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.
the results of a retrospective cohort study suggest.
A family history of psoriasis was associated with younger onset of psoriatic disease and the presence of enthesitis, while by contrast, a family history of psoriatic arthritis (PsA) was associated with lower risk of plaque psoriasis and higher risk of deformities, according to Dilek Solmaz, MD, of the University of Ottawa and her coauthors, who reported their findings in Arthritis Care & Research.
“The link between family history of psoriasis/psoriatic arthritis and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets,” the investigators wrote.
Most, if not all, previous studies evaluating family history have grouped psoriasis and PsA together, according to Dr. Solmaz and her colleagues, rather than looking at the individual effects of psoriasis or PsA family history that may lead to unique disease phenotypes, as was done in the present study.
The investigators based their retrospective analysis on patients recruited in a longitudinal, multicenter database in Turkey and Canada. The mean age of patients in the study was 48 years; nearly 65% were female.
Out of 1,393 patients in the database, 444 had a family history of psoriasis or PsA. That included 335 patients with a psoriasis-only family history and 74 with a family history of PsA; another 35 patients weren’t sure about having a family history of PsA or psoriasis and were left out of the analysis.
Plaque psoriasis was more common in individuals with a family history of only psoriasis, while pustular psoriasis was more common in those with a PsA family history, the investigators reported.
In multivariate analyses, having a family member with psoriasis was a risk factor for younger age of psoriasis onset (odds ratio, 0.976; 95% confidence interval, 0.964-0.989; P less than .001) as well as a higher risk for enthesitis (OR, 1.931; 95% CI, 1.276-2.922; P = .002) when compared against patients without a family history of psoriasis.
Patients with a family history of PsA were more likely to have deformities (OR, 2.557; 95% CI, 1.250-5.234; P less than .010) and lower risk of plaque-type psoriasis (OR, 0.417; 95% CI, 0.213-0.816; P less than .011) than patients without a family history of PsA.
Disease onset was earlier among patients with a family history of psoriasis at a mean of 28.1 years versus 31.9 years for those with a family history of PsA (P less than .001).
Dr. Solmaz and her colleagues reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.
SOURCE: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Family histories of psoriasis and psoriatic arthritis were linked to different skin phenotypes, disease severity, and musculoskeletal features.
Major finding: Compared with no family history, psoriasis family history was a risk factor for enthesitis (odds ratio, 1.931) and younger age of onset (OR, 0.976) while psoriatic arthritis family history was linked to higher risk of deformities (OR, 2.557) and lower risk of plaque-type psoriasis (OR, 0.417).
Study details: A retrospective analysis including 1,393 Turkish or Canadian patients enrolled in a psoriatic arthritis database.
Disclosures: The study authors reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.
Source: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.
TNF inhibitors improve BMD in ankylosing spondylitis
Long-term tumor necrosis factor inhibitor therapy improved bone mineral density but did not reduce vertebral fractures or radiographic progression in patients with ankylosing spondylitis, according to results from a prospective cohort study.
The study, published in the Journal of Bone and Mineral Research, not only confirms previous reports showing an improvement of the bone mineral density (BMD) during tumor necrosis factor inhibitor (TNFi) treatment in patients with ankylosing spondylitis but also an increase in the number and severity of vertebral fractures despite TNFi treatment.
K.J. Beek, of the Amsterdam Rheumatology and Immunology Centre in Amsterdam, and colleagues followed 135 patients with ankylosing spondylitis from the Amsterdam Spondyloarthritis cohort who were started on TNFi therapy after treatment failure of a minimum of two NSAIDs. Only study participants who were naive to TNFi therapy were enrolled in the study. The patients had a mean disease duration of nearly 12 years; 70% were men.
After 4 years of anti-TNF therapy, the proportion of patients with a low BMD of the hip on dual-energy x-ray absorptiometry significantly decreased from 40.1% to 31.8% (P = .03) and at the lumbar spine from 40.2% to 25.3% (P less than .001), respectively.
In addition, outcomes related to vertebral fractures, including incidence, prevalence, and severity, did not improve following 4 years of anti-TNF therapy. Vertebral fracture prevalence increased from 11.1% with at least one fracture to 19.3% with at least one fracture at the 4-year follow-up. Most of the vertebral fractures occurred in the thoracic rather than lumbar spine.
Radiographic progression significantly increased over the course of treatment, based on a rise in median modified Stoke Ankylosing Spondylitis Spinal Score from 4.0 at baseline to 6.5 at 4-year follow-up. Patients with vertebral fractures had significantly worse radiographic progression.
“These findings show a contradiction, with improvement of bone mineral density on the one hand but a worsening of the bone processes on the other hand, indicated by the increase of fractures and radiographic progression,” the investigators wrote.
They acknowledged a key limitation of the study was the observational design, which did not include a matched control group.
“A recommendation for future studies would be to replicate our results in larger groups of ankylosing spondylitis patients,” they concluded.
No information on study funding or disclosures was available.
SOURCE: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.
Long-term tumor necrosis factor inhibitor therapy improved bone mineral density but did not reduce vertebral fractures or radiographic progression in patients with ankylosing spondylitis, according to results from a prospective cohort study.
The study, published in the Journal of Bone and Mineral Research, not only confirms previous reports showing an improvement of the bone mineral density (BMD) during tumor necrosis factor inhibitor (TNFi) treatment in patients with ankylosing spondylitis but also an increase in the number and severity of vertebral fractures despite TNFi treatment.
K.J. Beek, of the Amsterdam Rheumatology and Immunology Centre in Amsterdam, and colleagues followed 135 patients with ankylosing spondylitis from the Amsterdam Spondyloarthritis cohort who were started on TNFi therapy after treatment failure of a minimum of two NSAIDs. Only study participants who were naive to TNFi therapy were enrolled in the study. The patients had a mean disease duration of nearly 12 years; 70% were men.
After 4 years of anti-TNF therapy, the proportion of patients with a low BMD of the hip on dual-energy x-ray absorptiometry significantly decreased from 40.1% to 31.8% (P = .03) and at the lumbar spine from 40.2% to 25.3% (P less than .001), respectively.
In addition, outcomes related to vertebral fractures, including incidence, prevalence, and severity, did not improve following 4 years of anti-TNF therapy. Vertebral fracture prevalence increased from 11.1% with at least one fracture to 19.3% with at least one fracture at the 4-year follow-up. Most of the vertebral fractures occurred in the thoracic rather than lumbar spine.
Radiographic progression significantly increased over the course of treatment, based on a rise in median modified Stoke Ankylosing Spondylitis Spinal Score from 4.0 at baseline to 6.5 at 4-year follow-up. Patients with vertebral fractures had significantly worse radiographic progression.
“These findings show a contradiction, with improvement of bone mineral density on the one hand but a worsening of the bone processes on the other hand, indicated by the increase of fractures and radiographic progression,” the investigators wrote.
They acknowledged a key limitation of the study was the observational design, which did not include a matched control group.
“A recommendation for future studies would be to replicate our results in larger groups of ankylosing spondylitis patients,” they concluded.
No information on study funding or disclosures was available.
SOURCE: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.
Long-term tumor necrosis factor inhibitor therapy improved bone mineral density but did not reduce vertebral fractures or radiographic progression in patients with ankylosing spondylitis, according to results from a prospective cohort study.
The study, published in the Journal of Bone and Mineral Research, not only confirms previous reports showing an improvement of the bone mineral density (BMD) during tumor necrosis factor inhibitor (TNFi) treatment in patients with ankylosing spondylitis but also an increase in the number and severity of vertebral fractures despite TNFi treatment.
K.J. Beek, of the Amsterdam Rheumatology and Immunology Centre in Amsterdam, and colleagues followed 135 patients with ankylosing spondylitis from the Amsterdam Spondyloarthritis cohort who were started on TNFi therapy after treatment failure of a minimum of two NSAIDs. Only study participants who were naive to TNFi therapy were enrolled in the study. The patients had a mean disease duration of nearly 12 years; 70% were men.
After 4 years of anti-TNF therapy, the proportion of patients with a low BMD of the hip on dual-energy x-ray absorptiometry significantly decreased from 40.1% to 31.8% (P = .03) and at the lumbar spine from 40.2% to 25.3% (P less than .001), respectively.
In addition, outcomes related to vertebral fractures, including incidence, prevalence, and severity, did not improve following 4 years of anti-TNF therapy. Vertebral fracture prevalence increased from 11.1% with at least one fracture to 19.3% with at least one fracture at the 4-year follow-up. Most of the vertebral fractures occurred in the thoracic rather than lumbar spine.
Radiographic progression significantly increased over the course of treatment, based on a rise in median modified Stoke Ankylosing Spondylitis Spinal Score from 4.0 at baseline to 6.5 at 4-year follow-up. Patients with vertebral fractures had significantly worse radiographic progression.
“These findings show a contradiction, with improvement of bone mineral density on the one hand but a worsening of the bone processes on the other hand, indicated by the increase of fractures and radiographic progression,” the investigators wrote.
They acknowledged a key limitation of the study was the observational design, which did not include a matched control group.
“A recommendation for future studies would be to replicate our results in larger groups of ankylosing spondylitis patients,” they concluded.
No information on study funding or disclosures was available.
SOURCE: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.
FROM THE JOURNAL OF BONE AND MINERAL RESEARCH
Key clinical point: Long-term therapy with tumor necrosis factor inhibitors was shown to benefit bone mineral density in ankylosing spondylitis patients, but not vertebral fracture outcomes or radiographic progression.
Major finding: The proportion of patients with a low bone mineral density of the hip decreased from 40.1% to 31.8% (P = .03) after 4 years of tumor necrosis factor inhibitor treatment.
Study details: A prospective cohort study of 135 patients with ankylosing spondylitis treated with a tumor necrosis factor inhibitor for up to 4 years.
Disclosures: No information on study funding or disclosures was available.
Source: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.
Frailty, diabetes increase fragility fracture risk
increasing their risk of fragility fracture, according to findings from a prospective cohort study.
A total of 3,149 participants (70% women) were included in the study, 138 (60% women) of whom had type 2 diabetes. The mean age was 65 years and mean follow-up was 9.2 years. Over the study period, 611 fragility fractures were reported, of which 35 were in patients with diabetes and 576 in patients without diabetes. Overall, 25.4% of patients with diabetes experienced a fragility fracture, compared with 19.1% of control patients. Diabetes was associated with a significantly increased risk of all fragility fractures (hazard ratio, 1.54). It was also significantly associated with risk of hip fracture (HR, 2.60) but not clinical spine fracture.
In a Cox model incorporating the interaction between frailty index (FI) scores and diabetes, there was a significant association between FI and overall fracture risk per 0.01-point FI increase (HR, 1.02; 95% confidence interval, 1.01-1.03) and per 0.10-point FI increase (HR, 1.19; 95% CI, 1.10-1.33). However, no interaction between frailty and diabetes was observed for hip or clinical spine fractures.
“Frailty status may aid in the understanding of the paradox and thus enhance the quality of assessment and care for diabetes,” wrote Guowei Li, MBBS, PhD, of McMaster University, Hamilton, Ont., and his colleagues, adding that “particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.”
Four study authors reported conflicts of interest with some pharmaceutical companies that manufacture therapies for osteoporosis.
SOURCE: Li G et al. Diabetes Care. 2019 Jan 28. doi: 10.2337/dc18-1965.
increasing their risk of fragility fracture, according to findings from a prospective cohort study.
A total of 3,149 participants (70% women) were included in the study, 138 (60% women) of whom had type 2 diabetes. The mean age was 65 years and mean follow-up was 9.2 years. Over the study period, 611 fragility fractures were reported, of which 35 were in patients with diabetes and 576 in patients without diabetes. Overall, 25.4% of patients with diabetes experienced a fragility fracture, compared with 19.1% of control patients. Diabetes was associated with a significantly increased risk of all fragility fractures (hazard ratio, 1.54). It was also significantly associated with risk of hip fracture (HR, 2.60) but not clinical spine fracture.
In a Cox model incorporating the interaction between frailty index (FI) scores and diabetes, there was a significant association between FI and overall fracture risk per 0.01-point FI increase (HR, 1.02; 95% confidence interval, 1.01-1.03) and per 0.10-point FI increase (HR, 1.19; 95% CI, 1.10-1.33). However, no interaction between frailty and diabetes was observed for hip or clinical spine fractures.
“Frailty status may aid in the understanding of the paradox and thus enhance the quality of assessment and care for diabetes,” wrote Guowei Li, MBBS, PhD, of McMaster University, Hamilton, Ont., and his colleagues, adding that “particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.”
Four study authors reported conflicts of interest with some pharmaceutical companies that manufacture therapies for osteoporosis.
SOURCE: Li G et al. Diabetes Care. 2019 Jan 28. doi: 10.2337/dc18-1965.
increasing their risk of fragility fracture, according to findings from a prospective cohort study.
A total of 3,149 participants (70% women) were included in the study, 138 (60% women) of whom had type 2 diabetes. The mean age was 65 years and mean follow-up was 9.2 years. Over the study period, 611 fragility fractures were reported, of which 35 were in patients with diabetes and 576 in patients without diabetes. Overall, 25.4% of patients with diabetes experienced a fragility fracture, compared with 19.1% of control patients. Diabetes was associated with a significantly increased risk of all fragility fractures (hazard ratio, 1.54). It was also significantly associated with risk of hip fracture (HR, 2.60) but not clinical spine fracture.
In a Cox model incorporating the interaction between frailty index (FI) scores and diabetes, there was a significant association between FI and overall fracture risk per 0.01-point FI increase (HR, 1.02; 95% confidence interval, 1.01-1.03) and per 0.10-point FI increase (HR, 1.19; 95% CI, 1.10-1.33). However, no interaction between frailty and diabetes was observed for hip or clinical spine fractures.
“Frailty status may aid in the understanding of the paradox and thus enhance the quality of assessment and care for diabetes,” wrote Guowei Li, MBBS, PhD, of McMaster University, Hamilton, Ont., and his colleagues, adding that “particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.”
Four study authors reported conflicts of interest with some pharmaceutical companies that manufacture therapies for osteoporosis.
SOURCE: Li G et al. Diabetes Care. 2019 Jan 28. doi: 10.2337/dc18-1965.
FROM DIABETES CARE
Psoriatic arthritis eludes early diagnosis
Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.
It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.
“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.
“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.
“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”
“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.
Focusing on patients with psoriasis
Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.
“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.
PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.
Her research group is now studying the associations among different biological drugs taken by patients with psoriasis and their subsequent incidence of PsA with use of medical records from about 4 million Israeli residents. Other studies are also looking at this, but they are all observational and therefore are subject to unidentified confounders, she noted. A more definitive demonstration of PsA protection would need a randomized trial.
“The idea of preventing the transition from psoriasis to PsA is an exciting concept. But currently, there are no established treatments for preventing transition of psoriasis to PsA. It’s an area of active research, and the holy grail of psoriatic disease research. We do not yet know whether successful treatment of skin psoriasis delays the onset of arthritis,” Dr. Reddy said in an interview.
“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
Widening the PsA diagnostic net
What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.
The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.
“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.
“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”
“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.
“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”
Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.
“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
The earliest indicators of PsA
Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).
Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).
In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).
These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.
The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)
The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”
Weight loss and other interventions
Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.
Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”
“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.
“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.
At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).
Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).
Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.
“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.
Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.
Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.
It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.
“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.
“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.
“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”
“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.
Focusing on patients with psoriasis
Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.
“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.
PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.
Her research group is now studying the associations among different biological drugs taken by patients with psoriasis and their subsequent incidence of PsA with use of medical records from about 4 million Israeli residents. Other studies are also looking at this, but they are all observational and therefore are subject to unidentified confounders, she noted. A more definitive demonstration of PsA protection would need a randomized trial.
“The idea of preventing the transition from psoriasis to PsA is an exciting concept. But currently, there are no established treatments for preventing transition of psoriasis to PsA. It’s an area of active research, and the holy grail of psoriatic disease research. We do not yet know whether successful treatment of skin psoriasis delays the onset of arthritis,” Dr. Reddy said in an interview.
“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
Widening the PsA diagnostic net
What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.
The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.
“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.
“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”
“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.
“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”
Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.
“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
The earliest indicators of PsA
Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).
Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).
In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).
These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.
The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)
The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”
Weight loss and other interventions
Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.
Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”
“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.
“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.
At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).
Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).
Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.
“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.
Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.
Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.
It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.
“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.
“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.
“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”
“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.
Focusing on patients with psoriasis
Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.
“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.
PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.
Her research group is now studying the associations among different biological drugs taken by patients with psoriasis and their subsequent incidence of PsA with use of medical records from about 4 million Israeli residents. Other studies are also looking at this, but they are all observational and therefore are subject to unidentified confounders, she noted. A more definitive demonstration of PsA protection would need a randomized trial.
“The idea of preventing the transition from psoriasis to PsA is an exciting concept. But currently, there are no established treatments for preventing transition of psoriasis to PsA. It’s an area of active research, and the holy grail of psoriatic disease research. We do not yet know whether successful treatment of skin psoriasis delays the onset of arthritis,” Dr. Reddy said in an interview.
“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
Widening the PsA diagnostic net
What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.
The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.
“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.
“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”
“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.
“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”
Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.
“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
The earliest indicators of PsA
Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).
Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).
In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).
These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.
The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)
The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”
Weight loss and other interventions
Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.
Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”
“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.
“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.
At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).
Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).
Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.
“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.
Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.
ICYMI: MRI-based treat-to-target approach offers no benefit for RA patients
Patients with RA in clinical remission who received an MRI-based treat-to-target strategy did not achieve superior disease activity remission rates (85% vs. 88%) or reduced radiographic progression (66% vs. 62%), compared with a conventional treat-to-target strategy, according to results of the Danish, 2-year, investigator-initiated, randomized, multicenter IMAGINE-RA trial published in JAMA (2019 Feb 5. doi: 10.1001/jama.2018.21362).
We covered this study at the 2018 European Congress of Rheumatology before it was published in the journal. Read the story at the link above.
Patients with RA in clinical remission who received an MRI-based treat-to-target strategy did not achieve superior disease activity remission rates (85% vs. 88%) or reduced radiographic progression (66% vs. 62%), compared with a conventional treat-to-target strategy, according to results of the Danish, 2-year, investigator-initiated, randomized, multicenter IMAGINE-RA trial published in JAMA (2019 Feb 5. doi: 10.1001/jama.2018.21362).
We covered this study at the 2018 European Congress of Rheumatology before it was published in the journal. Read the story at the link above.
Patients with RA in clinical remission who received an MRI-based treat-to-target strategy did not achieve superior disease activity remission rates (85% vs. 88%) or reduced radiographic progression (66% vs. 62%), compared with a conventional treat-to-target strategy, according to results of the Danish, 2-year, investigator-initiated, randomized, multicenter IMAGINE-RA trial published in JAMA (2019 Feb 5. doi: 10.1001/jama.2018.21362).
We covered this study at the 2018 European Congress of Rheumatology before it was published in the journal. Read the story at the link above.
FROM JAMA
Click for Credit: Missed HIV screening opps; aspirin & preeclampsia; more
Here are 5 articles from the February issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Short-term lung function better predicts mortality risk in SSc
To take the posttest, go to: https://bit.ly/2RrRuIY
Expires November 26, 2019
2. Healthier lifestyle in midlife women reduces subclinical carotid atherosclerosis
To take the posttest, go to: https://bit.ly/2TvDH5G
Expires November 28, 2019
3. Three commonly used quick cognitive assessments often yield flawed results
To take the posttest, go to: https://bit.ly/2G1qkHn
Expires November 28, 2019
4. Missed HIV screening opportunities found among subsequently infected youth
To take the posttest, go to: https://bit.ly/2HGa8Nm
Expires November 29, 2019
5. Aspirin appears underused to prevent preeclampsia in SLE patients
To take the posttest, go to: https://bit.ly/2G0dU2v
Expires January 2, 2019
Here are 5 articles from the February issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Short-term lung function better predicts mortality risk in SSc
To take the posttest, go to: https://bit.ly/2RrRuIY
Expires November 26, 2019
2. Healthier lifestyle in midlife women reduces subclinical carotid atherosclerosis
To take the posttest, go to: https://bit.ly/2TvDH5G
Expires November 28, 2019
3. Three commonly used quick cognitive assessments often yield flawed results
To take the posttest, go to: https://bit.ly/2G1qkHn
Expires November 28, 2019
4. Missed HIV screening opportunities found among subsequently infected youth
To take the posttest, go to: https://bit.ly/2HGa8Nm
Expires November 29, 2019
5. Aspirin appears underused to prevent preeclampsia in SLE patients
To take the posttest, go to: https://bit.ly/2G0dU2v
Expires January 2, 2019
Here are 5 articles from the February issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Short-term lung function better predicts mortality risk in SSc
To take the posttest, go to: https://bit.ly/2RrRuIY
Expires November 26, 2019
2. Healthier lifestyle in midlife women reduces subclinical carotid atherosclerosis
To take the posttest, go to: https://bit.ly/2TvDH5G
Expires November 28, 2019
3. Three commonly used quick cognitive assessments often yield flawed results
To take the posttest, go to: https://bit.ly/2G1qkHn
Expires November 28, 2019
4. Missed HIV screening opportunities found among subsequently infected youth
To take the posttest, go to: https://bit.ly/2HGa8Nm
Expires November 29, 2019
5. Aspirin appears underused to prevent preeclampsia in SLE patients
To take the posttest, go to: https://bit.ly/2G0dU2v
Expires January 2, 2019
Expert: There’s no single treatment for fibromyalgia
SAN DIEGO – There are many potential treatments for fibromyalgia, but a large number of them – NSAIDs, opioids, cannabis and more – come with caveats and nothing beats an old stand-by: physical rehabilitation.
With exercise, “we’re getting the muscles moving, and we’re getting [patients] used to stimulation that will hopefully deaden that pain response over time,” David E.J. Bazzo, MD, said at Pain Care for Primary Care. Still, “it’s going to take multiple things to best treat your patients.”
Fibromyalgia is unique, said Dr. Bazzo, professor of family medicine and public health at the University of California, San Diego. Diagnosis is based on self-reported symptoms since no laboratory tests are available. For diagnostic criteria, he recommends those released by the American College of Rheumatology in 2010 and 2011 and updated in 2016. The criteria, he said, recognize the importance of cognitive symptoms, unrefreshing sleep, fatigue, and certain somatic symptoms (Semin Arthritis Rheum. 2016;46[3]:319-29).
Poor sleep is an especially important problem in fibromyalgia, Dr. Bazzo said, although it’s “a bit of a chicken-and-egg discussion.” It’s not clear which comes first, but “we know that both happen hand-in-hand. We need to work on people’s sleep as one of the primary targets.”
When it comes to treatment, “you have to validate this person’s symptoms and say, ‘Yes, I believe you. I know that you are suffering, and that you’re having pain,’ ” Dr. Bazzo said at the meeting held by the American Pain Society and Global Academy for Medical Education. He advised clinicians to keep in mind conditions that can accompany fibromyalgia, such as depression, that may require other treatment options.
Dr. Bazzo offered advice about these approaches to treatment:
- Exercise. Research supports treadmill and cycle ergometry (BMJ 2002;325:185).
- Opioids. “There’s no convincing evidence that opioids have a role in treating fibromyalgia initially. If you’ve tried everything and patients have had problems, are just not responsive or had side effects, you could consider opioids. But that should be at the tail end of everything because the data is not there,” he said.
- Tramadol. “It’s like an opioid with potential for addiction,” he said. “Don’t just use it willy-nilly. Make sure you have a reason and a good plan. Would it be my first thing? No. Is it something that I keep in my back pocket when other things aren’t working? Perhaps. Would I use it before an opioid? For sure.”
- Second-line therapies. According to Dr. Bazzo, these include antiepileptics such as gabapentin and pregabalin, low-dose cyclobenzaprine, and dual reuptake inhibitors such as duloxetine. There are many other second-line options, he said, from behavioral approaches to yoga to guided physical therapy.
- NSAIDs. Not helpful.
- Cannabis. May interact with other medications.
- Pain clinics. Make sure you refer patients to a pain clinic that embraces a multidisciplinary approach, he said, not one that only offers “pain pills or shots.”
Dr. Bazzo reported no relevant conflicts of interest. The Global Academy for Medical Education and this news organization are owned by the same parent company.
SAN DIEGO – There are many potential treatments for fibromyalgia, but a large number of them – NSAIDs, opioids, cannabis and more – come with caveats and nothing beats an old stand-by: physical rehabilitation.
With exercise, “we’re getting the muscles moving, and we’re getting [patients] used to stimulation that will hopefully deaden that pain response over time,” David E.J. Bazzo, MD, said at Pain Care for Primary Care. Still, “it’s going to take multiple things to best treat your patients.”
Fibromyalgia is unique, said Dr. Bazzo, professor of family medicine and public health at the University of California, San Diego. Diagnosis is based on self-reported symptoms since no laboratory tests are available. For diagnostic criteria, he recommends those released by the American College of Rheumatology in 2010 and 2011 and updated in 2016. The criteria, he said, recognize the importance of cognitive symptoms, unrefreshing sleep, fatigue, and certain somatic symptoms (Semin Arthritis Rheum. 2016;46[3]:319-29).
Poor sleep is an especially important problem in fibromyalgia, Dr. Bazzo said, although it’s “a bit of a chicken-and-egg discussion.” It’s not clear which comes first, but “we know that both happen hand-in-hand. We need to work on people’s sleep as one of the primary targets.”
When it comes to treatment, “you have to validate this person’s symptoms and say, ‘Yes, I believe you. I know that you are suffering, and that you’re having pain,’ ” Dr. Bazzo said at the meeting held by the American Pain Society and Global Academy for Medical Education. He advised clinicians to keep in mind conditions that can accompany fibromyalgia, such as depression, that may require other treatment options.
Dr. Bazzo offered advice about these approaches to treatment:
- Exercise. Research supports treadmill and cycle ergometry (BMJ 2002;325:185).
- Opioids. “There’s no convincing evidence that opioids have a role in treating fibromyalgia initially. If you’ve tried everything and patients have had problems, are just not responsive or had side effects, you could consider opioids. But that should be at the tail end of everything because the data is not there,” he said.
- Tramadol. “It’s like an opioid with potential for addiction,” he said. “Don’t just use it willy-nilly. Make sure you have a reason and a good plan. Would it be my first thing? No. Is it something that I keep in my back pocket when other things aren’t working? Perhaps. Would I use it before an opioid? For sure.”
- Second-line therapies. According to Dr. Bazzo, these include antiepileptics such as gabapentin and pregabalin, low-dose cyclobenzaprine, and dual reuptake inhibitors such as duloxetine. There are many other second-line options, he said, from behavioral approaches to yoga to guided physical therapy.
- NSAIDs. Not helpful.
- Cannabis. May interact with other medications.
- Pain clinics. Make sure you refer patients to a pain clinic that embraces a multidisciplinary approach, he said, not one that only offers “pain pills or shots.”
Dr. Bazzo reported no relevant conflicts of interest. The Global Academy for Medical Education and this news organization are owned by the same parent company.
SAN DIEGO – There are many potential treatments for fibromyalgia, but a large number of them – NSAIDs, opioids, cannabis and more – come with caveats and nothing beats an old stand-by: physical rehabilitation.
With exercise, “we’re getting the muscles moving, and we’re getting [patients] used to stimulation that will hopefully deaden that pain response over time,” David E.J. Bazzo, MD, said at Pain Care for Primary Care. Still, “it’s going to take multiple things to best treat your patients.”
Fibromyalgia is unique, said Dr. Bazzo, professor of family medicine and public health at the University of California, San Diego. Diagnosis is based on self-reported symptoms since no laboratory tests are available. For diagnostic criteria, he recommends those released by the American College of Rheumatology in 2010 and 2011 and updated in 2016. The criteria, he said, recognize the importance of cognitive symptoms, unrefreshing sleep, fatigue, and certain somatic symptoms (Semin Arthritis Rheum. 2016;46[3]:319-29).
Poor sleep is an especially important problem in fibromyalgia, Dr. Bazzo said, although it’s “a bit of a chicken-and-egg discussion.” It’s not clear which comes first, but “we know that both happen hand-in-hand. We need to work on people’s sleep as one of the primary targets.”
When it comes to treatment, “you have to validate this person’s symptoms and say, ‘Yes, I believe you. I know that you are suffering, and that you’re having pain,’ ” Dr. Bazzo said at the meeting held by the American Pain Society and Global Academy for Medical Education. He advised clinicians to keep in mind conditions that can accompany fibromyalgia, such as depression, that may require other treatment options.
Dr. Bazzo offered advice about these approaches to treatment:
- Exercise. Research supports treadmill and cycle ergometry (BMJ 2002;325:185).
- Opioids. “There’s no convincing evidence that opioids have a role in treating fibromyalgia initially. If you’ve tried everything and patients have had problems, are just not responsive or had side effects, you could consider opioids. But that should be at the tail end of everything because the data is not there,” he said.
- Tramadol. “It’s like an opioid with potential for addiction,” he said. “Don’t just use it willy-nilly. Make sure you have a reason and a good plan. Would it be my first thing? No. Is it something that I keep in my back pocket when other things aren’t working? Perhaps. Would I use it before an opioid? For sure.”
- Second-line therapies. According to Dr. Bazzo, these include antiepileptics such as gabapentin and pregabalin, low-dose cyclobenzaprine, and dual reuptake inhibitors such as duloxetine. There are many other second-line options, he said, from behavioral approaches to yoga to guided physical therapy.
- NSAIDs. Not helpful.
- Cannabis. May interact with other medications.
- Pain clinics. Make sure you refer patients to a pain clinic that embraces a multidisciplinary approach, he said, not one that only offers “pain pills or shots.”
Dr. Bazzo reported no relevant conflicts of interest. The Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM PAIN CARE FOR PRIMARY CARE