Effectiveness and safety of the available preventive tuberculosis treatment regimens for children and adolescents: systematic review and network meta-analysis

Background Although children are at a higher risk of progressing to tuberculosis (TB) disease compared with adults, research and publications addressing TB management have mostly emphasised adult disease. Methods MEDLINE, Embase, CENTRAL and grey literature were searched from inception to 3 May 2021, and updated on 12 December 2024 for the systematic review and network meta-analysis (NMA). Randomised controlled trials of children and/or adolescents under 18 years with TB infection, contacts of drug-susceptible TB, without HIV, evaluating the effectiveness and safety of available regimens for the treatment of TB were included. Meta-analysis was conducted using a random effects model. Risk of bias was assessed using the Cochrane RoB tool 2. Effect estimates (RR and OR) are presented with 95% CIs. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Results Eleven studies were obtained. All network geometries had open and disconnected loops, except adverse reactions for which we conducted a full NMA. We found that 4 months of isoniazid and rifampicin (4HR) reduces the number of active TB cases at 1 year, 2 years and 5 years of follow-up (RR 0.49 (95% CI 0.32 to 0.76)) compared with isoniazid for 9 months (9H). The isoniazid + rifapentine for 3 months (3HP) regimen (RR 1.09 (95% CI 1.03 to 1.15)), 4HR (RR 1.07 (95% CI 1.01 to 1.14)) and rifampicin for 4 months (4R) (RR 1.12 (95% CI 1.05 to 1.20)) regimens have higher treatment adherence compared with 9H. High variability was found in the reporting of adverse reactions, which were more likely to occur with 3HP compared with 4HR (OR 4.56 (95% CI 1.22 to 16.96)) and 4R (OR 6.37 (95% CI 2.11 to 19.19)). Adverse reactions occur less frequently with 4R (OR 0.34 (95% CI 0.20 to 0.58)) compared with 9H. Conclusions This study synthesised available data on paediatric short and long-course regimens. Short course regimens may have higher adherence (3HP, 4HR, 4R) and may reduce active TB incidence (isoniazid + rifampicin for 3 months (3HR) and 4HR) compared with 9H. PROSPERO registration number CRD42021271512.