POS0168 ROTAVIRUS VACCINE IN OFFSPRING EXPOSED TO TUMOUR NECROSIS FACTOR INHIBITORS DOES NOT INCREASE DIARRHEA-ASSOCIATED HEALTHCARE EVENTS: REAL-WORLD EVIDENCE TO GUIDE BEST PRACTICES (2024)

Abstract

Background: Until recently, best practice guidelines recommended withholding rotavirus vaccine (a live vaccine) in offspring exposed in utero to any TNFi until 6 months of age due to fear of causing infection in immunosuppressed infants. As rotavirus is a common, severe form of gastroenteritis, particularly in unvaccinated infants, delaying vaccine administration until 6 months of age (instead of routine immunization starting at 2 months) may be associated with more diarrhea-associated morbidity. However, there is limited data on this topic. In 2022, ACR vaccination guidelines conditionally recommended administering the rotavirus vaccine to infants within the first 6 months of life based on three limited observational studies with a combined number of 58 TNFi-exposed offspring, with no clear severe adverse events after rotavirus vaccination. This highlights the need for larger studies to inform best practice guidelines and optimize outcomes.

Objectives: We compared risk of diarrhea-associated healthcare events in infants exposed in utero to TNFi according to rotavirus vaccine exposure in the first 6 months of life.

Methods: Using MarketScan, a United States (US) administrative database, we created a cohort of offspring born to mothers with chronic inflammatory diseases who received at least one prescription for TNFi during gestation between 2011 and 2021. We excluded infants born in the 13 US states with a state-funded universal rotavirus vaccine program as these infants have no private insurer claims for the vaccine. Rotavirus vaccine exposure was based on ≥1 procedure billing code for providing the pentavalent human-bovine reassortant (RV5) and/or the attenuated human (RV1) rotavirus vaccines. Rotavirus vaccination was classified as time-varying, thus a child contributed person-time as unexposed up to their first rotavirus vaccine dose, after which they contributed person-time as exposed to the vaccine. Follow-up began at 2 months of life, when a child could theoretically receive their first vaccine. The first instance of diarrhea-associated healthcare use was defined via relevant ICD-9/10 diagnostic billing codes at hospitalizations and/or outpatient physician visits in the first 2-6 months of life. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for diarrhea-associated healthcare use in infants exposed in utero to TNFi who received the rotavirus vaccine, compared with those TNFi-exposed infants who did not, within the first 2-6 months of life. Models were adjusted for maternal age, chronic inflammatory disease (e.g. rheumatoid arthritis, inflammatory bowel disease), medication use (i.e. corticosteroids, non-biologic immunomodulators), geographic region, year, and birth season (January-June vs July-December).

Results: A total of 3,089 offspring born to mothers with chronic inflammatory diseases were exposed to TNFi in utero (Table 1). Of these, 2,241 (72.5%) received at least one dose of the vaccine within 2-6 months. Maternal characteristics, including systemic corticosteroid and non-biologic immunomodulator use, were similar between vaccinated and unvaccinated infants. The incidence rate of diarrhea-associated healthcare events in infants receiving the rotavirus vaccine was 8.8 (95% CI 5.8, 12.8) per 100 person-years versus 9.1 (6.9, 11.7) per 100 person-years in unvaccinated infants. Compared with no rotavirus vaccine administration within the first 2-6 months of life, receiving the rotavirus vaccine was not associated with an overall increased risk of diarrhea-associated healthcare events (adjusted HR 0.98; 95% CI 0.61, 1.58).

Conclusion: In the largest study to date, receiving the rotavirus vaccine within 6 months after birth was not associated with an increase in diarrhea-related healthcare events in offspring exposed in utero to TNFi. Our findings provide compelling evidence to recommend not delaying rotavirus vaccination in TNFi-exposed offspring.

Acknowledgements: This research was funded by the Canadian Institutes of Health Research (CIHR) project grant awarded to EV. LKF is supported by a CIHR Canada Graduate Scholarships Doctoral Award. EV is supported by a salary support award from the Arthritis Society.

Disclosure of Interests: None declared.