Abstract L17: Remission Rates in Subjects With Active Early Rheumatoid Arthritis - 1 Year Results of the COMET Trial: Combination of Methotrexate and Etanercept in Active Early Rheumatoid Arthritis
Alan Baer, M.D.
Authors:
P. Emery, F. Breedveld, S. Hall, P. Durez, R. Pedersen, D. Robertson, B. Freundlich, D. J. Chang
Background:
The COMET trial compared the clinical efficacy and safety of etanercept (ETN) plus methotrexate (MTX) with MTX alone in patients with active early rheumatoid arthritis (RA). It is the first major clinical trial in RA to use remission as a primary endpoint. This double-blind, multi-national randomized, study consisted of two 12-month periods. The results at week 52 of the first portion of the study are reported here.
Methods:
Patients were eligible for this study if they had had RA for 2 years or less, had not previously received MTX therapy, and had active disease as defined by a Disease Activity Score in RA (DAS28) of 3.2 or greater and an elevation of the ESR (≥28 mm/hr) or of the CRP (≥20 mg/L). Of 542 patients enrolled, 274 were randomized to ETN + MTX and 268 to MTX alone. The primary endpoint was the proportion of patients who achieved at Week 52 a DAS28 score of <2.6, consistent with remission. Secondary endpoints included the proportions of patients achieving ACR 20, ACR 50, and ACR 70 composite responses at Week 52.
Results:
At Week 52, 50% of patients on ETN + MTX achieved remission as compared to 28% on MTX alone (P<0.001). Similarly, low disease activity (DAS28 ≤3.2) was achieved by 64% and 41% of patients in the ETN + MTX and MTX groups, respectively (P<0.001). These differences in response between therapeutic groups were significant by week 2 and at all time points thereafter. The percentages of patients achieving ACR20, ACR50, and ACR70 composite responses at Week 52 were also statistically significant between groups (Table). Serious adverse events were reported by 12.0% of the patients in the ETN + MTX group and 12.7% of the patients in the MTX group. There were no differences in rates of serious infections or malignancies. No cases of TB or demyelinating disease were reported.
n/N (%) of Patients Achieving Response at Week 52 |
|||
|
MTX |
ETN + MTX |
P |
DAS28 <2.6 |
73/263 (28) |
132/263 (50) |
<0.001 |
DAS28 <3.2 |
109/263 (41) |
170/265 (64) |
<0.001 |
|
|
|
|
ACR20 |
163/243 (67) |
220/256 (86) |
<0.001 |
ACR50 |
119/243 (49) |
181/256 (71) |
<0.001 |
ACR70 |
69/243 (28) |
124/256 (48) |
<0.001 |
Fisher's Exact test, last observation carried forward |
|||
Conclusions:
In this population of patients with early rheumatoid arthritis, half of those treated with etanercept plus methotrexate achieved remission at Week 52. The type and incidence of adverse events was commensurate with those observed in other trials with etanercept. These results add support for the use of combination therapy with methotrexate and etanercept early in rheumatoid arthritis.
Editorial Comment:
The strength of this study is the use of remission, defined by a DAS28 score of <2.6, as the primary endpoint. A remission is difficult to achieve in patients with established rheumatoid arthritis (i.e. disease duration > 2 years), yet 50% of the early RA patients achieved this endpoint on a combination regimen of methotrexate and etanercept. Thus, this therapeutic regimen has greater potency than methotrexate alone, an observation that has been supported by clinical trials in patients with established rheumatoid arthritis. Treatment of rheumatoid arthritis in its early stages with potent therapies can thus result in a high frequency of remission.
The term ‘remission’, as it is used in this study, is not comparable to a true remission where signs of disease are absent while the patient is off anti-rheumatic therapy. An important question is whether the patients with early RA who achieved remission in the COMET trial will continue to have minimal or no disease activity over several years, either with continued ETN and MTX treatment or following gradual withdrawal of one or both drugs.
