SPARTAN (SPondyloArthritis Research & Treatment Network): Annual Meeting

NEW YORK – A consensus group has developed evidence-based treatment recommendations for patients with psoriatic arthritis and nail involvement and raised the possibility of issuing them independent of recommendations for the skin, according to a report on the deliberations.

"The suggestion has been made to separate out skin from nail because the assessment is quite different to the point where you can potentially have patients with severe nail disease but limited skin disease," reported Dr. April W. Armstrong, director of the psoriasis program at the University of Colorado, Denver.

The proposal was made in the course of presenting the preliminary evidence-based recommendations on managing psoriatic arthritis (PsA) nail involvement to the full membership of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. GRAPPA is in the process of preparing a new set of PsA treatment recommendations.

The decision to address nails separately from skin was not a unanimous recommendation within the committee, and no conclusion was reached, but Dr. Armstrong brought the issue forward "to be clear about our ambiguity" regarding this specific aspect of how to best outline treatment options useful to clinicians.

Other recommendations, based on evidence, are more assured of making the final version, because they are evidence based. When presented at GRAPPA, which convened its most recent annual meeting jointly with the Spondyloarthritis Research & Treatment Network, each recommendation was graded for the quality of the evidence and strength of the consensus.

For example, the committee found little controlled evidence to support a significant benefit from topical therapies, including those commonly used, such as steroids and vitamin D analogs. Although the consensus committee concluded that the risk of adverse events is low and the costs are low to moderate, the efficacy is only modest. The strength for recommending topical therapies overall was characterized as "weak."

For procedural therapies, such as pulsed-dye laser or intralesional injections, no placebo-controlled trials could be identified by the committee, and the expert opinion of its members was that the efficacy is relatively low in general even if benefit is achieved in some individuals. The cost was characterized as low to moderate. The committee concluded that only a "weak" recommendation should be conferred to these types of interventions for nail involvement.

The proposed recommendation for oral therapies, such a methotrexate, cyclosporine, leflunomide, and acitretin, was considered "stronger than that for topical therapies" when nail involvement is moderate, but the committee also found supportive evidence of benefit to be of "low quality." Again, although recognizing that some PsA patients may benefit, the recommendation for oral therapies overall for nail involvement was characterized as weak.

For biologics, including both tumor necrosis factor (TNF) inhibitors and the interleukin 12/23 inhibitor ustekinumab, the consensus committee reported that there are good quality data showing efficacy in nails, including some studies showing superiority of TNF inhibitors to methotrexate and cyclosporine. For patients with moderate to severe nail involvement warranting the potential risks of these therapies, the preliminary recommendation for these agents was "strong" even if the costs of these therapies were characterized as "high to crazy."

One unresolved issue, however, is which strategy to recommend for placing nail involvement into "mild," "moderate," or "severe" categories. Objective scores, such as Nail Psoriasis Severity Index (NAPSI), were considered by the consensus committee to be helpful but insufficient.

"Perhaps in addition to objective scoring of nail disease, we should also take into account [the impact] on quality of life as well as function," Dr. Armstrong said.

The final GRAPPA treatment recommendations for nail involvement, as well as other aspects of PsA management, will be made after a discussion of the consensus group proposals over the next several months, followed by voting among the GRAPPA membership. As GRAPPA is an international organization, it is intended that final recommendations will be broadly applicable.

Dr. Armstrong reported financial relationships with AbbVie, Amgen, Janssen Biotech, Merck, Novartis, and Pfizer.

NEW YORK – A consensus group has developed evidence-based treatment recommendations for patients with psoriatic arthritis and nail involvement and raised the possibility of issuing them independent of recommendations for the skin, according to a report on the deliberations.

"The suggestion has been made to separate out skin from nail because the assessment is quite different to the point where you can potentially have patients with severe nail disease but limited skin disease," reported Dr. April W. Armstrong, director of the psoriasis program at the University of Colorado, Denver.

The proposal was made in the course of presenting the preliminary evidence-based recommendations on managing psoriatic arthritis (PsA) nail involvement to the full membership of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. GRAPPA is in the process of preparing a new set of PsA treatment recommendations.

The decision to address nails separately from skin was not a unanimous recommendation within the committee, and no conclusion was reached, but Dr. Armstrong brought the issue forward "to be clear about our ambiguity" regarding this specific aspect of how to best outline treatment options useful to clinicians.

Other recommendations, based on evidence, are more assured of making the final version, because they are evidence based. When presented at GRAPPA, which convened its most recent annual meeting jointly with the Spondyloarthritis Research & Treatment Network, each recommendation was graded for the quality of the evidence and strength of the consensus.

For example, the committee found little controlled evidence to support a significant benefit from topical therapies, including those commonly used, such as steroids and vitamin D analogs. Although the consensus committee concluded that the risk of adverse events is low and the costs are low to moderate, the efficacy is only modest. The strength for recommending topical therapies overall was characterized as "weak."

For procedural therapies, such as pulsed-dye laser or intralesional injections, no placebo-controlled trials could be identified by the committee, and the expert opinion of its members was that the efficacy is relatively low in general even if benefit is achieved in some individuals. The cost was characterized as low to moderate. The committee concluded that only a "weak" recommendation should be conferred to these types of interventions for nail involvement.

The proposed recommendation for oral therapies, such a methotrexate, cyclosporine, leflunomide, and acitretin, was considered "stronger than that for topical therapies" when nail involvement is moderate, but the committee also found supportive evidence of benefit to be of "low quality." Again, although recognizing that some PsA patients may benefit, the recommendation for oral therapies overall for nail involvement was characterized as weak.

For biologics, including both tumor necrosis factor (TNF) inhibitors and the interleukin 12/23 inhibitor ustekinumab, the consensus committee reported that there are good quality data showing efficacy in nails, including some studies showing superiority of TNF inhibitors to methotrexate and cyclosporine. For patients with moderate to severe nail involvement warranting the potential risks of these therapies, the preliminary recommendation for these agents was "strong" even if the costs of these therapies were characterized as "high to crazy."

One unresolved issue, however, is which strategy to recommend for placing nail involvement into "mild," "moderate," or "severe" categories. Objective scores, such as Nail Psoriasis Severity Index (NAPSI), were considered by the consensus committee to be helpful but insufficient.

"Perhaps in addition to objective scoring of nail disease, we should also take into account [the impact] on quality of life as well as function," Dr. Armstrong said.

The final GRAPPA treatment recommendations for nail involvement, as well as other aspects of PsA management, will be made after a discussion of the consensus group proposals over the next several months, followed by voting among the GRAPPA membership. As GRAPPA is an international organization, it is intended that final recommendations will be broadly applicable.

Dr. Armstrong reported financial relationships with AbbVie, Amgen, Janssen Biotech, Merck, Novartis, and Pfizer.

NEW YORK – A consensus group has developed evidence-based treatment recommendations for patients with psoriatic arthritis and nail involvement and raised the possibility of issuing them independent of recommendations for the skin, according to a report on the deliberations.

"The suggestion has been made to separate out skin from nail because the assessment is quite different to the point where you can potentially have patients with severe nail disease but limited skin disease," reported Dr. April W. Armstrong, director of the psoriasis program at the University of Colorado, Denver.

The proposal was made in the course of presenting the preliminary evidence-based recommendations on managing psoriatic arthritis (PsA) nail involvement to the full membership of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. GRAPPA is in the process of preparing a new set of PsA treatment recommendations.

The decision to address nails separately from skin was not a unanimous recommendation within the committee, and no conclusion was reached, but Dr. Armstrong brought the issue forward "to be clear about our ambiguity" regarding this specific aspect of how to best outline treatment options useful to clinicians.

Other recommendations, based on evidence, are more assured of making the final version, because they are evidence based. When presented at GRAPPA, which convened its most recent annual meeting jointly with the Spondyloarthritis Research & Treatment Network, each recommendation was graded for the quality of the evidence and strength of the consensus.

For example, the committee found little controlled evidence to support a significant benefit from topical therapies, including those commonly used, such as steroids and vitamin D analogs. Although the consensus committee concluded that the risk of adverse events is low and the costs are low to moderate, the efficacy is only modest. The strength for recommending topical therapies overall was characterized as "weak."

For procedural therapies, such as pulsed-dye laser or intralesional injections, no placebo-controlled trials could be identified by the committee, and the expert opinion of its members was that the efficacy is relatively low in general even if benefit is achieved in some individuals. The cost was characterized as low to moderate. The committee concluded that only a "weak" recommendation should be conferred to these types of interventions for nail involvement.

The proposed recommendation for oral therapies, such a methotrexate, cyclosporine, leflunomide, and acitretin, was considered "stronger than that for topical therapies" when nail involvement is moderate, but the committee also found supportive evidence of benefit to be of "low quality." Again, although recognizing that some PsA patients may benefit, the recommendation for oral therapies overall for nail involvement was characterized as weak.

For biologics, including both tumor necrosis factor (TNF) inhibitors and the interleukin 12/23 inhibitor ustekinumab, the consensus committee reported that there are good quality data showing efficacy in nails, including some studies showing superiority of TNF inhibitors to methotrexate and cyclosporine. For patients with moderate to severe nail involvement warranting the potential risks of these therapies, the preliminary recommendation for these agents was "strong" even if the costs of these therapies were characterized as "high to crazy."

One unresolved issue, however, is which strategy to recommend for placing nail involvement into "mild," "moderate," or "severe" categories. Objective scores, such as Nail Psoriasis Severity Index (NAPSI), were considered by the consensus committee to be helpful but insufficient.

"Perhaps in addition to objective scoring of nail disease, we should also take into account [the impact] on quality of life as well as function," Dr. Armstrong said.

The final GRAPPA treatment recommendations for nail involvement, as well as other aspects of PsA management, will be made after a discussion of the consensus group proposals over the next several months, followed by voting among the GRAPPA membership. As GRAPPA is an international organization, it is intended that final recommendations will be broadly applicable.

Dr. Armstrong reported financial relationships with AbbVie, Amgen, Janssen Biotech, Merck, Novartis, and Pfizer.

NEW YORK – A research consortium in psoriatic arthritis has been recently organized by a group of researchers at academic centers hoping to accelerate data collection by pooling resources.

Formed about 1 year ago, the research group, called PPACMAN (Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network) is currently open to those centers in which dermatologists and rheumatologists are already collaborating in the management of psoriatic arthritis (PsA).

"One of the advantages of this group is that we hope to pursue research goals with minimal costs and need for funding," explained Dr. Jose U. Scher, director of the arthritis clinic and codirector of the psoriatic arthritis center at NYU Langone Medical Center, New York. In addition to NYU, the collaborating centers include the Cleveland Clinic; the National Institutes of Health; the University of Pennsylvania, Philadelphia; the University of Utah, Salt Lake City; the University of Toronto, Harvard University’s Brigham and Women’s Hospital, Boston; North Shore-Long Island Jewish Health System, Manhasset, N.Y.; Oregon Health & Science University, Portland; the University of Rochester, N.Y.; and the National Psoriasis Foundation, Portland.

In outlining progress so far at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network, Dr. Scher reported on three initiatives underway.

Of these, the most ambitious may be a multicenter longitudinal cohort being created by collating electronic medical records of PsA patients from the participating centers. As it grows over time, this database has the potential to serve as a rich resource of information on PsA characteristics, treatment approaches, and outcomes.

"This is an example of how we can leverage data in PsA through collaboration with resources already devoted to clinical care," Dr. Scher reported. By collating the data from electronic medical records in compatible formats, the cohort data to some degree will collect themselves.

In addition, PPACMAN centers are participating in an effort to evaluate tools used by dermatologists to screen for PsA. According to Dr. Scher, this initiative is the first step in an effort to work toward identifying the screening approaches that are most effective.

"It is still unclear which tools are being used and their relative value for early detection of PsA in a practical sense," said Dr. Scher, referring to such screening instruments as the Psoriasis Arthritis Screening Evaluation. The goal is to document how instruments are being used currently and then to define strategies that best accelerate the time to diagnosis.

A third project being developed by the PPACMAN collaborative group involves the study of biomarkers. Biomarkers have enormous potential for predicting the course of PsA and guiding therapy, but the complex interaction of genetic, environmental, and immunologic factors complicates the effort to isolate their independent predictive value. In attempting to control for variables, studies conducted with a relatively large number of patients have a practical advantage.

"The principle of PPACMAN, integrated by highly driven and talented researchers, is that we can achieve more by working together," Dr. Scher explained. Indeed, he said that other centers with an interest in PsA are welcome to join as long as they have a program in which dermatologists and rheumatologists collaborate.

"This is a relatively new initiative, but we are excited about its potential," Dr. Scher said.

Dr. Scher reported no relevant financial relationships.

NEW YORK – A research consortium in psoriatic arthritis has been recently organized by a group of researchers at academic centers hoping to accelerate data collection by pooling resources.

Formed about 1 year ago, the research group, called PPACMAN (Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network) is currently open to those centers in which dermatologists and rheumatologists are already collaborating in the management of psoriatic arthritis (PsA).

"One of the advantages of this group is that we hope to pursue research goals with minimal costs and need for funding," explained Dr. Jose U. Scher, director of the arthritis clinic and codirector of the psoriatic arthritis center at NYU Langone Medical Center, New York. In addition to NYU, the collaborating centers include the Cleveland Clinic; the National Institutes of Health; the University of Pennsylvania, Philadelphia; the University of Utah, Salt Lake City; the University of Toronto, Harvard University’s Brigham and Women’s Hospital, Boston; North Shore-Long Island Jewish Health System, Manhasset, N.Y.; Oregon Health & Science University, Portland; the University of Rochester, N.Y.; and the National Psoriasis Foundation, Portland.

In outlining progress so far at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network, Dr. Scher reported on three initiatives underway.

Of these, the most ambitious may be a multicenter longitudinal cohort being created by collating electronic medical records of PsA patients from the participating centers. As it grows over time, this database has the potential to serve as a rich resource of information on PsA characteristics, treatment approaches, and outcomes.

"This is an example of how we can leverage data in PsA through collaboration with resources already devoted to clinical care," Dr. Scher reported. By collating the data from electronic medical records in compatible formats, the cohort data to some degree will collect themselves.

In addition, PPACMAN centers are participating in an effort to evaluate tools used by dermatologists to screen for PsA. According to Dr. Scher, this initiative is the first step in an effort to work toward identifying the screening approaches that are most effective.

"It is still unclear which tools are being used and their relative value for early detection of PsA in a practical sense," said Dr. Scher, referring to such screening instruments as the Psoriasis Arthritis Screening Evaluation. The goal is to document how instruments are being used currently and then to define strategies that best accelerate the time to diagnosis.

A third project being developed by the PPACMAN collaborative group involves the study of biomarkers. Biomarkers have enormous potential for predicting the course of PsA and guiding therapy, but the complex interaction of genetic, environmental, and immunologic factors complicates the effort to isolate their independent predictive value. In attempting to control for variables, studies conducted with a relatively large number of patients have a practical advantage.

"The principle of PPACMAN, integrated by highly driven and talented researchers, is that we can achieve more by working together," Dr. Scher explained. Indeed, he said that other centers with an interest in PsA are welcome to join as long as they have a program in which dermatologists and rheumatologists collaborate.

"This is a relatively new initiative, but we are excited about its potential," Dr. Scher said.

Dr. Scher reported no relevant financial relationships.

NEW YORK – A research consortium in psoriatic arthritis has been recently organized by a group of researchers at academic centers hoping to accelerate data collection by pooling resources.

Formed about 1 year ago, the research group, called PPACMAN (Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network) is currently open to those centers in which dermatologists and rheumatologists are already collaborating in the management of psoriatic arthritis (PsA).

"One of the advantages of this group is that we hope to pursue research goals with minimal costs and need for funding," explained Dr. Jose U. Scher, director of the arthritis clinic and codirector of the psoriatic arthritis center at NYU Langone Medical Center, New York. In addition to NYU, the collaborating centers include the Cleveland Clinic; the National Institutes of Health; the University of Pennsylvania, Philadelphia; the University of Utah, Salt Lake City; the University of Toronto, Harvard University’s Brigham and Women’s Hospital, Boston; North Shore-Long Island Jewish Health System, Manhasset, N.Y.; Oregon Health & Science University, Portland; the University of Rochester, N.Y.; and the National Psoriasis Foundation, Portland.

In outlining progress so far at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network, Dr. Scher reported on three initiatives underway.

Of these, the most ambitious may be a multicenter longitudinal cohort being created by collating electronic medical records of PsA patients from the participating centers. As it grows over time, this database has the potential to serve as a rich resource of information on PsA characteristics, treatment approaches, and outcomes.

"This is an example of how we can leverage data in PsA through collaboration with resources already devoted to clinical care," Dr. Scher reported. By collating the data from electronic medical records in compatible formats, the cohort data to some degree will collect themselves.

In addition, PPACMAN centers are participating in an effort to evaluate tools used by dermatologists to screen for PsA. According to Dr. Scher, this initiative is the first step in an effort to work toward identifying the screening approaches that are most effective.

"It is still unclear which tools are being used and their relative value for early detection of PsA in a practical sense," said Dr. Scher, referring to such screening instruments as the Psoriasis Arthritis Screening Evaluation. The goal is to document how instruments are being used currently and then to define strategies that best accelerate the time to diagnosis.

A third project being developed by the PPACMAN collaborative group involves the study of biomarkers. Biomarkers have enormous potential for predicting the course of PsA and guiding therapy, but the complex interaction of genetic, environmental, and immunologic factors complicates the effort to isolate their independent predictive value. In attempting to control for variables, studies conducted with a relatively large number of patients have a practical advantage.

"The principle of PPACMAN, integrated by highly driven and talented researchers, is that we can achieve more by working together," Dr. Scher explained. Indeed, he said that other centers with an interest in PsA are welcome to join as long as they have a program in which dermatologists and rheumatologists collaborate.

"This is a relatively new initiative, but we are excited about its potential," Dr. Scher said.

Dr. Scher reported no relevant financial relationships.

NEW YORK – Axial spondyloarthritis is not being seen by U.S. rheumatologists at a rate commensurate with prevalence, according to an expert providing the rationale for a major educational initiative.

In the United States, several studies, including the most recent, suggest that the prevalence of axSpA is at least as great as that of rheumatoid arthritis even though most rheumatologists see a much lower proportion of axSpA patients, according to Dr. Atul Deodhar, medical director of the rheumatology clinics at Oregon Health & Science University, Portland.

The reasons for this disparity are not fully understood, but it has prompted a major educational initiative by the Spondyloarthritis Research & Treatment Network (SPARTAN), according to Dr. Deodhar, who spoke at the joint meetings of SPARTAN and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. The goal of the initiative is to reduce the delay to diagnosis and to funnel these patients more efficiently to experts in inflammatory joint diseases.

The most recent U.S. prevalence estimate for axSpA is 0.7%, reported Dr. Deodhar, citing a study that employed Assessment of Spondyloarthritis International Society (ASAS) criteria (Arthritis Care Res. 2013;65:1299-306). Other studies have generated prevalence rates as high as 1.4%, but even this lower recent estimate exceeds the typically cited 0.6% estimated prevalence rate for RA, he said.

"One wonders where these patients are going," said Dr. Deodhar, emphasizing the relative infrequency with which axSpA is managed by U.S. rheumatologists.

Some of these patients are likely to be seen by orthopedists, chiropractors, internists, or other health care providers, but one concern is that many are not being seen at all or at least not until the disease has advanced. Dr. Deodhar cited evidence that the average delay to diagnosis of axSpA in the United States is 6-8 years, which is likely to worsen outcome.

"Several studies suggest that partial remission is about double when patients are caught early and treated appropriately," Dr. Deodhar said. However, although rheumatologists are in the best position to help axSpA patients, they might be part of the problem, he said.

"Rheumatologists have traditionally shied away from seeing patients with back pain, because 95% of these patients have mechanical pain for which rheumatologists do not have much to offer," Dr. Deodhar said.

Yet for those with an inflammatory etiology, rheumatologists can play an essential role in treatment that slows or halts progression. A SPARTAN initiative has been specifically planned to educate those health care providers likely to hear initial complaints of lower back pain as well as to increase attention to axSpA by rheumatologists.

For referral physicians, the initiatives are being focused on increasing awareness of inflammatory back pain and providing simple criteria for referral, according to Dr. Deodhar. The ASAS diagnostic criteria for axSpA are considered sensitive and specific, but simplified referral strategies may accelerate the time to a specialist consultation.

Several referral strategies are effective. Dr. Deodhar cited one study that tested two. In one strategy, a referral was made in patients younger than 45, with chronic back pain of at least 3 months, who met two of three screening criteria: inflammatory back pain, HLA-B27 positivity, or sacroiliitis on imaging. In the other, the same criteria were employed and patients had to have a positive family history of ankylosing spondylitis or a good treatment response to NSAIDs (J. Rheumatol. 2011;38:2452-60).

With the first strategy, "nearly 42% [41.8%] had definite axSpA," according to Dr. Deodhar. The slightly lower sensitivity of the other was not inferior statistically, but the first strategy was preferred for simplicity.

These types of referral strategies will be included in the SPARTAN educational initiatives being developed to improve early recognition of axSpA and to bring patients to the specialists most suited to offering effective management.

Dr. Deodhar reported financial relationships with Amgen, Abbott, Genentech, and Janssen.

NEW YORK – Axial spondyloarthritis is not being seen by U.S. rheumatologists at a rate commensurate with prevalence, according to an expert providing the rationale for a major educational initiative.

In the United States, several studies, including the most recent, suggest that the prevalence of axSpA is at least as great as that of rheumatoid arthritis even though most rheumatologists see a much lower proportion of axSpA patients, according to Dr. Atul Deodhar, medical director of the rheumatology clinics at Oregon Health & Science University, Portland.

The reasons for this disparity are not fully understood, but it has prompted a major educational initiative by the Spondyloarthritis Research & Treatment Network (SPARTAN), according to Dr. Deodhar, who spoke at the joint meetings of SPARTAN and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. The goal of the initiative is to reduce the delay to diagnosis and to funnel these patients more efficiently to experts in inflammatory joint diseases.

The most recent U.S. prevalence estimate for axSpA is 0.7%, reported Dr. Deodhar, citing a study that employed Assessment of Spondyloarthritis International Society (ASAS) criteria (Arthritis Care Res. 2013;65:1299-306). Other studies have generated prevalence rates as high as 1.4%, but even this lower recent estimate exceeds the typically cited 0.6% estimated prevalence rate for RA, he said.

"One wonders where these patients are going," said Dr. Deodhar, emphasizing the relative infrequency with which axSpA is managed by U.S. rheumatologists.

Some of these patients are likely to be seen by orthopedists, chiropractors, internists, or other health care providers, but one concern is that many are not being seen at all or at least not until the disease has advanced. Dr. Deodhar cited evidence that the average delay to diagnosis of axSpA in the United States is 6-8 years, which is likely to worsen outcome.

"Several studies suggest that partial remission is about double when patients are caught early and treated appropriately," Dr. Deodhar said. However, although rheumatologists are in the best position to help axSpA patients, they might be part of the problem, he said.

"Rheumatologists have traditionally shied away from seeing patients with back pain, because 95% of these patients have mechanical pain for which rheumatologists do not have much to offer," Dr. Deodhar said.

Yet for those with an inflammatory etiology, rheumatologists can play an essential role in treatment that slows or halts progression. A SPARTAN initiative has been specifically planned to educate those health care providers likely to hear initial complaints of lower back pain as well as to increase attention to axSpA by rheumatologists.

For referral physicians, the initiatives are being focused on increasing awareness of inflammatory back pain and providing simple criteria for referral, according to Dr. Deodhar. The ASAS diagnostic criteria for axSpA are considered sensitive and specific, but simplified referral strategies may accelerate the time to a specialist consultation.

Several referral strategies are effective. Dr. Deodhar cited one study that tested two. In one strategy, a referral was made in patients younger than 45, with chronic back pain of at least 3 months, who met two of three screening criteria: inflammatory back pain, HLA-B27 positivity, or sacroiliitis on imaging. In the other, the same criteria were employed and patients had to have a positive family history of ankylosing spondylitis or a good treatment response to NSAIDs (J. Rheumatol. 2011;38:2452-60).

With the first strategy, "nearly 42% [41.8%] had definite axSpA," according to Dr. Deodhar. The slightly lower sensitivity of the other was not inferior statistically, but the first strategy was preferred for simplicity.

These types of referral strategies will be included in the SPARTAN educational initiatives being developed to improve early recognition of axSpA and to bring patients to the specialists most suited to offering effective management.

Dr. Deodhar reported financial relationships with Amgen, Abbott, Genentech, and Janssen.

NEW YORK – Axial spondyloarthritis is not being seen by U.S. rheumatologists at a rate commensurate with prevalence, according to an expert providing the rationale for a major educational initiative.

In the United States, several studies, including the most recent, suggest that the prevalence of axSpA is at least as great as that of rheumatoid arthritis even though most rheumatologists see a much lower proportion of axSpA patients, according to Dr. Atul Deodhar, medical director of the rheumatology clinics at Oregon Health & Science University, Portland.

The reasons for this disparity are not fully understood, but it has prompted a major educational initiative by the Spondyloarthritis Research & Treatment Network (SPARTAN), according to Dr. Deodhar, who spoke at the joint meetings of SPARTAN and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. The goal of the initiative is to reduce the delay to diagnosis and to funnel these patients more efficiently to experts in inflammatory joint diseases.

The most recent U.S. prevalence estimate for axSpA is 0.7%, reported Dr. Deodhar, citing a study that employed Assessment of Spondyloarthritis International Society (ASAS) criteria (Arthritis Care Res. 2013;65:1299-306). Other studies have generated prevalence rates as high as 1.4%, but even this lower recent estimate exceeds the typically cited 0.6% estimated prevalence rate for RA, he said.

"One wonders where these patients are going," said Dr. Deodhar, emphasizing the relative infrequency with which axSpA is managed by U.S. rheumatologists.

Some of these patients are likely to be seen by orthopedists, chiropractors, internists, or other health care providers, but one concern is that many are not being seen at all or at least not until the disease has advanced. Dr. Deodhar cited evidence that the average delay to diagnosis of axSpA in the United States is 6-8 years, which is likely to worsen outcome.

"Several studies suggest that partial remission is about double when patients are caught early and treated appropriately," Dr. Deodhar said. However, although rheumatologists are in the best position to help axSpA patients, they might be part of the problem, he said.

"Rheumatologists have traditionally shied away from seeing patients with back pain, because 95% of these patients have mechanical pain for which rheumatologists do not have much to offer," Dr. Deodhar said.

Yet for those with an inflammatory etiology, rheumatologists can play an essential role in treatment that slows or halts progression. A SPARTAN initiative has been specifically planned to educate those health care providers likely to hear initial complaints of lower back pain as well as to increase attention to axSpA by rheumatologists.

For referral physicians, the initiatives are being focused on increasing awareness of inflammatory back pain and providing simple criteria for referral, according to Dr. Deodhar. The ASAS diagnostic criteria for axSpA are considered sensitive and specific, but simplified referral strategies may accelerate the time to a specialist consultation.

Several referral strategies are effective. Dr. Deodhar cited one study that tested two. In one strategy, a referral was made in patients younger than 45, with chronic back pain of at least 3 months, who met two of three screening criteria: inflammatory back pain, HLA-B27 positivity, or sacroiliitis on imaging. In the other, the same criteria were employed and patients had to have a positive family history of ankylosing spondylitis or a good treatment response to NSAIDs (J. Rheumatol. 2011;38:2452-60).

With the first strategy, "nearly 42% [41.8%] had definite axSpA," according to Dr. Deodhar. The slightly lower sensitivity of the other was not inferior statistically, but the first strategy was preferred for simplicity.

These types of referral strategies will be included in the SPARTAN educational initiatives being developed to improve early recognition of axSpA and to bring patients to the specialists most suited to offering effective management.

Dr. Deodhar reported financial relationships with Amgen, Abbott, Genentech, and Janssen.

NEW YORK – Patients with ankylosing spondylitis who used opiate analgesics were five times more likely to report depression than were those who did not, in a retrospective case-control study of 611 patients.

The relationship between opiate usage and depression was significant even though those who took antidepressants or anxiolytics were significantly less likely to use opiates, according to Dr. Jonathan D. Dau of the department of rheumatology at the University of Texas, Houston.

In the study, there were several highly significant distinctions between those who used opiate analgesics and those who did not, but none could be connected to inflammatory activity, Dr. Dau said.

"None of the objective measures of AS [ankylosing spondylitis] disease activity or progression were found to be associated with opiate usage. This adds confirmation to the hypothesis that pain associated with AS may develop from sources other than spinal inflammation alone," he said.

In data presented at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network, a large variety of parameters were compared between the 87 patients who took opiate analgesics intermittently (91%) or continuously (9%) and the remaining 524 who never took opiate analgesics over a follow-up period of up to 4 years. Three centers in addition to the University of Texas contributed AS patients to the analysis. The mean disease duration was 17.6 years.

Although there were no significant differences between users and nonusers of opiates for radiographic severity, as measured with the modified Stoke Ankylosing Spondylitis Spinal Score, or inflammation, as measured with C-reactive protein levels or erythrocyte sedimentation rate, opiate users scored high on subjective measures. Specifically, the odds ratio for a Bath AS Disease Activity Index score of 4 or greater was 5.460 (P less than .0001). The OR for a high patient global pain assessment was 4.240 (P less than .0001).

As for depression, the OR for opiate users relative to nonopiate users was 5.907 (P less than .0001) by self-report and 3.071 (P less than .0001) by the Center for Epidemiologic Study Depression scale. The authors also reported an OR for smoking among opiate users of 2.125 (P = .0018).

Conversely, an analysis of concomitant medication use found that antidepressants correlated with a 63% reduction (OR, 0.371; P = .0004) in the likelihood of opiate use. Anxiolytics correlated with a nearly 90% reduction (OR, 0.124; P less than .0001). There was no significant association with opiate use and use of either NSAIDs or tumor necrosis factor inhibitors.

However, the study found that opiate users were almost three times more likely to be taking prednisone (OR, 2.996; P = .0073) and more than eight times more likely to be taking muscle relaxants (OR, 8.458; P less than .0001). Dr. Dau observed that muscle relaxants on top of opiates "may provide a greater magnitude of pain relief taken together than when taken alone."

Because of the concerns about use of opiates, particularly their propensity to induce dependence, Dr. Dau suggested that it is important to further explore why some patients take these agents in addition to treatments targeted at disease activity. While standard medications such as NSAIDs and TNF inhibitors have been shown to relieve pain, they do not control somatic pain for all patients.

"This is especially true when the pain stems from processes other than inflammation," reported Dr. Dau. More data are needed to determine whether control of depression through antidepressants is a factor for reducing opiate use, he said.

Dr. Dau reported no relevant financial disclosures.

NEW YORK – Patients with ankylosing spondylitis who used opiate analgesics were five times more likely to report depression than were those who did not, in a retrospective case-control study of 611 patients.

The relationship between opiate usage and depression was significant even though those who took antidepressants or anxiolytics were significantly less likely to use opiates, according to Dr. Jonathan D. Dau of the department of rheumatology at the University of Texas, Houston.

In the study, there were several highly significant distinctions between those who used opiate analgesics and those who did not, but none could be connected to inflammatory activity, Dr. Dau said.

"None of the objective measures of AS [ankylosing spondylitis] disease activity or progression were found to be associated with opiate usage. This adds confirmation to the hypothesis that pain associated with AS may develop from sources other than spinal inflammation alone," he said.

In data presented at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network, a large variety of parameters were compared between the 87 patients who took opiate analgesics intermittently (91%) or continuously (9%) and the remaining 524 who never took opiate analgesics over a follow-up period of up to 4 years. Three centers in addition to the University of Texas contributed AS patients to the analysis. The mean disease duration was 17.6 years.

Although there were no significant differences between users and nonusers of opiates for radiographic severity, as measured with the modified Stoke Ankylosing Spondylitis Spinal Score, or inflammation, as measured with C-reactive protein levels or erythrocyte sedimentation rate, opiate users scored high on subjective measures. Specifically, the odds ratio for a Bath AS Disease Activity Index score of 4 or greater was 5.460 (P less than .0001). The OR for a high patient global pain assessment was 4.240 (P less than .0001).

As for depression, the OR for opiate users relative to nonopiate users was 5.907 (P less than .0001) by self-report and 3.071 (P less than .0001) by the Center for Epidemiologic Study Depression scale. The authors also reported an OR for smoking among opiate users of 2.125 (P = .0018).

Conversely, an analysis of concomitant medication use found that antidepressants correlated with a 63% reduction (OR, 0.371; P = .0004) in the likelihood of opiate use. Anxiolytics correlated with a nearly 90% reduction (OR, 0.124; P less than .0001). There was no significant association with opiate use and use of either NSAIDs or tumor necrosis factor inhibitors.

However, the study found that opiate users were almost three times more likely to be taking prednisone (OR, 2.996; P = .0073) and more than eight times more likely to be taking muscle relaxants (OR, 8.458; P less than .0001). Dr. Dau observed that muscle relaxants on top of opiates "may provide a greater magnitude of pain relief taken together than when taken alone."

Because of the concerns about use of opiates, particularly their propensity to induce dependence, Dr. Dau suggested that it is important to further explore why some patients take these agents in addition to treatments targeted at disease activity. While standard medications such as NSAIDs and TNF inhibitors have been shown to relieve pain, they do not control somatic pain for all patients.

"This is especially true when the pain stems from processes other than inflammation," reported Dr. Dau. More data are needed to determine whether control of depression through antidepressants is a factor for reducing opiate use, he said.

Dr. Dau reported no relevant financial disclosures.

NEW YORK – Patients with ankylosing spondylitis who used opiate analgesics were five times more likely to report depression than were those who did not, in a retrospective case-control study of 611 patients.

The relationship between opiate usage and depression was significant even though those who took antidepressants or anxiolytics were significantly less likely to use opiates, according to Dr. Jonathan D. Dau of the department of rheumatology at the University of Texas, Houston.

In the study, there were several highly significant distinctions between those who used opiate analgesics and those who did not, but none could be connected to inflammatory activity, Dr. Dau said.

"None of the objective measures of AS [ankylosing spondylitis] disease activity or progression were found to be associated with opiate usage. This adds confirmation to the hypothesis that pain associated with AS may develop from sources other than spinal inflammation alone," he said.

In data presented at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network, a large variety of parameters were compared between the 87 patients who took opiate analgesics intermittently (91%) or continuously (9%) and the remaining 524 who never took opiate analgesics over a follow-up period of up to 4 years. Three centers in addition to the University of Texas contributed AS patients to the analysis. The mean disease duration was 17.6 years.

Although there were no significant differences between users and nonusers of opiates for radiographic severity, as measured with the modified Stoke Ankylosing Spondylitis Spinal Score, or inflammation, as measured with C-reactive protein levels or erythrocyte sedimentation rate, opiate users scored high on subjective measures. Specifically, the odds ratio for a Bath AS Disease Activity Index score of 4 or greater was 5.460 (P less than .0001). The OR for a high patient global pain assessment was 4.240 (P less than .0001).

As for depression, the OR for opiate users relative to nonopiate users was 5.907 (P less than .0001) by self-report and 3.071 (P less than .0001) by the Center for Epidemiologic Study Depression scale. The authors also reported an OR for smoking among opiate users of 2.125 (P = .0018).

Conversely, an analysis of concomitant medication use found that antidepressants correlated with a 63% reduction (OR, 0.371; P = .0004) in the likelihood of opiate use. Anxiolytics correlated with a nearly 90% reduction (OR, 0.124; P less than .0001). There was no significant association with opiate use and use of either NSAIDs or tumor necrosis factor inhibitors.

However, the study found that opiate users were almost three times more likely to be taking prednisone (OR, 2.996; P = .0073) and more than eight times more likely to be taking muscle relaxants (OR, 8.458; P less than .0001). Dr. Dau observed that muscle relaxants on top of opiates "may provide a greater magnitude of pain relief taken together than when taken alone."

Because of the concerns about use of opiates, particularly their propensity to induce dependence, Dr. Dau suggested that it is important to further explore why some patients take these agents in addition to treatments targeted at disease activity. While standard medications such as NSAIDs and TNF inhibitors have been shown to relieve pain, they do not control somatic pain for all patients.

"This is especially true when the pain stems from processes other than inflammation," reported Dr. Dau. More data are needed to determine whether control of depression through antidepressants is a factor for reducing opiate use, he said.

Dr. Dau reported no relevant financial disclosures.

NEW YORK – Consistent evidence for a substantial increase in cardiovascular events remains elusive for patients with ankylosing spondylitis who have a broad range of CV risk factors.

"We can all agree that the risk factors for cardiovascular disease are higher in patients with AS [ankylosing spondylitis], but I think it is more controversial whether every AS patient faces a higher risk of events," observed Dr. Lianne Gensler, director of the ankylosing spondylitis clinic at the University of California, San Francisco.

Although this statement was made in reference to ischemic heart disease, the analysis presented by Dr. Gensler at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network appears to be relevant to valvular disease, arrhythmias, and left ventricular dysfunction. Other CV risk factors associated with AS include hypertension, aortic insufficiency, and conduction disorders.

Inconsistencies in studies of CV

The obstacle for drawing conclusions is the lack of consistency in the published studies that relate specifically to AS but are independent of other inflammatory joint diseases, such as rheumatoid arthritis. In a review, Dr. Gensler cited one meta-analysis of 17 studies published in 2011 that did not associate AS with increased CV events (Arthritis Care Res. 2011;63:557-63). Although several studies published subsequently did associate AS with an increased rate of events, there were others that did not.

In an analysis that was performed at her institution based on AS patient data from the Healthcare Cost and Utilization Project National Inpatient Sample, no difference could be found in in-hospital mortality due to CV events when AS patients were compared with non-AS patients stratified by age.

In regard to CV structural disease related to AS, there is substantial evidence that several abnormalities are more common in AS, but there is far less to document that these lead to an increased risk of events. For example, Dr. Gensler cited one study in which the prevalence of aortic insufficiency climbed from 2% in patients with 10 years’ AS duration to 12% in those with 30 years. In another, inflammation of the septum, a potential risk for conduction disorders, climbed from 3% to 90% in AS patients followed long-term.

Asymptomatic conduction disorders

Conduction disorders in general – and QRS disturbances in particular – have been commonly reported in AS patients, but typically in the absence of symptoms, according to Dr. Gensler. She cited one electrocardiogram study in which 30% of AS patients had QRS prolongation, but all were asymptomatic. In another study of 200 AS patients, conduction disorders were found in 33%, of which atrioventricular block was the most common. In this study, increased markers of inflammation did not correlate with conduction disorders in a multivariate analysis.

"Whether we should be doing anything to look for these [conduction disorders] when they do not have symptoms is a question that I will put out to the audience," Dr. Gensler said.

Effect of treatment on CV events

The effect of AS therapies, particularly tumor necrosis factor (TNF) inhibitors, on CV risk also remains incompletely understood. In one study cited by Dr. Gensler, improved endothelial function was observed in AS patients treated with a TNF inhibitor, suggesting a potential protective effect, but, again, no difference in event rates in AS patients has ever been documented between those on TNF inhibitors and those not on TNF inhibitors.

Overall, more data are needed to determine the effect of AS on the risk of CV events, but one risk factor deserves attention even if there is no specific evidence that it affects CV events, according to Dr. Gensler.

In AS, "we know that smoking is a risk for early-onset disease, more inflammation, more damage, and more progression, so I think this [smoking cessation] is one guideline we can take to heart and take home to our patients," she said.

Dr. Gensler reported financial relationships with UCB and AbbVie.

NEW YORK – Consistent evidence for a substantial increase in cardiovascular events remains elusive for patients with ankylosing spondylitis who have a broad range of CV risk factors.

"We can all agree that the risk factors for cardiovascular disease are higher in patients with AS [ankylosing spondylitis], but I think it is more controversial whether every AS patient faces a higher risk of events," observed Dr. Lianne Gensler, director of the ankylosing spondylitis clinic at the University of California, San Francisco.

Although this statement was made in reference to ischemic heart disease, the analysis presented by Dr. Gensler at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network appears to be relevant to valvular disease, arrhythmias, and left ventricular dysfunction. Other CV risk factors associated with AS include hypertension, aortic insufficiency, and conduction disorders.

Inconsistencies in studies of CV

The obstacle for drawing conclusions is the lack of consistency in the published studies that relate specifically to AS but are independent of other inflammatory joint diseases, such as rheumatoid arthritis. In a review, Dr. Gensler cited one meta-analysis of 17 studies published in 2011 that did not associate AS with increased CV events (Arthritis Care Res. 2011;63:557-63). Although several studies published subsequently did associate AS with an increased rate of events, there were others that did not.

In an analysis that was performed at her institution based on AS patient data from the Healthcare Cost and Utilization Project National Inpatient Sample, no difference could be found in in-hospital mortality due to CV events when AS patients were compared with non-AS patients stratified by age.

In regard to CV structural disease related to AS, there is substantial evidence that several abnormalities are more common in AS, but there is far less to document that these lead to an increased risk of events. For example, Dr. Gensler cited one study in which the prevalence of aortic insufficiency climbed from 2% in patients with 10 years’ AS duration to 12% in those with 30 years. In another, inflammation of the septum, a potential risk for conduction disorders, climbed from 3% to 90% in AS patients followed long-term.

Asymptomatic conduction disorders

Conduction disorders in general – and QRS disturbances in particular – have been commonly reported in AS patients, but typically in the absence of symptoms, according to Dr. Gensler. She cited one electrocardiogram study in which 30% of AS patients had QRS prolongation, but all were asymptomatic. In another study of 200 AS patients, conduction disorders were found in 33%, of which atrioventricular block was the most common. In this study, increased markers of inflammation did not correlate with conduction disorders in a multivariate analysis.

"Whether we should be doing anything to look for these [conduction disorders] when they do not have symptoms is a question that I will put out to the audience," Dr. Gensler said.

Effect of treatment on CV events

The effect of AS therapies, particularly tumor necrosis factor (TNF) inhibitors, on CV risk also remains incompletely understood. In one study cited by Dr. Gensler, improved endothelial function was observed in AS patients treated with a TNF inhibitor, suggesting a potential protective effect, but, again, no difference in event rates in AS patients has ever been documented between those on TNF inhibitors and those not on TNF inhibitors.

Overall, more data are needed to determine the effect of AS on the risk of CV events, but one risk factor deserves attention even if there is no specific evidence that it affects CV events, according to Dr. Gensler.

In AS, "we know that smoking is a risk for early-onset disease, more inflammation, more damage, and more progression, so I think this [smoking cessation] is one guideline we can take to heart and take home to our patients," she said.

Dr. Gensler reported financial relationships with UCB and AbbVie.

NEW YORK – Consistent evidence for a substantial increase in cardiovascular events remains elusive for patients with ankylosing spondylitis who have a broad range of CV risk factors.

"We can all agree that the risk factors for cardiovascular disease are higher in patients with AS [ankylosing spondylitis], but I think it is more controversial whether every AS patient faces a higher risk of events," observed Dr. Lianne Gensler, director of the ankylosing spondylitis clinic at the University of California, San Francisco.

Although this statement was made in reference to ischemic heart disease, the analysis presented by Dr. Gensler at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network appears to be relevant to valvular disease, arrhythmias, and left ventricular dysfunction. Other CV risk factors associated with AS include hypertension, aortic insufficiency, and conduction disorders.

Inconsistencies in studies of CV

The obstacle for drawing conclusions is the lack of consistency in the published studies that relate specifically to AS but are independent of other inflammatory joint diseases, such as rheumatoid arthritis. In a review, Dr. Gensler cited one meta-analysis of 17 studies published in 2011 that did not associate AS with increased CV events (Arthritis Care Res. 2011;63:557-63). Although several studies published subsequently did associate AS with an increased rate of events, there were others that did not.

In an analysis that was performed at her institution based on AS patient data from the Healthcare Cost and Utilization Project National Inpatient Sample, no difference could be found in in-hospital mortality due to CV events when AS patients were compared with non-AS patients stratified by age.

In regard to CV structural disease related to AS, there is substantial evidence that several abnormalities are more common in AS, but there is far less to document that these lead to an increased risk of events. For example, Dr. Gensler cited one study in which the prevalence of aortic insufficiency climbed from 2% in patients with 10 years’ AS duration to 12% in those with 30 years. In another, inflammation of the septum, a potential risk for conduction disorders, climbed from 3% to 90% in AS patients followed long-term.

Asymptomatic conduction disorders

Conduction disorders in general – and QRS disturbances in particular – have been commonly reported in AS patients, but typically in the absence of symptoms, according to Dr. Gensler. She cited one electrocardiogram study in which 30% of AS patients had QRS prolongation, but all were asymptomatic. In another study of 200 AS patients, conduction disorders were found in 33%, of which atrioventricular block was the most common. In this study, increased markers of inflammation did not correlate with conduction disorders in a multivariate analysis.

"Whether we should be doing anything to look for these [conduction disorders] when they do not have symptoms is a question that I will put out to the audience," Dr. Gensler said.

Effect of treatment on CV events

The effect of AS therapies, particularly tumor necrosis factor (TNF) inhibitors, on CV risk also remains incompletely understood. In one study cited by Dr. Gensler, improved endothelial function was observed in AS patients treated with a TNF inhibitor, suggesting a potential protective effect, but, again, no difference in event rates in AS patients has ever been documented between those on TNF inhibitors and those not on TNF inhibitors.

Overall, more data are needed to determine the effect of AS on the risk of CV events, but one risk factor deserves attention even if there is no specific evidence that it affects CV events, according to Dr. Gensler.

In AS, "we know that smoking is a risk for early-onset disease, more inflammation, more damage, and more progression, so I think this [smoking cessation] is one guideline we can take to heart and take home to our patients," she said.

Dr. Gensler reported financial relationships with UCB and AbbVie.

NEW YORK – Late initiation of tumor necrosis factor inhibitors in patients with ankylosing spondylitis more than doubles their risk of radiographic worsening, according to a prospective study that provides insight into the natural history of this disease.

"We are probably looking at a window of opportunity. If we capture patients with more acute lesions, we may be able to inhibit the processes that drive progression that cannot be reversed once the lesions are more mature," reported Dr. Nigil Haroon of the division of rheumatology at the University of Toronto.

The data presented by Dr. Haroon were characterized as the first to show a clear association between reduced ankylosing spondylitis (AS) damage and tumor necrosis factor (TNF) overall and early initiation of TNF inhibitors specifically. According to Dr. Haroon, earlier studies have not shown this association because of inadequate follow-up.

"AS is slowly progressive. Two years is not enough to see an effect," said Dr. Haroon, who noted that most TNF inhibitor trials have not exceeded this period. He believes at least 4 years of follow-up are needed.

Long follow-up is particularly relevant for showing benefit from anti-inflammatory therapy if, as described by Dr. Haroon, sustained inflammation is required to induce vertebral fat infiltration and if, in turn, this infiltration promotes formation of syndesmophytes. However, from the clinical perspective, there is now at least some evidence that early is better than late initiation of TNF inhibitors in AS patients at risk for progressive disease.

The clinical evidence is drawn from a five-center study with 334 patients published late last year and updated by Dr. Haroon at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (Arthritis Rheum. 2013;65:2645-54). However, Dr. Haroon primarily focused on the significance of these data as they relate to the natural history of AS.

In the study, the goal was to evaluate the impact of TNF inhibitors on spinal damage in AS. Overall, TNF inhibitors, vs. no TNF inhibitors, were associated with a 48% reduction in the odds of radiographic progression (P = .02), but the timing of TNF inhibitors was an independent predictor of benefit. In those who initiated TNF inhibitors 10 or more years after disease onset, the odds of progression was increased 2.4-fold (P = .03) relative to an earlier start. Duration of TNF inhibitor therapy was also inversely correlated with progression.

These findings are highly consistent with an independent series of studies conducted by Dr. Haroon and others who have linked sustained inflammation with vertebral fat infiltration. Visible on MRI, fat infiltration at the vertebral corners has been linked to metaplasia and the de novo syndesmophyte formation that characterizes radiographic progression.

"We are not 100% sure that inflammation and new bone formation are linked, but the evidence is accumulating," Dr. Haroon reported. The theory supported by the clinical study is that early control of inflammation aborts the pathologic process that leads first to vertebral fat infiltration and then to syndesmophyte formation.

Not all AS patients may benefit equally from TNF inhibitors from the perspective of disease progression. In the five-center study data presented by Dr. Haroon, only 30.5% of the patients experienced progression, defined by having at least a one unit per year increase in the mSASSS (modified Stokes AS Spine Score). Elevated baseline inflammatory markers, such as C-reactive protein, and smoking, for which there was a dose effect, were associated with progression after researchers controlled for baseline mSASSS totals. Other factors, particularly genetics, have also been strongly linked to risk of progression in AS.

Dr. Haroon reported no relevant financial relationships.

NEW YORK – Late initiation of tumor necrosis factor inhibitors in patients with ankylosing spondylitis more than doubles their risk of radiographic worsening, according to a prospective study that provides insight into the natural history of this disease.

"We are probably looking at a window of opportunity. If we capture patients with more acute lesions, we may be able to inhibit the processes that drive progression that cannot be reversed once the lesions are more mature," reported Dr. Nigil Haroon of the division of rheumatology at the University of Toronto.

The data presented by Dr. Haroon were characterized as the first to show a clear association between reduced ankylosing spondylitis (AS) damage and tumor necrosis factor (TNF) overall and early initiation of TNF inhibitors specifically. According to Dr. Haroon, earlier studies have not shown this association because of inadequate follow-up.

"AS is slowly progressive. Two years is not enough to see an effect," said Dr. Haroon, who noted that most TNF inhibitor trials have not exceeded this period. He believes at least 4 years of follow-up are needed.

Long follow-up is particularly relevant for showing benefit from anti-inflammatory therapy if, as described by Dr. Haroon, sustained inflammation is required to induce vertebral fat infiltration and if, in turn, this infiltration promotes formation of syndesmophytes. However, from the clinical perspective, there is now at least some evidence that early is better than late initiation of TNF inhibitors in AS patients at risk for progressive disease.

The clinical evidence is drawn from a five-center study with 334 patients published late last year and updated by Dr. Haroon at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (Arthritis Rheum. 2013;65:2645-54). However, Dr. Haroon primarily focused on the significance of these data as they relate to the natural history of AS.

In the study, the goal was to evaluate the impact of TNF inhibitors on spinal damage in AS. Overall, TNF inhibitors, vs. no TNF inhibitors, were associated with a 48% reduction in the odds of radiographic progression (P = .02), but the timing of TNF inhibitors was an independent predictor of benefit. In those who initiated TNF inhibitors 10 or more years after disease onset, the odds of progression was increased 2.4-fold (P = .03) relative to an earlier start. Duration of TNF inhibitor therapy was also inversely correlated with progression.

These findings are highly consistent with an independent series of studies conducted by Dr. Haroon and others who have linked sustained inflammation with vertebral fat infiltration. Visible on MRI, fat infiltration at the vertebral corners has been linked to metaplasia and the de novo syndesmophyte formation that characterizes radiographic progression.

"We are not 100% sure that inflammation and new bone formation are linked, but the evidence is accumulating," Dr. Haroon reported. The theory supported by the clinical study is that early control of inflammation aborts the pathologic process that leads first to vertebral fat infiltration and then to syndesmophyte formation.

Not all AS patients may benefit equally from TNF inhibitors from the perspective of disease progression. In the five-center study data presented by Dr. Haroon, only 30.5% of the patients experienced progression, defined by having at least a one unit per year increase in the mSASSS (modified Stokes AS Spine Score). Elevated baseline inflammatory markers, such as C-reactive protein, and smoking, for which there was a dose effect, were associated with progression after researchers controlled for baseline mSASSS totals. Other factors, particularly genetics, have also been strongly linked to risk of progression in AS.

Dr. Haroon reported no relevant financial relationships.

NEW YORK – Late initiation of tumor necrosis factor inhibitors in patients with ankylosing spondylitis more than doubles their risk of radiographic worsening, according to a prospective study that provides insight into the natural history of this disease.

"We are probably looking at a window of opportunity. If we capture patients with more acute lesions, we may be able to inhibit the processes that drive progression that cannot be reversed once the lesions are more mature," reported Dr. Nigil Haroon of the division of rheumatology at the University of Toronto.

The data presented by Dr. Haroon were characterized as the first to show a clear association between reduced ankylosing spondylitis (AS) damage and tumor necrosis factor (TNF) overall and early initiation of TNF inhibitors specifically. According to Dr. Haroon, earlier studies have not shown this association because of inadequate follow-up.

"AS is slowly progressive. Two years is not enough to see an effect," said Dr. Haroon, who noted that most TNF inhibitor trials have not exceeded this period. He believes at least 4 years of follow-up are needed.

Long follow-up is particularly relevant for showing benefit from anti-inflammatory therapy if, as described by Dr. Haroon, sustained inflammation is required to induce vertebral fat infiltration and if, in turn, this infiltration promotes formation of syndesmophytes. However, from the clinical perspective, there is now at least some evidence that early is better than late initiation of TNF inhibitors in AS patients at risk for progressive disease.

The clinical evidence is drawn from a five-center study with 334 patients published late last year and updated by Dr. Haroon at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (Arthritis Rheum. 2013;65:2645-54). However, Dr. Haroon primarily focused on the significance of these data as they relate to the natural history of AS.

In the study, the goal was to evaluate the impact of TNF inhibitors on spinal damage in AS. Overall, TNF inhibitors, vs. no TNF inhibitors, were associated with a 48% reduction in the odds of radiographic progression (P = .02), but the timing of TNF inhibitors was an independent predictor of benefit. In those who initiated TNF inhibitors 10 or more years after disease onset, the odds of progression was increased 2.4-fold (P = .03) relative to an earlier start. Duration of TNF inhibitor therapy was also inversely correlated with progression.

These findings are highly consistent with an independent series of studies conducted by Dr. Haroon and others who have linked sustained inflammation with vertebral fat infiltration. Visible on MRI, fat infiltration at the vertebral corners has been linked to metaplasia and the de novo syndesmophyte formation that characterizes radiographic progression.

"We are not 100% sure that inflammation and new bone formation are linked, but the evidence is accumulating," Dr. Haroon reported. The theory supported by the clinical study is that early control of inflammation aborts the pathologic process that leads first to vertebral fat infiltration and then to syndesmophyte formation.

Not all AS patients may benefit equally from TNF inhibitors from the perspective of disease progression. In the five-center study data presented by Dr. Haroon, only 30.5% of the patients experienced progression, defined by having at least a one unit per year increase in the mSASSS (modified Stokes AS Spine Score). Elevated baseline inflammatory markers, such as C-reactive protein, and smoking, for which there was a dose effect, were associated with progression after researchers controlled for baseline mSASSS totals. Other factors, particularly genetics, have also been strongly linked to risk of progression in AS.

Dr. Haroon reported no relevant financial relationships.

NEW YORK – After instruction by a nurse, patients with psoriatic arthritis do at least as well as nurses but better than physicians in counting tender and swollen joints, according to a cross-sectional study that employed ultrasound as a gold standard.

"Patient counts of swollen joints correlated with both effusion and synovitis as detected by ultrasound, suggesting that patients can learn to monitor their own disease," reported Dr. Agnes Szentpetery of the department of rheumatology at St. Vincent’s Hospital, Dublin.

In this study, described as the first ever conducted in psoriatic arthritis to compare joint counts by patients, nurses, physicians, and ultrasound (US), 50 patients with a mean age of 50 years were enrolled. All received instruction from a nurse on how to assess and count tender and swollen joints. The major focus of the correlations was in 34 joints assessed with US, although further correlations were made between patients, nurses, and physicians for 28 (JC28) and 66 swollen and 68 tender (JC 66/68) counts.

"Joint counts [confirming active disease] were higher for patients and nurses than for physicians," reported Dr. Szentpetery, who presented these data at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (SPARTAN). Doctor and nurse counts for swollen joints, unlike patient counts, did not correlate with US evidence of effusion, although they did for synovitis.

For tender joints, there was moderate or good agreement between patient and doctor for 11 joints, doctor and nurse for 12 joints, and patient and nurse for 19 joints. (This nurse was different from the one who provided instruction on joint counts.) However, correlation between any of these observers and US evidence of tender joints was uniformly poor.

Small joints in the hand, particularly the proximal interphalangeal joint, offered the best interobserver agreement for correlations, according to Dr. Szentpetery. Although no correlations rose above good and most were moderate between any two observers, Dr. Szentpetery stressed that patients performed at levels comparable with doctors and nurses, compared with US.

"Although this was a small study, the results support patient joint counts, and we have already begun routinely instructing patients in our clinic," Dr. Szentpetery reported.

Asked for a comment, Dr. John D. Reveille, professor of rheumatology and clinical immunogenetics at the University of Texas Health Sciences Center at Houston, said that he is remaining cautious until a larger study generates more data. He said that similar efforts to instruct patients to perform joint counts in rheumatoid arthritis failed to produce acceptable rates of accuracy.

"It may be possible to enlist patients to perform accurate joint counts if they are motivated and receive appropriate education, but you may need a special population and the right education," said Dr. Reveille, who is chair of SPARTAN’s executive committee.

However, joint counts are perceived to be so time consuming that many clinics do not perform them at all, according to Dr. Szentpetery. Moreover, she suggested that the absolute number of tender or swollen joints at any moment in time may be less important than the change in joint involvement after treatment is initiated, an outcome that may be best measured by patients.

"I agree that this is a small study, and more data are needed, but our data suggest patients may have a role in joint counts, which is an attractive strategy for reducing work for the clinicians," Dr. Szentpetery said.

Dr. Szentpetery and Dr. Reveille reported no relevant financial conflicts.

NEW YORK – After instruction by a nurse, patients with psoriatic arthritis do at least as well as nurses but better than physicians in counting tender and swollen joints, according to a cross-sectional study that employed ultrasound as a gold standard.

"Patient counts of swollen joints correlated with both effusion and synovitis as detected by ultrasound, suggesting that patients can learn to monitor their own disease," reported Dr. Agnes Szentpetery of the department of rheumatology at St. Vincent’s Hospital, Dublin.

In this study, described as the first ever conducted in psoriatic arthritis to compare joint counts by patients, nurses, physicians, and ultrasound (US), 50 patients with a mean age of 50 years were enrolled. All received instruction from a nurse on how to assess and count tender and swollen joints. The major focus of the correlations was in 34 joints assessed with US, although further correlations were made between patients, nurses, and physicians for 28 (JC28) and 66 swollen and 68 tender (JC 66/68) counts.

"Joint counts [confirming active disease] were higher for patients and nurses than for physicians," reported Dr. Szentpetery, who presented these data at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (SPARTAN). Doctor and nurse counts for swollen joints, unlike patient counts, did not correlate with US evidence of effusion, although they did for synovitis.

For tender joints, there was moderate or good agreement between patient and doctor for 11 joints, doctor and nurse for 12 joints, and patient and nurse for 19 joints. (This nurse was different from the one who provided instruction on joint counts.) However, correlation between any of these observers and US evidence of tender joints was uniformly poor.

Small joints in the hand, particularly the proximal interphalangeal joint, offered the best interobserver agreement for correlations, according to Dr. Szentpetery. Although no correlations rose above good and most were moderate between any two observers, Dr. Szentpetery stressed that patients performed at levels comparable with doctors and nurses, compared with US.

"Although this was a small study, the results support patient joint counts, and we have already begun routinely instructing patients in our clinic," Dr. Szentpetery reported.

Asked for a comment, Dr. John D. Reveille, professor of rheumatology and clinical immunogenetics at the University of Texas Health Sciences Center at Houston, said that he is remaining cautious until a larger study generates more data. He said that similar efforts to instruct patients to perform joint counts in rheumatoid arthritis failed to produce acceptable rates of accuracy.

"It may be possible to enlist patients to perform accurate joint counts if they are motivated and receive appropriate education, but you may need a special population and the right education," said Dr. Reveille, who is chair of SPARTAN’s executive committee.

However, joint counts are perceived to be so time consuming that many clinics do not perform them at all, according to Dr. Szentpetery. Moreover, she suggested that the absolute number of tender or swollen joints at any moment in time may be less important than the change in joint involvement after treatment is initiated, an outcome that may be best measured by patients.

"I agree that this is a small study, and more data are needed, but our data suggest patients may have a role in joint counts, which is an attractive strategy for reducing work for the clinicians," Dr. Szentpetery said.

Dr. Szentpetery and Dr. Reveille reported no relevant financial conflicts.

NEW YORK – After instruction by a nurse, patients with psoriatic arthritis do at least as well as nurses but better than physicians in counting tender and swollen joints, according to a cross-sectional study that employed ultrasound as a gold standard.

"Patient counts of swollen joints correlated with both effusion and synovitis as detected by ultrasound, suggesting that patients can learn to monitor their own disease," reported Dr. Agnes Szentpetery of the department of rheumatology at St. Vincent’s Hospital, Dublin.

In this study, described as the first ever conducted in psoriatic arthritis to compare joint counts by patients, nurses, physicians, and ultrasound (US), 50 patients with a mean age of 50 years were enrolled. All received instruction from a nurse on how to assess and count tender and swollen joints. The major focus of the correlations was in 34 joints assessed with US, although further correlations were made between patients, nurses, and physicians for 28 (JC28) and 66 swollen and 68 tender (JC 66/68) counts.

"Joint counts [confirming active disease] were higher for patients and nurses than for physicians," reported Dr. Szentpetery, who presented these data at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (SPARTAN). Doctor and nurse counts for swollen joints, unlike patient counts, did not correlate with US evidence of effusion, although they did for synovitis.

For tender joints, there was moderate or good agreement between patient and doctor for 11 joints, doctor and nurse for 12 joints, and patient and nurse for 19 joints. (This nurse was different from the one who provided instruction on joint counts.) However, correlation between any of these observers and US evidence of tender joints was uniformly poor.

Small joints in the hand, particularly the proximal interphalangeal joint, offered the best interobserver agreement for correlations, according to Dr. Szentpetery. Although no correlations rose above good and most were moderate between any two observers, Dr. Szentpetery stressed that patients performed at levels comparable with doctors and nurses, compared with US.

"Although this was a small study, the results support patient joint counts, and we have already begun routinely instructing patients in our clinic," Dr. Szentpetery reported.

Asked for a comment, Dr. John D. Reveille, professor of rheumatology and clinical immunogenetics at the University of Texas Health Sciences Center at Houston, said that he is remaining cautious until a larger study generates more data. He said that similar efforts to instruct patients to perform joint counts in rheumatoid arthritis failed to produce acceptable rates of accuracy.

"It may be possible to enlist patients to perform accurate joint counts if they are motivated and receive appropriate education, but you may need a special population and the right education," said Dr. Reveille, who is chair of SPARTAN’s executive committee.

However, joint counts are perceived to be so time consuming that many clinics do not perform them at all, according to Dr. Szentpetery. Moreover, she suggested that the absolute number of tender or swollen joints at any moment in time may be less important than the change in joint involvement after treatment is initiated, an outcome that may be best measured by patients.

"I agree that this is a small study, and more data are needed, but our data suggest patients may have a role in joint counts, which is an attractive strategy for reducing work for the clinicians," Dr. Szentpetery said.

Dr. Szentpetery and Dr. Reveille reported no relevant financial conflicts.

NEW YORK – There appears to be progress in the effort to convince the Food and Drug Administration that nonradiologic axial spondyloarthritis is a viable disease entity that deserves to be the target of therapeutic trials, according to an account of recent deliberations.

"We are happy that the FDA [now] agrees with the axSpA [axial spondyloarthritis] concept, the burden of disease, and the need to treat such patients," reported Dr. Atul Deodhar, professor of medicine and medical director of the rheumatology clinics at Oregon Health and Science University, Portland.

However, this is a process. The FDA "remains very concerned about the specificity of the ASAS [Assessment of Spondyloarthritis International Society] classification criteria," Dr. Deodhar said at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (SPARTAN).

Treatment trials for nonradiologic axSpA (nr-axSpA) followed the development of diagnostic criteria by ASAS in 2009 (Ann. Rheum. Dis. 2009;68:777-83). On the basis of randomized controlled trials in nr-axSpA patients with adalimumab (ABILITY-1) and both nr-axSpA and axSpA patients with certolizumab pegol (AS001), both drugs were approved by the European Medicines Agency for the treatment nr-axSpA. The same evidence, reviewed by an FDA advisory committee in July 2013, produced rejections the following October.

The major problem, according to Dr. Deodhar’s account, was that the FDA found the ASAS diagnostic criteria "overly broad," creating a potential for some low-risk patients to be prescribed therapies in which a favorable benefit-to-risk ratio could not be ensured. But the decision also denied these biologics to patients who could benefit.

"Rheumatologists were put in a difficult position, inducing some to label these patients as having ankylosing spondylitis to obtain third-party approval for therapies they needed," Dr. Deodhar observed. Concerned that patients with significant disability were being denied effective therapies, leaders of both SPARTAN and ASAS are attempting to work with the FDA to define more acceptable criteria.

In a joint letter from SPARTAN and ASAS to the FDA in early 2014 requesting a meeting, the key issues outlined for discussion included the need to recognize axSpA in general and nr-axSpA specifically as pathologies associated with significant morbidity and for which there is an unmet need for therapies.

At the meeting, held in June, both of these points and several others regarding the clinical importance of nr-axSpA and axSpA were conceded by the FDA officials, according to Dr. Deodhar. He recounted that some rheumatologists on staff at the FDA continue to see patients and were empathetic about the unmet need for therapies even while expressing concern about overuse of biologics.

The solution, in the opinion of FDA regulators, as described by Dr. Deodhar, is a better set of sensitive and specific diagnostic criteria for nr-axSpA that can reliably define those patients who benefit from biologics or other therapies when compared with the current standard of care. This is a goal now being pursued by SPARTAN in collaboration with ASAS. The American College of Rheumatology (ACR) and the European League Against Rheumatism may also be invited to participate.

The acknowledgment by the FDA that nr-axSpA is a disease entity that is poorly treated with current options is an important first step in a process that Dr. Deodhar and others believe will eventually lead to approval of tumor necrosis factor inhibitors.

Asked for a comment, Dr. David Borenstein, clinical professor of rheumatology at George Washington University Medical Center, Washington, said he is confident that diagnostic criteria acceptable to professional rheumatology organizations and the FDA will eventually be created.

"There has been some dissension about the reproducibility of the current axSpA criteria and how they might be used effectively by nonspecialists," agreed Dr. Borenstein, who is a past president of the ACR. "We need to tighten the criteria to make sure we are all talking about the same problem."

Dr. Deodhar reported financial relationships with Amgen, Abbott, Genentech, and Janssen.

NEW YORK – There appears to be progress in the effort to convince the Food and Drug Administration that nonradiologic axial spondyloarthritis is a viable disease entity that deserves to be the target of therapeutic trials, according to an account of recent deliberations.

"We are happy that the FDA [now] agrees with the axSpA [axial spondyloarthritis] concept, the burden of disease, and the need to treat such patients," reported Dr. Atul Deodhar, professor of medicine and medical director of the rheumatology clinics at Oregon Health and Science University, Portland.

However, this is a process. The FDA "remains very concerned about the specificity of the ASAS [Assessment of Spondyloarthritis International Society] classification criteria," Dr. Deodhar said at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (SPARTAN).

Treatment trials for nonradiologic axSpA (nr-axSpA) followed the development of diagnostic criteria by ASAS in 2009 (Ann. Rheum. Dis. 2009;68:777-83). On the basis of randomized controlled trials in nr-axSpA patients with adalimumab (ABILITY-1) and both nr-axSpA and axSpA patients with certolizumab pegol (AS001), both drugs were approved by the European Medicines Agency for the treatment nr-axSpA. The same evidence, reviewed by an FDA advisory committee in July 2013, produced rejections the following October.

The major problem, according to Dr. Deodhar’s account, was that the FDA found the ASAS diagnostic criteria "overly broad," creating a potential for some low-risk patients to be prescribed therapies in which a favorable benefit-to-risk ratio could not be ensured. But the decision also denied these biologics to patients who could benefit.

"Rheumatologists were put in a difficult position, inducing some to label these patients as having ankylosing spondylitis to obtain third-party approval for therapies they needed," Dr. Deodhar observed. Concerned that patients with significant disability were being denied effective therapies, leaders of both SPARTAN and ASAS are attempting to work with the FDA to define more acceptable criteria.

In a joint letter from SPARTAN and ASAS to the FDA in early 2014 requesting a meeting, the key issues outlined for discussion included the need to recognize axSpA in general and nr-axSpA specifically as pathologies associated with significant morbidity and for which there is an unmet need for therapies.

At the meeting, held in June, both of these points and several others regarding the clinical importance of nr-axSpA and axSpA were conceded by the FDA officials, according to Dr. Deodhar. He recounted that some rheumatologists on staff at the FDA continue to see patients and were empathetic about the unmet need for therapies even while expressing concern about overuse of biologics.

The solution, in the opinion of FDA regulators, as described by Dr. Deodhar, is a better set of sensitive and specific diagnostic criteria for nr-axSpA that can reliably define those patients who benefit from biologics or other therapies when compared with the current standard of care. This is a goal now being pursued by SPARTAN in collaboration with ASAS. The American College of Rheumatology (ACR) and the European League Against Rheumatism may also be invited to participate.

The acknowledgment by the FDA that nr-axSpA is a disease entity that is poorly treated with current options is an important first step in a process that Dr. Deodhar and others believe will eventually lead to approval of tumor necrosis factor inhibitors.

Asked for a comment, Dr. David Borenstein, clinical professor of rheumatology at George Washington University Medical Center, Washington, said he is confident that diagnostic criteria acceptable to professional rheumatology organizations and the FDA will eventually be created.

"There has been some dissension about the reproducibility of the current axSpA criteria and how they might be used effectively by nonspecialists," agreed Dr. Borenstein, who is a past president of the ACR. "We need to tighten the criteria to make sure we are all talking about the same problem."

Dr. Deodhar reported financial relationships with Amgen, Abbott, Genentech, and Janssen.

NEW YORK – There appears to be progress in the effort to convince the Food and Drug Administration that nonradiologic axial spondyloarthritis is a viable disease entity that deserves to be the target of therapeutic trials, according to an account of recent deliberations.

"We are happy that the FDA [now] agrees with the axSpA [axial spondyloarthritis] concept, the burden of disease, and the need to treat such patients," reported Dr. Atul Deodhar, professor of medicine and medical director of the rheumatology clinics at Oregon Health and Science University, Portland.

However, this is a process. The FDA "remains very concerned about the specificity of the ASAS [Assessment of Spondyloarthritis International Society] classification criteria," Dr. Deodhar said at the joint meetings of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network (SPARTAN).

Treatment trials for nonradiologic axSpA (nr-axSpA) followed the development of diagnostic criteria by ASAS in 2009 (Ann. Rheum. Dis. 2009;68:777-83). On the basis of randomized controlled trials in nr-axSpA patients with adalimumab (ABILITY-1) and both nr-axSpA and axSpA patients with certolizumab pegol (AS001), both drugs were approved by the European Medicines Agency for the treatment nr-axSpA. The same evidence, reviewed by an FDA advisory committee in July 2013, produced rejections the following October.

The major problem, according to Dr. Deodhar’s account, was that the FDA found the ASAS diagnostic criteria "overly broad," creating a potential for some low-risk patients to be prescribed therapies in which a favorable benefit-to-risk ratio could not be ensured. But the decision also denied these biologics to patients who could benefit.

"Rheumatologists were put in a difficult position, inducing some to label these patients as having ankylosing spondylitis to obtain third-party approval for therapies they needed," Dr. Deodhar observed. Concerned that patients with significant disability were being denied effective therapies, leaders of both SPARTAN and ASAS are attempting to work with the FDA to define more acceptable criteria.

In a joint letter from SPARTAN and ASAS to the FDA in early 2014 requesting a meeting, the key issues outlined for discussion included the need to recognize axSpA in general and nr-axSpA specifically as pathologies associated with significant morbidity and for which there is an unmet need for therapies.

At the meeting, held in June, both of these points and several others regarding the clinical importance of nr-axSpA and axSpA were conceded by the FDA officials, according to Dr. Deodhar. He recounted that some rheumatologists on staff at the FDA continue to see patients and were empathetic about the unmet need for therapies even while expressing concern about overuse of biologics.

The solution, in the opinion of FDA regulators, as described by Dr. Deodhar, is a better set of sensitive and specific diagnostic criteria for nr-axSpA that can reliably define those patients who benefit from biologics or other therapies when compared with the current standard of care. This is a goal now being pursued by SPARTAN in collaboration with ASAS. The American College of Rheumatology (ACR) and the European League Against Rheumatism may also be invited to participate.

The acknowledgment by the FDA that nr-axSpA is a disease entity that is poorly treated with current options is an important first step in a process that Dr. Deodhar and others believe will eventually lead to approval of tumor necrosis factor inhibitors.

Asked for a comment, Dr. David Borenstein, clinical professor of rheumatology at George Washington University Medical Center, Washington, said he is confident that diagnostic criteria acceptable to professional rheumatology organizations and the FDA will eventually be created.

"There has been some dissension about the reproducibility of the current axSpA criteria and how they might be used effectively by nonspecialists," agreed Dr. Borenstein, who is a past president of the ACR. "We need to tighten the criteria to make sure we are all talking about the same problem."

Dr. Deodhar reported financial relationships with Amgen, Abbott, Genentech, and Janssen.