This case study is part of the broader TARGET EU project (EUPAS1000000539), which aims to advance the regulatory use of real-world data through the application of target trial emulation and estimand methodologies.
Background: Nirsevimab, a recombinant monoclonal antibody approved by EMA in September 2022, provides sustained protection throughout the RSV season with a single dose by binding to the RSV F protein and preventing viral entry. While systematic reviews demonstrate nirsevimab effectiveness (OR 0.17,95%CI 0.12–0.23; I2=85.8%, for RSV-related hospitalization), most real-world evidence comes from Spain, France, and the US, with only one small Italian regional study.
Objectives: The primary objective is to assess nirsevimab effectiveness in preventing RSV-LRTI hospitalization within 6 months of administration among infants ≤12months compared to no immunization within the Italian healthcare system.
Methods: We will conduct a cohort study using PEDIANET from October 2024 to March 2025. Exposed infants are those receiving nirsevimab; controls are unexposed infants. Inclusion criteria: age <12months, born at ≥29weeks gestational age. Exclusion criteria: ongoing LRTI infection, maternal RSV vaccination during pregnancy, or palivizumab eligibility. Time zero for exposed infants is the first nirsevimab administration date; controls are matched 1:1 on age group (≤3.0, >3.0–≤6.0, >6.0 months) and calendar week of exposure. Follow-up is six months, ending at outcome occurrence, death, disenrollment, or study end. The primary outcome is RSV-LRTI hospitalization and confounders include age, sex, prior LRTI episodes, healthcare utilization (visits and antibiotic prescriptions), and area deprivation index, all measured before time zero. Inverse probability of treatment weighting using propensity scores estimated via logistic regression will adjust for confounding. Stabilized weights will be applied in log-binomial regression models to estimate marginal risk ratios.