Initiation of biologic monotherapy in pregnancy for active Inflammatory Bowel Disease is not associated with an increased risk of adverse outcomes

Abstract

Background: Active inflammatory bowel disease (IBD) in pregnancy may require initiation of corticosteroids or biological therapy to control disease. Data from real world experience is required to understand their safety and the impact on disease and pregnancy outcomes. Method(s): A multi-centre retrospective cohort study across 16 UK hospitals included pregnant patients with active IBD, defined by symptoms and/or raised faecal calprotectin (FCP >= 250 mug/g) or C-reactive protein (CRP >= 5 mg/L) plus >=1 of: Treatment change, IBD-related hospitalisation, or IBD surgery during pregnancy. Logistic regression models were used to determine relative risk ratios (RRR). Multivariable analyses adjusted for maternal age, BMI, smoking status at conception, and disease severity (based on physician global assessment). Result(s): Three hundred and ninety-nine pregnancies were analysed. In response to active disease, topical therapy was added in 38.1%, oral 5-ASA in 22.6% (19.0% had dose optimisation). Budesonide was used in 13.3% and systemic corticosteroids in 33.1%. Thiopurines were started in 3.8% and optimised in 3.0%. A new biologic was commenced in 15.5%: infliximab 44.3%, adalimumab 27.9%, vedolizumab 13.1%, Ustekinumab 9.8%, Golimumab 3.3% and Risankizumab 1.6%. The mean gestation at initiation was 18 weeks (SD +/- 9.7 weeks) for systemic corticosteroids and 20 weeks (SD +/- 8.0 weeks) for biologics. Initiation of corticosteroids (n = 90) or biologics (n = 30) alone was not associated with increased risk of adverse pregnancy or neonatal outcomes on multivariable analysis. Patients who received combination steroids and biologics (n = 32) during pregnancy had a higher inflammatory burden at time of flare, with median (IQR) CRP 15.0 (7.5-41.0) mg/L vs biologics 9.0 (4.0-18.0) mg/L or corticosteroids 10.0. (5.0-29.0) mg/L, p = 0.011; and median (IQR) FCP 1500 (600-2800) mug/g vs biologics 600 (512-2507) mug/g or corticosteroids 659 (484-1720) mug/g, p = 0.109. Combination therapy was associated with higher risk of preterm birth (RRR 3.74, 95% CI 1.07-13.04; p = 0.038), emergency caesarean section (RRR 4.42, 95% CI 1.45-13.47; p = 0.009) and NICU admission (RRR 5.00, 95% CI 1.07-23.44; p = 0.041) on multivariable analysis. Conclusion(s): Findings from this study support the safety of timely escalation to achieve disease control in pregnancy. The higher rate of adverse pregnancy outcomes observed with combined immunosuppression likely reflects the impact of underlying disease severity. By focusing on a cohort with active IBD we were able to account for the effects of disease severity on outcomes and have demonstrated the importance of effective treatment for active IBD during pregnancy.