Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Human Genetics, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
J Crohns Colitis. 2019 Jul 25;13(7):838-845. doi: 10.1093/ecco-jcc/jjz009.
Decreased thiopurine S-methyltransferase [TPMT] enzyme activity increases the risk of haematological adverse drug reactions [ADRs] in patients treated with thiopurines. Clinical studies have shown that in patients with inflammatory bowel disease [IBD], pharmacogenetic TPMT-guided thiopurine treatment reduces this risk of ADRs. The aim of this study was to investigate whether this intervention impacts on healthcare costs and/or quality of life.
An a priori defined cost-effectiveness analysis was conducted in the Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory bowel disease Clinics [TOPIC] trial, a randomized controlled trial performed in 30 Dutch hospitals. Patients diagnosed with IBD [age ≥18 years] were randomly assigned to the intervention [i.e. pre-treatment genotyping] or control group. Total costs in terms of volumes of care, and effects in quality-adjusted life years [QALYs], based on EuroQol-5D3L utility scores, were measured for 20 weeks. Mean incremental cost savings and QALYs with confidence intervals were calculated using non-parametric bootstrapping with 1000 replications.
The intervention group consisted of 381 patients and the control group 347 patients. The mean incremental cost savings were €52 per patient [95% percentiles -682, 569]. Mean incremental QALYs were 0.001 [95% percentiles -0.009, 0.010]. Sensitivity analysis showed that the results were robust for potential change in costs of screening, costs of biologicals and costs associated with productivity loss.
Genotype-guided thiopurine treatment in IBD patients reduced the risk of ADRs among patients carrying a TPMT variant, without increasing overall healthcare costs and resulting in comparable quality of life, as compared to standard treatment.
硫嘌呤 S-甲基转移酶 [TPMT] 酶活性降低会增加接受硫嘌呤治疗的患者发生血液学药物不良反应 [ADR] 的风险。临床研究表明，在炎症性肠病 [IBD] 患者中，基于遗传药理学的 TPMT 指导的硫嘌呤治疗可降低这种 ADR 风险。本研究旨在探讨这种干预措施是否会影响医疗保健成本和/或生活质量。
在 30 家荷兰医院进行的炎症性肠病诊所中通过遗传药理学检测优化硫嘌呤治疗 [TOPIC] 试验中，进行了一项预先定义的成本效益分析。该试验纳入了诊断为 IBD（年龄≥18 岁）的患者，随机分配至干预组（即治疗前基因分型）或对照组。在 20 周内，以护理量为单位测量总成本，并根据 EuroQol-5D3L 效用评分测量生活质量调整生命年 [QALY] 的变化。采用非参数自举法（重复 1000 次）计算平均增量成本节约和置信区间内的 QALY。
干预组包括 381 例患者，对照组包括 347 例患者。每位患者的平均增量成本节约为 52 欧元[95% 置信区间为-682 欧元，569 欧元]。平均增量 QALY 为 0.001[95% 置信区间为-0.009，0.010]。敏感性分析表明，在筛查成本、生物制剂成本和与生产力损失相关的成本发生潜在变化的情况下，结果具有稳健性。
与标准治疗相比，IBD 患者的基于遗传药理学的硫嘌呤治疗可降低携带 TPMT 变异的患者发生 ADR 的风险，同时不会增加总体医疗保健成本，且生活质量相当。
