Rapid review showed that real‐world results on how nirsevimab prevented respiratory syncytial virus hospitalisations were similar to randomised trials

The respiratory syncytial virus (RSV) has been the most common cause of infant hospitalisation in high-income countries. Large, randomised trials have shown that novel protective strategies, including maternal vaccinations and nirsevimab monoclonal antibody therapy, have been very effective in preventing these.1 Nirsevimab was approved by the American Food and Drug Administration in summer 2023 and some countries recommended it as prophylaxis for all infants during winter 2023–2024. This rapid review analysed the first real-word studies on the impact of nirsevimab on infant RSV hospitalisation. The PubMed and Scopus databases were searched for studies on nirsevimab published from 1 January 2023 to 1 April 2024, without language restrictions. We focused on observational studies that compared the numbers or incidence of RSV hospitalisations in infants who were or were not immunised with nirsevimab and those that compared consecutive RSV seasons. The main outcome was the RSV hospitalisation rate. Two authors (IK and MR) read the abstracts of the 158 papers that were identified, and one author (IK) read the 12 full texts, extracted the data and assessed them against the risk of bias in non-randomised studies of interventions. The review finally focused on three observational cohort studies, from Luxembourg, Spain and the USA2-4 (Table 1). They all had a high risk of bias because the authors had not controlled for confounding and possible selection bias and outcome measurement bias. Neonates born during the study period Infants born from 1 January 2023 to 30 September 2023 (catch-up immunisation) Infants under 2 years of age with risk factors for severe disease All infants aged <8 months, born during, or entering, their first RSV season Infants aged 8–19 months at increased risk for severe RSV disease and entering their second RSV season The study from Luxembourg compared the number of RSV hospitalisations from October 2023 to December 2023 to the same time period in the previous year and they had decreased by 69%. The number of infants under 6 months of age admitted to the intensive care unit decreased by 68%, and the overall duration of hospitalisation was notably lower: 3.4 days in 2023 versus 5.6 days in 2022. Two-thirds (65%) of the 72 hospitalised infants under 6 months of age had not received nirsevimab in 2023.2 The Spanish study used a Bayesian approach to estimate the effectiveness of the prophylaxis. It compared the RSV screening detection rates between those who did and did not receive nirsevimab and also applied a test-negativity design. The pooled effectiveness of nirsevimab against RSV hospitalisation was 84% (95% credible interval 77%–90%) and it varied from 69 to 97% in the three study regions. The pooled test-negativity designed effectiveness was 70% (95% credible interval 38%–89%).3 The American study estimated the effectiveness using a test-negative case–control design, and it was 90% (95% confidence interval 75%–96%) against RSV hospitalisations. The median time from nirsevimab to respiratory symptoms was 45 days.4 The crude effectiveness rates of 70%–90% in these three studies were similar to the effect sizes in the original randomised trials.1 However, the results may have less relevance in areas like Northern Europe, where high epidemic peak RSV seasons are followed by lower epidemic peak RSV seasons. The COVID-19 pandemic disrupted this pattern, and it is possible that the effectiveness of these observational studies was due to changes in the RSV season dynamics and severity.5 A clear limitation of the Luxembourg study was that it was based on absolute rates, not population-based estimates. Another limitation of all three studies was the short monitoring periods of just 3–4 months, although epidemic peaks occurred in both European studies during the study periods. Furthermore, the low 4%–14% nirsevimab coverage in the USA study caused imprecise estimates. Larger studies are needed to monitor the real-world effectiveness of nirsevimab, and reliable surveillance of epidemic dynamics is continuously needed. In conclusion, the first real-world effectiveness estimates were similar to those in the original randomised trials. The three studies had rather small sample sizes but may provide an important insight into the first population-level estimations and provide practical information for national decision-makers. The rollout of nirsevimab is expected to grow and it is important that large observational nationwide studies monitor both its effectiveness and possible harm. Furthermore, it will be very interesting to see how long nirsevimab remains effective, as antibody levels decline over time. Ilari Kuitunen: Conceptualization; investigation; writing – original draft; funding acquisition; methodology; visualization; formal analysis; data curation. Marjo Renko: Conceptualization; investigation; writing – review and editing; validation; project administration; supervision; resources. None.