Individuals with recent-onset rheumatoid arthritis treated according to disease activity score for 2 years appear to gain little benefit from conventional disease-modifying antirheumatic drugs after initial methotrexate failure, according to the results of a post hoc analysis of the randomized, multicenter, controlled BeSt study.
Overall, 162 of the 244 study patients (66%) failed 2 years of initial methotrexate (MTX) therapy. A subsequent addition of, or switch to, sulfasalazine (SSA), failed in 108 of 138 patients (78%). Subsequent leflunomide monotherapy failed in 47 of 54 patients (87%), while MTX plus SSA and hydroxychloroquine failed in 28 of 44 patients (64%), reported Dr. Sjoerd M. van der Kooij of the Leiden (the Netherlands) University Medical Center and colleagues. However, 34 of 48 patients (71%) who switched to MTX plus infliximab did have treatment success.
Overall, the median total Sharp/van der Heijde score progression was significantly greater among “MTX failures” than “MTX successes” (3 units vs. 1 unit, respectively), regardless of response to subsequent disease-modifying antirheumatic drugs (DMARDs) (Ann. Rheum. Dis. 2007 Feb. 9 [Epub doi:10.1136/ard.2006.066662]).
“This observation confirms earlier studies suggesting that adequate, early suppression of disease activity is paramount for the suppression of joint damage progression,” wrote Dr. van der Kooij and colleagues.
“MTX successes” included the 79 patients who achieved a disease activity score (DAS) of 2.4 after 2 years of methotrexate monotherapy. “MTX failures” included the 66% of patients in the study who initially received MTX 15–25 mg/wk but who discontinued the drug because of toxicity or failure to achieve a DAS of 2.4 or less after 2 years, according to the investigators. These patients were then randomized to receive either sequential monotherapy or a step-up combination therapy. A higher DAS at baseline and female sex were significantly and independently predictive of MTX failure.
Dr. van der Kooij and colleagues suggested that, following the failure of initial MTX therapy, treatment with an anti-tumor necrosis factor agent should not be delayed, given that “switching to or adding other conventional DMARDs offers little chance of clinical efficacy and allows progression of joint damage.”
BeST is supported by the Dutch government and the Dutch College of Health Insurance Companies.