Diarrhoea events in offspring exposed to tumour necrosis factor inhibitors and rotavirus vaccine: a population-based cohort study

OBJECTIVES: Previously, TNF inhibitor (TNFi)-exposed infants were recommended to withhold rotavirus vaccination until 6 months due to infection risk. Guidelines have recently supported earlier vaccination, although safety data remain limited. We aimed to compare diarrhoea risk (during early [1.5-6 months] and later [6-24 months] infancy) in TNFi-exposed infants who received rotavirus vaccination before 6 months vs those unvaccinated by 6 months. METHODS: We identified 3167 TNFi-exposed offspring in MarketScan commercial claims born to mothers with chronic inflammatory diseases between 2011 and 2021. Early vaccination was defined as ≥1 rotavirus dose between 1.5 and 6 months and modelled as time-varying. Diarrhoea events were identified using ICD-9/10 codes from hospitalizations, outpatient visits or emergency department visits. Cox proportional hazards models estimated hazard ratios (HR) and 95% CI for diarrhoea events in vaccinated vs unvaccinated infants. RESULTS: Among TNFi-exposed offspring, no statistically significant association was found between early vaccination and diarrhoea risk during early (101 events; HR 1.04; 95% CI 0.65, 1.68) or later infancy (283 events; HR 1.16; 95% CI 0.87, 1.55). Patterns remained consistent among infants exposed to TNFi in the third trimester (1.5-6 months: HR 1.07; 95% CI 0.62, 1.85; 6-24 months: HR 1.10; 95% CI 0.79, 1.52) and those exposed to high-placental transfer TNFi in the third trimester (1.5-6 months: HR 0.93; 95% CI 0.51, 1.70; 6-24 months: HR 1.09; 95% CI 0.77, 1.56). CONCLUSION: Early rotavirus vaccination in TNFi-exposed infants did not increase diarrhoea risk, even for those exposed late in pregnancy. Findings support early vaccination and reinforce updated recommendations.