User login
VIDEO: Minimal disease activity criteria sought for axial spondyloarthritis
DENVER – U.S. rheumatologists plan to develop new criteria to define minimal disease activity in patients with axial spondyloarthritis to better gauge in routine clinical practice how well these patients respond to treatment.
A score on the Ankylosing Spondylitis Disease Activity Score (ASDAS) of less than 1.3 is the most commonly used measure today of minimal disease activity, but the ASDAS isn’t suitable for point-of-care assessment in routine practice because of the need for a C-reactive protein level or erythrocyte sedimentation rate.
“In the clinic, ASDAS is very difficult or next to impossible to do” because it needs CRP or ESR, which are “never available at the point of care,” Atul A. Deodhar, MD, said in an interview at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN). Another limitation of ASDAS is that it focuses exclusively on musculoskeletal measures and does not take into account extra-articular manifestations of axial spondyloarthritis such as those in the eye, gastrointestinal tract, or skin.
“We would like a clinical measurement that might tell us that a patient is appropriately treated and at minimal disease activity,” said Dr. Deodhar, professor of medicine and medical director of the rheumatology clinics at Oregon Health & Science University in Portland.
As outgoing chair of SPARTAN, Dr. Deodhar introduced a proposal that SPARTAN develop new minimal disease activity criteria for patients with axial spondyloarthritis, presenting the rationale for this project at the meeting along with the incoming chair Lianne S. Gensler, MD.
“We want a way to measure disease activity at a stage that is not full remission but with enough of a reduction in disease activity to make a difference,” said Dr. Gensler, director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco. Another frequently used gauge of minimal disease activity in axial spondyloarthritis, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), is flawed by being totally based on subjective measurements without input from the attending rheumatologist, Dr. Gensler said.
The SPARTAN leadership will try to partner in this effort with the OMERACT (Outcome Measures in Rheumatology) program, the Assessment of Spondyloarthritis International Society (ASAS), or both, but if necessary SPARTAN will develop new minimal disease activity criteria on its own, Dr. Deodhar said.
Dr. Deodhar has received research support from 10 drug companies. Dr. Gensler has been a consultant to or has received research support from AbbVie, Amgen, Janssen, Novartis, and UCB.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
DENVER – U.S. rheumatologists plan to develop new criteria to define minimal disease activity in patients with axial spondyloarthritis to better gauge in routine clinical practice how well these patients respond to treatment.
A score on the Ankylosing Spondylitis Disease Activity Score (ASDAS) of less than 1.3 is the most commonly used measure today of minimal disease activity, but the ASDAS isn’t suitable for point-of-care assessment in routine practice because of the need for a C-reactive protein level or erythrocyte sedimentation rate.
“In the clinic, ASDAS is very difficult or next to impossible to do” because it needs CRP or ESR, which are “never available at the point of care,” Atul A. Deodhar, MD, said in an interview at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN). Another limitation of ASDAS is that it focuses exclusively on musculoskeletal measures and does not take into account extra-articular manifestations of axial spondyloarthritis such as those in the eye, gastrointestinal tract, or skin.
“We would like a clinical measurement that might tell us that a patient is appropriately treated and at minimal disease activity,” said Dr. Deodhar, professor of medicine and medical director of the rheumatology clinics at Oregon Health & Science University in Portland.
As outgoing chair of SPARTAN, Dr. Deodhar introduced a proposal that SPARTAN develop new minimal disease activity criteria for patients with axial spondyloarthritis, presenting the rationale for this project at the meeting along with the incoming chair Lianne S. Gensler, MD.
“We want a way to measure disease activity at a stage that is not full remission but with enough of a reduction in disease activity to make a difference,” said Dr. Gensler, director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco. Another frequently used gauge of minimal disease activity in axial spondyloarthritis, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), is flawed by being totally based on subjective measurements without input from the attending rheumatologist, Dr. Gensler said.
The SPARTAN leadership will try to partner in this effort with the OMERACT (Outcome Measures in Rheumatology) program, the Assessment of Spondyloarthritis International Society (ASAS), or both, but if necessary SPARTAN will develop new minimal disease activity criteria on its own, Dr. Deodhar said.
Dr. Deodhar has received research support from 10 drug companies. Dr. Gensler has been a consultant to or has received research support from AbbVie, Amgen, Janssen, Novartis, and UCB.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
DENVER – U.S. rheumatologists plan to develop new criteria to define minimal disease activity in patients with axial spondyloarthritis to better gauge in routine clinical practice how well these patients respond to treatment.
A score on the Ankylosing Spondylitis Disease Activity Score (ASDAS) of less than 1.3 is the most commonly used measure today of minimal disease activity, but the ASDAS isn’t suitable for point-of-care assessment in routine practice because of the need for a C-reactive protein level or erythrocyte sedimentation rate.
“In the clinic, ASDAS is very difficult or next to impossible to do” because it needs CRP or ESR, which are “never available at the point of care,” Atul A. Deodhar, MD, said in an interview at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN). Another limitation of ASDAS is that it focuses exclusively on musculoskeletal measures and does not take into account extra-articular manifestations of axial spondyloarthritis such as those in the eye, gastrointestinal tract, or skin.
“We would like a clinical measurement that might tell us that a patient is appropriately treated and at minimal disease activity,” said Dr. Deodhar, professor of medicine and medical director of the rheumatology clinics at Oregon Health & Science University in Portland.
As outgoing chair of SPARTAN, Dr. Deodhar introduced a proposal that SPARTAN develop new minimal disease activity criteria for patients with axial spondyloarthritis, presenting the rationale for this project at the meeting along with the incoming chair Lianne S. Gensler, MD.
“We want a way to measure disease activity at a stage that is not full remission but with enough of a reduction in disease activity to make a difference,” said Dr. Gensler, director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco. Another frequently used gauge of minimal disease activity in axial spondyloarthritis, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), is flawed by being totally based on subjective measurements without input from the attending rheumatologist, Dr. Gensler said.
The SPARTAN leadership will try to partner in this effort with the OMERACT (Outcome Measures in Rheumatology) program, the Assessment of Spondyloarthritis International Society (ASAS), or both, but if necessary SPARTAN will develop new minimal disease activity criteria on its own, Dr. Deodhar said.
Dr. Deodhar has received research support from 10 drug companies. Dr. Gensler has been a consultant to or has received research support from AbbVie, Amgen, Janssen, Novartis, and UCB.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE 2016 SPARTAN ANNUAL MEETING
TNF inhibitors slow hip deterioration in ankylosing spondylitis
DENVER – Treatment with a tumor necrosis factor inhibitor strongly linked with protection against progressive hip deterioration in observational data from 576 patients with ankylosing spondylitis enrolled in a prospective U.S. cohort.
But tumor necrosis factor (TNF) inhibitor treatment had less than full success for treating spondyloarthritis (SpA) disease activity in results from a separate registry study of 596 U.S. veterans diagnosed with SpA. About two-thirds were on a TNF inhibitor, and among these recipients, about 40% had suboptimal disease control, Delamo Bekele, MBBS, said at the annual meeting of the Spondyloarthritis (SpA) Research and Treatment Network.
This substantial rate of SpA patients with high disease activity despite TNF inhibitor treatment “suggests a need for more aggressive treatment,” with either a higher TNF inhibitor dosage or by treatment with a different biological drug, said Dr. Bekele, a rheumatologist at Howard University Hospital in Washington.
The analysis that assessed the impact of TNF inhibitor treatment on hip status used data from 576 AS patients enrolled in the Prospective Study of Outcomes in AS (PSOAS) at any of five U.S. centers. PSOAS included patients diagnosed with AS for at least 20 years, and the new study focused on patients who had undergone hip imaging at least twice while in the study and who entered with a Bath AS Radiologic Index (BASRI) hip score of less than 4. The analysis considered patients to have experienced progressive hip deterioration if they had a follow-up BASRI score that was at least two points higher than their baseline score. During a median 3 years of follow-up, 25 patients had this level of hip-disease progression.
A multivariate analysis showed that the rate of hip disease progression was cut by 98% among patients on TNF inhibitor treatment, compared with those not on a TNF inhibitor, a highly significant difference between the two subgroups, reported Daphne Scaramangas-Plumley, MD, a rheumatologist at Cedars-Sinai Medical Center in Los Angeles. The only other variable identified that also correlated with the risk of hip progression was a patient’s hip score at baseline: For every additional point of the BASRI hip score the rate of later worsening rose by 60%.
The second study involved 596 U.S. veterans diagnosed with a type of SpA and enrolled in the Program to Understand the Longterm Outcomes in Spondyloarthritis (PULSAR) registry study at any of seven U.S. Department of Veterans Affairs centers. The analysis showed that about 64% of these SpA patients were receiving a TNF inhibitor. Among these patients on a TNF inhibitor, about 40% continued to have a Bath AS Disease Activity Index (BASDAI) score of 4 or higher, a level high enough to flag an inadequate response to current treatment.
Dr. Scaramangas-Plumley and Dr. Bekele had no disclosures.
On Twitter @mitchelzoler
DENVER – Treatment with a tumor necrosis factor inhibitor strongly linked with protection against progressive hip deterioration in observational data from 576 patients with ankylosing spondylitis enrolled in a prospective U.S. cohort.
But tumor necrosis factor (TNF) inhibitor treatment had less than full success for treating spondyloarthritis (SpA) disease activity in results from a separate registry study of 596 U.S. veterans diagnosed with SpA. About two-thirds were on a TNF inhibitor, and among these recipients, about 40% had suboptimal disease control, Delamo Bekele, MBBS, said at the annual meeting of the Spondyloarthritis (SpA) Research and Treatment Network.
This substantial rate of SpA patients with high disease activity despite TNF inhibitor treatment “suggests a need for more aggressive treatment,” with either a higher TNF inhibitor dosage or by treatment with a different biological drug, said Dr. Bekele, a rheumatologist at Howard University Hospital in Washington.
The analysis that assessed the impact of TNF inhibitor treatment on hip status used data from 576 AS patients enrolled in the Prospective Study of Outcomes in AS (PSOAS) at any of five U.S. centers. PSOAS included patients diagnosed with AS for at least 20 years, and the new study focused on patients who had undergone hip imaging at least twice while in the study and who entered with a Bath AS Radiologic Index (BASRI) hip score of less than 4. The analysis considered patients to have experienced progressive hip deterioration if they had a follow-up BASRI score that was at least two points higher than their baseline score. During a median 3 years of follow-up, 25 patients had this level of hip-disease progression.
A multivariate analysis showed that the rate of hip disease progression was cut by 98% among patients on TNF inhibitor treatment, compared with those not on a TNF inhibitor, a highly significant difference between the two subgroups, reported Daphne Scaramangas-Plumley, MD, a rheumatologist at Cedars-Sinai Medical Center in Los Angeles. The only other variable identified that also correlated with the risk of hip progression was a patient’s hip score at baseline: For every additional point of the BASRI hip score the rate of later worsening rose by 60%.
The second study involved 596 U.S. veterans diagnosed with a type of SpA and enrolled in the Program to Understand the Longterm Outcomes in Spondyloarthritis (PULSAR) registry study at any of seven U.S. Department of Veterans Affairs centers. The analysis showed that about 64% of these SpA patients were receiving a TNF inhibitor. Among these patients on a TNF inhibitor, about 40% continued to have a Bath AS Disease Activity Index (BASDAI) score of 4 or higher, a level high enough to flag an inadequate response to current treatment.
Dr. Scaramangas-Plumley and Dr. Bekele had no disclosures.
On Twitter @mitchelzoler
DENVER – Treatment with a tumor necrosis factor inhibitor strongly linked with protection against progressive hip deterioration in observational data from 576 patients with ankylosing spondylitis enrolled in a prospective U.S. cohort.
But tumor necrosis factor (TNF) inhibitor treatment had less than full success for treating spondyloarthritis (SpA) disease activity in results from a separate registry study of 596 U.S. veterans diagnosed with SpA. About two-thirds were on a TNF inhibitor, and among these recipients, about 40% had suboptimal disease control, Delamo Bekele, MBBS, said at the annual meeting of the Spondyloarthritis (SpA) Research and Treatment Network.
This substantial rate of SpA patients with high disease activity despite TNF inhibitor treatment “suggests a need for more aggressive treatment,” with either a higher TNF inhibitor dosage or by treatment with a different biological drug, said Dr. Bekele, a rheumatologist at Howard University Hospital in Washington.
The analysis that assessed the impact of TNF inhibitor treatment on hip status used data from 576 AS patients enrolled in the Prospective Study of Outcomes in AS (PSOAS) at any of five U.S. centers. PSOAS included patients diagnosed with AS for at least 20 years, and the new study focused on patients who had undergone hip imaging at least twice while in the study and who entered with a Bath AS Radiologic Index (BASRI) hip score of less than 4. The analysis considered patients to have experienced progressive hip deterioration if they had a follow-up BASRI score that was at least two points higher than their baseline score. During a median 3 years of follow-up, 25 patients had this level of hip-disease progression.
A multivariate analysis showed that the rate of hip disease progression was cut by 98% among patients on TNF inhibitor treatment, compared with those not on a TNF inhibitor, a highly significant difference between the two subgroups, reported Daphne Scaramangas-Plumley, MD, a rheumatologist at Cedars-Sinai Medical Center in Los Angeles. The only other variable identified that also correlated with the risk of hip progression was a patient’s hip score at baseline: For every additional point of the BASRI hip score the rate of later worsening rose by 60%.
The second study involved 596 U.S. veterans diagnosed with a type of SpA and enrolled in the Program to Understand the Longterm Outcomes in Spondyloarthritis (PULSAR) registry study at any of seven U.S. Department of Veterans Affairs centers. The analysis showed that about 64% of these SpA patients were receiving a TNF inhibitor. Among these patients on a TNF inhibitor, about 40% continued to have a Bath AS Disease Activity Index (BASDAI) score of 4 or higher, a level high enough to flag an inadequate response to current treatment.
Dr. Scaramangas-Plumley and Dr. Bekele had no disclosures.
On Twitter @mitchelzoler
AT THE 2016 SPARTAN ANNUAL MEETING
Key clinical point: Ankylosing spondylitis patients on tumor necrosis factor inhibitor treatment had substantially better maintenance of hip function. In a second study, 40% of spondyloarthritis patients on a TNF inhibitor failed to receive adequate treatment efficacy.
Major finding: Tumor necrosis factor inhibitor treatment cut the rate of hip deterioration by 98%, compared with treatment without a biological drug.
Data source: PSOAS, a prospective observational study of 576 U.S. spondyloarthritis patients, and 596 U.S. veterans with SpA enrolled in the PULSAR registry study.
Disclosures: Dr. Scaramangas-Plumley and Dr. Bekele had no disclosures.
Routine cardiac screening in spondyloarthritis shown unneeded
DENVER – The largest controlled assessment of structural cardiac disease in patients with axial spondyloarthritis (SpA) failed to show any excess above a matched healthy sample, a finding that boosts recent guidelines that recommended against routine cardiac assessments in these patients.
“These findings provide the first evidence to support current recommendations against routine echocardiographic screening in asymptomatic patients with axial spondyloarthritis,” Risheen Reejhsinghani, MD, said at the annual meeting of the Spondyloarthritis Research and Treatment Network.
“If a patient has symptoms of cardiac disease – uncontrolled hypertension, dyspnea, or chest pain – then you would do the appropriate testing as you would for anyone,” said Dr. Reejhsinghani, a cardiologist at the University of California, San Francisco.
Past reports from small and often uncontrolled groups of patients with ankylosing spondylitis (AS) had suggested a possible link between the disease and structural heart disease. The 2015 treatment recommendations for AS and axial SpA from the American College of Rheumatology and other organizations included a “strong” recommendation against screening for cardiac conduction defects or for valvular heart disease (Arthritis Rheum. 2016 Feb;68[2]:282-98).
The prospective study by Dr. Reejhsinghani and her associates enrolled 154 patients diagnosed with axial SpA and 51 age-matched controls recruited from Health eHeart participants, a community-based heart disease study run from San Francisco. Additional matching by hypertension status refined the population to 133 patients with axial SpA matched with 51 healthy controls. The researchers also did another prespecified analysis that compared the 51 controls with 94 age- and hypertension-matched patients who fulfilled the 1984 modified New York criteria for a specific diagnosis of AS. Overall, nearly two-thirds of the people in the study were men, they averaged about 43 years old, and the average duration from AS diagnosis was 18 years.
The researchers performed systematic cardiac examination by transthoracic echo in all 205 participants that examined them for aortic root size, aortic regurgitation, diastolic dysfunction, and size of the aortic annulus, sinotubular junction, and ascending aorta. These examinations identified an unusually large aortic root diameter in about 5% of the cases and 2% of the controls. Aortic insufficiency (regurgitation) occurred in about 40% of the cases and 50% of the controls. An analysis of the cases and controls that was matched for age and hypertension showed a diastolic dysfunction prevalence of 17% in the cases and 27% in the controls. None of the between-group differences were statistically significant. The results were similar for the entire age-matched group studied, the age- and hypertension-matched subgroup, and the AS subgroup.
Future studies need to examine the possible impact that various treatments, including biologics, have on the prevalence of cardiac disorders, Dr. Reejhsinghani said.
On Twitter @mitchelzoler
Some patients with ankylosing spondylitis develop aortic insufficiency and need aortic valve replacements. Historically, clinicians worried about this risk and this led to a debate when an American College of Rheumatology panel recently developed ankylosing spondylitis treatment recommendations. This committee, on which I participated, decided to strongly recommend against routine screening with ECG or echocardiography. When we made that decision, we did not have these new data; we based our recommendation largely on our concerns about the cost efficacy of routine screening of asymptomatic patients.
|
Dr. David T.Y. Yu |
The new findings reported by Dr. Reejhsinghani show for certain that we do not need routine structural screening on these patients. It’s certainly appropriate to assess a patient with ECG and echo if they have persistent hypertension, dyspnea, or other cardiac symptoms. I would also do further testing in an ankylosing spondylitis patient with a heart murmur, and it is also appropriate to keep in mind a possible increased risk in spondyloarthritis patients for ischemic cardiovascular diseases.
The data reported by Dr. Reejhsinghani are convincing, especially because of the matching she did to control for age and presence of hypertension.
David T.Y. Yu, MD, is a rheumatologist at the University of California, Los Angeles. He made these comments in an interview. He had no disclosures.
Some patients with ankylosing spondylitis develop aortic insufficiency and need aortic valve replacements. Historically, clinicians worried about this risk and this led to a debate when an American College of Rheumatology panel recently developed ankylosing spondylitis treatment recommendations. This committee, on which I participated, decided to strongly recommend against routine screening with ECG or echocardiography. When we made that decision, we did not have these new data; we based our recommendation largely on our concerns about the cost efficacy of routine screening of asymptomatic patients.
|
|
Dr. David T.Y. Yu |
The new findings reported by Dr. Reejhsinghani show for certain that we do not need routine structural screening on these patients. It’s certainly appropriate to assess a patient with ECG and echo if they have persistent hypertension, dyspnea, or other cardiac symptoms. I would also do further testing in an ankylosing spondylitis patient with a heart murmur, and it is also appropriate to keep in mind a possible increased risk in spondyloarthritis patients for ischemic cardiovascular diseases.
The data reported by Dr. Reejhsinghani are convincing, especially because of the matching she did to control for age and presence of hypertension.
David T.Y. Yu, MD, is a rheumatologist at the University of California, Los Angeles. He made these comments in an interview. He had no disclosures.
Some patients with ankylosing spondylitis develop aortic insufficiency and need aortic valve replacements. Historically, clinicians worried about this risk and this led to a debate when an American College of Rheumatology panel recently developed ankylosing spondylitis treatment recommendations. This committee, on which I participated, decided to strongly recommend against routine screening with ECG or echocardiography. When we made that decision, we did not have these new data; we based our recommendation largely on our concerns about the cost efficacy of routine screening of asymptomatic patients.
|
|
Dr. David T.Y. Yu |
The new findings reported by Dr. Reejhsinghani show for certain that we do not need routine structural screening on these patients. It’s certainly appropriate to assess a patient with ECG and echo if they have persistent hypertension, dyspnea, or other cardiac symptoms. I would also do further testing in an ankylosing spondylitis patient with a heart murmur, and it is also appropriate to keep in mind a possible increased risk in spondyloarthritis patients for ischemic cardiovascular diseases.
The data reported by Dr. Reejhsinghani are convincing, especially because of the matching she did to control for age and presence of hypertension.
David T.Y. Yu, MD, is a rheumatologist at the University of California, Los Angeles. He made these comments in an interview. He had no disclosures.
DENVER – The largest controlled assessment of structural cardiac disease in patients with axial spondyloarthritis (SpA) failed to show any excess above a matched healthy sample, a finding that boosts recent guidelines that recommended against routine cardiac assessments in these patients.
“These findings provide the first evidence to support current recommendations against routine echocardiographic screening in asymptomatic patients with axial spondyloarthritis,” Risheen Reejhsinghani, MD, said at the annual meeting of the Spondyloarthritis Research and Treatment Network.
“If a patient has symptoms of cardiac disease – uncontrolled hypertension, dyspnea, or chest pain – then you would do the appropriate testing as you would for anyone,” said Dr. Reejhsinghani, a cardiologist at the University of California, San Francisco.
Past reports from small and often uncontrolled groups of patients with ankylosing spondylitis (AS) had suggested a possible link between the disease and structural heart disease. The 2015 treatment recommendations for AS and axial SpA from the American College of Rheumatology and other organizations included a “strong” recommendation against screening for cardiac conduction defects or for valvular heart disease (Arthritis Rheum. 2016 Feb;68[2]:282-98).
The prospective study by Dr. Reejhsinghani and her associates enrolled 154 patients diagnosed with axial SpA and 51 age-matched controls recruited from Health eHeart participants, a community-based heart disease study run from San Francisco. Additional matching by hypertension status refined the population to 133 patients with axial SpA matched with 51 healthy controls. The researchers also did another prespecified analysis that compared the 51 controls with 94 age- and hypertension-matched patients who fulfilled the 1984 modified New York criteria for a specific diagnosis of AS. Overall, nearly two-thirds of the people in the study were men, they averaged about 43 years old, and the average duration from AS diagnosis was 18 years.
The researchers performed systematic cardiac examination by transthoracic echo in all 205 participants that examined them for aortic root size, aortic regurgitation, diastolic dysfunction, and size of the aortic annulus, sinotubular junction, and ascending aorta. These examinations identified an unusually large aortic root diameter in about 5% of the cases and 2% of the controls. Aortic insufficiency (regurgitation) occurred in about 40% of the cases and 50% of the controls. An analysis of the cases and controls that was matched for age and hypertension showed a diastolic dysfunction prevalence of 17% in the cases and 27% in the controls. None of the between-group differences were statistically significant. The results were similar for the entire age-matched group studied, the age- and hypertension-matched subgroup, and the AS subgroup.
Future studies need to examine the possible impact that various treatments, including biologics, have on the prevalence of cardiac disorders, Dr. Reejhsinghani said.
On Twitter @mitchelzoler
DENVER – The largest controlled assessment of structural cardiac disease in patients with axial spondyloarthritis (SpA) failed to show any excess above a matched healthy sample, a finding that boosts recent guidelines that recommended against routine cardiac assessments in these patients.
“These findings provide the first evidence to support current recommendations against routine echocardiographic screening in asymptomatic patients with axial spondyloarthritis,” Risheen Reejhsinghani, MD, said at the annual meeting of the Spondyloarthritis Research and Treatment Network.
“If a patient has symptoms of cardiac disease – uncontrolled hypertension, dyspnea, or chest pain – then you would do the appropriate testing as you would for anyone,” said Dr. Reejhsinghani, a cardiologist at the University of California, San Francisco.
Past reports from small and often uncontrolled groups of patients with ankylosing spondylitis (AS) had suggested a possible link between the disease and structural heart disease. The 2015 treatment recommendations for AS and axial SpA from the American College of Rheumatology and other organizations included a “strong” recommendation against screening for cardiac conduction defects or for valvular heart disease (Arthritis Rheum. 2016 Feb;68[2]:282-98).
The prospective study by Dr. Reejhsinghani and her associates enrolled 154 patients diagnosed with axial SpA and 51 age-matched controls recruited from Health eHeart participants, a community-based heart disease study run from San Francisco. Additional matching by hypertension status refined the population to 133 patients with axial SpA matched with 51 healthy controls. The researchers also did another prespecified analysis that compared the 51 controls with 94 age- and hypertension-matched patients who fulfilled the 1984 modified New York criteria for a specific diagnosis of AS. Overall, nearly two-thirds of the people in the study were men, they averaged about 43 years old, and the average duration from AS diagnosis was 18 years.
The researchers performed systematic cardiac examination by transthoracic echo in all 205 participants that examined them for aortic root size, aortic regurgitation, diastolic dysfunction, and size of the aortic annulus, sinotubular junction, and ascending aorta. These examinations identified an unusually large aortic root diameter in about 5% of the cases and 2% of the controls. Aortic insufficiency (regurgitation) occurred in about 40% of the cases and 50% of the controls. An analysis of the cases and controls that was matched for age and hypertension showed a diastolic dysfunction prevalence of 17% in the cases and 27% in the controls. None of the between-group differences were statistically significant. The results were similar for the entire age-matched group studied, the age- and hypertension-matched subgroup, and the AS subgroup.
Future studies need to examine the possible impact that various treatments, including biologics, have on the prevalence of cardiac disorders, Dr. Reejhsinghani said.
On Twitter @mitchelzoler
AT THE 2016 SPARTAN ANNUAL MEETING
Key clinical point: Patients with axial spondyloarthritis or ankylosing spondylitis had no excess prevalence of structural cardiac abnormalities in the largest controlled study yet reported.
Major finding: Aortic insufficiency occurred in about 40% of the axial spondyloarthritis cases and 50% of the matched controls.
Data source: A prospective, matched case and control study with 205 total subjects from a single U.S. center.
Disclosures: Dr. Reejhsinghani had no disclosures.
FDA accepting comments on draft guidelines on compounding law
The Food and Drug Administration is currently accepting public comments on the agency’s proposed plans to implement a law that will restrict compounding of human drug products.
A statement issued by the FDA provides links to two draft guidances that describe how the agency “would implement provisions of federal law that restrict compounding human drug products that are essentially copies of commercially available or approved drug products.” One draft guidance and the legal restrictions referenced therein are relevant to physicians and pharmacists, as well as state-licensed pharmacies or federal facilities that compound drugs, according to the FDA. The other guidance applies to outsourcing facilities.
Although compounded drug products, such as a medication made without a dye for a patient allergic to that dye, or a medication made into liquid form for a patient who cannot swallow a pill, “may benefit certain patients whose medical needs cannot be met by a commercially available or an FDA-approved drug product,” the FDA statement said. “Taking compounded drug products that are essentially copies of a commercially available or approved drug needlessly exposes patients to drug products that FDA has not evaluated for safety, effectiveness, and quality. In addition, the compounded drugs may not have been produced according to appropriate quality standards. Such compounding would also undermine the new drug approval and over-the-counter drug monograph systems in the United States.”
The statement refers to serious adverse events, including infections and deaths that have resulted from “poor-quality” compounded drugs.
Written or electronic comments can be submitted until Oct. 11, and information on submitting comments is available at regulations.gov.
The Food and Drug Administration is currently accepting public comments on the agency’s proposed plans to implement a law that will restrict compounding of human drug products.
A statement issued by the FDA provides links to two draft guidances that describe how the agency “would implement provisions of federal law that restrict compounding human drug products that are essentially copies of commercially available or approved drug products.” One draft guidance and the legal restrictions referenced therein are relevant to physicians and pharmacists, as well as state-licensed pharmacies or federal facilities that compound drugs, according to the FDA. The other guidance applies to outsourcing facilities.
Although compounded drug products, such as a medication made without a dye for a patient allergic to that dye, or a medication made into liquid form for a patient who cannot swallow a pill, “may benefit certain patients whose medical needs cannot be met by a commercially available or an FDA-approved drug product,” the FDA statement said. “Taking compounded drug products that are essentially copies of a commercially available or approved drug needlessly exposes patients to drug products that FDA has not evaluated for safety, effectiveness, and quality. In addition, the compounded drugs may not have been produced according to appropriate quality standards. Such compounding would also undermine the new drug approval and over-the-counter drug monograph systems in the United States.”
The statement refers to serious adverse events, including infections and deaths that have resulted from “poor-quality” compounded drugs.
Written or electronic comments can be submitted until Oct. 11, and information on submitting comments is available at regulations.gov.
The Food and Drug Administration is currently accepting public comments on the agency’s proposed plans to implement a law that will restrict compounding of human drug products.
A statement issued by the FDA provides links to two draft guidances that describe how the agency “would implement provisions of federal law that restrict compounding human drug products that are essentially copies of commercially available or approved drug products.” One draft guidance and the legal restrictions referenced therein are relevant to physicians and pharmacists, as well as state-licensed pharmacies or federal facilities that compound drugs, according to the FDA. The other guidance applies to outsourcing facilities.
Although compounded drug products, such as a medication made without a dye for a patient allergic to that dye, or a medication made into liquid form for a patient who cannot swallow a pill, “may benefit certain patients whose medical needs cannot be met by a commercially available or an FDA-approved drug product,” the FDA statement said. “Taking compounded drug products that are essentially copies of a commercially available or approved drug needlessly exposes patients to drug products that FDA has not evaluated for safety, effectiveness, and quality. In addition, the compounded drugs may not have been produced according to appropriate quality standards. Such compounding would also undermine the new drug approval and over-the-counter drug monograph systems in the United States.”
The statement refers to serious adverse events, including infections and deaths that have resulted from “poor-quality” compounded drugs.
Written or electronic comments can be submitted until Oct. 11, and information on submitting comments is available at regulations.gov.
FDA advisory panel unanimously backs biosimilars for Humira, Enbrel
The Food and Drug Administration’s Arthritis Advisory Committee, together with an added complement of dermatologists and gastroenterologists, unanimously recommended during meetings on July 12 and 13 that the agency license a biosimilar Humira (adalimumab) that is made by Amgen and a biosimilar Enbrel (etanercept) that is made by Sandoz for many of the same indications held by the reference drugs.
The FDA advisory panel that endorsed biosimilar Humira recommended the agent’s approval in a 26-0 vote for many, but not all of the indications currently assigned to Humira itself: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis in patients at least 4 years old, plaque psoriasis, adult Crohn’s disease, and adult ulcerative colitis.
A slightly different group of 20 advisory panel members (without any gastroenterologists) voted 20-0 in favor of the FDA granting biosimilar Enbrel all five of the indications now held by Enbrel: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, and plaque psoriasis.
The biosimilar Humira and the biosimilar Enbrel are, respectively, the third and fourth candidate biosimilars to emerge from the FDA’s development program and receive advisory committee scrutiny and support. The first agent through the process, biosimilar filgrastim (Zarxio) received FDA approval in 2015 and is available in the United States. Although the second biosimilar through the process, the tumor necrosis factor inhibitor Inflectra that is biosimilar Remicade (infliximab), received FDA approval in April of this year, it has not yet become available for sale, although a spokeswoman for the company that will market it, Pfizer, said that the company expects to start U.S. sales of Inflectra before the end of 2016.
While the Arthritis Advisory Committee ended each of its daylong deliberations for each of the two candidate biosimilars with unanimous support, the panelists’ discussions among themselves and with FDA staffers reflected some uncertainty with the biosimilar concept, especially during the first day when they focused on biosimilar Humira. The major sticking point revolved around the regulatory pathway to approval first established by the Biologics Price Competition and Innovation Act of 2009 and subsequently refined by the FDA that allows a candidate biosimilar to establish its biosimilarity primarily though the results of analytical studies that establish that the candidate molecule is highly similar to the reference molecule. This approval scheme uses clinical trials in a confirmatory role to establish biosimilarity rather than as the linchpin of approval.
It also means that the FDA can grant clinical indications to the biosimilar drug based not on the results from clinical trials, but based entirely on what have already been demonstrated as safe and effective clinical applications for the reference drug. For example, the biosimilar Humira underwent testing in two clinical studies showing similar efficacy and safety as Humira in patients with rheumatoid arthritis and in patients with plaque psoriasis, but received endorsements based on extrapolations for an additional five indications. Biosimilar Enbrel was compared with Enbrel in patients with plaque psoriasis only and still received extrapolated indications for the additional four rheumatologic conditions.
“This is a new level of extrapolation, across indications,” noted Sarah E. Streett, MD, a gastroenterologist at Stanford (Calif.) University, one of several panelists who initially voiced uncertainty about the concept.
But FDA staffer Nikolay P. Nikolov, MD, who led the agency’s presentation, assured the panelists that the concept of extrapolation was at the heart of biosimilar development and regulatory assessment.
“We have confidence from the data that the two molecules [the reference drug and biosimilar drug] are so similar that we can rely on the safety and efficacy of the reference product. The premise of our approach to biosimilars is that this is not a new molecule that we know nothing about.”
The other uncertainty about biosimilar Humira and biosimilar Enbrel that raised concerns of many panelists were the prospects for nonmedical switching once these drugs reach the market. Nonmedical switching refers to when an insurance company or pharmacy benefit manager substitutes a biosimilar for a reference drug without approval from or even the knowledge of the prescribing physician or the patient. Many of the people who spoke during the public forum period on both days of hearings voiced their concerns about this prospect.
“Nonmedical switching is a major concern of clinicians and policy makers, and we need greater clarification from the FDA,” said committee chair Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School in Boston.
“I see a remarkable disconnect between the public’s concerns [about nonmedical switching] and the charge to the committee. These are essential issues that need a forum to be aired out,” said panelist Steven F. Solga, MD, chief of gastroenterology at St. Luke’s Hospital in Bethlehem, Pa.
Dr. Nikolov assured committee members that the FDA recognized this concern and was working on it. “We appreciate the disconnect between the charge and the concerns of the community. I assure you that the issues brought up will be part of our discussions so we can get this [biosimilar pathway] implemented the right way.”
According to the FDA’s regulations, a biosimilar designation does not allow for nonmedical switching, something that could only happen under a related but distinct designation known as interchangeability. During the committee meeting on July 13, a FDA staffer said that the agency is currently developing guidance for an “interchangeable” designation and plans to have it available before then end of 2016.
On Twitter @mitchelzoler
The Food and Drug Administration’s Arthritis Advisory Committee, together with an added complement of dermatologists and gastroenterologists, unanimously recommended during meetings on July 12 and 13 that the agency license a biosimilar Humira (adalimumab) that is made by Amgen and a biosimilar Enbrel (etanercept) that is made by Sandoz for many of the same indications held by the reference drugs.
The FDA advisory panel that endorsed biosimilar Humira recommended the agent’s approval in a 26-0 vote for many, but not all of the indications currently assigned to Humira itself: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis in patients at least 4 years old, plaque psoriasis, adult Crohn’s disease, and adult ulcerative colitis.
A slightly different group of 20 advisory panel members (without any gastroenterologists) voted 20-0 in favor of the FDA granting biosimilar Enbrel all five of the indications now held by Enbrel: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, and plaque psoriasis.
The biosimilar Humira and the biosimilar Enbrel are, respectively, the third and fourth candidate biosimilars to emerge from the FDA’s development program and receive advisory committee scrutiny and support. The first agent through the process, biosimilar filgrastim (Zarxio) received FDA approval in 2015 and is available in the United States. Although the second biosimilar through the process, the tumor necrosis factor inhibitor Inflectra that is biosimilar Remicade (infliximab), received FDA approval in April of this year, it has not yet become available for sale, although a spokeswoman for the company that will market it, Pfizer, said that the company expects to start U.S. sales of Inflectra before the end of 2016.
While the Arthritis Advisory Committee ended each of its daylong deliberations for each of the two candidate biosimilars with unanimous support, the panelists’ discussions among themselves and with FDA staffers reflected some uncertainty with the biosimilar concept, especially during the first day when they focused on biosimilar Humira. The major sticking point revolved around the regulatory pathway to approval first established by the Biologics Price Competition and Innovation Act of 2009 and subsequently refined by the FDA that allows a candidate biosimilar to establish its biosimilarity primarily though the results of analytical studies that establish that the candidate molecule is highly similar to the reference molecule. This approval scheme uses clinical trials in a confirmatory role to establish biosimilarity rather than as the linchpin of approval.
It also means that the FDA can grant clinical indications to the biosimilar drug based not on the results from clinical trials, but based entirely on what have already been demonstrated as safe and effective clinical applications for the reference drug. For example, the biosimilar Humira underwent testing in two clinical studies showing similar efficacy and safety as Humira in patients with rheumatoid arthritis and in patients with plaque psoriasis, but received endorsements based on extrapolations for an additional five indications. Biosimilar Enbrel was compared with Enbrel in patients with plaque psoriasis only and still received extrapolated indications for the additional four rheumatologic conditions.
“This is a new level of extrapolation, across indications,” noted Sarah E. Streett, MD, a gastroenterologist at Stanford (Calif.) University, one of several panelists who initially voiced uncertainty about the concept.
But FDA staffer Nikolay P. Nikolov, MD, who led the agency’s presentation, assured the panelists that the concept of extrapolation was at the heart of biosimilar development and regulatory assessment.
“We have confidence from the data that the two molecules [the reference drug and biosimilar drug] are so similar that we can rely on the safety and efficacy of the reference product. The premise of our approach to biosimilars is that this is not a new molecule that we know nothing about.”
The other uncertainty about biosimilar Humira and biosimilar Enbrel that raised concerns of many panelists were the prospects for nonmedical switching once these drugs reach the market. Nonmedical switching refers to when an insurance company or pharmacy benefit manager substitutes a biosimilar for a reference drug without approval from or even the knowledge of the prescribing physician or the patient. Many of the people who spoke during the public forum period on both days of hearings voiced their concerns about this prospect.
“Nonmedical switching is a major concern of clinicians and policy makers, and we need greater clarification from the FDA,” said committee chair Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School in Boston.
“I see a remarkable disconnect between the public’s concerns [about nonmedical switching] and the charge to the committee. These are essential issues that need a forum to be aired out,” said panelist Steven F. Solga, MD, chief of gastroenterology at St. Luke’s Hospital in Bethlehem, Pa.
Dr. Nikolov assured committee members that the FDA recognized this concern and was working on it. “We appreciate the disconnect between the charge and the concerns of the community. I assure you that the issues brought up will be part of our discussions so we can get this [biosimilar pathway] implemented the right way.”
According to the FDA’s regulations, a biosimilar designation does not allow for nonmedical switching, something that could only happen under a related but distinct designation known as interchangeability. During the committee meeting on July 13, a FDA staffer said that the agency is currently developing guidance for an “interchangeable” designation and plans to have it available before then end of 2016.
On Twitter @mitchelzoler
The Food and Drug Administration’s Arthritis Advisory Committee, together with an added complement of dermatologists and gastroenterologists, unanimously recommended during meetings on July 12 and 13 that the agency license a biosimilar Humira (adalimumab) that is made by Amgen and a biosimilar Enbrel (etanercept) that is made by Sandoz for many of the same indications held by the reference drugs.
The FDA advisory panel that endorsed biosimilar Humira recommended the agent’s approval in a 26-0 vote for many, but not all of the indications currently assigned to Humira itself: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis in patients at least 4 years old, plaque psoriasis, adult Crohn’s disease, and adult ulcerative colitis.
A slightly different group of 20 advisory panel members (without any gastroenterologists) voted 20-0 in favor of the FDA granting biosimilar Enbrel all five of the indications now held by Enbrel: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, and plaque psoriasis.
The biosimilar Humira and the biosimilar Enbrel are, respectively, the third and fourth candidate biosimilars to emerge from the FDA’s development program and receive advisory committee scrutiny and support. The first agent through the process, biosimilar filgrastim (Zarxio) received FDA approval in 2015 and is available in the United States. Although the second biosimilar through the process, the tumor necrosis factor inhibitor Inflectra that is biosimilar Remicade (infliximab), received FDA approval in April of this year, it has not yet become available for sale, although a spokeswoman for the company that will market it, Pfizer, said that the company expects to start U.S. sales of Inflectra before the end of 2016.
While the Arthritis Advisory Committee ended each of its daylong deliberations for each of the two candidate biosimilars with unanimous support, the panelists’ discussions among themselves and with FDA staffers reflected some uncertainty with the biosimilar concept, especially during the first day when they focused on biosimilar Humira. The major sticking point revolved around the regulatory pathway to approval first established by the Biologics Price Competition and Innovation Act of 2009 and subsequently refined by the FDA that allows a candidate biosimilar to establish its biosimilarity primarily though the results of analytical studies that establish that the candidate molecule is highly similar to the reference molecule. This approval scheme uses clinical trials in a confirmatory role to establish biosimilarity rather than as the linchpin of approval.
It also means that the FDA can grant clinical indications to the biosimilar drug based not on the results from clinical trials, but based entirely on what have already been demonstrated as safe and effective clinical applications for the reference drug. For example, the biosimilar Humira underwent testing in two clinical studies showing similar efficacy and safety as Humira in patients with rheumatoid arthritis and in patients with plaque psoriasis, but received endorsements based on extrapolations for an additional five indications. Biosimilar Enbrel was compared with Enbrel in patients with plaque psoriasis only and still received extrapolated indications for the additional four rheumatologic conditions.
“This is a new level of extrapolation, across indications,” noted Sarah E. Streett, MD, a gastroenterologist at Stanford (Calif.) University, one of several panelists who initially voiced uncertainty about the concept.
But FDA staffer Nikolay P. Nikolov, MD, who led the agency’s presentation, assured the panelists that the concept of extrapolation was at the heart of biosimilar development and regulatory assessment.
“We have confidence from the data that the two molecules [the reference drug and biosimilar drug] are so similar that we can rely on the safety and efficacy of the reference product. The premise of our approach to biosimilars is that this is not a new molecule that we know nothing about.”
The other uncertainty about biosimilar Humira and biosimilar Enbrel that raised concerns of many panelists were the prospects for nonmedical switching once these drugs reach the market. Nonmedical switching refers to when an insurance company or pharmacy benefit manager substitutes a biosimilar for a reference drug without approval from or even the knowledge of the prescribing physician or the patient. Many of the people who spoke during the public forum period on both days of hearings voiced their concerns about this prospect.
“Nonmedical switching is a major concern of clinicians and policy makers, and we need greater clarification from the FDA,” said committee chair Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School in Boston.
“I see a remarkable disconnect between the public’s concerns [about nonmedical switching] and the charge to the committee. These are essential issues that need a forum to be aired out,” said panelist Steven F. Solga, MD, chief of gastroenterology at St. Luke’s Hospital in Bethlehem, Pa.
Dr. Nikolov assured committee members that the FDA recognized this concern and was working on it. “We appreciate the disconnect between the charge and the concerns of the community. I assure you that the issues brought up will be part of our discussions so we can get this [biosimilar pathway] implemented the right way.”
According to the FDA’s regulations, a biosimilar designation does not allow for nonmedical switching, something that could only happen under a related but distinct designation known as interchangeability. During the committee meeting on July 13, a FDA staffer said that the agency is currently developing guidance for an “interchangeable” designation and plans to have it available before then end of 2016.
On Twitter @mitchelzoler
Radiographic vertebral fractures common in ankylosing spondylitis patients
Radiographic vertebral fractures occur frequently in patients with ankylosing spondylitis, according to Dr. Fiona Maas and her associates.
At baseline, 59 (20%) of the 292 patients included in a prospective cohort study had radiographic vertebral fractures. During a 2-year follow-up period, 15 patients developed new fractures and 7 patients experienced an increase in severity of current fractures. A significant majority of fractures were defined as mild, and most were located in the mid-thoracic and thoracolumbar regions of the spine.
Fractures were more likely in patients who were older, had a higher body mass index, had smoked for long durations, had larger occiput-to-wall distances, had more spinal radiographic damage, and had lower hip bone mineral density (BMD). Patients who developed new fractures during the study period were older and had lower hip BMD. Incidence and prevalence of fractures was reduced in patients who were receiving nonsteroidal anti-inflammatory drugs (NSAIDs) at baseline.
“The influence of anti-inflammatory drugs (e.g. NSAIDs, TNF-alpha inhibitors), anti-osteoporotic treatment (e.g. calcium/vitamin D supplements, bisphosphonates), and lifestyle changes (e.g. smoking cessation, body weight control, physical exercise) on the development of vertebral fractures in AS should be further investigated in a large study population with long-term follow-up,” the investigators concluded.
Find the full study in Arthritis Care & Research (doi: 10.1002/acr.22980).
Radiographic vertebral fractures occur frequently in patients with ankylosing spondylitis, according to Dr. Fiona Maas and her associates.
At baseline, 59 (20%) of the 292 patients included in a prospective cohort study had radiographic vertebral fractures. During a 2-year follow-up period, 15 patients developed new fractures and 7 patients experienced an increase in severity of current fractures. A significant majority of fractures were defined as mild, and most were located in the mid-thoracic and thoracolumbar regions of the spine.
Fractures were more likely in patients who were older, had a higher body mass index, had smoked for long durations, had larger occiput-to-wall distances, had more spinal radiographic damage, and had lower hip bone mineral density (BMD). Patients who developed new fractures during the study period were older and had lower hip BMD. Incidence and prevalence of fractures was reduced in patients who were receiving nonsteroidal anti-inflammatory drugs (NSAIDs) at baseline.
“The influence of anti-inflammatory drugs (e.g. NSAIDs, TNF-alpha inhibitors), anti-osteoporotic treatment (e.g. calcium/vitamin D supplements, bisphosphonates), and lifestyle changes (e.g. smoking cessation, body weight control, physical exercise) on the development of vertebral fractures in AS should be further investigated in a large study population with long-term follow-up,” the investigators concluded.
Find the full study in Arthritis Care & Research (doi: 10.1002/acr.22980).
Radiographic vertebral fractures occur frequently in patients with ankylosing spondylitis, according to Dr. Fiona Maas and her associates.
At baseline, 59 (20%) of the 292 patients included in a prospective cohort study had radiographic vertebral fractures. During a 2-year follow-up period, 15 patients developed new fractures and 7 patients experienced an increase in severity of current fractures. A significant majority of fractures were defined as mild, and most were located in the mid-thoracic and thoracolumbar regions of the spine.
Fractures were more likely in patients who were older, had a higher body mass index, had smoked for long durations, had larger occiput-to-wall distances, had more spinal radiographic damage, and had lower hip bone mineral density (BMD). Patients who developed new fractures during the study period were older and had lower hip BMD. Incidence and prevalence of fractures was reduced in patients who were receiving nonsteroidal anti-inflammatory drugs (NSAIDs) at baseline.
“The influence of anti-inflammatory drugs (e.g. NSAIDs, TNF-alpha inhibitors), anti-osteoporotic treatment (e.g. calcium/vitamin D supplements, bisphosphonates), and lifestyle changes (e.g. smoking cessation, body weight control, physical exercise) on the development of vertebral fractures in AS should be further investigated in a large study population with long-term follow-up,” the investigators concluded.
Find the full study in Arthritis Care & Research (doi: 10.1002/acr.22980).
FROM ARTHRITIS CARE & RESEARCH
Adalimumab approved to treat noninfectious uveitis
The U.S. Food and Drug Administration has approved adalimumab for treatment of noninfectious intermediate, posterior, and panuveitis in adults, making it the only approved drug for the condition that is not a corticosteroid.
The approval marks the 10th approved indication for adalimumab (Humira) in the United States. It was recently approved for this indication in the European Union as well.
Patients on adalimumab had about half the risk of those on placebo to experience treatment failure (a combination of uveitis flare and decrease in visual acuity) in two pivotal phase III studies, VISUAL-I (hazard ratio, 0.5 for VISUAL-I; P less than .001) and VISUAL-II (HR, 0.57; P = .004). In the trials, patients were treated with an 80-mg loading dose of adalimumab at baseline, followed by a 40-mg subcutaneous injection at week 1 and then 40 mg every other week for up to 80 weeks.
“These approvals provide a valuable option for patients experiencing flare and vision impairment associated with this group of inflammatory diseases of the eye,” Glenn J. Jaffe, MD, of Duke University, Durham, N.C., said in an announcement from the manufacturer of adalimumab, AbbVie. “Data from the robust VISUAL clinical trial program demonstrate the value of Humira as a treatment option for patients with these serious diseases.”
The U.S. Food and Drug Administration has approved adalimumab for treatment of noninfectious intermediate, posterior, and panuveitis in adults, making it the only approved drug for the condition that is not a corticosteroid.
The approval marks the 10th approved indication for adalimumab (Humira) in the United States. It was recently approved for this indication in the European Union as well.
Patients on adalimumab had about half the risk of those on placebo to experience treatment failure (a combination of uveitis flare and decrease in visual acuity) in two pivotal phase III studies, VISUAL-I (hazard ratio, 0.5 for VISUAL-I; P less than .001) and VISUAL-II (HR, 0.57; P = .004). In the trials, patients were treated with an 80-mg loading dose of adalimumab at baseline, followed by a 40-mg subcutaneous injection at week 1 and then 40 mg every other week for up to 80 weeks.
“These approvals provide a valuable option for patients experiencing flare and vision impairment associated with this group of inflammatory diseases of the eye,” Glenn J. Jaffe, MD, of Duke University, Durham, N.C., said in an announcement from the manufacturer of adalimumab, AbbVie. “Data from the robust VISUAL clinical trial program demonstrate the value of Humira as a treatment option for patients with these serious diseases.”
The U.S. Food and Drug Administration has approved adalimumab for treatment of noninfectious intermediate, posterior, and panuveitis in adults, making it the only approved drug for the condition that is not a corticosteroid.
The approval marks the 10th approved indication for adalimumab (Humira) in the United States. It was recently approved for this indication in the European Union as well.
Patients on adalimumab had about half the risk of those on placebo to experience treatment failure (a combination of uveitis flare and decrease in visual acuity) in two pivotal phase III studies, VISUAL-I (hazard ratio, 0.5 for VISUAL-I; P less than .001) and VISUAL-II (HR, 0.57; P = .004). In the trials, patients were treated with an 80-mg loading dose of adalimumab at baseline, followed by a 40-mg subcutaneous injection at week 1 and then 40 mg every other week for up to 80 weeks.
“These approvals provide a valuable option for patients experiencing flare and vision impairment associated with this group of inflammatory diseases of the eye,” Glenn J. Jaffe, MD, of Duke University, Durham, N.C., said in an announcement from the manufacturer of adalimumab, AbbVie. “Data from the robust VISUAL clinical trial program demonstrate the value of Humira as a treatment option for patients with these serious diseases.”
Pharma jousts statistically for an ankylosing spondylitis edge
Now that the interleukin-17 inhibitor secukinumab and tumor necrosis factor inhibitors are competing options for treatment of patients with ankylosing spondylitis, the companies that make those drugs must feel pressure to find some sort of advantage for their agents.
How else to explain the remarkable pair of similar post hoc analyses presented in June at the European Congress of Rheumatology in London? One of the analyses was funded by Novartis – the company that markets secukinumab (Cosentyx) – and included several Novartis employees as coauthors. The second study, presented immediately afterward in the main session at the meeting devoted to ankylosing spondylitis (AS) treatments, had backing from AbbVie, which markets adalimumab (Humira), the largest-selling tumor necrosis factor inhibitor worldwide, and had several AbbVie employees as coauthors.
Both analyses used a “matching adjusted indirect comparison,” a fairly new way to compare the performance of interventions studied in two totally independent trials by propensity matching patients from each of the two trials. It’s purportedly a way to make a legitimate comparison in the absence of head-to-head data.
Making the two reports even more surreal was their use of essentially the same data.
The first report came from Walter P. Maksymowych, MD, an AS clinician and researcher from the University of Alberta, who with his coauthors used data collected on secukinumab in the MEASURE 1 pivotal trial and on adalimumab in the ATLAS pivotal trial. He spent much of his presentation describing the methods behind the indirect comparison, and I don’t think I can be blamed for calling the results of this Novartis-sponsored analysis predictable: overall better performance by secukinumab, compared “indirectly” with adalimumab for clinical responses and patient quality of life.
The second report, the one sponsored by AbbVie, came from Keith A. Betts, PhD, a biostatistician who works for the Analysis Group, an international consulting firm. He also used the ATLAS database as the source for adalimumab outcomes, and differed marginally from Dr. Maksymowych by taking data on secukinumab patients from both the MEASURE 1 and MEASURE 2 pivotal trials. Although Dr. Betts also used the matching adjusted indirect comparison approach and broadened his data source modestly, his results showed a distinctly different outcome: similar efficacy for the two drugs. Dr. Betts also included a cost efficacy analysis, and in this part adalimumab showed superior performance after he factored in the cost per responding AS patient.
During the combined discussion period following the two talks, both presenters defended the legitimacy of their approaches, although Dr. Maksymowych conceded that these indirect comparisons are “hypothesis generating rather than producing a definitive answer.” But a couple of active European AS researchers rose to comment from the floor and discredit the whole process.
“These two presentations show why I am not a proponent of indirect comparisons. The statistical models squeeze the data until they confess,” said Robert Landewé, MD, an AS specialist at the University of Amsterdam. “This is now a commercial rather than a scientific clash between two important drugs. I challenge these companies to perform a head-to-head trial. Indirect comparisons are not good,” he concluded, to a round of audience applause.
“There are so many methodological issues,” said Désirée van der Heijde, MD, another Dutch AS clinician and researcher who rose to critique both studies. “The only thing you can rely on is head-to-head trials.”
I later spoke with Dr. Maksymowych, and he expressed some pessimism about the prospects for a fully-powered, head-to-head trial of an interleukin-17 inhibitor and tumor necrosis factor inhibitor because it would need to enroll so many patients. “Randomized studies of active comparators need to be huge because it’s hard to show improvements when the response rates are high,” he said. Plus, he added, it isn’t entirely about a drug’s efficacy against AS spinal symptoms anyway.
“We also have to think about the impact of treatment on other aspects of this disease, such as psoriasis and colitis, as well as radiographic disease progression,” he said. These aspects of the activity of both classes of drugs have not received much study in AS patients until now.
In other words, the battle between treatment options for AS has just begun, and seems likely to be fought on many fronts.
On Twitter @mitchelzoler
Now that the interleukin-17 inhibitor secukinumab and tumor necrosis factor inhibitors are competing options for treatment of patients with ankylosing spondylitis, the companies that make those drugs must feel pressure to find some sort of advantage for their agents.
How else to explain the remarkable pair of similar post hoc analyses presented in June at the European Congress of Rheumatology in London? One of the analyses was funded by Novartis – the company that markets secukinumab (Cosentyx) – and included several Novartis employees as coauthors. The second study, presented immediately afterward in the main session at the meeting devoted to ankylosing spondylitis (AS) treatments, had backing from AbbVie, which markets adalimumab (Humira), the largest-selling tumor necrosis factor inhibitor worldwide, and had several AbbVie employees as coauthors.
Both analyses used a “matching adjusted indirect comparison,” a fairly new way to compare the performance of interventions studied in two totally independent trials by propensity matching patients from each of the two trials. It’s purportedly a way to make a legitimate comparison in the absence of head-to-head data.
Making the two reports even more surreal was their use of essentially the same data.
The first report came from Walter P. Maksymowych, MD, an AS clinician and researcher from the University of Alberta, who with his coauthors used data collected on secukinumab in the MEASURE 1 pivotal trial and on adalimumab in the ATLAS pivotal trial. He spent much of his presentation describing the methods behind the indirect comparison, and I don’t think I can be blamed for calling the results of this Novartis-sponsored analysis predictable: overall better performance by secukinumab, compared “indirectly” with adalimumab for clinical responses and patient quality of life.
The second report, the one sponsored by AbbVie, came from Keith A. Betts, PhD, a biostatistician who works for the Analysis Group, an international consulting firm. He also used the ATLAS database as the source for adalimumab outcomes, and differed marginally from Dr. Maksymowych by taking data on secukinumab patients from both the MEASURE 1 and MEASURE 2 pivotal trials. Although Dr. Betts also used the matching adjusted indirect comparison approach and broadened his data source modestly, his results showed a distinctly different outcome: similar efficacy for the two drugs. Dr. Betts also included a cost efficacy analysis, and in this part adalimumab showed superior performance after he factored in the cost per responding AS patient.
During the combined discussion period following the two talks, both presenters defended the legitimacy of their approaches, although Dr. Maksymowych conceded that these indirect comparisons are “hypothesis generating rather than producing a definitive answer.” But a couple of active European AS researchers rose to comment from the floor and discredit the whole process.
“These two presentations show why I am not a proponent of indirect comparisons. The statistical models squeeze the data until they confess,” said Robert Landewé, MD, an AS specialist at the University of Amsterdam. “This is now a commercial rather than a scientific clash between two important drugs. I challenge these companies to perform a head-to-head trial. Indirect comparisons are not good,” he concluded, to a round of audience applause.
“There are so many methodological issues,” said Désirée van der Heijde, MD, another Dutch AS clinician and researcher who rose to critique both studies. “The only thing you can rely on is head-to-head trials.”
I later spoke with Dr. Maksymowych, and he expressed some pessimism about the prospects for a fully-powered, head-to-head trial of an interleukin-17 inhibitor and tumor necrosis factor inhibitor because it would need to enroll so many patients. “Randomized studies of active comparators need to be huge because it’s hard to show improvements when the response rates are high,” he said. Plus, he added, it isn’t entirely about a drug’s efficacy against AS spinal symptoms anyway.
“We also have to think about the impact of treatment on other aspects of this disease, such as psoriasis and colitis, as well as radiographic disease progression,” he said. These aspects of the activity of both classes of drugs have not received much study in AS patients until now.
In other words, the battle between treatment options for AS has just begun, and seems likely to be fought on many fronts.
On Twitter @mitchelzoler
Now that the interleukin-17 inhibitor secukinumab and tumor necrosis factor inhibitors are competing options for treatment of patients with ankylosing spondylitis, the companies that make those drugs must feel pressure to find some sort of advantage for their agents.
How else to explain the remarkable pair of similar post hoc analyses presented in June at the European Congress of Rheumatology in London? One of the analyses was funded by Novartis – the company that markets secukinumab (Cosentyx) – and included several Novartis employees as coauthors. The second study, presented immediately afterward in the main session at the meeting devoted to ankylosing spondylitis (AS) treatments, had backing from AbbVie, which markets adalimumab (Humira), the largest-selling tumor necrosis factor inhibitor worldwide, and had several AbbVie employees as coauthors.
Both analyses used a “matching adjusted indirect comparison,” a fairly new way to compare the performance of interventions studied in two totally independent trials by propensity matching patients from each of the two trials. It’s purportedly a way to make a legitimate comparison in the absence of head-to-head data.
Making the two reports even more surreal was their use of essentially the same data.
The first report came from Walter P. Maksymowych, MD, an AS clinician and researcher from the University of Alberta, who with his coauthors used data collected on secukinumab in the MEASURE 1 pivotal trial and on adalimumab in the ATLAS pivotal trial. He spent much of his presentation describing the methods behind the indirect comparison, and I don’t think I can be blamed for calling the results of this Novartis-sponsored analysis predictable: overall better performance by secukinumab, compared “indirectly” with adalimumab for clinical responses and patient quality of life.
The second report, the one sponsored by AbbVie, came from Keith A. Betts, PhD, a biostatistician who works for the Analysis Group, an international consulting firm. He also used the ATLAS database as the source for adalimumab outcomes, and differed marginally from Dr. Maksymowych by taking data on secukinumab patients from both the MEASURE 1 and MEASURE 2 pivotal trials. Although Dr. Betts also used the matching adjusted indirect comparison approach and broadened his data source modestly, his results showed a distinctly different outcome: similar efficacy for the two drugs. Dr. Betts also included a cost efficacy analysis, and in this part adalimumab showed superior performance after he factored in the cost per responding AS patient.
During the combined discussion period following the two talks, both presenters defended the legitimacy of their approaches, although Dr. Maksymowych conceded that these indirect comparisons are “hypothesis generating rather than producing a definitive answer.” But a couple of active European AS researchers rose to comment from the floor and discredit the whole process.
“These two presentations show why I am not a proponent of indirect comparisons. The statistical models squeeze the data until they confess,” said Robert Landewé, MD, an AS specialist at the University of Amsterdam. “This is now a commercial rather than a scientific clash between two important drugs. I challenge these companies to perform a head-to-head trial. Indirect comparisons are not good,” he concluded, to a round of audience applause.
“There are so many methodological issues,” said Désirée van der Heijde, MD, another Dutch AS clinician and researcher who rose to critique both studies. “The only thing you can rely on is head-to-head trials.”
I later spoke with Dr. Maksymowych, and he expressed some pessimism about the prospects for a fully-powered, head-to-head trial of an interleukin-17 inhibitor and tumor necrosis factor inhibitor because it would need to enroll so many patients. “Randomized studies of active comparators need to be huge because it’s hard to show improvements when the response rates are high,” he said. Plus, he added, it isn’t entirely about a drug’s efficacy against AS spinal symptoms anyway.
“We also have to think about the impact of treatment on other aspects of this disease, such as psoriasis and colitis, as well as radiographic disease progression,” he said. These aspects of the activity of both classes of drugs have not received much study in AS patients until now.
In other words, the battle between treatment options for AS has just begun, and seems likely to be fought on many fronts.
On Twitter @mitchelzoler
NSAID plus TNFi linked to less ankylosing spondylitis progression
LONDON – Patients with ankylosing spondylitis who remained on long-term treatment with a nonsteroidal anti-inflammatory drug and a tumor necrosis factor inhibitor had significantly less new spinal-bone formation in a cross-sectional analysis of a multicenter cohort of 527 U.S. patients.
A related analysis of the same cohort also showed significantly less ankylosing spondylitis (AS) progression as measured by radiographic progression among patients who received treatment with a tumor necrosis factor–alpha (TNF) inhibitor for 2.1-3.5 years regardless of their treatment with a nonsteroidal anti-inflammatory drug (NSAID), although this link trended to a stronger effect among the patients taking both, Lianne S. Gensler, MD, reported in a pair of posters at the European Congress of Rheumatology.
These finding suggest “there may be synergy between NSAIDs and TNF inhibitors [for slowing or preventing progression] in a select group of AS patients at high risk for progression,” said Dr. Gensler, a rheumatologist and director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco.
But Dr. Gensler also cautioned that these findings are merely “hypothesis generating” and should not be used as a rationale to place or maintain AS patients on long-term treatment with an NSAID, a TNF inhibitor, or both drugs.
“You treat the disease burden. The message is absolutely not to always put AS patients on both types of drugs. When an AS patient is well controlled on a TNF inhibitor alone, I would not tell them to also take a NSAID,” she said in an interview. “This is only relevant for patients who require treatment with both drug classes because of their clinical status.”
As the list of treatment options for patients with AS grows – it now includes NSAIDs, TNF inhibitors, and the interleukin-17 inhibitor secukinumab (Cosentyx) – the impact of these agents on disease progression as assessed by radiography and new bone formation becomes a new dimension to start to consider in addition to the standard criterion of immediate clinical response, Dr. Gensler explained. AS progression “is another factor to think about as we decide on treatment strategies. There is growing evidence that long-term treatment with a tumor necrosis factor inhibitor and with a NSAID have potential roles in disease modification.” But the evidence is indirect, from cohort studies that make cause and effect assessments difficult because of possible unidentified confounding factors, she noted.
“There has never been a randomized, controlled trial examining the disease-modifying effects of a TNF inhibitor because you can’t keep patients on placebo for a long enough time to see this benefit,” Dr. Gensler said. It takes a long time to see progression in AS patients, she noted.
A prior cohort analysis run by Dr. Gensler and her associates found evidence for an effect of long-term treatment with a TNF inhibitor and reduced AS progression measured using the modified Stoke AS Spine Score (mSASSS), compared with AS patients not on a TNF inhibitor in a propensity-score matched analysis of 334 patients. A link between TNF inhibitor use and a discernible difference in mSASSS only occurred when patients were on TNF inhibitor treatment for at least 3.9 years (Arthritis Rheum. 2013 Oct;65[10]:2645-54). In addition, a separate report at the EULAR congress on 168 AS patients maintained on treatment with secukinumab for 2 years showed evidence for slowed progression of mSASSS scores, compared with historical controls as well as with similar patients who were not on secukinumab treatment for as long a period of time.
The new analysis reported by Dr. Gensler looked at 527 AS patients in the multicenter Prospective Study of Outcomes in AS cohort followed for a median of 3.7 years. Clinicians participating in this cohort saw patients every 6 months, and radiographic assessments by mSASSS and for new bone formation occurred every 2 years. At entry into the registry, about 57% of patients received a TNF inhibitor and about 63% received an NSAID, with a third on an NSAID only, 27% on a TNF inhibitor only, 30% on both drugs, and 10% receiving neither drug.
The analysis showed that among patients followed for 2.1-3.5 years, the fraction of patients on a TNF inhibitor who showed progression of their mSASSS was 77% lower than patients not on a TNF inhibitor, a statistically significant difference, Dr. Gensler reported. The researchers saw no statistically significant difference in mSASSS progression rates between the patients on a TNF inhibitor at baseline and those not on a TNF inhibitor at baseline among patients followed for 2 years and among those followed for more than 3.5 years, although the analysis did show nominally higher levels of response among TNF-inhibitor users followed for more than 3.5 years. Dr. Gensler speculated that one reason for the loss of a statistically significant difference during longer follow-up could be that fewer patients reached these levels of prolonged follow-up, making statistically significant differences harder to see. This analysis also showed a strong trend for less progression among the patients treated with an NSAID, a 51% relative reduction in mSASSS progression, compared with patients not taking an NSAID, but this relationship just missed statistical significance.
A second analysis by Dr. Gensler and her associates used data from the same cohort but focused on new bone formation during follow-up. This analysis again showed a statistically significant, 72% reduction in this outcome among patients taking a TNF inhibitor at baseline, compared with those not on a TNF inhibitor, when followed for 2.1-3.5 years, with no statistically significant relationship seen among patients followed for less or more time, Dr. Gensler reported. However, the results from this analysis also showed a statistically significant impact from NSAID treatment: Patients on a TNF inhibitor and an NSAID at baseline had 67% less new bone formation, compared with those who received a TNF inhibitor but were not on an NSAID at baseline.
Dr. Gensler has been a consultant to or investigator funded by AbbVie, Amgen, Janssen, Novartis, and UCB. The Prospective Study of Outcomes in Ankylosing Spondylitis receives no commercial support.
On Twitter @mitchelzoler
LONDON – Patients with ankylosing spondylitis who remained on long-term treatment with a nonsteroidal anti-inflammatory drug and a tumor necrosis factor inhibitor had significantly less new spinal-bone formation in a cross-sectional analysis of a multicenter cohort of 527 U.S. patients.
A related analysis of the same cohort also showed significantly less ankylosing spondylitis (AS) progression as measured by radiographic progression among patients who received treatment with a tumor necrosis factor–alpha (TNF) inhibitor for 2.1-3.5 years regardless of their treatment with a nonsteroidal anti-inflammatory drug (NSAID), although this link trended to a stronger effect among the patients taking both, Lianne S. Gensler, MD, reported in a pair of posters at the European Congress of Rheumatology.
These finding suggest “there may be synergy between NSAIDs and TNF inhibitors [for slowing or preventing progression] in a select group of AS patients at high risk for progression,” said Dr. Gensler, a rheumatologist and director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco.
But Dr. Gensler also cautioned that these findings are merely “hypothesis generating” and should not be used as a rationale to place or maintain AS patients on long-term treatment with an NSAID, a TNF inhibitor, or both drugs.
“You treat the disease burden. The message is absolutely not to always put AS patients on both types of drugs. When an AS patient is well controlled on a TNF inhibitor alone, I would not tell them to also take a NSAID,” she said in an interview. “This is only relevant for patients who require treatment with both drug classes because of their clinical status.”
As the list of treatment options for patients with AS grows – it now includes NSAIDs, TNF inhibitors, and the interleukin-17 inhibitor secukinumab (Cosentyx) – the impact of these agents on disease progression as assessed by radiography and new bone formation becomes a new dimension to start to consider in addition to the standard criterion of immediate clinical response, Dr. Gensler explained. AS progression “is another factor to think about as we decide on treatment strategies. There is growing evidence that long-term treatment with a tumor necrosis factor inhibitor and with a NSAID have potential roles in disease modification.” But the evidence is indirect, from cohort studies that make cause and effect assessments difficult because of possible unidentified confounding factors, she noted.
“There has never been a randomized, controlled trial examining the disease-modifying effects of a TNF inhibitor because you can’t keep patients on placebo for a long enough time to see this benefit,” Dr. Gensler said. It takes a long time to see progression in AS patients, she noted.
A prior cohort analysis run by Dr. Gensler and her associates found evidence for an effect of long-term treatment with a TNF inhibitor and reduced AS progression measured using the modified Stoke AS Spine Score (mSASSS), compared with AS patients not on a TNF inhibitor in a propensity-score matched analysis of 334 patients. A link between TNF inhibitor use and a discernible difference in mSASSS only occurred when patients were on TNF inhibitor treatment for at least 3.9 years (Arthritis Rheum. 2013 Oct;65[10]:2645-54). In addition, a separate report at the EULAR congress on 168 AS patients maintained on treatment with secukinumab for 2 years showed evidence for slowed progression of mSASSS scores, compared with historical controls as well as with similar patients who were not on secukinumab treatment for as long a period of time.
The new analysis reported by Dr. Gensler looked at 527 AS patients in the multicenter Prospective Study of Outcomes in AS cohort followed for a median of 3.7 years. Clinicians participating in this cohort saw patients every 6 months, and radiographic assessments by mSASSS and for new bone formation occurred every 2 years. At entry into the registry, about 57% of patients received a TNF inhibitor and about 63% received an NSAID, with a third on an NSAID only, 27% on a TNF inhibitor only, 30% on both drugs, and 10% receiving neither drug.
The analysis showed that among patients followed for 2.1-3.5 years, the fraction of patients on a TNF inhibitor who showed progression of their mSASSS was 77% lower than patients not on a TNF inhibitor, a statistically significant difference, Dr. Gensler reported. The researchers saw no statistically significant difference in mSASSS progression rates between the patients on a TNF inhibitor at baseline and those not on a TNF inhibitor at baseline among patients followed for 2 years and among those followed for more than 3.5 years, although the analysis did show nominally higher levels of response among TNF-inhibitor users followed for more than 3.5 years. Dr. Gensler speculated that one reason for the loss of a statistically significant difference during longer follow-up could be that fewer patients reached these levels of prolonged follow-up, making statistically significant differences harder to see. This analysis also showed a strong trend for less progression among the patients treated with an NSAID, a 51% relative reduction in mSASSS progression, compared with patients not taking an NSAID, but this relationship just missed statistical significance.
A second analysis by Dr. Gensler and her associates used data from the same cohort but focused on new bone formation during follow-up. This analysis again showed a statistically significant, 72% reduction in this outcome among patients taking a TNF inhibitor at baseline, compared with those not on a TNF inhibitor, when followed for 2.1-3.5 years, with no statistically significant relationship seen among patients followed for less or more time, Dr. Gensler reported. However, the results from this analysis also showed a statistically significant impact from NSAID treatment: Patients on a TNF inhibitor and an NSAID at baseline had 67% less new bone formation, compared with those who received a TNF inhibitor but were not on an NSAID at baseline.
Dr. Gensler has been a consultant to or investigator funded by AbbVie, Amgen, Janssen, Novartis, and UCB. The Prospective Study of Outcomes in Ankylosing Spondylitis receives no commercial support.
On Twitter @mitchelzoler
LONDON – Patients with ankylosing spondylitis who remained on long-term treatment with a nonsteroidal anti-inflammatory drug and a tumor necrosis factor inhibitor had significantly less new spinal-bone formation in a cross-sectional analysis of a multicenter cohort of 527 U.S. patients.
A related analysis of the same cohort also showed significantly less ankylosing spondylitis (AS) progression as measured by radiographic progression among patients who received treatment with a tumor necrosis factor–alpha (TNF) inhibitor for 2.1-3.5 years regardless of their treatment with a nonsteroidal anti-inflammatory drug (NSAID), although this link trended to a stronger effect among the patients taking both, Lianne S. Gensler, MD, reported in a pair of posters at the European Congress of Rheumatology.
These finding suggest “there may be synergy between NSAIDs and TNF inhibitors [for slowing or preventing progression] in a select group of AS patients at high risk for progression,” said Dr. Gensler, a rheumatologist and director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco.
But Dr. Gensler also cautioned that these findings are merely “hypothesis generating” and should not be used as a rationale to place or maintain AS patients on long-term treatment with an NSAID, a TNF inhibitor, or both drugs.
“You treat the disease burden. The message is absolutely not to always put AS patients on both types of drugs. When an AS patient is well controlled on a TNF inhibitor alone, I would not tell them to also take a NSAID,” she said in an interview. “This is only relevant for patients who require treatment with both drug classes because of their clinical status.”
As the list of treatment options for patients with AS grows – it now includes NSAIDs, TNF inhibitors, and the interleukin-17 inhibitor secukinumab (Cosentyx) – the impact of these agents on disease progression as assessed by radiography and new bone formation becomes a new dimension to start to consider in addition to the standard criterion of immediate clinical response, Dr. Gensler explained. AS progression “is another factor to think about as we decide on treatment strategies. There is growing evidence that long-term treatment with a tumor necrosis factor inhibitor and with a NSAID have potential roles in disease modification.” But the evidence is indirect, from cohort studies that make cause and effect assessments difficult because of possible unidentified confounding factors, she noted.
“There has never been a randomized, controlled trial examining the disease-modifying effects of a TNF inhibitor because you can’t keep patients on placebo for a long enough time to see this benefit,” Dr. Gensler said. It takes a long time to see progression in AS patients, she noted.
A prior cohort analysis run by Dr. Gensler and her associates found evidence for an effect of long-term treatment with a TNF inhibitor and reduced AS progression measured using the modified Stoke AS Spine Score (mSASSS), compared with AS patients not on a TNF inhibitor in a propensity-score matched analysis of 334 patients. A link between TNF inhibitor use and a discernible difference in mSASSS only occurred when patients were on TNF inhibitor treatment for at least 3.9 years (Arthritis Rheum. 2013 Oct;65[10]:2645-54). In addition, a separate report at the EULAR congress on 168 AS patients maintained on treatment with secukinumab for 2 years showed evidence for slowed progression of mSASSS scores, compared with historical controls as well as with similar patients who were not on secukinumab treatment for as long a period of time.
The new analysis reported by Dr. Gensler looked at 527 AS patients in the multicenter Prospective Study of Outcomes in AS cohort followed for a median of 3.7 years. Clinicians participating in this cohort saw patients every 6 months, and radiographic assessments by mSASSS and for new bone formation occurred every 2 years. At entry into the registry, about 57% of patients received a TNF inhibitor and about 63% received an NSAID, with a third on an NSAID only, 27% on a TNF inhibitor only, 30% on both drugs, and 10% receiving neither drug.
The analysis showed that among patients followed for 2.1-3.5 years, the fraction of patients on a TNF inhibitor who showed progression of their mSASSS was 77% lower than patients not on a TNF inhibitor, a statistically significant difference, Dr. Gensler reported. The researchers saw no statistically significant difference in mSASSS progression rates between the patients on a TNF inhibitor at baseline and those not on a TNF inhibitor at baseline among patients followed for 2 years and among those followed for more than 3.5 years, although the analysis did show nominally higher levels of response among TNF-inhibitor users followed for more than 3.5 years. Dr. Gensler speculated that one reason for the loss of a statistically significant difference during longer follow-up could be that fewer patients reached these levels of prolonged follow-up, making statistically significant differences harder to see. This analysis also showed a strong trend for less progression among the patients treated with an NSAID, a 51% relative reduction in mSASSS progression, compared with patients not taking an NSAID, but this relationship just missed statistical significance.
A second analysis by Dr. Gensler and her associates used data from the same cohort but focused on new bone formation during follow-up. This analysis again showed a statistically significant, 72% reduction in this outcome among patients taking a TNF inhibitor at baseline, compared with those not on a TNF inhibitor, when followed for 2.1-3.5 years, with no statistically significant relationship seen among patients followed for less or more time, Dr. Gensler reported. However, the results from this analysis also showed a statistically significant impact from NSAID treatment: Patients on a TNF inhibitor and an NSAID at baseline had 67% less new bone formation, compared with those who received a TNF inhibitor but were not on an NSAID at baseline.
Dr. Gensler has been a consultant to or investigator funded by AbbVie, Amgen, Janssen, Novartis, and UCB. The Prospective Study of Outcomes in Ankylosing Spondylitis receives no commercial support.
On Twitter @mitchelzoler
AT THE EULAR 2016 CONGRESS
Key clinical point: Ankylosing spondylitis patients treated with a TNF inhibitor plus an NSAID had the lowest level of new bone formation during treatment for more than 2 years.
Major finding: Patients on a TNF inhibitor and an NSAID had 67% less new bone formation, compared with patients not on an NSAID.
Data source: Cross-sectional cohort study of 527 patients with ankylosing spondylitis enrolled in the Prospective Study of Outcomes in Ankylosing Spondylitis.
Disclosures: Dr. Gensler has been a consultant to or investigator funded by AbbVie, Amgen, Janssen, Novartis, and UCB. The Prospective Study of Outcomes in Ankylosing Spondylitis receives no commercial support.
NSAID plus TNFi linked to less ankylosing spondylitis progression
LONDON – Patients with ankylosing spondylitis who remained on long-term treatment with a nonsteroidal anti-inflammatory drug and a tumor necrosis factor inhibitor had significantly less new spinal-bone formation in a cross-sectional analysis of a multicenter cohort of 527 U.S. patients.
A related analysis of the same cohort also showed significantly less ankylosing spondylitis (AS) progression as measured by radiographic progression among patients who received treatment with a tumor necrosis factor–alpha (TNF) inhibitor for 2.1-3.5 years regardless of their treatment with a nonsteroidal anti-inflammatory drug (NSAID), although this link trended to a stronger effect among the patients taking both, Lianne S. Gensler, MD, reported in a pair of posters at the European Congress of Rheumatology.
These finding suggest “there may be synergy between NSAIDs and TNF inhibitors [for slowing or preventing progression] in a select group of AS patients at high risk for progression,” said Dr. Gensler, a rheumatologist and director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco.
But Dr. Gensler also cautioned that these findings are merely “hypothesis generating” and should not be used as a rationale to place or maintain AS patients on long-term treatment with an NSAID, a TNF inhibitor, or both drugs.
“You treat the disease burden. The message is absolutely not to always put AS patients on both types of drugs. When an AS patient is well controlled on a TNF inhibitor alone, I would not tell them to also take a NSAID,” she said in an interview. “This is only relevant for patients who require treatment with both drug classes because of their clinical status.”
As the list of treatment options for patients with AS grows – it now includes NSAIDs, TNF inhibitors, and the interleukin-17 inhibitor secukinumab (Cosentyx) – the impact of these agents on disease progression as assessed by radiography and new bone formation becomes a new dimension to start to consider in addition to the standard criterion of immediate clinical response, Dr. Gensler explained. AS progression “is another factor to think about as we decide on treatment strategies. There is growing evidence that long-term treatment with a tumor necrosis factor inhibitor and with a NSAID have potential roles in disease modification.” But the evidence is indirect, from cohort studies that make cause and effect assessments difficult because of possible unidentified confounding factors, she noted.
“There has never been a randomized, controlled trial examining the disease-modifying effects of a TNF inhibitor because you can’t keep patients on placebo for a long enough time to see this benefit,” Dr. Gensler said. It takes a long time to see progression in AS patients, she noted.
A prior cohort analysis run by Dr. Gensler and her associates found evidence for an effect of long-term treatment with a TNF inhibitor and reduced AS progression measured using the modified Stoke AS Spine Score (mSASSS), compared with AS patients not on a TNF inhibitor in a propensity-score matched analysis of 334 patients. A link between TNF inhibitor use and a discernible difference in mSASSS only occurred when patients were on TNF inhibitor treatment for at least 3.9 years (Arthritis Rheum. 2013 Oct;65[10]:2645-54). In addition, a separate report at the EULAR congress on 168 AS patients maintained on treatment with secukinumab for 2 years showed evidence for slowed progression of mSASSS scores, compared with historical controls as well as with similar patients who were not on secukinumab treatment for as long a period of time.
The new analysis reported by Dr. Gensler looked at 527 AS patients in the multicenter Prospective Study of Outcomes in AS cohort followed for a median of 3.7 years. Clinicians participating in this cohort saw patients every 6 months, and radiographic assessments by mSASSS and for new bone formation occurred every 2 years. At entry into the registry, about 57% of patients received a TNF inhibitor and about 63% received an NSAID, with a third on an NSAID only, 27% on a TNF inhibitor only, 30% on both drugs, and 10% receiving neither drug.
The analysis showed that among patients followed for 2.1-3.5 years, the fraction of patients on a TNF inhibitor who showed progression of their mSASSS was 77% lower than patients not on a TNF inhibitor, a statistically significant difference, Dr. Gensler reported. The researchers saw no statistically significant difference in mSASSS progression rates between the patients on a TNF inhibitor at baseline and those not on a TNF inhibitor at baseline among patients followed for 2 years and among those followed for more than 3.5 years, although the analysis did show nominally higher levels of response among TNF-inhibitor users followed for more than 3.5 years. Dr. Gensler speculated that one reason for the loss of a statistically significant difference during longer follow-up could be that fewer patients reached these levels of prolonged follow-up, making statistically significant differences harder to see. This analysis also showed a strong trend for less progression among the patients treated with an NSAID, a 51% relative reduction in mSASSS progression, compared with patients not taking an NSAID, but this relationship just missed statistical significance.
A second analysis by Dr. Gensler and her associates used data from the same cohort but focused on new bone formation during follow-up. This analysis again showed a statistically significant, 72% reduction in this outcome among patients taking a TNF inhibitor at baseline, compared with those not on a TNF inhibitor, when followed for 2.1-3.5 years, with no statistically significant relationship seen among patients followed for less or more time, Dr. Gensler reported. However, the results from this analysis also showed a statistically significant impact from NSAID treatment: Patients on a TNF inhibitor and an NSAID at baseline had 67% less new bone formation, compared with those who received a TNF inhibitor but were not on an NSAID at baseline.
Dr. Gensler has been a consultant to or investigator funded by AbbVie, Amgen, Janssen, Novartis, and UCB. The Prospective Study of Outcomes in Ankylosing Spondylitis receives no commercial support.
On Twitter @mitchelzoler
LONDON – Patients with ankylosing spondylitis who remained on long-term treatment with a nonsteroidal anti-inflammatory drug and a tumor necrosis factor inhibitor had significantly less new spinal-bone formation in a cross-sectional analysis of a multicenter cohort of 527 U.S. patients.
A related analysis of the same cohort also showed significantly less ankylosing spondylitis (AS) progression as measured by radiographic progression among patients who received treatment with a tumor necrosis factor–alpha (TNF) inhibitor for 2.1-3.5 years regardless of their treatment with a nonsteroidal anti-inflammatory drug (NSAID), although this link trended to a stronger effect among the patients taking both, Lianne S. Gensler, MD, reported in a pair of posters at the European Congress of Rheumatology.
These finding suggest “there may be synergy between NSAIDs and TNF inhibitors [for slowing or preventing progression] in a select group of AS patients at high risk for progression,” said Dr. Gensler, a rheumatologist and director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco.
But Dr. Gensler also cautioned that these findings are merely “hypothesis generating” and should not be used as a rationale to place or maintain AS patients on long-term treatment with an NSAID, a TNF inhibitor, or both drugs.
“You treat the disease burden. The message is absolutely not to always put AS patients on both types of drugs. When an AS patient is well controlled on a TNF inhibitor alone, I would not tell them to also take a NSAID,” she said in an interview. “This is only relevant for patients who require treatment with both drug classes because of their clinical status.”
As the list of treatment options for patients with AS grows – it now includes NSAIDs, TNF inhibitors, and the interleukin-17 inhibitor secukinumab (Cosentyx) – the impact of these agents on disease progression as assessed by radiography and new bone formation becomes a new dimension to start to consider in addition to the standard criterion of immediate clinical response, Dr. Gensler explained. AS progression “is another factor to think about as we decide on treatment strategies. There is growing evidence that long-term treatment with a tumor necrosis factor inhibitor and with a NSAID have potential roles in disease modification.” But the evidence is indirect, from cohort studies that make cause and effect assessments difficult because of possible unidentified confounding factors, she noted.
“There has never been a randomized, controlled trial examining the disease-modifying effects of a TNF inhibitor because you can’t keep patients on placebo for a long enough time to see this benefit,” Dr. Gensler said. It takes a long time to see progression in AS patients, she noted.
A prior cohort analysis run by Dr. Gensler and her associates found evidence for an effect of long-term treatment with a TNF inhibitor and reduced AS progression measured using the modified Stoke AS Spine Score (mSASSS), compared with AS patients not on a TNF inhibitor in a propensity-score matched analysis of 334 patients. A link between TNF inhibitor use and a discernible difference in mSASSS only occurred when patients were on TNF inhibitor treatment for at least 3.9 years (Arthritis Rheum. 2013 Oct;65[10]:2645-54). In addition, a separate report at the EULAR congress on 168 AS patients maintained on treatment with secukinumab for 2 years showed evidence for slowed progression of mSASSS scores, compared with historical controls as well as with similar patients who were not on secukinumab treatment for as long a period of time.
The new analysis reported by Dr. Gensler looked at 527 AS patients in the multicenter Prospective Study of Outcomes in AS cohort followed for a median of 3.7 years. Clinicians participating in this cohort saw patients every 6 months, and radiographic assessments by mSASSS and for new bone formation occurred every 2 years. At entry into the registry, about 57% of patients received a TNF inhibitor and about 63% received an NSAID, with a third on an NSAID only, 27% on a TNF inhibitor only, 30% on both drugs, and 10% receiving neither drug.
The analysis showed that among patients followed for 2.1-3.5 years, the fraction of patients on a TNF inhibitor who showed progression of their mSASSS was 77% lower than patients not on a TNF inhibitor, a statistically significant difference, Dr. Gensler reported. The researchers saw no statistically significant difference in mSASSS progression rates between the patients on a TNF inhibitor at baseline and those not on a TNF inhibitor at baseline among patients followed for 2 years and among those followed for more than 3.5 years, although the analysis did show nominally higher levels of response among TNF-inhibitor users followed for more than 3.5 years. Dr. Gensler speculated that one reason for the loss of a statistically significant difference during longer follow-up could be that fewer patients reached these levels of prolonged follow-up, making statistically significant differences harder to see. This analysis also showed a strong trend for less progression among the patients treated with an NSAID, a 51% relative reduction in mSASSS progression, compared with patients not taking an NSAID, but this relationship just missed statistical significance.
A second analysis by Dr. Gensler and her associates used data from the same cohort but focused on new bone formation during follow-up. This analysis again showed a statistically significant, 72% reduction in this outcome among patients taking a TNF inhibitor at baseline, compared with those not on a TNF inhibitor, when followed for 2.1-3.5 years, with no statistically significant relationship seen among patients followed for less or more time, Dr. Gensler reported. However, the results from this analysis also showed a statistically significant impact from NSAID treatment: Patients on a TNF inhibitor and an NSAID at baseline had 67% less new bone formation, compared with those who received a TNF inhibitor but were not on an NSAID at baseline.
Dr. Gensler has been a consultant to or investigator funded by AbbVie, Amgen, Janssen, Novartis, and UCB. The Prospective Study of Outcomes in Ankylosing Spondylitis receives no commercial support.
On Twitter @mitchelzoler
LONDON – Patients with ankylosing spondylitis who remained on long-term treatment with a nonsteroidal anti-inflammatory drug and a tumor necrosis factor inhibitor had significantly less new spinal-bone formation in a cross-sectional analysis of a multicenter cohort of 527 U.S. patients.
A related analysis of the same cohort also showed significantly less ankylosing spondylitis (AS) progression as measured by radiographic progression among patients who received treatment with a tumor necrosis factor–alpha (TNF) inhibitor for 2.1-3.5 years regardless of their treatment with a nonsteroidal anti-inflammatory drug (NSAID), although this link trended to a stronger effect among the patients taking both, Lianne S. Gensler, MD, reported in a pair of posters at the European Congress of Rheumatology.
These finding suggest “there may be synergy between NSAIDs and TNF inhibitors [for slowing or preventing progression] in a select group of AS patients at high risk for progression,” said Dr. Gensler, a rheumatologist and director of the Ankylosing Spondylitis Clinic at the University of California, San Francisco.
But Dr. Gensler also cautioned that these findings are merely “hypothesis generating” and should not be used as a rationale to place or maintain AS patients on long-term treatment with an NSAID, a TNF inhibitor, or both drugs.
“You treat the disease burden. The message is absolutely not to always put AS patients on both types of drugs. When an AS patient is well controlled on a TNF inhibitor alone, I would not tell them to also take a NSAID,” she said in an interview. “This is only relevant for patients who require treatment with both drug classes because of their clinical status.”
As the list of treatment options for patients with AS grows – it now includes NSAIDs, TNF inhibitors, and the interleukin-17 inhibitor secukinumab (Cosentyx) – the impact of these agents on disease progression as assessed by radiography and new bone formation becomes a new dimension to start to consider in addition to the standard criterion of immediate clinical response, Dr. Gensler explained. AS progression “is another factor to think about as we decide on treatment strategies. There is growing evidence that long-term treatment with a tumor necrosis factor inhibitor and with a NSAID have potential roles in disease modification.” But the evidence is indirect, from cohort studies that make cause and effect assessments difficult because of possible unidentified confounding factors, she noted.
“There has never been a randomized, controlled trial examining the disease-modifying effects of a TNF inhibitor because you can’t keep patients on placebo for a long enough time to see this benefit,” Dr. Gensler said. It takes a long time to see progression in AS patients, she noted.
A prior cohort analysis run by Dr. Gensler and her associates found evidence for an effect of long-term treatment with a TNF inhibitor and reduced AS progression measured using the modified Stoke AS Spine Score (mSASSS), compared with AS patients not on a TNF inhibitor in a propensity-score matched analysis of 334 patients. A link between TNF inhibitor use and a discernible difference in mSASSS only occurred when patients were on TNF inhibitor treatment for at least 3.9 years (Arthritis Rheum. 2013 Oct;65[10]:2645-54). In addition, a separate report at the EULAR congress on 168 AS patients maintained on treatment with secukinumab for 2 years showed evidence for slowed progression of mSASSS scores, compared with historical controls as well as with similar patients who were not on secukinumab treatment for as long a period of time.
The new analysis reported by Dr. Gensler looked at 527 AS patients in the multicenter Prospective Study of Outcomes in AS cohort followed for a median of 3.7 years. Clinicians participating in this cohort saw patients every 6 months, and radiographic assessments by mSASSS and for new bone formation occurred every 2 years. At entry into the registry, about 57% of patients received a TNF inhibitor and about 63% received an NSAID, with a third on an NSAID only, 27% on a TNF inhibitor only, 30% on both drugs, and 10% receiving neither drug.
The analysis showed that among patients followed for 2.1-3.5 years, the fraction of patients on a TNF inhibitor who showed progression of their mSASSS was 77% lower than patients not on a TNF inhibitor, a statistically significant difference, Dr. Gensler reported. The researchers saw no statistically significant difference in mSASSS progression rates between the patients on a TNF inhibitor at baseline and those not on a TNF inhibitor at baseline among patients followed for 2 years and among those followed for more than 3.5 years, although the analysis did show nominally higher levels of response among TNF-inhibitor users followed for more than 3.5 years. Dr. Gensler speculated that one reason for the loss of a statistically significant difference during longer follow-up could be that fewer patients reached these levels of prolonged follow-up, making statistically significant differences harder to see. This analysis also showed a strong trend for less progression among the patients treated with an NSAID, a 51% relative reduction in mSASSS progression, compared with patients not taking an NSAID, but this relationship just missed statistical significance.
A second analysis by Dr. Gensler and her associates used data from the same cohort but focused on new bone formation during follow-up. This analysis again showed a statistically significant, 72% reduction in this outcome among patients taking a TNF inhibitor at baseline, compared with those not on a TNF inhibitor, when followed for 2.1-3.5 years, with no statistically significant relationship seen among patients followed for less or more time, Dr. Gensler reported. However, the results from this analysis also showed a statistically significant impact from NSAID treatment: Patients on a TNF inhibitor and an NSAID at baseline had 67% less new bone formation, compared with those who received a TNF inhibitor but were not on an NSAID at baseline.
Dr. Gensler has been a consultant to or investigator funded by AbbVie, Amgen, Janssen, Novartis, and UCB. The Prospective Study of Outcomes in Ankylosing Spondylitis receives no commercial support.
On Twitter @mitchelzoler
AT THE EULAR 2016 CONGRESS
Key clinical point: Ankylosing spondylitis patients treated with a TNF inhibitor plus an NSAID had the lowest level of new bone formation during treatment for more than 2 years.
Major finding: Patients on a TNF inhibitor and an NSAID had 67% less new bone formation, compared with patients not on an NSAID.
Data source: Cross-sectional cohort study of 527 patients with ankylosing spondylitis enrolled in the Prospective Study of Outcomes in Ankylosing Spondylitis.
Disclosures: Dr. Gensler has been a consultant to or investigator funded by AbbVie, Amgen, Janssen, Novartis, and UCB. The Prospective Study of Outcomes in Ankylosing Spondylitis receives no commercial support.
