Economic Evaluation of Bruton's Tyrosine Kinase Inhibitors for Chronic Lymphocytic Leukaemia in South Africa.

backgroundTargeted therapy with Bruton's tyrosine kinase inhibitors has demonstrated promising efficacy and safety outcomes in both untreated and relapsed or refractory chronic lymphocytic leukaemia (CLL); however, evidence regarding their cost effectiveness remains limited. This study evaluated the cost effectiveness of ibrutinib, acalabrutinib, and zanubrutinib for the treatment of CLL from the perspective of South Africa's public healthcare system.

methodsA partitioned survival model was developed with three health states: progression-free survival (PFS), progression, and death. The model used a 10-year time horizon with a cycle length of 28 days. Clinical inputs were derived from reference trials representing untreated and relapsed or refractory CLL populations. As no head-to-head trials directly compare all three Bruton's tyrosine kinase (BTK) inhibitors, a naïve (unadjusted) indirect comparison was used, with survival curves sourced independently from pivotal trials for each agent. The distribution of patients in each health state over time was estimated using extrapolated PFS and overall survival (OS) curves for each treatment strategy. Utility values were obtained from published literature, and cost data from national public-sector tariffs. The model estimated total costs, life-years (LYs) gained, and quality-adjusted life-years (QALYs) gained. Outcomes were based on calculated incremental cost effectiveness, with costs and effects discounted at 5.0% per year. Deterministic and probabilistic sensitivity analyses were conducted to test the robustness of the results.

resultsIn the base-case analysis, acalabrutinib versus ibrutinib resulted in an incremental cost-effectiveness ratio of US$1206 per LY gained and US$2124 per QALY gained in untreated CLL patients and US$1140 per LY gained and US$2104 per QALY gained in relapsed or refractory CLL patients. Zanubrutinib was dominant in both populations compared to ibrutinib, providing greater health benefits at lower total costs. In untreated CLL, zanubrutinib resulted in 0.32 more QALYs and cost savings of US$9086 per patient; in the relapsed or refractory CLL, it yielded 0.35 additional QALYs with US$6052 in savings. Additionally, acalabrutinib was more effective but more costly than zanubrutinib, with incremental cost-effectiveness ratio (ICERs) of US$24,010 per QALY gained in untreated CLL patients and US$33,009 per QALY gained in relapsed or refractory CLL patients. The model was most sensitive to drug acquisition costs and costs incurred in the progression-free health state. Probabilistic sensitivity analysis confirmed that zanubrutinib had the highest probability of being cost effective, at 61% in untreated and 65% in relapsed or refractory CLL patients at a willingness-to-pay threshold of US$3407 per QALY. Acalabrutinib showed a 23% and 22% probability of being cost effective in the respective groups, while ibrutinib had the lowest cost-effectiveness likelihood.

conclusionZanubrutinib may be a cost-saving and clinically superior treatment option for both untreated and relapsed/refractory CLL compared to ibrutinib in South Africa's public healthcare system. Its dominance is driven by lower acquisition and adverse event costs, paired with favourable survival and quality-of-life outcomes. Acalabrutinib may also represent a cost-effective alternative compared to ibrutinib, providing meaningful clinical benefit at acceptable additional cost. These results support the prioritisation of zanubrutinib for public sector access and reimbursement, while highlighting acalabrutinib's value in selected patient scenarios.