Treatment with isoniazid or rifampin for latent tuberculosis infection: population-based study of hepatotoxicity, completion and costs
Treatment with isoniazid or rifampin for latent tuberculosis infection: population-based study of hepatotoxicity, completion and costs
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DOI：
10.1183/13993003.02048-2019
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发表时间：
2020-03-01
影响因子：
24.3
通讯作者：
Menzies, Dick
中科院分区：
文献类型：
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作者：
Ronald, Lisa A.;FitzGerald, J. Mark;Menzies, Dick
临床试验表明，与 9 个月异烟肼 (9H) 相比，4 个月利福平 (4R) 治疗潜伏性结核感染 (LTBI) 的肝毒性更小，依从性更好。我们的目标是使用省级卫生行政数据，比较加拿大魁北克省一般人群中严重肝脏不良事件和治疗完成的频率以及 LTBI 方案 4R 和 9H 的直接卫生系统成本。我们的回顾性队列包括 2003 年至 2007 年间开始使用利福平或异烟肼方案的所有患者。我们根据住院记录估计肝毒性，根据社区药房记录估计治疗完成情况，并根据账单记录和报告估计直接成本。费用表。我们使用logistic（肝毒性）、对数二项式（完成）和gamma（成本）回归比较利福平和异烟肼，并调整年龄、合并症和其他混杂因素。10 559 名个体开始 LTBI 治疗（9684 名异烟肼；875 名利福平）。利福平患者年龄较大，基线合并症较多。异烟肼 (n=15) 的严重肝毒性风险高于利福平 (n=1)，调整后 OR=2.3 (95% CI: 0.3-16.1)；使用异烟肼进行了两次肝移植，并有 1 例死亡，而使用利福平则没有一例死亡。总体而言，没有合并症的患者肝毒性风险较低（0.1% 与 1.0%）。 4R 完成率 (53.5%) 高于 9H (36.9%)，调整后 RR=1.5 (95% CI: 1.3-1.7)。利福平的每位患者平均费用低于异烟肼：调整后的费用比=0.7（95% CI：0.5-0.9）。调整年龄和合并症后，4R 的严重肝毒性风险和直接费用低于 9H，且完成率更高。接受 9H 治疗的 3 名患者因严重肝毒性导致死亡或进行肝移植，而接受 4R 治疗的患者则没有出现这种情况。
Clinical trials suggest less hepatotoxicity and better adherence with 4 months rifampin (4R) versus 9 months isoniazid (9H) for treating latent tuberculosis infection (LTBI). Our objectives were to compare frequencies of severe hepatic adverse events and treatment completion, and direct health system costs of LTBI regimens 4R and 9H, in the general population of the province of Quebec, Canada, using provincial health administrative data.Our retrospective cohort included all patients starting rifampin or isoniazid regimens between 2003 and 2007. We estimated hepatotoxicity from hospitalisation records, treatment completion from community pharmacy records and direct costs from billing records and fee schedules. We compared rifampin to isoniazid using logistic (hepatotoxicity), log-binomial (completion), and gamma (costs) regression, with adjustment for age, co-morbidities and other confounders.10 559 individuals started LTBI treatment (9684 isoniazid; 875 rifampin). Rifampin patients were older with more baseline co-morbidities. Severe hepatotoxicity risk was higher with isoniazid (n=15) than rifampin (n=1), adjusted OR=2.3 (95% CI: 0.3-16.1); there were two liver transplants and one death with isoniazid and none with rifampin. Overall, patients without co-morbidities had lower hepatotoxicity risk (0.1% versus 1.0%). 4R completion (53.5%) was higher than 9H (36.9%), adjusted RR=1.5 (95% CI: 1.3-1.7). Mean costs per patient were lower for rifampin than isoniazid: adjusted cost ratio=0.7 (95% CI: 0.5-0.9).Risk of severe hepatotoxicity and direct costs were lower, and completion was higher, for 4R than 9H, after adjustment for age and co-morbidities. Severe hepatotoxicity resulted in death or liver transplant in three patients receiving 9H, compared with no patients receiving 4R.