Initiating etanercept-methotrexate therapy before trying triple therapy in patients with rheumatoid arthritis (RA) had a marginal clinical benefit while significantly raising treatment costs, according to research published in the Annals of Internal Medicine.
“[I]n 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,” Nick Bansback, PhD, from the University of British Columbia and St Paul’s Hospital in Vancouver, British Columbia, Canada, and colleagues wrote in their study. “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.”
Dr Bansback and colleagues analyzed 324 patients from the Rheumatoid Arthritis Comparison of Active Therapies (RACAT) trial who received etanercept-methotrexate or triple therapy of conventional disease-modifying anti-rheumatic drugs sulfasalazine, hydroxychloroquine, and methotrexate after not responding to methotrexate (15 to 25 mg per week) for a minimum of 12 weeks. The researchers developed a lifetime analysis model that simulated patient RA radiographic and functional disease, and performed a health-related quality of life analysis in quality-adjusted life-years using the EuroQol 5-dimensions questionnaire (EQ- 5D) as well as an economic analysis for incremental cost-effectiveness ratios (ICER) of each therapy.
At 24 weeks, the quality-adjusted life year (QALY) for the etanercept-methotrexate group was .358 compared with .353 in the triple-therapy group (between-group distance 0.004; 95% CI, 0.004-0.012) and was 0.743 at 48 weeks in the etanercept-methotrexate group compared with 0.726 in the triple therapy group (between-group difference 0.016; 95% CI, 0.007-0.039). However, the drug price for the etanercept-methotrexate group at 24 weeks was $11,295 compared with $343 in the triple-therapy group, and the price at 48 weeks was $19,634 in the etanercept-methotrexate group compared with $3,680 in the triple-therapy group.
The researchers found the ICER for the etanercept-methotrexate group was $2.7 million QALY at 24 weeks compared with the triple-therapy group, and that number decreased to $0.98 million at 48 weeks due to 27% of the etanercept-methotrexate group changing to biologic therapy. Overall, the ICER was $521,520 QALY per patient for patients in the etanercept-methotrexate group for an additional 0.15 lifetime QALY and an incremental gain of $77,290.
“Of importance, the implication of this study is not that biologics should be withheld from patients with RA not completely controlled by methotrexate alone,” Dr Bansback and colleagues wrote. “Rather, the study demonstrates the cost savings that would result from prescribing triple therapy first, before a biologic, for such patients. 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.”
Summary & Clinical Applicability
In a related editorial, Elena Losina, PhD, and Jeffrey N. Katz, MD, MSc, from Brigham and Women’s Hospital in Boston, Massachusetts, wrote that the researchers provided a “clear, detailed description of the model structure, data inputs, and model validation,” but their analysis uses a health status score and utility score dose-response relationship that may underrepresent the effect of biologics in the study.
“By using a dose-response rather than a threshold function, the model may have diminished the effect of biologics, which may be more likely to produce the large gains in patients achieving remission,” Drs Losina and Katz wrote. “The value of preserving joints versus slowing structural deterioration was not depicted explicitly in the current model structure, likely diminishing the effect of biologics’ capacity to prevent joint destruction.”
Limitations & Disclosures
The researchers noted that the analysis did not consider the possibility of differing adverse events in the etanercept-methotrexate and triple-therapy groups, and patient simulation did not account for a heterogeneous patient population.
Disclosures: Dr Bansback received grants from Canadian Institutes for Health Research. Dr O’Dell received nonfinancial support from the US Department of Veterans Affairs. Dr Keystone received grants and personal fees from Abbott Laboratories, Amgen, AstraZeneca, Bristol-Myers Squibb, Hoffmann-La Roche, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB; received fees from Biotest, Crescendo Bioscience, Genentech, and Merck; and received grants from Sanofi- Aventis. Dr Mikuls received fees from Pfizer and grants from Bristol-Myers Squibb and Roche. Dr Anis received grants from Canadian Institutes for Health Research, grants and personal fees from Pfizer, personal fees from Sanofi, and grants from AbbVie.
- Bansback N, Phibbs CS, Sun H, et al. Triple therapy versus biologic therapy for active rheumatoid arthritis: A cost-effectiveness analysis [published online May 30, 2017]. Ann Intern Med. doi:10.7326/M16-0713
- Losina E, Katz JN. Improvement at any cost? The art and science of choosing treatment strategies for rheumatoid arthritis [published online May 30, 2017]. Ann Intern Med. doi:10.7326/M17-1176