Pharmacoeconomic Report: Nintedanib (Ofev)
Indication: Chronic Fibrosing Interstitial Lung Diseases
CADTH Common Drug Review
The INBUILD study reported that, in adult patients with progressive fibrosing interstitial lung disease (PF-ILD), the difference in mortality between nintedanib (NIN) plus best supportive care (BSC) compared with BSC alone was not statistically significant over 52 weeks. However, the assumed and extrapolated difference in mortality is a key driver in the economic analysis.
CADTH undertook reanalyses to address limitations relating to the following: the extrapolations of overall survival by selecting a gamma function which estimated more clinically plausible net survival benefits; modified the extrapolation of time to the discontinuation of NIN to a log-normal function to reflect what clinical experts considered to be more clinically plausible based on their existing experience with this drug; and, selected an alternate prediction model for change in forced vital capacity percent predicted (FVCPP) for BSC based on one that applied the same covariates as those used for the NIN plus BSC prediction model. Based on CADTH reanalysis, the incremental cost-effectiveness ratio (ICER) for NIN plus BSC compared with BSC was $154,688 per quality-adjusted life-year (QALY) gained, which aligned with the sponsor’s findings. The probability that NIN plus BSC was cost-effective at a willingness-to-pay threshold of $50,000 per QALY gained was 8%. A reduction of 77% in the price of NIN was required to improve its cost-effectiveness, relative to BSC, and generate an ICER less than $50,000 per QALY. While the survival benefit of NIN plus BSC relative to BSC alone, as estimated in the CADTH reanalysis (i.e., 1.38 additional life-years), was considered reasonable by the clinical experts consulted by CADTH, it is important to note that the INBUILD study was unable to demonstrate a statistically significant difference in mortality. In a scenario analysis where no survival benefit for NIN was assumed, the ICER for NIN plus BSC versus BSC increased to $317,832 per QALY gained. To address, in part, the heterogeneity of PF-ILD, subgroup analyses were further conducted for the usual interstitial pneumonia (UIP)-like and non-UIP fibrotic patterns. The ICER for NIN plus BSC for the UIP-like fibrotic pattern subgroup was $135,208 per QALY gained while the ICER for the non-UIP pattern subgroup was $185,321 per QALY gained when compared with BSC.
The results of CADTH’s reanalyses remain uncertain as the model is sensitive to the survival benefit modelled and the regression model used to predict decreases in FVCPP over time. Both inputs represent substantial sources of uncertainty in the model and CADTH was unable to validate these aspects in the absence of long-term clinical efficacy data for NIN. Furthermore, given a lack of studies reporting the measurement properties of FVCPP in patients with PF-ILD, CADTH was unable to incorporate an evidence-based FVCPP cut-off to define disease progression.
Version: Final (with redactions)
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