Benefit of Add-on Methotrexate in Psoriatic Arthritis Remains Uncertain

By Scott Baltic

NEW YORK - Whether adding methotrexate to a tumor necrosis factor blocker improves the course of psoriatric arthritis is still unclear after a systematic review, researchers say.

The review, published online October 27 in Rheumatology, included 11 articles and three conference abstracts reporting on six randomized controlled trials (RCTs) testing five TNF inhibitors: adalimumab, etanercept, golimumab, infliximab and certolizumab pegol.

The study also included seven published articles and one conference abstract reporting data from six registries in Norway, Sweden, Finland, Denmark and the UK.

"This systematic review addresses an important clinical issue, namely, whether TNF inhibitor therapy and methotrexate are additive or synergistic in the treatment of patients with (psoriatric arthritis)," Dr. Arthur Kavanaugh, of the University of California, San Diego, who was not connected with the study, told Reuters Health by e-mail.

"Unfortunately," he continued, "the designs of the studies reviewed in this paper do not allow a definitive answer to that question. In all of the RCTs, for example, patients were allowed, but not required to be on MTX. They were, however, required to have disease activity. That may have obviated the ability to see synergy. The registry studies suggest that there may be some benefit to the combination."

Dr. Kavanaugh said his comments were based not on information from the systematic review, but from having read the relevant reports when they were first published.

The European League Against Rheumatism and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis do not currently recommend the use of MTX in conjunction with TNF inhibitors because of the lack of research to support such use, note Dr. Frank Behrens of the Goethe Institute in Frankfurt am Main, Germany, and colleagues in their report of the review.

Still, they say, combination therapy is not uncommon, for various reasons that include the potential effect of MTX on the formation of anti-drug antibodies, particularly with monoclonal antibody TNF inhibitors.

"Most RCTs found no differences in efficacy for peripheral arthritis between patients treated with or without MTX. However, the studies were not powered to answer this question," the authors wrote.

One of the six RCTs (GO-REVEAL) indicated that giving MTX with golimumab might reduce structural progression, while another (IMPACT 2) showed a greater difference in radiographic progression at one year between the infliximab and placebo groups with concomitant MTX.

A third trial (PRESTA) found some benefit of MTX for skin symptoms in patients with severe skin symptoms receiving a specific dose of etanercept.

"Overall," the researchers wrote, "there is little evidence to guide physicians treating patients with psoriatic arthritis as to whether TNF inhibitors should be used as monotherapy or in combination with MTX."

One option, they added, "might be to add a TNF inhibitor in patients with inadequate response to MTX. Following a good response, MTX could be tapered and then possibly withdrawn, although drug survival data suggest that this may not be advisable with mAb agents. An alternative strategy could be to initiate TNF inhibitor monotherapy and add MTX if a partial response is seen."

Pfizer provided an unrestricted grant for the research and writing of the report.

The authors did not respond to a request for comment.

SOURCE: https://bit.ly/1BbmKCb

Rheumatology (Oxford) 2014.

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