International Guidelines Say Use Treat-to-Target for SpA, PsA

Janis C. Kelly

July 19, 2017

Updated guidelines for axial spondyloarthritis (SpA) and peripheral spondyloarthritis (PsA) include stronger support for treating to the target of remission, but one expert worries they may result in overtreatment.

An international task force published the recommendations online July 6 in the Annals of Rheumatic Diseases. These recommendations update guidelines previously released in 2012.

"The recommendations are significant in two key areas," David I. Daikh, MD, PhD, professor of medicine; Kenneth H. Fye Chair in Rheumatology; and director, Rheumatology Fellowship Program, University of California, San Francisco, and chief, Rheumatology Section, San Francisco VA Medical Center, California, told Medscape Medical News.

"They indicate that treat-to-target should be the standard and general approach to care of SpA and PsA. And further, they emphasize that the targets should be clinical remission or inactive disease. The major challenge to the group and to the field is that the optimal measures of disease activity are not fully agreed upon, and in some cases [are] in need of further development and validation." Dr Daikh was not involved in developing the recommendations.

For clinicians, the update is most important in strengthening several 2012 recommendations by incorporating higher-quality evidence now available from studies performed since then, and by providing recommendations on the basis of new data on disease activity scores for axial SpA and PsA to guide treatment choices in practice and also in clinical trials, Josef S. Smolen, MD, told Medscape Medical News. Dr Smolen is professor of internal medicine at the University of Vienna; chairman, Department of Rheumatology, Vienna General Hospital; and chairman, 2nd Department of Medicine, Center for Rheumatic Diseases, Hietzing Hospital, Vienna, Austria.

One change from the 2012 guidance is the stronger emphasis on treatment to target, based in part on PsA data from the TICOPA trial.

"As mentioned in the paper, two trials on [treatment to target] in axial SpA are ongoing (TICOSPA and STRIKE), and the research agenda also calls for another trial in PsA. We also need data for peripheral SpA aside from PsA, such as reactive arthritis or arthritis associated with inflammatory bowel disease," Dr Smolen added.

Dr Smolen also noted a new emphasis on the use of continuous measures to determine disease activity, such as the use of the Ankylosing Spondylitis Disease Activity Score for SpA and the Disease Activity Index for Psoriatic Arthritis. He said, "These scores allow for determination of disease activity throughout the whole disease course, as well as definition of targets. If one wants to only look for a target, then Minimal Disease Activity for PsA is an option." The authors also emphasize shared decision-making between the clinician and the patient.

"The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including [PsA]. An important improvement is that almost half of the new updated recommendations are based on evidence," Muhammad A. Khan, MBBS, professor of medicine, Case Western Reserve University, Cleveland, Ohio, told Medscape Medical News.

"Among these evidence-based recommendations, the most important is a new formulation for how to measure disease activity. Thus, [Ankylosing Spondylitis Disease Activity Score] has been recommended as the 'preferred' disease activity measure to define the target when treating patients with axial SpA. It was also recommended that [Disease Activity Index for Psoriatic Arthritis], and alternatively [Minimal Disease Activity], should be considered to define the target when treating PsA."

Dr Khan, who was not involved in the study, said that the most important unresolved question was whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. "This unresolved question constitutes an important research agenda for the future," he said.

The task force consisted of rheumatologists, dermatologists, patients, and a health professional. They used a systematic literature review, discussion, and voting to develop the 2017 update. This resulted in five overarching principles and 11 recommendations.

"Of particular importance, the current recommendations do not address any specific type of treatment but rather deal with a general approach to treating SpA; management recommendations, in contrast, deal with specific drugs for particular situations and have been specifically developed by respective committees, focusing on differences in management depending on the predominance of activity in specific disease domains," the authors explain.

One change from 2012 is a greater emphasis on reducing inflammation, Dr Smolen said. "We have more data that the inflammatory response, such as the presence of elevated/high [C-reactive protein] levels, is associated with more damage in both axial SpA and PsA."

Another change is a more complex consideration of the role of imaging. "Imaging should be used for diagnostic purposes primarily, but not for follow-up. There is no evidence that sonography is helpful in the follow-up of PsA, and the use of MRI in the follow-up of axial SpA is time- and cost-consuming," Dr Smolen told Medscape Medical News.

"Many unanswered questions about optimal treatment of SpA remain. The optimal disease measures for each condition, [for example], axial spondyloarthritis and psoriatic spondyloarthropathy, as well as the role of multidimensional composite disease activity scores are important unanswered questions," Dr Daikh said. "Other important questions include whether imaging remission should be a treatment target and the role of imaging in following treatment responses in SpA. One of the strengths of the recommendations is that the task force laid out a detailed research agenda for the future."

Biased Recommendations

Norton M. Hadler, MD, is less convinced. Dr Hadler, who is emeritus professor of medicine and microbiology/immunology, University of North Carolina at Chapel Hill, was not involved in the task force. He told Medscape Medical News, "The update strengthens the 2012 recommendations, but that reflects the bias inherent in this collection of recommenders much more than the compelling nature of the published studies or the validity of the observational clinimetrics. The masthead is replete with the usual suspects: Clinical investigators with particular interests in SpA and PsA who know each other in this context and who have relationships with one or many of the purveyors of relevant pharmaceuticals.

"Furthermore, the entire undertaking is underwritten by AbbVie. The issue of 'conflict of interest' is less relevant than what I call 'the folly of peer review'. These 'thought leaders' speak a common language, share a common experience, and enjoy a common set of expectations, all of which are nurtured by the promise of their translational research. It would be very difficult to maintain any degree of equipoise in such a community."

Dr Hadler expressed concern that the treat-to-target criterion and emphasis on early, aggressive treatment might result in overtreatment. "This principle translates to considering mild disease to be ominous and spontaneous remission to be transient. To that end, these authors remind us that the pharmaceutical armamentarium stands at the ready with putatively effective solutions (all of which have limits in efficacy).... Given the therapeutic philosophy and prejudice of the authorship, can one envision a 'shared decision' that might favor expectant observation or the use of symptomatic interventions, or the use of older [disease-modifying antirheumatic drugs] or topical treatment for limited psoriatic involvement?" he said.

"Many patients have persistently mild disease, and many others enter into spontaneous relative or absolute remissions. Many patients/people with or without these diseases develop back pain or rash or joint pain as coincidental, incidental, self-limited episodes that do not merit interventions carrying any important degree of risk. Will these 'updated recommendations' advantage the vast majority of people/patients who have little risk of severe disease?" Dr Hadler added.

The study was supported in part by a grant from AbbVie to the Medical University of Vienna. Dr Smolen reports receiving grant support from and/or providing expert advice to AbbVie, Amgen, Astra-Zeneca, BMS, Boehringer-Ingelheim, Celgene, Celltrion, Gilead, Glaxo, Iltoo, Janssen, Lilly, Pfizer, MSD, Roche, Samsung, Novartis-Sandoz, and UCB. Other coauthors report receiving honoraria, consulting fees, speaking fees, and/or grant support from AbbVie, Janssen, MSD, Novartis, Roche Astra-Zeneca, BMS, Medac, Pfizer, Roche, UCB, Chugai, Grünenthal, Sun Pharma, Samsung, Sandoz, Lilly, Celgene, Centocor, Boehringer, Galapagos, Gilead, and Sanofi Takeda. Dr. Daikh and Dr. Hadler have disclosed no relevant financial relationships.

Ann Rheum Dis. Published online July 6, 2017. Full text

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