Treating Rheumatoid Arthritis Patients With Biosimilars Versus Leflunomide: An Economic Evaluation

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A study explores the cost-effectiveness of combining methotrexate with various drugs as a way to combat failed methotrexate monotherapy.

Image Credit: Adobe Stock Images/DouceFleur.com

Image Credit: Adobe Stock Images/DouceFleur.com

As some may be aware, rheumatoid arthritis (RA) is an inflammatory joint disease that can result in not only permanent joint destruction, but overall physical and mental impairment.1 As a way to combat RA, methotrexate has been prescribed for safety and efficacy purposes, but more than 50% of patients have dealt with failed methotrexate monotherapy, signifying an “inadequate response” with one year.2

In order to this problem, the latest clinical guidelines suggest using methotrexate in combination with several synthetic disease-modifying antirheumatic drugs (csDMARDs, including cyclosporine, hydroxychloroquine), leflunomide). However, the cost-effectiveness evidence of taking this route is still uncertain.

As a result, an economic evaluation study published in JAMA Network Open3 sought to solve this mystery.

The aforementioned economic evaluation occurred at a Hong Kong public institution using a multistate Markov disease transition model that simulated the lifetime disease progression and cost for RA patients, using 2022 monetary value. Scenario and sensitivity analyses were performed to test the internal validity of the modeling conclusion. Participants featured patients who were diagnosed with RA from 2000 to 2021 who were gathered retrospectively from local electronic medical records in order to design model input parameters, while the statistical analysis was performed from January 2023 to March 2024.

The model was designed to evaluate three competing treatment sequences that started with biosimilar infliximab (CT-P13), biosimilar adalimumab (ABP-501), and leflunomide; all were used with methotrexate, as clinical guidelines recommended.

Results indicated that in total, 25,099 RA patients with RA were identified (mean [standard deviation] age, 56 [17] years; 19,469 [72.7%] women). In the base-case analysis, the lifetime health care cost and quality-adjusted life-years (QALYs) for the treatment sequence initiated with leflunomide came out $154,632 and 14.82 QALYs, respectively; for biosimilar infliximab, they were $152 326 and 15.35 QALYs; and for biosimilar adalimumab, they were $145,419 and 15.55 QALYs. The biosimilar sequences demonstrated lower costs and greater QALYs than that of the leflunomide sequence. When it came down to the deterministic sensitivity analysis, the incremental cost-effectiveness ratio (US$/QALY) that analyzed biosimilar infliximab sequence alongside leflunomide sequence and biosimilar adalimumab sequence alongside leflunomide sequence ranged from −15,797 to −8,615 and −9,088 to 10 ,238, respectively, which were all below the predefined willingness-to-pay threshold ($48, 555/QALY gain). The probabilistic sensitivity analysis showed that the probability of treatment sequence initiated with leflunomide, biosimilar infliximab, and biosmilar adalimumab being cost-effective out of 10 000 iterations was 0%, 9%, and 91%, respectively.

In terms of limitations, since there was not any local evidence, treatment efficacies were principally pulled from independent randomized controlled trials with heterogeneity in patients’ demographic and clinical profiles.

The investigators concluded that, “From the Hong Kong Public institution perspective, treatment sequences initiated with biosimilar DMARDs were cost-effective compared with treatment sequence initiated with leflunomide among patients with RA and an inadequate methotrexate response. This study can serve to inform health care stakeholders, rheumatologists, and patients with the unmet needs of bDMARDs about the benefits and financial feasibility of biosimilar DMARDs.”

Reference

1. Safiri S, Kolahi AA, Hoy D, et al. Global, regional and national burden of rheumatoid arthritis 1990-2017: a systematic analysis of the Global Burden of Disease study 2017. Ann Rheum Dis. 2019;78(11):1463-1471. doi:10.1136/annrheumdis-2019-215920

2. Chatzidionysiou K, Sfikakis PP. Low rates of remission with methotrexate monotherapy in rheumatoid arthritis: review of randomised controlled trials could point towards a paradigm shift. RMD Open. 2019;5(2):e000993. doi:10.1136/rmdopen-2019-000993

3. Peng K, Chan SCW, Wang Y, et al. Cost-Effectiveness of Biosimilars vs Leflunomide in Patients With Rheumatoid Arthritis. JAMA Netw Open. 2024;7(6):e2418800. doi:10.1001/jamanetworkopen.2024.18800

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