Gallardo Carmen R, Rigau Comas David, Valderrama Rodríguez Angélica, Roqué i Figuls Marta, Parker Lucy Anne, Caylà Joan, Bonfill Cosp Xavier
Preventive Medicine and Healthcare Quality Service, Hospital Universitario San Juan de Alicante, Ctra. Nacional. 332 Alicante-Valencia, s/n, Alicante, Alicante, Spain, 03550.
Cochrane Database Syst Rev. 2016 May 17;2016(5):CD009913. doi: 10.1002/14651858.CD009913.pub2.
People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended.
To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis.
We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015.
Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB.
Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a meta-analysis. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
We included 13 randomized controlled trials (RCTs) in the review, which enrolled 5824 participants. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants.Overall there is little or no difference detected between FDCs and single-drug formulations for most outcomes reported. We did not detect a difference in treatment failure between FDCs compared with single-drug formulations (RR 1.28, 95% CI 0.82 to 2.00; 3606 participants, seven trials, moderate quality evidence). Relapse may be more frequent in people treated with FDCs compared to single-drug formulations, although the confidence interval (CI) includes no difference (RR 1.28, 95% CI 1.00 to 1.64; 3621 participants, 10 trials, low quality evidence). We did not detect any difference in death between fixed-dose and single-drug formulation groups (RR 0.96, 95% CI 0.67 to 1.39; 4800 participants, 11 trials, moderate quality evidence).When we compared FDCs with single-drug formulations we found little or no difference for sputum smear or culture conversion at the end of treatment (RR 0.99, 95% CI 0.96 to 1.02; 2319 participants, seven trials, high quality evidence), for serious adverse events (RR 1.45, 95% CI 0.90 to 2.33; 3388 participants, six trials, moderate quality evidence), and for adverse events that led to discontinuation of therapy (RR 0.96, 95% CI 0.56 to 1.66; 5530 participants, 13 trials, low quality evidence).We conducted a sensitivity analysis excluding studies at high risk of bias and this did not alter the review findings.
AUTHORS' CONCLUSIONS: Fixed-dose combinations and single-drug formulations probably have similar effects for treating people with newly diagnosed pulmonary TB.
新诊断出肺结核的患者通常会接受标准的一线治疗方案，该方案包括两个月的异烟肼、利福平、吡嗪酰胺和乙胺丁醇，随后是四个月的异烟肼和利福平。这些药物的固定剂量组合（FDCs）被广泛推荐。
比较固定剂量组合抗结核方案与单药制剂治疗新诊断肺结核患者的疗效、安全性和可接受性。
我们检索了Cochrane传染病小组专业注册库；Cochrane对照试验中心注册库（CENTRAL，发表于《Cochrane图书馆》，2015年第11期）；MEDLINE（1966年至2015年11月20日）；EMBASE（1980年至2015年11月20日）；LILACS（1982年至2015年11月20日）；对照试验元注册库；以及世界卫生组织国际临床试验注册平台（WHO ICTRP），检索截至2015年11月20日，无语言限制。
比较固定剂量组合与单药制剂在新诊断肺结核成年患者（15岁及以上）中使用情况的随机对照试验。
两位综述作者独立评估纳入研究，评估偏倚风险并从纳入试验中提取数据。对于二分数据我们使用风险比（RRs），对于连续数据使用均差（MDs）及9５%置信区间（CIs）。我们尝试用风险比及其95%置信区间评估治疗对事件发生时间测量指标的影响。我们使用Cochrane“偏倚风险”评估工具确定纳入试验中的偏倚风险。异质性较小时我们使用固定效应模型，异质性中等时使用随机效应模型。我们用I²统计值75%或更高表示显著异质性，此时我们不进行Meta分析。我们使用推荐分级的评估、制定和评价（GRADE）方法评估证据质量。
我们在综述中纳入了13项随机对照试验（RCTs），共纳入5824名参与者。试验发表于1987年至2015年期间，纳入的参与者为结核病高流行国家新诊断肺结核的治疗患者。只有两项试验报告了纳入参与者的HIV感染状况。总体而言，对于报告的大多数结局，固定剂量组合与单药制剂之间几乎没有差异。与单药制剂相比，我们未发现固定剂量组合在治疗失败方面存在差异（RR 1.28，95% CI 0.82至2.00；3606名参与者，7项试验，中等质量证据）。与单药制剂相比，接受固定剂量组合治疗的患者复发可能更频繁，尽管置信区间包含无差异情况（RR 1.28，95% CI 1.00至1.64；3621名参与者，10项试验，低质量证据）。我们未发现固定剂量组与单药制剂组在死亡方面存在差异（RR 0.96，95% CI 0.67至1.39；4800名参与者，11项试验，中等质量证据）。当我们比较固定剂量组合与单药制剂时，我们发现在治疗结束时痰涂片或培养转阴方面几乎没有差异（RR 0.99，95% CI 0.96至1.02；2319名参与者，7项试验，高质量证据），在严重不良事件方面（RR 1.45，95% CI 0.90至2.33；3388名参与者，6项试验，中等质量证据），以及在导致治疗中断的不良事件方面（RR 0.96，95% CI 0.56至1.66；5530名参与者，13项试验，低质量证据）。我们进行了敏感性分析，排除了高偏倚风险的研究，这并未改变综述结果。
固定剂量组合和单药制剂在治疗新诊断肺结核患者方面可能具有相似的效果。
