BOSTON, Massachusetts—Fat is "a proinflammatory tissue," and being obese (BMI >30) can halve a rheumatoid arthritis (RA) patient's chance at remission with combinations of conventional DMARDs, Marjatta Leirisalo-Repo, MD, reported at the American College of Rheumatology meeting.¹ Adding infliximab to the combination substantially overcame this problem, restoring remission probability to ~60%, regardless of BMI.

"Unless you are fat, with the flexible combination regimen we used, you probably do not need infliximab. However, it is important to remember that a rising proportion of arthritis patients are either overweight (BMI >25) or obese (BMI >30)," lead author Dr. Leirisalo-Repo told Musculoskeletal Report in an interview.

3 DMARDs plus prednisolone, with or without infliximab

Dr. Leirisalo-Repo reported results from the NEO-RACo trial, a double-blind, placebo-controlled study on early RA. During the first 6 months of treatment, patients received combination (COMBI) treatment with methotrexate (maximum 25 mg/week), sulfasalazine (maximum 2g/day), hydroxychloroquine, and prednisolone (7.5 mg/day) plus either infliximab (INF) or placebo.

"We have been very actively trying to induce remission with traditional DMARDs. We asked whether we could induce remission by combining 3 conventional DMARDs and a standard dose of prednisone," said Dr. Leirisalo-Repo. Dosing of methotrexate was adjusted using a "flexible control" strategy to individualize treatment and to achieve remission in as many patients as possible. "The aim of the study was to induce remission. The key question was whether adding infliximab would produce better response in these early, active intervention patients," Dr. Leirisalo-Repo continued.

The researchers enrolled 100 patients aged <65 with early active RA who had not received previous DMARD therapy. COMBI was started in all patients who were randomized to also receive INF (3 mg/kg) or placebo at weeks 4, 6, 10, 18, and 26. DMARD switching was allowed in cases of inefficacy or intolerability, but use of three DMARDs and prednisone was required.

"With combination therapy, with or without infliximab, about 50% of patients overall were in remission at 12 months. We define remission as no joint pain, no fatigue, no swollen joints, no tender joints, normal erythrocyte sedimentation rate, and normal C-reactive protein levels," Dr. Leirisalo-Repo said.
 
At 6 months, 53% of patients were in remission (COMBI + placebo 47%, COMBI + INF 58%, ns) and at 12 months 52% were in remission (COMBI + placebo 45%, COMBI + INF 58%, ns).

At 6 months, remission rates with COMBI plus placebo were 63% for patients with normal BMI, 35% for overweight patients, 25% for obese patients(P for linearity = .023, adjusted for baseline DAS28 and sex). Remission was not affected by BMI in the COMBI plus INF group. Remission rates were 55% for normal weight patients, 68% for overweight patients, and 46% for obese patients (P = .88).

At 12 months the remission rates according to weight in COMBI plus placebo group were 58%, 35%, and 25% (P for linearity = .034). Remission rates in the COMBI plus INF group 45%, 74%, and 55% (P = .4), respectively.

The burden of inflammatory fat

"The probability of reaching remission during the first 12 months was very dependent on the patient's body mass index. In patients who had normal BMI, it did not matter whether you had infliximab added to combination DMARD therapy—both groups did equally well. However, as BMI increased, there was a linear decrease in the probability of remission with the combination. If you add infliximab, the remission rate is constant," Dr. Leirisalo-Repo commented.

She emphasized that the important factor is fat, estimated by BMI, not just body weight. A tall, heavy, fit person would not have a reduced chance of remission. "As one of my colleagues observed, the problem with many patients is not that they are too heavy, but that they are too short!"

During the discussion of the study, several attendees raised the question of whether, in view of the increasing girth of the population, it might be time to consider BMI-based dosing for conventional DMARDs.


       Effect of Body Mass Index on Chance of Remission in RA





Legend:
COMBI = methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone
INFL = infliximab













Adapted from Leirisalo-Repo M, et al. American College of Rheumatology Meeting, 2007.¹


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