FDA needs convincing on nonradiologic axial spondyloarthritis

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.