Monoclonal Antibodies for the Prevention of Respiratory Syncytial Virus Disease in Infants: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background & Objective: Respiratory syncytial virus (RSV) continues to be a leading cause of lower respiratory tract disease and hospitalization during infancy. With newer long-acting monoclonal antibodies, including clesrovimab, an updated synthesis of randomized evidence is required to define overall efficacy and safety. Methodology: We conducted a systematic review following PRISMA guidelines and performed pairwise random-effects meta-analysis of randomized controlled trials evaluating monoclonal antibodies for RSV prophylaxis in infants. PubMed/MEDLINE, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov were searched from inception through June 2026. After removing duplicate records, the active arms sharing a common control were combined to avoid double-counting. Dichotomous outcomes were synthesized as risk ratios (RRs) with 95% confidence intervals (CIs); heterogeneity was quantified using I². Risk of bias was assessed using Cochrane RoB 2, and certainty of evidence using GRADE principles. Results: Seven unique RCTs randomized 11,523 infants and evaluated palivizumab, motavizumab, suptavumab, nirsevimab, and clesrovimab. Monoclonal antibody prophylaxis reduced RSV-related hospitalization (RR 0.28, 95% CI 0.14–0.53; I²=83%) and medically attended RSV-associated lower respiratory tract infection (RR 0.35, 95% CI 0.20–0.61; I²=89%). Agent-specific hospitalization analyses were consistent for nirsevimab (RR 0.25, 95% CI 0.13–0.48; I²=0%) and clesrovimab (RR 0.15, 95% CI 0.07–0.30; I²=0%). ICU admission was reduced (RR 0.21, 95% CI 0.05–0.79; I²=43%), while mortality and mechanical ventilation were not significantly different. Serious adverse events were lower overall (RR 0.81, 95% CI 0.70–0.93; I²=32%). Excluding suptavumab, which showed limited activity against circulating RSV-B escape variants, reduced heterogeneity for RSV-LRTI while preserving a significant benefit. Conclusion: RSV monoclonal antibody prophylaxis substantially reduces clinically important RSV morbidity without increasing serious adverse events. High class-level heterogeneity supports agent-specific interpretation, while consistent effects for nirsevimab and clesrovimab strengthen evidence for long-acting prophylaxis across infant populations in contemporary practice. Key Words: Monoclonal Antibodies, Respiratory Syncitial Infections, Infants.