Nirsevimab Effectiveness Against Severe RSV Holds Up in Real-World Study

The monoclonal antibody nirsevimab (Beyfortus) protected young infants against hospitalization for respiratory syncytial virus (RSV), pediatric intensive care unit (PICU) admissions, and mechanical ventilation, according to the French prospective ENVIE study.

In a logistic regression model, nirsevimab was estimated to be 83% effective in preventing hospitalization from RSV bronchiolitis (95% CI 73.4-89.2) in infants younger than 12 months of age, Naim Ouldali, MD, PhD, of the Robert Debré University Hospital in Paris, France, and colleagues reported in the New England Journal of Medicine.

Researchers also found that nirsevimab was 69.6% effective against RSV bronchiolitis leading to PICU admission (95% CI 42.9-83.8) and 67.2% effective against RSV-associated bronchiolitis requiring ventilatory support (95% CI 38.6-82.5).

“This real-world study … indicated that nirsevimab prophylaxis was effective against RSV-associated bronchiolitis leading to hospitalization among infants younger than 12 months of age, including those with severe cases,” Ouldali and authors wrote.

Among infants with at least one risk factor for bronchiolitis, effectiveness of nirsevimab was lower (64.8%) in preventing hospitalization (95% CI -17.2 to 89.4), but absolute numbers in this group were small, the authors noted. Nirsevimab effectiveness appeared to be similar among infants younger than 3 months of age and older infants, the authors found.

“This is an important study that shows over 80% effectiveness of nirsevimab therapy against RSV-associated hospitalization in a short study period, highlighting the importance of administering this monoclonal to young infants prior to RSV circulation,” Natasha Halasa, MD, MPH, of Vanderbilt University in Nashville, Tennessee, who wasn’t involved with the study, told MedPage Today.

“It is important to ensure that nirsevimab reaches all infants, including those in low- and middle-income countries, where the majority of RSV-attributable deaths occur,” Halasa emphasized.

Researchers used a case-control study design that included 690 infants who had been hospitalized for RSV-associated bronchiolitis (case patients) matched with 345 infants who had clinical visits to the same hospitals for reasons other than RSV (control patients). Case patient median age was 3.1 months and matched controls had a median age of 3.4 months.

For the primary endpoint of hospitalization due to RSV bronchiolitis, 8.7% of case patients had received nirsevimab at least 7 days before the date of the hospital visit, whereas 28.1% of the matched controls had received nirsevimab.

Among case patients, 14% with RSV bronchiolitis requiring PICU admission had received nirsevimab whereas 32.2% of case-matched controls had received the monoclonal antibody, And, among case patients requiring ventilatory support, 14.3% had received nirsevimab versus 30.5% of controls.

The results of this real-world study need to be put in perspective with the findings of the prelicensure phase III trials, the authors wrote.

For example, the MELODY trial found that nirsevimab had a somewhat lower efficacy of 74.5% in preventing an RSV-related lower respiratory tract infection in infants that required medical attention, whereas the HARMONIE trial showed that nirsevimab was about 83% effective at preventing hospitalizations from RSV, similar to the findings of this study. The differences in effectiveness may reflect when outcomes were assessed, they pointed out. In the current trial, effectiveness was assessed at 3 months — similar to the HARMONIE trial — but in the MELODY trial, it was assessed at 150 days, the authors explained.

It is likely that nirsevimab effectiveness decreases over time, they wrote. “Overall, these findings suggest that campaigns that start each year at the beginning of the RSV outbreak, as is done for influenza, rather than continuous treatment of newborns throughout the year, may improve the usefulness of the nirsevimab program,” they noted.

In the U.S., the FDA approved nirsevimab for passive immunization for infants against RSV in July 2023 and the CDC’s Advisory Committee on Immunization Practices issued recommendations for its use in August 2023. Currently, the CDC recommends one dose of nirsevimab for infants younger than 8 months of age and born shortly before or who are entering their first RSV season if 1) their mother did not receive a maternal RSV vaccine during pregnancy; 2) the mother’s RSV vaccination status is unknown; or 3) the infant was born within 14 days of maternal RSV vaccination.

The authors acknowledged several limitations of their study, including that its observational case-control study design precluded drawing causative conclusions. Also, researchers assessed nirsevimab effectiveness very early after France’s initiation of the free-of-charge nirsevimab campaign in September 2023, so the assessment period was relatively short. Shortages of nirsevimab during the program may have led to differential access among socioeconomic groups, resulting in bias. Also, subgroup analyses were underpowered and therefore were exploratory only, the authors pointed out.