For patients with active, early stage, moderate-to-severe rheumatoid arthritis, a combination treatment with methotrexate and etanercept can improve remission and radiographic non-progression rates within one year in comparison with just methotrexate. Additionally, more patients are also able to remain employed. These conclusions are published in an article released early Online on July 16, 2008 in The Lancet.

Rheumatoid arthritis is an autoimmune disorder in which the immune system attacks the joints, causing arthritic inflammation and damage. It can also extend to other parts of the body. Early in therapy, successful treatments induce remission, usually by reducing or eliminating inflammation. If progression of the disease is caught at an early stage, when it can be most destructive, serious joint damage could be prevented.

To investigate potential treatment methods for rheumatoid arthritis, Paul Emery, Professor of Rheumatology, University of Leeds, UK and Leeds Teaching Hospitals Trust, UK, performed the COMET study, a randomized trial comparing combination treatment with individual treatment. A total 542 patients with early moderate-to-severe RA for 3-24 months who had not been treated with methotrexate were randomle assigned to one of the following groups: only methotrexate (268 patients), or methotrexate and etanercept (274 patients). Methotrexate was administered with a starting dose of 7.5 mg per week to a maximum 20 mg per week at the end of 8 weeks. The entanercept was administered at 50 mg per week. A disease activity score (DAS28) was evaluated with a radiographic non-progression measure (Sharp score) after one year.

It was found that 50% of patients who were given the combined treatment achieved remission, while 94% of this group had a good to moderate response. In comparison, the methotrexate only group had a 28% remission rate, making the combined group members almost twice as likely to achieve remission. In a comparison of radiographic non-progression, 80% of combined treatment patients achieved the mark, while only 58% achieved this in the only methotrexate group. The serious adverse events were similar in the two groups.

The authors summarize their findings while making a statement about the increased functionality of patients who are able to bring rheumatoid arthritis into remission early. “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.”

According to the authors, this is data is evidence for the combined treatment. “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.”

Dr Joel Kremer, Center for Rheumatology, Albany Medical College, Albany, NY, USA, contributed an accompanying comment stating that there must be a specific system for ensuring that this kind of therapy is cost effective and efficiently implemented. “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.” He says.

Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial
Paul Emery, Ferdinand C Breedveld, Stephen Hall, Patrick Durez, David J Chang, Deborah Robertson, Amitabh Singh, Ronald D Pedersen, Andrew S Koenig, Bruce Freundlich
Published Online The Lancet July 16, 2008
DOI:10.1016/S0140- 6736(08)61000-4
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COMET’s path, and the new biologicals in rheumatoid arthritis
Joel M Kremer
Published Online The Lancet July 16, 2008
DOI:10.1016/S0140- 6736(08)61001-6
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Written by Anna Sophia McKenney