复治涂阳肺结核继续期治疗方案的循证评价

Evidence-Based Assessment of Continuation Phase Treatment Regimens for Category II Tuberculosis

目的循证评价复治涂阳肺结核继续期治疗方案,为WHO基本药物目录(WHOEML)调整及国家指南更新提供依据。方法计算机检索官方网站和CBMdisc(1978～2006),Cochrane图书馆(2006年第4期),DARE(1994～2006),MEDLINE(1950～2006),EMBASE(1974～2006),BIOSISPreviews(1997～2006)等数据库,同时手检相关杂志和参考文献。按照纳入、排除标准严格选择文献。对纳入文献分类分级,循证分析。结果共纳入28篇RCT,4篇CCT,11篇叙述性研究和5篇WHO/国家指南。WHO及高结核负担国家结核防治指南中Ⅱ类结核治疗继续期均使用利福平、异烟肼和乙胺丁醇,但疗程、剂量有差异。此外,此3药也较多用于其它类型结核。结论建议将利福平(R)、异烟肼(H)和乙胺丁醇(E)固定剂量联用(FDC-RHE)纳入WHOEML2007用于复治涂阳肺结核的治疗;HRE剂量比例建议为1∶1∶2,剂量为H150mg,R150mg,E300mg。最佳剂量尚须根据更多高质量临床研究以指导调整。有必要开展对WHO及高结核负担国家结核防治指南有效性、安全性、经济性和适用性的临床研究,并对其进行系统评价,以考察结核用药方案效果,指导指南更新和资源合理配置,提高治疗绩效。有必要加强替代/备选药物研究,开发有效、安全、经济、适用的抗结核药物及药物组合用于耐药结核的防治。

Objective To assess the rationale for including rifampicin150/isoniazid75/ethambuto/275mg fixed dose, combination oral tablets/3-FDC R150H75E275/in the WHO Model List of Essential Medicines （WHO EML） for treatment of category II tuberculosis （TB II） and to provide evidence for the updating of national guidelines. Methods We searched Chinese Biomedical Database （CBM, 1978 to 2006）, The Cochrane Library, Issue 4, 2006, the Database of Abstracts of Reviews of Effects （1994 to 2006, the Centre for Reviews and Dissemination website）, MEDLINE （1950 to 2006）, EMBASE （1974 to 2006）, BIOSIS Previews （1997 to 2006）, websites for grey literature and the references of studies. We applied inclusion and exclusion criteria in assessing the studies we found and eligible studies were graded following an assessment of their quality. Results Thirty-six randomized controlled trials, 4 controlled clinical trials, 11 descriptive studies and 5 WHO/national guidelines were included. Rifampicin （R）, isoniazid （H） and ethambutol （E） were used in the ccontinuation phase （CP） of TB II in guidelines of WHOand high tuberculosis （TB） burden countries, but the course of treatment and dosage regimens varied. R, H and E were also widely used in conditions of pulmonary tuberculosis （PTB）, extrapulmonary tuberculosis （EPTB） and pulmonary diseases caused by nontuberculous mycobacteria （NTM）. Conclusions It is recommended that FDC RHE be included in WHO EML for the treatment of TB II.The suggested dosage ratio of RHE is 1 ： 1＂2, which needs to be adjusted based on more solid clinical evidence. High quality clinical studies and systematic reviews on the effectiveness, safety, economics and applicability of WHO and national guidelines and their outcomes in high TB burden countries are needed to guide their updating, promote rational resource allocation and improve cost effectiveness. Alternative drugs or drug combinations with good profile of effectiveness, safety, economics, and applicability for the prevention and treatment of drug-resistant tuberculosis are also needed to be developed.