Triple DMARD therapy vs. methotrexate monotherapy: Which is best in treating early rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic disease that causes pain, stiffness, swelling, destruction leading to limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

Researchers in the Netherlands analyzed data on 281 patients with recent-onset RA who participated in a single-blinded, randomized clinical trial of RA therapies called the treatment in the Rotterdam Early Arthritis Cohort, or tREACH. Current guidelines do not recommend triple DMARD therapy of methotrexate, sulfasalazine and hydroxychloroquine for all newly diagnosed RA patients, although several clinical trials concluded that triple DMARD therapy was better than methotrexate monotherapy. Principal motive of disregarding triple DMARD therapy was the fact that the results were skewed by the use of glucocorticoids. There are also safety concern issues. The researchers sought to compare triple DMARD therapy with methotrexate, and to compare two methods of using glucocorticoids as bridging therapy.

"There is still debate on the most appropriate initial treatment regimen in patients with newly diagnosed RA," explains Pascal de Jong, PhD, Department of Internal Medicine, Erasmus MC; and lead investigator of the study. "The most important discussion herein is that of initial methotrexate monotherapy versus a combination of DMARDs. Therefore, we investigated in our tREACH trial if triple DMARD therapy was better than methotrexate monotherapy independent of corticosteroids at treating RA symptoms."

Participants were randomly split into three groups, each given different induction therapy regimens. The first group of 91 patients received triple DMARD therapy, or 25mg methotrexate per week, 2g of sulfasalazine per day and 400mg of hydroxycholorquine per day, in addition to 120mg of intramuscular glucocorticoids once. The second group of 93 patients received the same triple DMARD therapy with a tapered dose of oral glucocorticoids starting at 15mg per day. The third group of 97 patients received 25mg of methotrexate per week with a similarly tapered dose of oral glucocorticoids, starting at 15mg per day. Participants were 68 percent female and their average duration of having RA symptoms was 166 days. At the beginning of the study, 267 (95 percent) of the participants fulfilled the 2010 ACR Criteria for RA, 216 (77 percent) tested positive for anti-citrullinated protein antibodies (ACPA) and 48 (17 percent) showed evidence of joint erosions.

Participants were examined every three months to assess their progress, including measuring disease activity scores and collecting data from the Health Assessment Questionnaire. After 12 months of therapy, the researchers also analyzed X-ray progression.

The researchers found that after one year of triple DMARD therapy, patients had a better clinical effectiveness than monotherapy. The burden of the disease over time was less in groups receiving triple DMARD therapy compared with patients receiving methotrexate monotherapy. At three months, less treatment failure occurred in both the triple therapy groups, resulting in 40 percent fewer prescriptions of biologic drugs. This difference remained over time. No significant difference was seen between the two glucocorticoid bridging therapy approaches. Over the time period studied, 19 percent of the first group, 23 percent of the second group and 21 percent of the third group showed radiographic progression of their RA. No differences in serious side effects were found between the three groups.

The researchers concluded that for patients with early-onset RA, triple DMARD therapy is better than methotrexate monotherapy, even after one year of therapy, because treatment goals are attained faster and maintained with fewer biologic treatments. Either oral or intramuscular glucocorticoids may be equally effective as bridging therapy for these patients.

"We recommend initial triple DMARD therapy over methotrexate monotherapy as the first choice in newly diagnosed RA patients because treatment goals are attained faster and maintained with 40 percent fewer biological," explains, Dr. de Jong.

Patients should talk to their rheumatologists to determine their best course of treatment.