(256) Effect of Tumor Necrosis Factor Inhibitor Use During Pregnancy on Gestational Diabetes Mellitus Among Patients With Inflammatory Bowel Disease: A Nationwide Cohort Study

Background: Women with inflammatory bowel disease (IBD) are often at an increased risk of gestational diabetes (GDM) during pregnancy. Tumor necrosis factor inhibitors (TNFis), the mainstay of management of IBD, have been reported to exert an anti-diabetic effect by improving insulin resistance. However, whether their use in IBD patients during pregnancy leads to a decreased risk of GDM remains insufficiently explored.

Objectives: To assess the risk of GDM associated with the use of TNFi compared to non-biologics among pregnant women with IBD.

Methods: This nationwide cohort study was conducted using the Health Insurance and Review Assessment database from South Korea between 2009 and 2022, which includes all pregnant women with IBD who gave a live birth. The exposure of interest was TNFi, with non-biologics (5-aminosalicylates, thiopurines) used as comparators given their absence of known effects on blood glucose levels. Patients were considered exposed when there was an overlapping prescription of the study drug from the last menstrual period (LMP) to LMP + 140 days. The outcome was the development of GDM, which was assessed from LMP + 141 days until delivery. To adjust potential imbalances in >50 pre-defined covariates, we applied propensity score based overlap weighting. We used a generalized linear mixed model with the Poisson likelihood to calculate the risk ratio (RR) and 95% confidence intervals (CIs). Further, subgroup analyses were performed according to indication (Crohn’s disease, ulcerative colitis), age group (≤ 35, > 35), concurrent corticosteroid use, and duration of exposure (≤ 90, > 90 days).

Results: A total of 2,520 pregnancies with IBD were identified, of which 335 (13.3%) pregnancies were exposed to TNFi and 2,185 (86.7%) were exposed to non-biologics. GDM occurred in 6.9% of the pregnancies exposed to TNFi as compared with 10.3% of those exposed to non-biologics. The crude RR was 0.66 (95% CI 0.44 – 1.01), and the weighted RR was 0.69 (0.53 – 0.89). Those who were ≤ 35 years old significantly exhibited a greater effect (0.57, 0.39 – 0.83) compared to those > 35 years old (0.95, 0.53 – 1.69). Other subgroup analyses showed a significant decrease in the risk of GDM among patients exposed to the study drug for both ≤ 90 days (0.68, 0.48 – 0.98) and > 90 days (0.67, 0.48 – 0.95). Those with Crohn’s disease (0.55, 0.31 – 0.95) and patients not concurrently using corticosteroids (0.68, 0.50 – 0.93) demonstrated a decreased risk while their counterparts demonstrated null results.

Conclusions: In this large Korean cohort, we found a decreased risk of GDM among patients with IBD who used TNFis, compared to non-biologics users. The risk of gestational diabetes may become a consideration in the decision-making process when choosing treatment options for pregnant women with an IBD flare.