Cost-Effectiveness of Biosimilars vs Leflunomide in Patients With Rheumatoid Arthritis.

Importance: Among patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate, a treatment sequence initiated with biosimilar disease-modifying antirheumatic drugs (DMARDs) provides better clinical efficacy compared with conventional synthetic DMARDs recommended by current treatment guidelines; but its cost-effectiveness evidence remains unclear. Objective: To evaluate the cost-effectiveness of the treatment sequence initiated with biosimilar DMARDs after failure with methotrexate vs leflunomide and inform formulary listing decisions. Design, Setting, and Participants: This economic evaluation's cost-effectiveness analysis was performed at a Hong Kong public institution using the Markov disease transition model to simulate the lifetime disease progression and cost for patients with RA, using monetary value in 2022. Scenario and sensitivity analyses were performed to test the internal validity of the modeling conclusion. Participants included patients diagnosed with RA from 2000 to 2021 who were retrieved retrospectively from local electronic medical records to generate model input parameters. Statistical analysis was performed from January 2023 to March 2024. Interventions: The model assesses 3 competing treatment sequences initiated with biosimilar infliximab (CT-P13), biosimilar adalimumab (ABP-501), and leflunomide; all used in combination with methotrexate. Main Outcomes and Measures: Lifetime health care cost and quality-adjusted life-years (QALYs) of the simulated cohort. Results: In total, 25 099 patients with RA were identified (mean [SD] age, 56 [17] years; 19 469 [72.7%] women). In the base-case analysis, the lifetime health care cost and QALYs for the treatment sequence initiated with leflunomide were US $154 632 and 14.82 QALYs, respectively; for biosimilar infliximab, they were US $152 326 and 15.35 QALYs, respectively; and for biosimilar adalimumab, they were US $145 419 and 15.55 QALYs, respectively. Both biosimilar sequences presented lower costs and greater QALYs than the leflunomide sequence. In the deterministic sensitivity analysis, the incremental cost-effectiveness ratio (US$/QALY) comparing biosimilar infliximab sequence vs leflunomide sequence and biosimilar adalimumab sequence vs leflunomide sequence ranged from -15 797 to -8615 and -9088 to 10 238, respectively, all below the predefined willingness-to-pay threshold (US $48 555/QALY gain). In the probabilistic sensitivity analysis, 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. Conclusions and Relevance: In this economic evaluation study, the treatment sequences initiated with biosimilar DMARDs were cost-effective compared with the treatment sequence initiated with leflunomide in managing patients with RA who experienced failure with the initial methotrexate treatment. These results suggest the need to update clinical treatment guidelines for initiating biosimilars immediately after the failure of methotrexate for patients with RA.

The cost of teriflunomide in the treatment of relapsing-remitting multiple sclerosis.

AIMS: Teriflunomide, used globally to treat multiple sclerosis (MS) and widely subsidised for this indication including in Australia and New Zealand, is the main metabolite of leflunomide, an older immune-modulating drug. Leflunomide therefore represents a potential alternative therapy for MS. Teriflunomide is about 50-500 times more expensive than leflunomide, depending on prices in each jurisdiction. I wished to study how this situation arose. METHODS: Web search to obtain the publicly available minutes of eight international regulatory bodies that have approved teriflunomide for the governments of the US, Canada, Europe, England, Scotland, Australia (TGA and PBS) and New Zealand, and examination of the processes and minuted discussions concerning the metabolic, efficacy, toxicity and cost relationship between teriflunomide and leflunomide. RESULTS: The relationship between the two drugs and their relative efficacy or toxicity in MS was considered by three of eight agencies (Food and Drug Administration (FDA), European Medicines Agency (EMA) and the Canadian Agency for Drugs and Technology in Health (CADTH)). The remaining agencies accepted teriflunomide applications at face value, assessed cost-effectiveness against contemporaneous drugs used for treating MS, and did not discuss the potential role of leflunomide as a therapy for MS. No agency minuted the implications of the cost difference. CONCLUSIONS: Efficacy for leflunomide in MS is likely but unproven. The sponsor presented a case for teriflunomide that was within the established procedures for drug agencies in establishing cost-effectiveness, and agencies did not stray from their normal procedures. As a result, an opportunity to decrease the cost of treating MS has been missed. Though off-label use of leflunomide is possible, this is unlikely without a publicly-funded trial to demonstrate non-inferiority with regard to efficacy and safety.