Ke Ching-Hua, Chung Wen-Hung, Wen Yen-Hsia, Huang Yaw-Bin, Chuang Hung-Yi, Tain You-Lin, Wang Yu-Ching Lily, Wu Cheng-Chih, Hsu Chien-Ning
From the School of Pharmacy, and Department of Public Health and Center of Excellence for Environmental Medicine, Kaohsiung Medical University; Department of Pharmacy, Kaohsiung Medical University, Chung-Ho Memorial Hospital; Department of Pediatrics, and Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung; Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
C.H. Ke, MSc, School of Pharmacy, Kaohsiung Medical University; W.H. Chung, MD, PhD, Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University; Y.H. Wen, PhD, School of Pharmacy, Kaohsiung Medical University; Y.B. Huang, PhD, School of Pharmacy, Kaohsiung Medical University, and Department of Pharmacy, Chung-Ho Memorial Hospital; H.Y. Chuang, MD, PhD, Department of Public Health and Center of Excellence for Environmental Medicine, Kaohsiung Medical University; Y.L. Tain, MD, PhD, Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University; Y.C. Wang, MSc, Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital; C.C. Wu, MSc, Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital; C.N. Hsu, PhD, School of Pharmacy, Kaohsiung Medical University, and Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital.
J Rheumatol. 2017 Jun;44(6):835-843. doi: 10.3899/jrheum.151476. Epub 2017 Apr 1.
Patients with an HLA-B58:01 allele have an increased risk of developing severe cutaneous adverse drug reactions (SCAR) when treated with allopurinol. Although one-off pharmacogenetic testing may prevent life-threatening adverse drug reactions, testing prior to allopurinol initiation incurs additional costs. The study objective was to evaluate the cost-effectiveness of HLA-B58:01 screening compared with using other available urate-lowering agents (ULA).
A decision-analytical model was used to compare direct medical costs and effectiveness [including lifetime saved, quality-adjusted life-yrs (QALY) gained] in treating new patients with the following options: (1) genetic screening followed by allopurinol prescribing for noncarriers of HLA-B*58:01, (2) prescribing benzbromarone without screening, (3) prescribing febuxostat without screening, and (4) prescribing allopurinol without screening. A 1-year time frame and third-party payer perspective were modeled for both the entire cohort (base-case) and for the subgroup of patients with chronic kidney disease (CKD).
The incremental cost-effectiveness ratio of genetic screening prior to ULA therapy was estimated as New Taiwan (NT) $234,610 (US$7508) per QALY gained in the base-case cohort. For patients with CKD, it was estimated as NT$230,925 (US$7390) per QALY. The study results were sensitive to the probability of benzbromarone/febuxostat-related hypersensitivity, and a negative predicted value of genotyping.
HLA-B58:01 screening gave good value for money in preventing allopurinol-induced SCAR in patients indicated for ULA therapy. In addition to the costs of genotyping, it is important to monitor ULA safety closely in adopting HLA-B58:01 screening in practice.
携带HLA - B58:01等位基因的患者在使用别嘌醇治疗时发生严重皮肤药物不良反应（SCAR）的风险增加。虽然一次性的药物遗传学检测可预防危及生命的药物不良反应，但在开始使用别嘌醇之前进行检测会产生额外费用。本研究的目的是评估与使用其他可用的降尿酸药物（ULA）相比，HLA - B58:01筛查的成本效益。
采用决策分析模型，比较以下治疗新患者方案的直接医疗成本和有效性[包括挽救的生命时长、获得的质量调整生命年（QALY）]：（1）对HLA - B*58:01非携带者进行基因筛查后开具别嘌醇；（2）不进行筛查直接开具苯溴马隆；（3）不进行筛查直接开具非布司他；（4）不进行筛查直接开具别嘌醇。针对整个队列（基础病例）以及慢性肾脏病（CKD）患者亚组，构建了为期1年的时间框架和第三方支付方视角的模型。
在基础病例队列中，ULA治疗前进行基因筛查的增量成本效益比估计为每获得1个QALY需新台币234,610元（7508美元）。对于CKD患者，估计为每获得1个QALY需新台币230,925元（7390美元）。研究结果对苯溴马隆/非布司他相关超敏反应的概率以及基因分型的阴性预测值敏感。
HLA - B58:01筛查在预防ULA治疗适应证患者的别嘌醇诱导的SCAR方面具有良好的性价比。除基因分型成本外，在实际应用HLA - B58:01筛查时密切监测ULA安全性也很重要。
