Treatment for rheumatoid arthritis: first, second and third options

This review examined the various treatment options for patients with rheumatoid arthritis. 

Disease-modifying anti-rheumatic drugs (DMARDs) are a group of medications used for treating patients with rheumatoid arthritis. Commonly used DMARDs include methotrexate (Rheumatrex, Trexall), sulfasalazine (Azulfidine) and hydroxychloroquine (Plaquenil). Biological drugs (medicine extracted from biological sources) are also used to treat rheumatoid arthritis. Commonly used biological drugs include etanercept (Enbrel) and infliximab (Remicade).

Most guidelines support the use of methotrexate as the first treatment for rheumatoid arthritis. Studies have shown that 25% to 40% of patients will improve with methotrexate alone. It is unclear whether patients who do not improve with methotrexate should receive additional DMARDs or biological therapies next.

The authors reviewed the results from 3 trials to determine the best order of treatments. The trials compared the use of triple therapy (combination of the three drugs methotrexate, sulfasalazine and hydroxychloroquine) to the use of biological drugs.

The first trial included 755 patients being treated for the first time. The trial found that initial methotrexate therapy followed by triple therapy was no worse than initial triple therapy. It also showed that DMARDs were as effective as methotrexate plus etanercept (a biological drug).

The second trial compared methotrexate plus infliximab to triple therapy in 258 patients who had not improved with methotrexate alone. This trial found that patients in both groups had the same results after 2 years.

The third trial also included patients who had not improved with methotrexate alone. It included 353 patients who received either triple therapy or etanercept plus methotrexate. After 48 weeks there was no significant difference in the level of improvement between the two groups. There was also no significant difference in joint damage or side-effects after either treatment. This trial also showed that patients who did not respond to triple therapy could switch to etanercept plus methotrexate. The opposite was also true, patients could switch from etanercept plus methotrexate to triple therapy. 

The authors concluded that methotrexate should be the first treatment for most rheumatoid arthritis patients. They suggest that if methotrexate is not effective the next step should be triple therapy. After a year they suggest adding biological therapies if the other treatments have failed.