《4个月含利福喷丁抗结核治疗方案疗效观察》解读

doi:10.3969/j.issn.1000-6621.2021.12.004

摘要/Abstract

摘要：

2021年5月,《新英格兰医学杂志》发表了一篇《4个月含利福喷丁抗结核治疗方案疗效观察》的多中心、开放、随机对照非劣效Ⅲ期临床试验研究的论文。2021年6月,世界卫生组织向全球推荐了该方案。该研究设计严谨、合理,质量控制系统、全面,研究结果可信。研究结果显示,4个月含利福喷丁抗结核治疗方案在治疗效果、安全性及耐受性等方面均不劣于6个月标准化疗方案。该方案中利福喷丁使用剂量(1200mg/d)是中国药典规定(成人用量为600mg/次,1~2次/周)的7~14倍。抗结核药物应用是造成中国药物性肝损伤的主要原因之一。中国目前利福平应用有一定比例达不到现行推荐剂量(600mg/d),主要原因是医务人员对肝损伤的顾虑。结合中国药典规定、全国利福平使用情况及影响因素等综合分析,该短程方案在中国推广应用前需要开展试点研究,并出台相关专业指导意见。

关键词: 利福喷丁, 莫西沙星, 临床方案, 药物疗法,联合, 评论, 基于问题的学习

Abstract:

In May 2021, the New England Journal of Medicine published a multi-center, open, randomized controlled non-inferiority phase Ⅲ clinical trial study of the Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis. World Health Organization recommended this chemotherapy regimen to all of the world in June 2021. Upon review and analysis, the clinical trial study was with rigorous and reasonable research design,systematic and comprehensive quality control measures, and the research results were credible. The study results showed that the 4-month anti-tuberculosis chemotherapy regimen was not inferior to the 6-month standard chemotherapy regimen in terms of therapeutic effect, safety and tolerability. The dosage of rifapentine (1200 mg/d) in this regimen is 7-14 times of that recommended by Chinese Pharmacopoeia (600 mg per time for adults, 1-2 times per week). Usage of anti-tuberculosis drugs is one of the important cause of drug-induced liver damage in China. At present, a certain proportion of rifampicin in China does not reach the current recommended dose (600 mg/d), mainly due to medical staff’s concerns about liver injury. Combined with the comprehensive analysis of Chinese Pharmacopoeia regulations, national rifampicin use and influencing factors, this short-course regimen needs to be piloted before it is promoted and applied in China, and relevant professional guidance should be issued.

Key words: Rifapentine, Moxifloxacin, Clinical protocols, Drug therapy,combination, Comment, Problem-based learning

贺晓新, 李波, 周林. 《4个月含利福喷丁抗结核治疗方案疗效观察》解读[J]. 中国防痨杂志, 2021, 43(12): 1243-1247. doi: 10.3969/j.issn.1000-6621.2021.12.004

HE Xiao-xin, LI Bo, ZHOU Lin. Interpretation of Four-month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis[J]. Chinese Journal of Antituberculosis, 2021, 43(12): 1243-1247. doi: 10.3969/j.issn.1000-6621.2021.12.004

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参考文献 17

[1]	Dorman SE, Nahid P, Kurbatova EV, et al. Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis. N Engl J Med, 2021, 384(18):1705-1718. doi: 10.1056/NEJMoa2033400. doi: 10.1056/NEJMoa2033400 URL
[2]	World Health Organization. Treatment of drug-susceptible tuberculosis: rapid communication. Geneva: World Health Organization, 2021.
[3]	Fox W, Ellard GA, Mitchison DA. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946—1986, with relevant subsequent publications. Int J Tuberc Lung Dis, 1999, 3(10 Suppl 2):S231-279.
[4]	Fox W, Mitchison DA. Short-course chemotherapy for pulmonary tuberculosis. Am Rev Respir Dis, 1975, 111(3):325-353. doi: 10.1164/arrd.1975.111.3.325. doi: 10.1164/arrd.1975.111.3.325
[5]	国家药典委员会. 中华人民共和国药典临床用药须知(2010年版). 化学药和生物制品卷. 北京: 中国医药科技出版社, 2021:784-785.
[6]	de Steenwinkel JE, Aarnoutse RE, de Knegt GJ, et al. Optimization of the rifampin dosage to improve the therapeutic efficacy in tuberculosis treatment using a murine model. Am J Respir Crit Care Med, 2013, 187(10):1127-1134. doi: 10.1164/rccm.201207-1210OC. doi: 10.1164/rccm.201207-1210OC URL
[7]	Rosenthal IM, Tasneen R, Peloquin CA, et al. Dose-ranging comparison of rifampin and rifapentine in two pathologically distinct murine models of tuberculosis. Antimicrob Agents Chemother, 2012, 56(8):4331-4340. doi: 10.1128/AAC.00912-12. doi: 10.1128/AAC.00912-12 pmid: 22664964
[8]	Diacon AH, Patientia RF, Venter A, et al. Early bactericidal activity of high-dose rifampin in patients with pulmonary tuberculosis evidenced by positive sputum smears. Antimicrob Agents Chemother, 2007, 51(8):2994-2996. doi: 10.1128/AAC.01474-06. doi: 10.1128/AAC.01474-06 pmid: 17517849
[9]	Svensson EM, Svensson RJ, Te Brake LHM, et al. The Potential for Treatment Shortening With Higher Rifampicin Doses: Relating Drug Exposure to Treatment Response in Patients With Pulmonary Tuberculosis. Clin Infect Dis, 2018, 67(1):34-41. doi: 10.1093/cid/ciy026. doi: 10.1093/cid/ciy026 pmid: 29917079
[10]	Rosenthal IM, Zhang M, Almeida D, et al. Isoniazid or moxifloxacin in rifapentine-based regimens for experimental tuberculosis? Am J Respir Crit Care Med, 2008, 178(9):989-993. doi: 10.1164/rccm.200807-1029OC. doi: 10.1164/rccm.200807-1029OC URL
[11]	Dooley KE, Bliven-Sizemore EE, Weiner M, et al. Safety and pharmacokinetics of escalating daily doses of the antituberculosis drug rifapentine in healthy volunteers. Clin Pharmacol Ther, 2012, 91(5):881-888. doi: 10.1038/clpt.2011.323. doi: 10.1038/clpt.2011.323 pmid: 22472995
[12]	Gillespie SH, Crook AM, McHugh TD, et al. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med, 2014, 371(17):1577-1587. doi: 10.1056/NEJMoa1407426. doi: 10.1056/NEJMoa1407426 URL
[13]	Nunn AJ, Phillips PP, Mitchison DA. Timing of relapse in short-course chemotherapy trials for tuberculosis. Int J Tuberc Lung Dis, 2010, 14(2):241-242. pmid: 20074418
[14]	国家药品监督管理局药品评价中心, 国家药品不良反应监测中心. 关于发布国家药品不良反应监测年度报告(2019年)的通告. 2020-04-10.
[15]	刘旭东, 王炳元. 我国药物性肝损害2003—2008年文献调查分析. 临床误诊误治, 2010, 23(5):487-488. doi: 10.3969/j.issn.1002-3429.2010.z1.004. doi: 10.3969/j.issn.1002-3429.2010.z1.004
[16]	Zhou Y, Yang L, Liao Z, et al. Epidemiology of drug-induced liver injury in China: a systematic analysis of the Chinese litera-ture including 21,789 patients. Eur J Gastroenterol Hepatol, 2013, 25(7):825-829. doi: 10.1097/MEG.0b013e32835f6889. doi: 10.1097/MEG.0b013e32835f6889 URL
[17]	Ostapowicz G, Fontana RJ, Schiødt FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med, 2002, 137(12):947-954. doi: 10.7326/0003-4819-137-12-200212170-00007. doi: 10.7326/0003-4819-137-12-200212170-00007 pmid: 12484709