OBJECTIVES: To assess the cost-effectiveness of ibrutinib in the treatment of patients with RR CLL, an incurable disease with limited treatment options, from the perspective of the English National Health Service (NHS). This analysis formed a key component of the appraisal by the National Institute for Health and Care Excellence (NICE).

METHODS: A three-state partitioned-survival model was used to extrapolate progression-free survival (PFS) and overall survival (OS) over a 20-year time horizon. Cost-effectiveness was estimated in RR CLL patients receiving ibrutinib vs ofatumumab (RESONATE) and vs bendamustine+rituximab (BR), idelalisib+rituximab (IR), and physician’s choice (PC) (relative efficacy based on indirect treatment comparisons). The PC comparator reflects that there was no standard of care in England and was comprised of the comparators listed within the final NICE scope. Utility values were either derived from RESONATE EQ-5D data or based on published sources and were age-adjusted. Costs of drug acquisition and administration, adverse event management, and clinical management were taken from the British National Formulary and NHS Reference costs. Costs and benefits were discounted at 3.5% p.a. Uncertainty was tested through deterministic, probabilistic, and scenario analyses.

RESULTS: The lifetime incremental health gains measured in quality-adjusted life years (QALYs) for ibrutinib were 2.48 vs ofatumumab, 3.07 vs PC, 1.82 vs IR, and 3.36 vs BR. The incremental cost-effectiveness ratios (ICERs) were £53,245, £52,787, £53,644, and £49,023, respectively; a confidential patient access scheme ensured the true ICERs were lower. Sensitivity analyses suggested that choice of extrapolation as well as duration of ibrutinib treatment benefit were the most influential parameters.

CONCLUSIONS: The unprecedented survival benefit of ibrutinib resulted in considerable QALY gains vs all comparators even when the conservative assumptions of the NICE Committee were considered. Ibrutinib is a cost-effective treatment for RR CLL patients at an end-of-life threshold in England.