Biosimilars More Cost-Effective Than Leflunomide After Methotrexate Failure in RA

Among patients with rheumatoid arthritis (RA) who don’t respond to methotrexate, starting treatment with biosimilar disease-modifying antirheumatic drugs (DMARDs) may offer better outcomes at a lower cost than leflunomide, according to new research.¹ These findings strengthen the case for revising treatment guidelines to prioritize biosimilars in early treatment sequencing.

This new economic evaluation supports updating rheumatoid arthritis guidelines to favor biosimilar disease-modifying antirheumatic drugs over leflunomide after methotrexate failure. | Image credit: Evrymmnt - stock.adobe.com

This economic evaluation analysis is published in JAMA Network Open.

“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,” wrote the researchers of the study. “These results suggest the need to update clinical treatment guidelines for initiating biosimilars immediately after the failure of methotrexate for patients with RA.”

Oral methotrexate is the standard first-line treatment for patients with RA, but about 25% of patients discontinue it within a year.² Methotrexate failure, defined as stopping the drug or adding another antirheumatic agent, is typically driven by adverse effects and/or insufficient effectiveness.

The analysis used a Markov disease transition model to simulate the lifetime progression, costs, and health outcomes of patients with RA who did not respond adequately to methotrexate.¹ Conducted at a public institution in Hong Kong, the analysis incorporated clinical and cost data from 25,099 patients diagnosed with RA between 2000 and 2021, using monetary values standardized to 2022. Parameters were derived from retrospective electronic medical records, and the interventions evaluated included 3 treatment sequences initiated with either biosimilar infliximab, biosimilar adalimumab, or leflunomide, each in combination with methotrexate. Scenario and sensitivity analyses were conducted to assess the robustness of the findings and validate the model’s conclusions.

Treatment sequences initiated with biosimilar DMARDs were both more effective and less costly than those initiated with leflunomide following methotrexate failure, according to the findings. Specifically, the biosimilar adalimumab sequence resulted in the lowest lifetime health care cost ($145,419) and the highest gain in quality-adjusted life-years (QALYs, 15.55) compared with biosimilar infliximab ($152,326; QALYs, 15.35 ) and leflunomide ($154,632; QALYs,14.82).

Furthermore, sensitivity analysis showed negative or low incremental cost-effectiveness ratios, all well below the predefined willingness-to-pay threshold of $48,555 per QALY. Additional analysis further supported these findings, with biosimilar adalimumab having a 91% probability of being the most cost-effective option out of 10,000 model iterations compared with just 9% for biosimilar infliximab and 0% for leflunomide.

However, the researchers noted several study limitations, including reliance on randomized controlled data with different patient profiles and potentially overstated treatment efficacy, as trial populations were often biologic-naive. Additionally, the model did not account for productivity gains, likely underestimating the cost benefits of biosimilars. Although results may not generalize beyond Hong Kong, sensitivity analyses suggest biosimilars could be cost-effective in other high-income countries with similar drug pricing and willingness-to-pay thresholds.

Despite these limitations, the researchers believe the study highlights the cost-effectiveness of DMARDS compared with leflunomide in patients with RA after methotrexate failure.

“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,” wrote the researchers. “This study can serve to inform health care stakeholders, rheumatologists, and patients with the unmet needs of bDMARDs [biosimilar DMARDs] about the benefits and financial feasibility of biosimilar DMARDs.”

References

1. 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

2. Bluett J, Sergeant JC, MacGregor AJ, et al. Risk factors for oral methotrexate failure in patients with inflammatory polyarthritis: results from a UK prospective cohort study. Arthritis Res Ther. 2018;20(1):50. doi:10.1186/s13075-018-1544-9