Perinatal use of targeted synthetic DMARDs and maternal-neonatal outcomes in autoimmune disease: A population-based cohort study

OBJECTIVES: While targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) have advanced autoimmune disease management, the paucity of perinatal safety data limits evidence-based decision-making in pregnancy. We aimed to characterize patterns of tsDMARD utilization and evaluate associations between perinatal tsDMARD exposure and maternal and neonatal outcomes, among females with autoimmune disease. METHODS: We used linked population-based administrative health databases from British Columbia, Canada (2002-2022). Our study cohort included females with autoimmune disease ('mothers') and ≥1 pregnancy, with tsDMARD-exposed pregnancies matched (on disease type, live birth, etc.) to unexposed pregnancies. We examined 6 maternal (e.g., preeclampsia/eclampsia), 11 fetal/neonatal (e.g., congenital anomaly) and 5 fetal/neonatal-maternal outcomes (e.g., Caesarean delivery) using Fisher's exact test. Pregnancies was the unit of analysis. RESULTS: Among 29,749 mothers with autoimmune disease, 19 pregnancies were exposed to tsDMARDs during the perinatal period. Of these, 7 (36.8%) pregnancies were exposed 1-year preconception, with complete discontinuation by the second trimester. Among maternal outcomes, we observed a non-significant association with gestational diabetes (unadjusted odds ratio [uOR] 0.95, 95% confidence interval [CI] 0.13-7.01, p = 0.96). Among fetal/neonatal outcomes, we observed one significant association with preterm birth (uOR 13.45, 95% CI 2.12-85.21, p = 0.01). Among fetal/neonatal-maternal outcomes, we observed a non-significant association with Caesarean delivery (uOR 2.21, 95% CI 0.46-10.74, p = 0.32). CONCLUSIONS: Our study provides timely evidence on the perinatal safety of tsDMARDs and demonstrates how population-based data can be leveraged to address confounding in rare exposures. Studies like ours are critical for future data pooling and synthesis to strengthen the evidence on emerging drugs in pregnancy.