布鲁顿酪氨酸激酶抑制剂治疗慢性淋巴细胞白血病的快速卫生技术评估

Rapid health technology assessment of the bruton tyrosine kinase inhibitors for the treatment of chronic lymphocytic leukemia

关键词:  快速卫生技术评估  伊布替尼  泽布替尼  阿卡替尼  慢性淋巴细胞白血病

Key words:  rapid health technology assessment  ibrutinib  zanubrutinib  acalabrutinib  chronic lymphocytic leukemia

摘要:

目的 通过快速卫生技术评估（rHTA）评价三种布鲁顿酪氨酸激酶抑制剂（BTKi）治疗慢性淋巴细胞白血病(CLL)的临床价值。方法 系统检索PubMed、Embase、Cochrane Library等数据库，以及卫生技术评估（HTA）机构的相关网站和数据库遴选相关研究。由两名研究者独立完成文献筛选、质量评价及数据提取与分析。同时采用半结构化访谈和封闭式问卷调查获取专家建议。最终从疗效、安全性、经济性、创新性、适用性和可及性六个维度进行证据整合与呈现。结果 共纳入33项研究，包括13项系统综述（SR）/meta分析(荟萃分析)、10项药物经济学研究和10份HTA报告。在疗效方面，BTKi的无进展生存期（PFS）和总生存期（OS）显著长于化学治疗、免疫治疗及化学免疫治疗方案。其中泽布替尼和阿可替尼可进一步延长CLL患者的PFS。安全性方面，BTKi总体耐受性良好，但更易出现高血压、出血事件和心脏毒性。HTA报告和药物经济学研究均提示泽布替尼总用药成本更低，较伊布替尼更具成本-效果优势。BTKi作为具有新型作用机制的口服制剂，多数专家认为其适用性优于化学免疫治疗方案。在专家评估的可及性评分中，泽布替尼在三种BTKi中得分最高。结论 基于现有有限证据，推荐三种BTKi用于中国CLL患者的治疗，其中泽布替尼在中国更具经济性、安全性和可及性优势，可能为CLL患者带来更大的临床价值。

Abstract:

ABSTRACT: OBJECTIVE Through a Rapid Health Technology Assessment (rHTA), we evaluated three bruton tyrosine kinase inhibitors (BTKi) in the treatment of chronic lymphocytic leukemia (CLL), providing the evidence-based basis for the clinical application of CLL patients. METHODS A systematic retrieve on databases including PubMed, Embase, and Cochrane Library, as well as relevant websites and databases of Health Technology Assessment (HTA) agencies. Then, two authors performed data extraction and analysis, literature screening and quality assessment independently. Meanwhile, semi-structured interviews and closed-ended questionnaires were conducted to obtain expert’s suggestions and opinions. Finally, evidence was concluded and depicted in terms of 6 dimensions: efficacy, safety, economy, innovation, suitability, and accessibility. RESULTS 33 studies were included, including 13 systematic reviews (SR)/meta-analyses, 10 economics studies, and 10 HTA reports. In terms of efficacy, the progression-free survival (PFS) and overall survival (OS) of BTKi were significantly longer than chemotherapy, immunotherapy, and chemoimmunotherapy. Zanubrutinib and acalabrutinib could further prolong the PFS of CLL patients. In terms of safety, BTKi were well tolerated, but hypertension, bleeding events, and cardiotoxicity were more likely to be observed. Zanubrutinib had a lower total drug cost and was more cost-effective than ibrutinib in the HTA reports and economics studies. BTKi, with novel mechanisms of action, can be administered orally, the majority of experts endorsed that the suitability of BTKi were superior to chemoimmunotherapy. Zanubrutinib received higher accessibility scores of three BTKi evaluated by experts. CONCLUSION Based on the existing limited evidence, three BTKi are recommended for the treatment of CLL in China. Among the three BTKi, zanubrutinib is more economical, safe, and accessible in China, and may be of greater clinical value for CLL patients.