MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology and Center for Tuberculosis, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
These authors contributed equally to this work.
Eur Respir J. 2018 Dec 20;52(6). doi: 10.1183/13993003.01470-2018. Print 2018 Dec.
Latent tuberculosis infection (LTBI) management is now a critical component of the World Health Organization's End TB Strategy.In this randomised controlled trial (Chinese Clinical Trial Registry identifier ChiCTR-IOR-15007202), two short-course regimens with rifapentine plus isoniazid (a 3-month once-weekly regimen and a 2-month twice-weekly regimen) were initially designed to be evaluated for rural residents aged 50-69 years with LTBI in China.Due to the increasingly rapid growth and unexpected high frequency of adverse effects, the treatments were terminated early (after 8 weeks for the once-weekly regimen and after 6 weeks for the twice-weekly regimen). In the modified intention-to-treat analysis on the completed doses, the cumulative rate of active disease during 2 years of follow-up was 1.21% (14 out of 1155) in the untreated controls, 0.78% (10 out of 1284) in the group that received the 8-week once-weekly regimen and 0.46% (six out of 1299) in the group that received the 6-week twice-weekly regimen. The risk of active disease was decreased, with an adjusted hazard ratio of 0.63 (95% CI 0.27-1.43) and 0.41 (95% CI 0.15-1.09) for the treatments, respectively. No significant difference was found in the occurrence of hepatotoxicity (1.02% (13 out of 1279) 1.17% (15 out of 1279); p=0.704).The short regimens tested must be used with caution among the elderly because of the high rates of adverse effects. Further work is necessary to test the ultrashort regimens in younger people with LTBI.
潜伏性结核感染（LTBI）管理现在是世界卫生组织终结结核病战略的一个关键组成部分。在这项随机对照试验（中国临床试验注册中心注册号 ChiCTR-IOR-15007202）中，最初设计了两种利福平加异烟肼的短程方案（3 个月每周 1 次方案和 2 个月每周 2 次方案），用于评估中国 50-69 岁 LTBI 农村居民。由于增长迅速且不良反应发生率高得令人意外，治疗提前结束（每周 1 次方案治疗 8 周，每周 2 次方案治疗 6 周）。在按意向治疗原则进行的修改分析中，在 2 年的随访期间，未治疗对照组中活动性疾病的累积发生率为 1.21%（14/1155），8 周每周 1 次方案组为 0.78%（10/1284），6 周每周 2 次方案组为 0.46%（6/1299）。治疗组的疾病活性风险降低，调整后的危险比分别为 0.63（95%CI 0.27-1.43）和 0.41（95%CI 0.15-1.09）。未发现肝毒性（1.02%（13/1279）与 1.17%（15/1279）；p=0.704）的发生率存在差异。由于不良反应发生率高，这些短程方案在老年人中必须谨慎使用。需要进一步研究在 LTBI 的年轻人中测试超短程方案。
