DENVER (FRONTLINE MEDICAL NEWS)The Spondyloarthritis Research and Treatment Network has voted decisively to create new classification criteria for axial spondyloarthritis, including both ankylosing spondylitis and nonradiographic axial spondyloarthritis.

Following the vote, in which 64% of SPARTAN members attending the group’s annual meeting voted that “this is the right time to proceed,” comoderator Dr. Liron Caplan declared, “This is a very strong push. We’ll need to begin work on our proposal immediately.”

The detailed proposal will contain the justification for new classification criteria as well as outline how SPARTAN will go about creating the criteria in an evidence-based manner with input and financing from industry and patient support groups. The proposal needs to be filed by next March in order to be considered for roughly $135,000 in joint funding from the American College of Rheumatology and the European League Against Rheumatism.

A major impetus for the ambitious project was a frank conversation SPARTAN officers had in the Spring of 2014 with officials at the Food and Drug Administration. The rheumatologists sought an explanation for the FDA’s seemingly counterintuitive rejection of adalimumab (Humira) and certolizumab pegol (Cimzia) for treatment of nonradiographic axial spondyloarthritis (nr-axSpA) on the basis of the very same randomized, controlled trials that earlier resulted in approval for that indication by the European Medicines Agency.

The FDA representatives deemed the Assessment of SpondyloArthritis Society (ASAS) classification criteria (Ann Rheum Dis. 2009;68:777-83) used in those and other SpA trials to be overly broad. They felt the ASAS criteria lack sufficient sensitivity and specificity to ensure that large numbers of patients with fibromyalgia – a far more common disorder – wouldn’t be misclassified as having SpA and treated inappropriately with biologics, which aren’t effective in fibromyalgia, explained Dr. John D. Reveille , professor and vice-chair of rheumatology at the University of Texas, Houston, who attended the meeting.

“The only physicians who can prescribe an approved anti-TNF drug or other biologic in Europe are rheumatologists. The reason the FDA was nervous about approving drugs using the ASAS criteria is because any physician in the U.S. can prescribe those drugs once they’re approved. So the authorities made a regulatory decision about who the people are who are educated or not educated in the diagnosis and management of patients with SpA,” according to Dr. Michael H. Weisman , chair and director of rheumatology at Cedars-Sinai Medical Center in Los Angeles.

Dr. Caplan of the University of Colorado, Denver, observed that developing new and improved criteria for SpA will be a multiyear endeavor. A top goal is to shed light on the natural history of nr-axSpA, about which almost nothing is known. This will probably entail developing a sizable cohort of patients with nr-axSpA, following them for 5 years or so to see who develops ankylosing spondylitis, then looking back to identify reliable predictors.

The SPARTAN vote was preceded by a formal debate on the merits of replacing the ASAS criteria. Dr. Muhammad Asim Khan , professor of medicine at Case Western Reserve University, Cleveland, who 30 years ago was a pioneer in the concept of spondylitic disease without x-ray evidence of sacroiliitis, argued that the ASAS criteria aren’t adequately doing what disease classification criteria are supposed to do: provide a simple, clear means of identifying a homogeneous population for clinical trials. By letting in substantial numbers of patients with fibromyalgia, the criteria water down the clinical outcomes of investigational therapies for SpA.

The opposing argument was provided by ASAS representative Dr. Filip Van den Bosch. He conceded the ASAS classification criteria “aren’t perfect,” but over time they have become familiar to rheumatologists worldwide.

“Modifying the criteria will lead to years of uncertainty,” argued Dr. Van den Bosch, professor of rheumatology at Ghent (Belgium) University.

If, as some have proposed, SPARTAN were to tighten the ASAS criteria by insisting that a patient lacking x-ray evidence of sacroiliitis must possess three or four SpA features instead of the two now required, the result would be a drastic reduction in the sensitivity of the criteria, he continued.

“The challenge of making a correct diagnosis of axSpA cannot be solved by modifying the ASAS criteria. I cannot think of a new SpA feature that’s been identified in the last 5 years that could be added on top of what’s already in there,” the rheumatologist said.

What’s needed, he added, is a concerted effort to better educate physicians about axSpA, including interpretation of spinal x-rays and MRIs, the disease’s signs and symptoms, and how to differentiate SpA from other disorders that cause back pain.

While nearly two-thirds of the SPARTAN membership voted in favor of developing new classification criteria, some prominent voices were raised in dissent.

“I agree with Filip,” said Dr. Weisman. “The problem is not with the criteria, it’s who’s using them.”

Dr. Robert D. Inman , professor of medicine at the University of Toronto, predicted “it’s an exercise in futility” to try to come up with a single set of classification criteria that will provide the high degree of sensitivity that patients and clinicians want so that people who present with early axSpA are not missed while at the same time providing the maximum specificity that payers and regulatory officials seek.

Dr. Sindhu Johnson , who as cochair of the ACR Classification Criteria Subcommittee has shepherded the development of new criteria for a number of rheumatologic diseases, offered the SPARTAN group some practical tips. Because European studies tend to be comprised of monoethnic cohorts, the ACR will look favorably upon a successful SPARTAN effort to incorporate African Americans, Asians, Native Americans, and other minorities in their study cohorts. And SPARTAN should be open and receptive to critical feedback from stakeholders during the criteria development process.

“Get buy in. There’s no point in developing criteria that are extremely rigorous scientifically but that the global community feels are useless, that use tests they don’t have access to. This is one of the criticisms around the Sjögren’s criteria: they require ophthalmologic testing and salivary gland biopsy, and for rheumatologists – even academic rheumatologists at recruiting centers for clinical trials – they don’t have access to this, or it takes too much time. You need to come up with something pragmatic to get buy in,” advised Dr. Johnson of the University of Toronto.

By the way, she added, if the project wins ACR and EULAR funding it can only be named an ACR/EULAR product. “No other organization can be named in the headline,” according to Dr. Johnson.