Biosimilar DMARDs cost-effective vs leflunomide in RA patients after MTX failure

An economic evaluation study by the University of Hong Kong (HKU) found treatment with biosimilar disease-modifying antirheumatic drugs (DMARDs) to be cost-effective compared with leflunomide in patients with rheumatoid arthritis (RA) who failed initial treatment with methotrexate (MTX).

Over half of RA patients fail MTX monotherapy due to inadequate response within 1 year. [RMD Open 2019;5(2):e000993] Current clinical guidelines recommend adding conventional synthetic DMARDs (csDMARDs; eg, leflunomide, cyclosporine, hydroxychloroquine) to MTX in the absence of poor prognostic factors. [Clin Rheumatol 2019;38:3331-3350; Ann Rheum Dis 2023;82:3-18] If combination therapy fails, a combination of biological DMARDs (bDMARDs; eg, infliximab, etanercept, adalimumab) and MTX is recommended as the next treatment step. However, recent evidence from clinical trials and practice suggests that initiating bDMARDs immediately after MTX monotherapy failure offers improved clinical response and drug retention rates compared with intermediate use of csDMARDs. [Lancet 2012;379:1712-1720; Clin Ther 2023;45:e177-e186]

A major barrier to use of bDMARDs in Hong Kong is their substantial cost. [BMJ Open 2023;13:e069681] “Biosimilars of infliximab and adalimumab have been approved in Hong Kong since 2020, with a price reduction range of 54–87 percent vs reference products,” wrote the researchers, “[However], according to the latest public Drug Formulary in Hong Kong, neither the originator nor biosimilar bDMARDs are reimbursed for patients with inadequate MTX response, unless they fulfill the local financial assistance programme’s clinical and income eligibility requirements. Consequently, most patients are required to pay out of pocket, which leads to considerable underuse bDMARDs. The present study therefore examined the cost-effectiveness of treatment sequences initiated with biosimilar infliximab or adalimumab vs frequently used leflunomide among patients with inadequate MTX response to inform biosimilar formulary enlisting decisions.”

The 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. The model assessed three competing treatment sequences initiated with biosimilar infliximab, biosimilar adalimumab, and leflunomide, all of which were used in combination with MTX. [JAMA Network Open 2024;7:e2418800]

In total, 25,099 RA patients (mean age, 56 years; women, 72.7 percent) were identified through a territory-wide electronic medical record database. In base-case analysis, the lifetime healthcare cost was USD 154,632 for leflunomide, USD 152,326 for biosimilar infliximab and USD 145,419 for biosimilar adalimumab. Respective quality-adjusted life-years (QALYs), which measure utility for health states across disease activity, were 14.82, 15.35 and 15.55.

“Treatment sequence initiated with biosimilar DMARDs were associated with improved QALYs and reduced healthcare costs. The cost of supportive care [USD 2,891 per course] in Hong Kong is much higher than the medication cost. Treatment sequences initiated with biosimilar DMARDs slow down disease progression, therefore reducing the time patients spend on supportive care, leading to lower overall treatment costs,” explained the researchers.

The cost-effectiveness conclusion remained unchanged in the deterministic sensitivity analysis. In the probabilistic sensitivity analysis, the probabilities of treatment sequences initiated with leflunomide, biosimilar infliximab and biosimilar adalimumab being a cost-effective strategy out of 10,000 iterations were 0 percent, 9 percent and 91 percent, respectively, at the predefined willingness-to-pay threshold.

“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 MTX response,” concluded the researchers.