Treatment shortening and relapse control in drug-susceptible pulmonary tuberculosis: a network meta-analysis of randomized trials

Drug-susceptible pulmonary tuberculosis (DS-PTB) is conventionally treated with a 6-month multidrug regimen, but prolonged treatment may compromise adherence, prompting efforts to develop shorter and effective therapeutic strategies. However, the comparative long-term effectiveness of alternative regimens, particularly their ability to prevent relapse, remains uncertain. We systematically searched multiple databases from inception through August 31, 2025, for randomized controlled trials enrolling adolescents and adults with DS-PTB. Regimens were classified according to treatment duration and architecture, including standard 6-month therapy, rifamycin-intensified strategies, structurally modified 6-month regimens, 4-month treatment-shortening approaches, and intended 8-week multidrug regimens. A random-effects pairwise meta-analysis and a fixed-effect consistency network meta-analysis (NMA) compared treatment success, relapse/recurrence-related outcomes, and mortality. Eight randomized controlled trials involving 10,244 participants were included. Six source trials involving 8,457 randomized participants contributed to the quantitative synthesis and informed a 14-node NMA; outcome data from 6,752 participants contributed to 12 shortened-regimen-versus-standard comparisons in the pairwise meta-analysis. Two trials involving 1,787 participants were summarized narratively because their thrice-weekly control regimens were not considered exchangeable with the daily reference regimen. In the pooled pairwise analysis, shortened-duration regimens were associated with a higher risk of trial-defined unfavorable long-term outcomes than the 6-month standard regimen (RR = 1.68, 95% CI 1.37–2.06; P Systematic review registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251267175.