Abraham Yishak, Assefa Dawit Getachew, Hailemariam Tesfahunegn, Gebrie Desye, Debela Dejene Tolossa, Geleta Simon Tsegaye, Tesfaye Dagmawit, Joseph Michele, Manyazewal Tsegahun
College of Health Sciences, Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), Addis Ababa University, P.O. Box 9086, Addis Ababa, Ethiopia.
Department of Nursing, College of Medicine and Health Science, Dilla University, Dilla, Ethiopia.
BMC Infect Dis. 2024 Oct 1;24(1):1087. doi: 10.1186/s12879-024-09960-3.
Drug-resistant tuberculosis (DR-TB) remains a threat to public health. Shorter regimens have been proposed as potentially valuable treatments for multidrug or rifampicin resistant tuberculosis (MDR/RR-TB). We undertook a systematic review and network meta-analysis to evaluate the efficacy and safety of shorter MDR/RR-TB regimens.
We searched PubMed/MEDLINE, Cochrane Center for Clinical Trials (CENTRAL), Scopus, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, US Food and Drug Administration, and Chinese Clinical Trial Registry for primary articles published from 2013 to July 2023. Favorable (cured and treatment completed) and unfavorable (treatment failure, death, loss to follow-up, and culture conversion) outcomes were assessed as the main efficacy outcomes, while adverse events were assessed as the safety outcomes. The network meta-analysis was performed using R Studio version 4.3.1 and the Netmeta package. The study protocol adhered to the PRISMA-NMA guidelines and was registered in PROSPERO (CRD42023434050).
We included 11 eligible studies (4 randomized control trials and 7 cohorts) that enrolled 3,548 patients with MDR/RR-TB. Treatment with a 6-month combination of BdqLzdLfxZTrd/Eto/H had two times more favorable outcomes [RR 2.2 (95% CI 1.22, 4.13), P = 0.0094], followed by a 9-11 month combination of km/CmMfx/LfxPtoCfzZEHh [RR1.67 (95% CI 1.45, 1.92), P < 0.001] and a 6-month BdqPaLzdMfx [RR 1.64 (95% CI 1.24, 2.16), P < 0.0005] compared to the standard longer regimens. Treatment with 6 months of BdqPaLzdMfx [RR 0.33 (95% CI 0.2, 0.55), P < 0.0001] had a low risk of severe adverse events, followed by 6 months of BdqPaLzd [RR 0.36 (95% CI 0.22, 0.59), P ≤ 0.001] and BdqPaLzdCfz [RR 0.54 (95% CI 0.37, 0.80), P < 0.0001] than standard of care.
Treatment of patients with RR/MDR-TB using shorter regimens of 6 months BdqLzdLfxZTrd/Eto/H, 9-11 months km/CmMfx/LfxPtoCfzZEHh, and 6 months BdqPaLzdMfx provides significantly higher cure and treatment completion rates compared to the standard longer MDR/RR-TB. However, 6BdqPaLzdMfx, 6BdqPaLzd, and 6BdqPaLzdCfz short regimens are significantly associated with decreased severity of adverse events. The findings are in support of the current WHO-recommended 6-month shorter regimens.
耐多药结核病（DR-TB）仍然是对公共卫生的一大威胁。较短疗程已被提议作为治疗耐多药或利福平耐药结核病（MDR/RR-TB）的潜在有效疗法。我们进行了一项系统评价和网状Meta分析，以评估较短疗程的MDR/RR-TB治疗方案的疗效和安全性。
我们检索了PubMed/MEDLINE、Cochrane临床试验中心（CENTRAL）、Scopus、ClinicalTrials.gov、世界卫生组织国际临床试验注册平台、美国食品药品监督管理局以及中国临床试验注册中心，以获取2013年至2023年7月发表的原始文章。将良好结局（治愈和完成治疗）和不良结局（治疗失败、死亡、失访和培养转阴）作为主要疗效结局进行评估，而将不良事件作为安全性结局进行评估。使用R Studio 4.3.1版本和Netmeta软件包进行网状Meta分析。本研究方案遵循PRISMA-NMA指南，并在PROSPERO（CRD42023434050）上进行了注册。
我们纳入了11项符合条件的研究（4项随机对照试验和7项队列研究），共纳入3548例MDR/RR-TB患者。与标准的较长疗程相比，使用BdqLzdLfxZTrd/Eto/H进行6个月联合治疗的良好结局多出两倍[相对风险（RR）2.2（95%置信区间1.22，4.13），P = 0.0094]，其次是使用km/CmMfx/LfxPtoCfzZEHh进行9 - 11个月联合治疗[RR 1.67（95%置信区间1.45，1.92），P < 0.001]以及使用BdqPaLzdMfx进行6个月治疗[RR 1.64（95%置信区间1.24，2.16），P < 0.0005]。使用BdqPaLzdMfx进行6个月治疗[RR 0.33（95%置信区间0.2，0.55），P < 0.0001]发生严重不良事件的风险较低，其次是使用BdqPaLzd进行6个月治疗[RR 0.36（95%置信区间0.22，0.59），P ≤ 0.001]以及使用BdqPaLzdCfz进行治疗[RR 0.54（95%置信区间0.37，0.80），P < 0.0001]，均低于标准治疗。
与标准的较长疗程的MDR/RR-TB治疗方案相比，使用6个月的BdqLzdLfxZTrd/Eto/H、9 - 11个月的km/CmMfx/LfxPtoCfzZEHh以及6个月的BdqPaLzdMfx等较短疗程治疗RR/MDR-TB患者，治愈率和治疗完成率显著更高。然而，6个月的BdqPaLzdMfx、6个月的BdqPaLzd以及6个月的BdqPaLzdCfz等短疗程与不良事件严重程度降低显著相关。这些研究结果支持了世界卫生组织目前推荐的6个月较短疗程。
