Compared with methotrexate monotherapy, combined treatment with methotrexate and etanercept is associated with higher rates of clinical remission and radiographic non-progression in patients with early moderate-to-severe rheumatoid arthritis, new research indicates.
The best method of achieving remission in early rheumatoid arthritis is to reduce or eliminate inflammation, thereby stopping the disease process before joint damage occurs, Dr. Paul Emery, from the University of Leeds, UK, and co-researchers note in the July 16th online issue of The Lancet.
While conventional disease-modifying anti-rheumatic drugs have proven effective in inducing clinical remission, there is evidence that this does not always mean that radiographic progression has been stopped, according to the report. Recent research suggests that combining methotrexate with an anti-tumor necrosis factor agent may be best at achieving both effects.
To investigate further, Dr. Emery's team conducted the Combination of Methotrexate and Etanercept in Early, Active Rheumatoid Arthritis (COMET) trial, in which 542 patients were treated with methotrexate alone or with etanercept. Methotrexate was titrated from 7.5 to 20 mg/week by week eight and etanercept was given at a dose of 50 mg/week.
Based on the disease activity score in 28 joints (DAS28), 50 per cent of patients treated with combined therapy achieved clinical remission at 52 weeks compared with 28 per cent of those given methotrexate alone (p < 0.0001). The rate of radiographic non-progression was also higher in the combined treatment group versus the monotherapy group: 80 per cent vs. 59 per cent (p < 0.0001).
No significant differences in adverse events were noted between the groups, the authors report.
At this point, "the relevant question is whether the difference between the clinical and radiographic response to methotrexate alone versus the combination is worth the additional cost, inconvenience, and potential toxic effects?" Dr. Joel M. Kremer, from Albany Medical College in New York, comments in a related editorial.
The answers to this and other issues "lie with data collection in registries," he concludes, and "are not yet entirely in."
Lancet 2008
