Omaha, NB—Triple therapy is the most cost-effective next step after methotrexate monotherapy fails in rheumatoid arthritis (RA) patients, according to a new analysis.

The comprehensive cost-effectiveness analysis published in Arthritis Care & Research suggests that turning to biologic therapy at that point offers only minimal incremental benefit at high cost.

Typically, RA patients are first treated with drugs such as methotrexate and relatively inexpensive conventional disease-modifying antirheumatic drugs. If symptoms persist, current guidelines from the American College of Rheumatology urge adding a biologic medication, such as etanercept, to the treatment regimen.

Results of the Rheumatoid Arthritis Comparison of Active Therapies (RACAT) trial appear to run counter to those recommendations. Instead of the biologics-first approach, the study found that triple therapy—a combination of sulfasalazine, hydroxychloroquine, and methotrexate—appears to be as effective as switching directly to biologics.

Yet Nebraska Medical Center–led researchers pointed out that few RA patients end up being transitioned to triple therapy.

For the study, which was funded by the U.S. Department of Veterans Affairs and the Canadian Institutes for Health Research, the costs and benefits of etanercept-methotrexate first versus triple therapy first were compared in 353 patients enrolled in the RACAT trial. Participants all continued to have uncontrolled symptoms of RA after at least 12 weeks of methotrexate therapy.

Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured at 24 months and a lifetime.

While study authors had hypothesized that etanercept would improve outcomes beyond the trial period due to prevention of joint erosions, their analysis indicated that next-line treatment with the biologic therapy provided only slightly greater benefits.

The lifetime analysis suggests that first-line biologic treatment would result in 0.15 additional lifetime QALYs, but at an incremental cost-effectiveness ratio of $521,520 per QALY per patient—which far exceeds what is considered reasonable in the U.S. healthcare system, according to the report.

“In RA patients with suboptimal methotrexate response randomized to receive triple therapy or methotrexate-etanercept, the former was found to be significantly more durable,” study authors conclude. “Given cost differences and similar outcomes, the variable durability demonstrated provides additional evidence supporting conventional combinations over biologic combinations as the first choice after methotrexate inadequate response.”

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