Triple Therapy More Cost-Effective Than MTX + Biologic in RA

Janis C. Kelly

May 30, 2017

Patients with active rheumatoid arthritis (RA) did as well when switched from methotrexate (MTX) monotherapy to triple-drug therapy (MTX, sulfasalazine, and hydroxychloroquine) as when the biologic drug etanercept was added to ongoing MTX. Triple therapy saved more than $500,000 per patient for each year of good-quality life gained, the researchers found.

Nick Bansback, PhD, from the University of British Columbia and St Paul's Hospital, Vancouver, British Columbia, Canada, and colleagues report their findings in an article published online May 30 in the Annals of Internal Medicine.

The authors estimate that a policy requiring that triple therapy be prescribed before a biologic regimen "might save millions of dollars in health care expenditures." They note that currently only about 2.5% of patients with RA are moved to triple therapy rather than biologic therapy after solo MTX proves to be inadequate.

"[I]n patients who have RA not adequately controlled by [MTX] alone, we found that the additional costs associated with using etanercept–[MTX] before triple therapy do not provide good value," the authors write. "Even from a long-term perspective, under optimistic scenarios, first-line therapy with etanercept–[MTX] or other biologics likely is not a cost-effective use of resources compared with using triple therapy first."

The cost-effectiveness analysis used data from the Rheumatoid Arthritis Comparison of Active Therapies (RACAT) trial, which had previously shown that triple therapy was neither inferior to nor less safe than MTX plus a biologic for patients with RA not controlled by MTX monotherapy. The researchers examined the cost-effectiveness of triple therapy compared with etanercept–MTX in these patients.

The RACAT study was a multicenter, randomized, double-blind study that enrolled 353 participants, all of whom had received MTX at stable doses of 15 to 25 mg/week for at least 12 weeks, but had an inadequate response, with median Disease Activity Scores (DAS28) of 5.8 and 5.9 in the triple-therapy and etanercept groups, respectively.

The researchers randomly assigned patients to receive triple therapy (n = 178) or etanercept–MTX (n = 175). At 24 weeks, patients who did not have a decrease of at least 1.2 in DAS28 score (the minimum considered clinically significant) were switched to the other therapy. This included 27.0% of patients initially assigned to triple therapy and 26.7% of patients initially assigned to etanercept–MTX.

The authors note that the RACAT outcomes not only confirmed noninferiority of triple therapy compared with etanercept–MTX but also showed that patients who did not have DAS28 improvement of at least 1.2 could still achieve good responses when switched to the other therapy after 24 weeks.

The outcome measures in the cost-effectiveness analysis included incremental costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. The researchers report that:

  • Drug costs at 24 weeks were $343 for triple therapy vs $11,295 for etanercept–MTX.

  • Drug costs at 48 weeks were $3680 for triple therapy vs $19,634 for etanercept–MTX.

  • Accumulated QALYs were 0.353 for triple therapy vs 0.358 for etanercept–MTX over the course of 24 weeks and 0.726 vs 0.743 over the course of 48 weeks.

  • The incremental cost-effectiveness ratio for etanercept–MTX vs triple therapy was $2.7 million per QALY gained over the course of 24 weeks.

  • After the treatment adjustment at 24 weeks, the incremental cost-effectiveness ratio for etanercept–MTX decreased to $0.98 million per QALY gained over the course of 48 weeks.

The researchers also used a lifetime analysis model to estimate the cost differences over time in relation to QALY gained. The cost of an additional 55 days of perfect health was $521,520 greater with etanercept–MTX compared with triple therapy. A cost of $100,000 per QALY is generally considered to be the limit of "affordable." The authors estimate the probability that a biologic-first strategy would be cost-effective at this threshold to be 0.1%.

"We calculated that the annual acquisition cost of a biologic would have to be less than one third of its current price for it to be considered cost-effective at the threshold of $100 000 per QALY," they write.

"The high incremental cost-effectiveness ratios documented by Bansback and colleagues comparing [biologic and conventional disease-modifying antirheumatic drugs] suggest that the difference in effectiveness between the 2 strategies may be too small to justify the large difference in cost," Elena Losina, PhD, and Jeffrey N. Katz, MD, from Brigham and Women's Hospital, Boston, Massachusetts, write in an accompanying editorial.

"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 RA but also for those with other chronic conditions."

The researchers also note that triple therapy "has been promoted for more than a decade but currently is used far less than biologics as a first-line treatment after [MTX] failure." For example, they note a Veterans Affairs study of patients with RA that showed that only 2.5% had been prescribed triple therapy before a biologic.

The researchers stress that their study should not be taken to mean that biologics should be withheld from patients with RA who continue to have active disease despite MTX monotherapy, but, rather, that clinicians should consider the cost savings from trying triple therapy before moving on to biologic therapy for such patients. They write, "This study shows that for every patient who tries triple therapy before a biologic, payers will save an average of $78 000 over the patient's lifetime, and most of that savings will accrue within the first 10 years."

"Results of this evaluation suggest that patients who have RA and no contraindications to triple-[conventional disease-modifying antirheumatic drug] therapy should use it instead of biologics as the next regimen if [MTX] alone fails to control symptoms and radiographic progression," Dr Losina and Dr Katz conclude.

The study was funded by the Cooperative Studies Program of the Department of Veterans Affairs and the Canadian Institutes for Health Research. Amgen donated the placebo etanercept. Dr Bansback reports receiving grants from the Canadian Institutes for Health Research during the conduct of the study. One coauthor reports receiving nonfinancial support from the US Department of Veterans Affairs during the conduct of the study. Other coauthors report receiving grants and personal fees from Abbott Laboratories, Amgen, AstraZeneca, Bristol-Myers Squibb, Hoffmann-La Roche, Eli Lilly and Company, Janssen, Novartis, Pfizer, UCB, Biotest, Crescendo Bioscience, Genentech, Merck, Sanofi-Aventis, and Roche Genentech. The editorialists have disclosed no relevant financial relationships.

Ann Intern Med. Published online May 30, 2017. Article abstract, Editorial extract

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