One clesrovimab dose matched five monthly palivizumab injections, and a second-season dose was tolerated

Design

randomised, partially masked, palivizumab-controlled phase 3 trial at 110 sites in 27 countries (SMART)

Population

997 palivizumab-eligible infants with prematurity, chronic lung disease of prematurity or haemodynamically significant congenital heart disease; median age 2.6 months

Primary outcome

proportion of participants experiencing adverse events in season 1

Effect

adverse events comparable between groups; RSV-associated medically attended lower respiratory infection 3.2% (95% CI 1.8-5.2) vs 3.4% (2.0-5.6) through day 150; second-season 210 mg dose tolerated, 7.3% (4.4-11.4) through day 180

SMART randomised 997 palivizumab-eligible infants — those with prematurity, chronic lung disease of prematurity or haemodynamically significant congenital heart disease — across 110 sites in 27 countries. One group received a single 105 mg dose of clesrovimab, the other up to five monthly doses of palivizumab at 15 mg/kg. The primary outcome was safety, and adverse event rates were comparable between groups.

RSV-associated medically attended lower respiratory infection through day 150 was 3.2% with clesrovimab and 3.4% with palivizumab. A second-season open-label 210 mg dose in 276 children who remained at risk was well tolerated, with total RSV-associated medically attended infection of 7.3% through day 180.

The substance here is logistics rather than pharmacology. Five monthly injections through a season means five clinic visits, five chances to miss a dose, and a cost structure that puts palivizumab out of reach for most families paying out of pocket. One dose per season is a different proposition for a parent and a different proposition for a service.

The second-season data matter because children with chronic lung disease of prematurity or significant congenital heart disease do not stop being at risk when the first season ends, and until now the evidence for redosing was thin.

• Identify high-risk infants before the season starts, not during it — a single-dose product only helps if it is given in time
• Count the visits when discussing options with a family; five monthly injections is the real comparator, not one
• Keep children with chronic lung disease or significant congenital heart disease on the at-risk list into a second season
• Check current availability and cost in India before raising the option; neither monoclonal is universally accessible here
• This trial was powered for safety, not for superiority on infection — read the incidence figures as descriptive

The statistics, in plain English

The primary outcome was the observed proportion of participants with adverse events, so the trial was designed to detect safety problems rather than to prove one product prevents more infection than the other. The infection figures — 3.2% (95% CI 1.8-5.2) against 3.4% (2.0-5.6) — have overlapping intervals and come from a secondary, descriptive objective; they support 'no obvious difference' and should not be read as a demonstration of equivalence. The season 2 figure of 7.3% (4.4-11.4) has no randomised comparator at all, because that phase was open-label with everyone receiving clesrovimab.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.