Long-term benefits of initial combination therapy for rheumatoid arthritis

Oct 30 2005

A progressive, inflammatory disease affecting the joints and organs, rheumatoid arthritis (RA) claims more than two million Americans, mostly women over age 40, among its victims.

While a cure has yet to be found, the treatment of RA patients has changed considerably over the last two decades. Today, the goal of therapy is not simply symptom relief, but the prevention of long-term structural damage and functional decline. Toward this end, various disease-modifying antirheumatic drugs (DMARDs) have been proven effective in clinical trials, on their own and in tandem with various tumor necrosis factor (TNF) antagonists. While the recent increase in therapeutic options offers much promise, it has left doctors grappling with the question: What is the best treatment strategy for a patient newly diagnosed with RA?

The results of a long-term study, featured in the November 2005 issue of Arthritis & Rheumatism, provide clear answers. A team of researchers in the Netherlands compared the four most widely sanctioned and commonly prescribed treatment strategies for very early RA on 508 patients. Primarily women, with a mean age of 54, the patients had suffered disease symptoms for an average of 23 weeks before entering the trial. After randomly assigning the patients to one of four treatment strategies, the researchers closely monitored the effects and benefits for each group over the course of one year.

Group 1 (126 patients) received standard DMARD therapy, starting with methotrexate. Group 2 (121 patients) was assigned to step-combination therapy, starting with methotrexate only, adding other DMARDs and prednisone. Group 3 (133 patients) started with a combination of methotrexate, sulphasalazine and prednisone. Group 4 (128 patients) started with a combination of methotrexate and infliximab. For all groups, drug dosages were increased or switched to other (combinations of) drugs according to the treatment protocol to achieve a state of low disease activity.

At the end of the year, every group demonstrated measurable improvements, with 32 percent of all the patients achieving clinical remission of their disease. However, patients who had received initial combination therapy--either with prednisone (group 3) or with infliximab (group 4)--had significantly less progression of radiographic joint damage than did patients treated with DMARDs only (group 1), or patients assigned to step-up combination therapy (group 2). The number of patients without any progression of radiographic joint damage was also higher in groups 3 and 4 than in groups 1 and 2. Furthermore, RA patients in both initial combination therapy groups experienced earlier functional improvement than did patients in either the DMARD monotherapy or step-up combination therapy group, according to scores of the Dutch version of the Health Assessment Questionnaire. Overall, patients who received initial combination therapy experienced no more side effects than patients in the other two groups.

"Patients in groups 3 and 4 had the benefit of a more rapid relief of symptoms and improvement of physical function," observes the author, B. A. C. Dijkmans, M.D. "In addition, there is the possibility that effective suppression of disease activity during the early phases of the disease may ameliorate the long-term joint damage and poor physical function and, ideally, even induce true clinical remission without the need for ongoing DMARD treatment."

Should any patient with newly diagnosed RA be treated with a single DMARD? Would choosing this established course always make a patient vulnerable to increased disease severity? That question can only be answered with further research.