Comparative Outcomes in Pregnant Patients with Rheumatoid Arthritis Treated with and Without Tumor Necrosis Factor Inhibitors: A Systematic Review and Meta-Analysis

Objectives Pregnant patients with higher rheumatoid arthritis (RA) disease activity are at increased risk of perinatal complications.[1] There is a paucity of safety data for continuation of tumor necrosis factor inhibitors (TNFi) in pregnancy.[2] A knowledge gap exists as to whether pregnant patients with RA who use TNFi experience different rates of perinatal outcomes compared to those who do not use TNFi. The objective was to identify differences in outcomes among patients with RA who are treated with and without TNFi during pregnancy. Methods Using a protocol prospectively registered on PROSPERO, systematic review of MEDLINE, EMBASE, Web of Science, Scopus, CENTRAL, and Google Scholar was performed according to PRISMA guidelines. Studies reporting outcomes comparing patients with RA who did and did not receive TNFi during pregnancy were included. Collected outcomes included: 3rd trimester DAS28-CRP, congenital anomalies, pregnancy loss, small for gestation age (SGA), preterm birth, and serious maternal and neonatal infections. Using RevMan version 5.4 with fixed effects modeling if I2 <25%, binary outcomes were analyzed using Mantel-Haenszel risk ratio and continuous outcomes were calculated using inverse variance method as mean difference. Results Outcome data from 9 patient populations were included. There were no significant differences between patients who did and did not use TNFi with regard to congenital anomalies (RR = 1.13; 95% CI 0.62-2.08, p = 0.69), SGA (RR = 0.89; 95% CI 0.56-1.41, p = 0.61), and preterm birth (RR = 0.99; 95% CI 0.76-1.31, p = 0.97) (Figure 1). Among outcomes with 3 or fewer studies reporting, there were no significant differences in 3rd trimester DAS28-CRP scores (mean difference = 0.08; 95% CI -0.11-0.26, p = 0.41), pregnancy loss (RR = 1.03; 95% CI 0.26-4.19 p = 0.96), serious maternal infection (RR = 0.94; 95% CI 0.32-2.76, p = 0.91), and serious neonatal/infant infection (RR = 1.02; 95% CI 0.35-3.00, p = 0.97). Figure 1. Forest plots comparing congenital anomalies (A), small for gestational age (B), and preterm birth (C) among pregnant patients with rheumatoid arthritis who did and did not receive TNFi during prenatal period. Data are depicted by using risk ratios with 95% confidence intervals. CI, confidence interval; TNFi, tumour necrosis factor inhibitor; M-H, Mantel-Haenszel. Conclusion To our knowledge, this is the first meta-analysis evaluating outcomes in pregnant women with RA only, treated with or without anti-TNF inhibitors. Among patients with RA, TNFi use in pregnancy does not appear to be associated with congenital anomalies, SGA, or preterm birth. This could help inform patient counselling around the continuation of TNFi in the prenatal period in this particular patient population. Additional original research is required to determine whether the similarities in disease activity are confounded by low sample size, selection bias, additional medication use, and timing of TNFi discontinuation. References [1.] Lv J. BMC Pregnancy Childbirth 2023;23:724. [2.] Sammaritano L. Arthritis Care Res (Hoboken) 2020;72:461-88.