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Step-up therapy favored for early rheumatoid arthritis

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – After about a year, patients with early aggressive rheumatoid arthritis have the same improvement in disease activity whether treated initially with methotrexate plus additional agents as needed or with immediate combination therapy, investigators report.

“Initial use of methotrexate monotherapy with the addition of sulfasalazine plus hydroxychloroquine – or etanercept, if necessary, after 6 months – is a reasonable therapeutic strategy for early RA,” conclude the authors of the report in Arthritis & Rheumatism online April 16.

Dr. Larry W. Moreland at the University of Pittsburgh, Pennsylvania, and colleagues point out that a step-up strategy is the traditional approach to treating early RA, starting with methotrexate followed by incremental addition of other disease-modifying antirheumatic drugs (DMARDs). On the other hand, it has been shown that fewer patients progress to severe disability if they receive early intensive treatment with a combination of agents.

The team therefore conducted a 2-year study comparing the two approaches, and at the same time compared oral triple therapy to methotrexate plus etanercept.

Seven hundred and fifty five patients with a more severe RA phenotype were enrolled and assigned to one of four treatment arms: immediate combination therapy with methotrexate plus etanercept or methotrexate plus sulfasalazine plus hydroxychloroquine; or initial methotrexate monotherapy with a step-up to one of the combination therapies at week 24 for those who had a poor response.

Clinical response was measured by a 28-joint disease activity score with an erythrocyte sedimentation rate (DAS28-ESR). At week 24, this score was better in the combination arms (3.6) than in those on methotrexate monotherapy (4.6). However, from week 48 to 102, the score was the same (3.2) in the immediate combination arm as in the step-up arm.

Furthermore, at that time point, there was no statistical difference in the DAS28-ESR score between patients treated initially with oral triple therapy (3.1) versus methotrexate plus etanercept (3.2; p=0.42), the authors report.

Discussing the applicability of the results to clinical practice, Dr. Moreland and colleagues observe, “There were similar 2-year improvements in outcomes across groups in functional status and pain and relatively little differences among groups in radiographic progression.”

They conclude, “These data strongly suggest that the cost-effectiveness of less expensive triple therapy may be positive relative to anti-TNF therapy.”


Arthr Rheum 2012.