Combination drug therapy could substantially improve symptoms of rheumatoid arthritis

The combination of two drugs – both partly effective for rheumatoid arthritis patients when given individually – could be an important development in substantially reducing symptoms and joint destruction for people with rheumatoid arthritis, conclude authors of a study in this week’s issue of THE LANCET.

Rheumatoid arthritis affects around 1% of people worldwide. Etanercept and methotrexate are known to be effective in the treatment of rheumatoid arthritis; however, no data exist on concurrent initiation or use of the combination compared with either drug alone.

Lars Klareskog from the Karolinska Institute, Sweden, and colleagues studied 686 patients with current rheumatoid arthritis who were randomly allocated treatment with either etanercept (25 mg subcutaneously twice a week) or oral methotrexate (up to 20 mg every week), or combination of both treatments. Clinical response was assessed by criteria of the American College of Rheumatology (ACR) and by disease activity score (DAS).

ACR scores were better for symptom relief after 6 months for patients given combination treatment than for patients receiving individual drug therapy, and remission after one year (defined from DAS scores) occurred in 35% of patients given combination treatment compared with 16% of patients given etanercept monotherapy and 13% given methotrexate monotherapy. Combination therapy was also more effective for effects on joint destruction measured by radiography-resulting in a statistically significant improvement on a score for joint erosion.

Dr Klareskog comments: ‘This is the first demonstration that erosions in established rheumatoid arthritis can improve over time in a group of patients within a controlled clinical trial, thus providing evidence that repair of joints destroyed by the disease may be a biological and clinical possibility’. (quote by e-mail; does not appear in published paper).

In an accompanying Commentary (p 670), Armin Schnabel from Sana Rheumazentrum Baden-W’berg, Germany, comments : ‘Studies examining early versus delayed onset of immunosuppressive treatment and high versus low initial intensity of treatment suggest that effective treatment needs to be started during a critical time early in the course of the disease. During this window of opportunity, inflammation seems to be particularly susceptible to treatment and long-term preservation of structure and function probably relies heavily on the initiation of effective immunosuppression during this particular time span. Most trials involving antagonists of tumour necrosis factor, including ATTRACT, ARMADA, and TEMPO, comprised patients with disease of several years’ duration. The next generation of trials will target patients with recent onset of disease and these trials are essential to support, or refute, the concept of the window of opportunity. If timing turns out to be the critical factor it seems to be, the benefits of disease-modifying antirheumatic drugs, biologicals, and the various combinations thereof will need to be reassessed.’