Monoclonal Antibodies for the Prevention of Respiratory Syncytial Virus in Infants and Children: An Updated Systematic Review and Network Meta-analysis

Background and Objective: Motivated by the emergence of a long-acting monoclonal antibody (clesrovimab), the availability of data from the complete MELODY trial cohort, and results from a large randomized trial (HARMONIE), we updated our prior network meta-analysis to evaluate the efficacy and safety of monoclonal antibodies for preventing severe respiratory syncytial virus (RSV) infection in infants. Methods: We searched for randomized controlled trials that examined the efficacy and safety of RSV infection prophylaxis with clesrovimab, motavizumab, nirsevimab, palivizumab, and suptavumab versus one another or placebo or no prophylaxis in infants. We performed a frequentist framework random-effects network meta-analysis and used the Grading of Recommendations, Assessments, Developments and Evaluation (GRADE) approach to assess the certainty of evidence. Results: Eighteen trials enrolling 33,283 infants were included. Clesrovimab (odds ratio [OR] 0.08, 95% confidence interval [CI] 0.02–0.37, moderate certainty), motavizumab (OR 0.12; 95% CI 0.07–0.19, moderate certainty), and nirsevimab (OR 0.20, 95% CI 0.11–0.34; moderate certainty) were associated with reductions in the rate of severe respiratory syncytial virus infection. Nirsevimab, motavizumab, clesrovimab, and intramuscular palivizumab were associated with reductions in RSV infection, and several agents were also associated with reduced hospitalization. Motavizumab and nirsevimab, and clesrovimab were associated with reductions in broader lower respiratory tract infection-related outcomes. Motavizumab reduced both mechanical ventilation use and intensive care unit admission. No significant differences were found in all-cause mortality and drug-related or serious adverse events. Conclusions: This updated network meta-analysis confirmed that the effectiveness and safety of clesrovimab were comparable to those of established monoclonal antibodies. Motavizumab, nirsevimab, and clesrovimab showed benefits for broader lower respiratory tract infection-related outcomes.