May 29, 2017
3 min read

Biologic therapy not cost-effective for RA after methotrexate fails

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact

Initiating biologic therapy in patients with rheumatoid arthritis when methotrexate monotherapy fails increases costs substantially and provides minimal incremental benefit compared with triple therapy, according to data published in Annals of Internal Medicine.

The researchers suggest that triple therapy be used first before switching to a biologic strategy because it could reduce patients’ out-of-pocket costs and not expose them to serious side effects associated with biologic therapy.

“The American College of Rheumatology recommends that biologic therapy be initiated in patients with rheumatoid arthritis whose disease is not controlled by a combination of conventional disease modifying antirheumatic drugs (DMARDs),” Nick Bansback, PhD, from the University of British Columbia and St. Paul’s Hospital in Canada, and colleagues wrote.

While biologics are expensive, many experts suggest that their health benefits outweigh their additional costs, Bansback and colleagues noted.

“However, the cost-effectiveness studies used as the rationale for this suggestion compared biologics with individual DMARDs instead of a combination of these agents in patients with [rheumatoid arthritis] not controlled by methotrexate monotherapy,” they added.

The researchers studied the cost-effectiveness of triple therapy as a first-line strategy compared with Enbrel (etanercept, Amgen) with methotrexate for patients with active rheumatoid arthritis who were unresponsive to methotrexate after at least 12 weeks of therapy (n = 353). The researchers performed a within-trial analysis based on data from the Rheumatoid Arthritis Comparison of Active Therapies and a lifetime analysis based on a decision analytic model that extrapolated incremental costs and quality-adjusted life years (QALYs) to a 50-year time horizon.

The within-trial analysis suggested that slightly more QALYs, but significantly higher drug costs, were associated with etanercept–methotrexate as first-line therapy. Other costs between strategies did not differ significantly. First-line etanercept–methotrexate and triple therapy had incremental cost-effectiveness ratios of $2.7 million per QALY and $0.98 million per QALY over 24 and 48 weeks, respectively.

Results of the lifetime analysis indicated that etanercept–methotrexate as first-line therapy would result in an additional lifetime QALY of 0.15; however, this would cost an incremental $77,290, resulting in an incremental cost-effectiveness ratio of $521,520 per QALY per patient.

The researchers noted that this figure is well above what is considered to be acceptable in the American health care system.

“In patients who have [rheumatoid arthritis] not adequately controlled by methotrexate alone, we found that the additional costs associated with using etanercept–methotrexate before triple therapy do not provide good value,” Bansback and colleagues concluded. “Even from a long-term perspective, under optimistic scenarios, first-line therapy with etanercept–methotrexate or other biologics likely is not a cost-effective use of resources compared with using triple therapy first.”


In an accompanying editorial, Elena Losina, PhD, and Jeffrey N. Katz, MD, MSc, both from Brigham and Women’s Hospital, praise Bansback and colleagues for describing the model structure, data inputs and model validation clearly. However, they note that the model relied on a dose-response relationship rather than a threshold function which may have reduced the effect of biologics.

In addition, there was lack of consistency between the trial design and reporting of the cost-effectiveness analysis, but the authors did perform extensive sensitivity analyses that supported the robustness of their findings, according to Losina and Katz.

“The high incremental cost-effectiveness ratios documented by Bansback and colleagues comparing [biologic] DMARDs with [conventional] DMARDs suggest that the difference in effectiveness between the two strategies may be too small to justify the large difference in cost,” Bansback and colleagues concluded. “This observation suggests that if biosimilars can deliver the same clinical benefits at a fraction of the cost, they may offer new opportunities to revise cost-effectiveness estimates. In the meantime, the results of Bansback and colleagues remind us that promoting small improvements at any cost, at levels above those well-accepted by U.S. willingness-to-pay thresholds, may further strain our limited resources and limit access to care not only for patients with [rheumatoid arthritis] but also for those with other chronic conditions.” – by Alaina Tedesco

Disclosure: Bansback and colleagues report primary funding from the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, Canadian Institutes for Health Research and an interagency agreement with the National Institutes of Health–American Recovery and Reinvestment Act. Losina and Katz report no relevant financial disclosures.