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Biologics Can Change the Face of RA


 

EXPERT ANALYSIS FROM THE PERSPECTIVES IN RHEUMATIC DISEASES 2011

SAN FRANCISCO – Rheumatologists can prescribe drugs that can not only drive rheumatoid arthritis into remission but can also achieve some repair to the joints damaged by inflammation, according to Dr. Marc D. Cohen.

"In rheumatology, remission can never mean no disease. It just means not very much disease," said Dr. Cohen, emeritus professor of medicine at the Mayo Clinic, Rochester, Minn., and acting chief and professor of medicine at National Jewish Medical and Research Center in Denver.

"Rheumatologists need to be better sellers of what we can do. If you are not interested in changing the face of this disease, what are you doing?" he asked at the Perspectives in Rheumatic Diseases 2011 meeting.

In a review of the data on the efficacy of various biologic drugs in rheumatoid arthritis (RA), Dr. Cohen pointed out that, until the advent of biologics, there were no good trial data on the efficacy of methotrexate in RA. "The biologics are the best thing that ever happened to methotrexate, believe me," he said.

The study that put methotrexate on the map was the SWEFOT, in which investigators put all patients with RA on a trial of methotrexate before randomizing them to either triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine or to methotrexate plus a tumor necrosis factor inhibitor (TNFi). The findings from the methotrexate-monotherapy portion of the trial showed that 30% of the patients improved on methotrexate alone (Lancet 2009;374:459-66).

Because of these findings, all patients get a trial of methotrexate first, as quickly as possible, ramping up the dose over 1-2 months, to see what happens. What may get overlooked is the investigators’ note that, while a subset of patients experience clinical benefit from methotrexate monotherapy, radiographic disease progression continues despite methotrexate making the patients feel better.

There is no way to predict which 30% may respond clinically to methotrexate. That is one reason why one may want to rush through ramping up the dose.

Commonly, the next step in treating RA is to apply triple therapy. Further findings from the SWEFOT trial of 487 patients with RA symptoms of less than 1 year’s duration showed that clinically at 2 years the two treatment groups were the same in terms of Disease Activity Score (DAS). However, patients given triple therapy had more radiographic progression than did those given a TNFi plus methotrexate.

"Is that important to your patient? I am not sure. The problem is that we have no way to measure that. We need a point system. If you have RA in your right big toe and you are a piano player that is probably not as bad as having wrist disease. Maybe we should weight them."

The bottom line is that the addition of a TNFi to the treatment regimen of someone who did not respond completely to methotrexate will improve the clinical and radiologic response in two to three times the number of patients (Lancet 2007;370:1861-74).

This combination approach does not capture everyone.

This is part of the motivation behind the push for primary care physicians to recognize RA early and get the patients to the rheumatologists for biologic therapy early. When the biologics are given aggressively within the first 6 months of the disease, "we may be able to reset the disease, turn it off," he said.

In some cases, x-rays show repair of the joint damage when biologics are given early enough, he said at the meeting, which was sponsored in part by the Skin Disease Education Foundation (SDEF).

Dr. Paul Emery, professor of rheumatology and head of the academic unit of musculoskeletal medicine at the University of Leeds (England), presented data at the 2011 EULAR Congress showing that after patients achieved remission with methotrexate and a biologic, they could be maintained on methotrexate. This approach has the advantage of maintaining remission with a less-costly drug that also poses fewer potentially adverse effects than a biologic agent. "We do not know the right combination initially, but it is being examined," said Dr. Cohen.

SDEF and this news organization are owned by Elsevier.

Dr. Cohen reported having no relevant conflicts of interest to disclose.

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