Paternal Exposure to Immunosuppressive and/or Biologic Agents and Birth Outcomes in Patients with Immune-Mediated Inflammatory Diseases.

ABSTRACT Background and Aims We conducted a retrospective cohort study to inform the safety of exposure to immunosuppressive and/or biologic agents around conception in expectant fathers with immune-mediated inflammatory diseases (IMIDs) on birth outcomes. Methods Using a de-identified administrative claims database (OptumLabs® Data Warehouse), we identified 7,453 expectant fathers with IMIDs (inflammatory bowel diseases, rheumatoid arthritis, psoriasis/psoriatic arthritis, ankylosing spondylitis) linked to newborns, with peri-conception medication exposure between 38-60 weeks prior to newborn delivery date (34-58 weeks prior for pre-term newborns), and neonatal follow-up for 3 months after delivery date. Through logistic regression, adjusting for paternal age and race (and in a subset for maternal age, race, presence of IMIDs and non-singleton births), we compared the risk of major congenital malformations (primary outcome) and preterm birth and low birthweight in fathers exposed to thiopurines (n=461), methotrexate (n=171), TNFα antagonists (n=1082) or non-TNF-targeting biologic agents (n=132) vs. fathers not exposed to any of these medications (n=5607). Results As compared to unexposed fathers (3.4% prevalence of major congenital malformations), exposure to thiopurines (RR, 1.12 [95% CI, 0.66-1.76]), methotrexate (RR, 0.67 [0.21-1.55]), TNFα antagonists (RR, 1.14 [0.81-1.57]), and non-TNF-targeting biologic agents (RR, 1.75 [0.80-3.24]) was not associated with increased risk of major congenital malformations. No association was observed between paternal medication exposure and risk of preterm birth or low birth weight. Results were stable on sub-analyses of linked father-mother-newborn triads. Conclusions In a large cohort study of 7,453 expectant fathers with IMIDs, exposure to immunosuppressive or biologic agents around conception was not associated with increased risk of adverse birth outcomes.