COMET: Remission Rate of 70% With Very Early Combination Treatment of RA

Alice Goodman

June 23, 2010

June 23, 2010 (Rome, Italy) — Very early treatment of patients with rheumatoid arthritis (RA) with a disease duration of 4 months or less is a superior strategy to treating patients with RA of 4 months to 2 years in duration, according to a 1-year post hoc analysis of the COMET (Combination of Methotrexate and Etanercept in Active Early Rheumatoid Arthritis) trial, presented here at the European League Against Rheumatism (EULAR) Congress 2010.

Very early treatment with the combination of etanercept and methotrexate, in particular, halted the structural progression of the disease in approximately 80% of patients, reported lead author Paul Emery, MD, president of EULAR and professor of rheumatology at the University of Leeds, United Kingdom, during a late-breaking clinical science session.

"RA patients with moderate to severe active disease benefit from very early and continuous treatment, particularly with etanercept plus methotrexate. Delaying methotrexate does not increase remission and permits more radiographic progression of disease," said Dr. Emery. "This exploratory analysis is important for our further understanding of the optimal timing of intervention for moderate to severe RA patients."

The exploratory post hoc analysis was designed to examine the concept of the "window of opportunity," he continued.

The COMET trial was a 24-month randomized double-blind 2-period study designed to compare the combination of etanercept plus methotrexate with methotrexate alone in patients with early moderate to severe RA (Disease Activity Score [DAS]28 ≥3.2).

For the first year, 50% of the patients treated with the combination achieved remission (DAS28 <2.6), compared with 28% treated with methotrexate alone.

The post hoc analysis was performed to determine whether very early RA (VERA) intervention (≤4 months) improved remission and low disease activity rates at 52 weeks, compared with early RA (ERA) treatment (from 4 months to 2 years).

Clinical outcomes were evaluated in 417 patients, radiographic nonprogression was evaluated in 406 patients, and the Health Assessment Questionnaire (HAQ) was administered at week 52 in 412 patients.

At baseline, mean DAS28 and HAQ scores were similar in all 4 subgroups (VERA and ERA for etanercept plus methotrexate and methotrexate alone). DAS28 clinical remission (<2.6) at 1 year was observed in nearly 70% of the 63 VERA patients treated with etanercept plus methotrexate and in nearly 48% of the 157 ERA patients treated with the combination (P = .0035).

In patients treated with methotrexate alone, only 35% of the 49 VERA patients and 32% of the 148 ERA patients achieved clinical remission (no significant difference).

Low disease activity was observed in a significantly greater percentage of VERA than ERA patients treated with combination therapy (80% vs 62%; P = .0138). No significant difference in low disease activity was observed between VERA and ERA patients treated with methotrexate alone.

At 1 year, no radiographic progression of joint damage was seen in the VERA and ERA groups treated with etanercept plus methotrexate. Radiographic progression was measured by the change in the modified Total Sharp Score (mTSS ≤0.5). Mean change from baseline in mTSS was 0.31 in VERA patients and 0.21 in ERA patients (not significantly different). However, methotrexate alone resulted in radiographic nonprogression in 74% of the 46 VERA patients and in 50% of the 142 ERA patients (P = .0055).

"The change in the methotrexate arm showed that late treatment caused permanent x-ray damage going forward," Dr. Emery stated. "This study supports intervention in a very early phase."

Study Does Not Support VERA With Methotrexate Alone

"This reanalysis of the COMET data is of real interest, as it looks at the idea of 'the earlier the better' in COMET patients, whose disease is relatively early anyway. The analysis does show that the combination of etanercept and methotrexate, when given very early, results in more frequent DAS remission than when given a few months later," said Daniel E. Furst, MD, who commented on this study in an interview with Medscape Rheumatology. Dr. Furst is the Carl M. Pierson Professor of Rheumatology at the University of California, Los Angeles.

He said that the combination works well and early, but that this was not true for the methotrexate group. "The earlier the better does not seem to hold for all groups, so the principle of the irretrievable window of opportunity is not proven by these data," Dr. Furst stated.

The study was supported by Pfizer. Dr. Emery has disclosed no relevant financial relationships. Dr. Furst reports receiving grant/research support from Abbott, Actelion, Amgen, BMS, Genentech, Gilead, GSK, Nitec, Novartis, Roche, UCB, Wyeth, and XOMA; being a consultant for Abbott, Actelion, Amgen, BMS, Biogen Idec, Centocor, Cenentech, Gilead, GSK, Merck, Nitec, Novartis, UCB, Wyeth, and XOMA; being an employee of: CORRONA; receiving honoraria from Abbott, Actelion, Amgen, BMS, Biogen Idec, Centocor, Genentech, Gilead, Merck, and Nitec; and being on the speakers bureau for Abbott, Actelion, and UCB.

European League Against Rheumatism (EULAR) Congress 2010: Abstract LB 0001. Presented June 19, 2010.


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