According to the results from the second year of the COMET trial, early use of the combination of etanercept and methotrexate in rheumatoid arthritis (RA) appears to be superior to methotrexate monotherapy in terms of both clinical and radiographical outcomes.

The COMET trial randomised 542 patients with early moderate-to-severe RA who were methotrexate-naïve to methotrexate (MTX; 7.5-20mg/week; n=268) or MTX (same dose) plus etanercept (50mg/week; n=274).  Initial results from the COMET trial, published in the Lancet in 2008, showed that a higher proportion of the combination treatment group achieved clinical remission and radiographical non-progression at 52 weeks (these were the co-primary endpoints; see NeLM news summary at the link below for further details).

The current publication details the two-year findings from this study – the purpose of this was to evaluate how continuation of and alterations to the initial therapy affect long-term remission and radiographical progression.   At study baseline, the subjects were randomised to one of the four following groups:

EM/EM: Combination etanercept and MTX in both years (n=111)
EM/E: Combination treatment in year one and then etanercept alone in year two (n=111)
M/EM: MTX monotherapy in year one then combination treatment in year two (n=90)
M/M: MTX monotherapy for both years (n=99)

All those who completed the first year were eligible for enrolment in the second year (n=411; 398 valid for evaluation of clinical efficacy).  Overall, 64 patients discontinued the study between week 52 and week 104 (the last observation carried forward [LOCF] method of analysis was used).  The main findings were as follows:

• After two years of treatment, remission (a Disease Activity Score in 28 joints [DAS28] <2.6) was achieved by 62/108 (57%) subjects in the EM/EM group, 54/108 (50%) in the EM/E group, 51/88 (58%) in the M/EM group, and 33/94 (35%) subjects in the M/M group (P<0.01 for the EM/EM and M/EM groups versus the M/M group).

• 4.5 persons (95% CI 2.7-12.7) would have to be treated with EM/EM rather than M/M regimen over two years to achieve one DAS remission.

• Radiographical non-progression (change in the modified Sharp/van der Heijde score  0.5) at year 2 was achieved by 89/99 (90%), 74/99 (75%), 59/79 (75%), and 56/83 (67%), respectively (P<0.01 for EM/EM versus each of the other groups).

The researchers report that no new safety signals or between-group differences in serious adverse events were identified.  They conclude that these results “underscore a growing body of evidence that demonstrates the important sustained clinical benefits of intensive therapy in early RA.”