Treatment of Latent Tuberculosis Infection: An Updated Network Meta-analysis.

BACKGROUND:Treatment of latent tuberculosis infection (LTBI) is an important component of tuberculosis (TB) control, and this study updates a previous network meta-analysis of the best LTBI treatment options to inform public health action and programmatic management of LTBI. PURPOSE:To evaluate the comparative efficacy and harms of LTBI treatment regimens aimed at preventing active TB among adults and children. DATA SOURCES:PubMed, Embase, and Web of Science from indexing to 8 May 2017; clinical trial registries; and conference abstracts. No language restrictions were applied. STUDY SELECTION:Randomized controlled trials that evaluated human LTBI treatments and recorded at least 1 of 2 prespecified end points (hepatotoxicity and prevention of active TB). DATA EXTRACTION:2 investigators independently extracted data from eligible studies and assessed study quality according to a standard protocol. DATA SYNTHESIS:The network meta-analysis of 8 new and 53 previously included studies showed that isoniazid regimens of 6 months (odds ratio [OR], 0.65 [95% credible interval {CrI}, 0.50 to 0.83]) or 12 to 72 months (OR, 0.50 [CrI, 0.41 to 0.62]), rifampicin-only regimens (OR, 0.41 [CrI, 0.19 to 0.85]), rifampicin-isoniazid regimens of 3 to 4 months (OR, 0.53 [CrI, 0.36 to 0.78]), rifampicin-isoniazid-pyrazinamide regimens (OR, 0.35 [CrI, 0.19 to 0.61]), and rifampicin-pyrazinamide regimens (OR, 0.53 [CrI, 0.33 to 0.84]) were efficacious compared with placebo. Evidence existed for efficacy of weekly rifapentine-isoniazid regimens compared with no treatment (OR, 0.36 [CrI, 0.18 to 0.73]). No conclusive evidence showed that HIV status altered treatment efficacy. LIMITATION:Evidence was sparse for many comparisons and hepatotoxicity outcomes, and risk of bias was high or unknown for many studies. CONCLUSION:Evidence exists for the efficacy and safety of 6-month isoniazid monotherapy, rifampicin monotherapy, and combination therapies with 3 to 4 months of isoniazid and rifampicin. PRIMARY FUNDING SOURCE:U.K. National Institute for Health Research. (PROSPERO: CRD42016037871).