
Combination treatment with methotrexate and etanercept in patients with active, early, moderate-to-severe rheumatoid arthritis (RA) improves both remission and radiographic non-progression rates within one year compared with the standard treatment of methotrexate alone. This treatment also increases the ability of patients to remain in employment. These are the conclusions of authors of an article published early online and in an upcoming edition of The Lancet.
Remission is the best outcome for early therapy, and is best achieved by reducing or eliminating inflammation, thereby stopping radiographic progression at an early stage when the disease is most destructive and before joint damage occurs. Paul Emery, Arthritis Research Campaign Professor of Rheumatology, University of Leeds, UK and Leeds Teaching Hospitals Trust, UK, and colleagues did the COMET study — a randomized trial to test the effects of combination treatment with methotrexate and etanercept compared with methotrexate alone.
A total of 542 patients who had not previously used methotrexate and had early moderate-to-severe RA for 3-24 months were randomly assigned to receive either methotrexate alone or methotrexate plus etanercept.
The researchers found 50% of patients given combined treatment achieved clinical remission after 1 year compared with 28% given methotrexate alone, making those given combined treatment almost twice as likely to achieve remission. In the combined treatment group, 80% of patients achieved radiographic non-progression, compared with 59% in the methotrexate-only group, a difference of 21% favouring combined treatment. Serious adverse events were similar between groups.
The authors say: "The COMET trial showed that patients who received combination therapy have a nearly three-fold reduction in work stoppage compared with those who took high-dose methotrexate alone. The ability to remain a productive member of the workforce has implications for patients, employers, and society as a whole. The effect of RA is especially significant for women aged 55-64 years, because they have a high incidence of stopping work early…..nearly a quarter of patients who were in employment at baseline in the COMET trial had stopped working at least once by the end of 1 year compared with about a tenth in the combination group."
The authors conclude: "The results of the COMET trial suggest that remission is an achievable goal in patients with early severe RA within the first year of therapy with etanercept plus methotrexate….The positive clinical outcomes in the combination treatment group also seem to determine the ability of patients to remain in employment. Furthermore, these outcomes appear to be achieved without exposing patients to significant additional risk."
In an accompanying Comment, Dr Joel Kremer, Center for Rheumatology, Albany Medical College, Albany, NY, USA, says in order to show that treatments such as the combination therapy in COMET are cost effective and efficacious in the long-term, countries must make use of national registries. He says: "Experts in health economics can apply rigorous formulae to quality of life and disability, while factoring in cost of drugs and their toxic effects, to establish whether the promising data in these investigations are sustained, and whether the new biological agents are cost effective."