3G-03 - Risk of Pregnancy Loss with Vedolizumab Use during Pregnancy Compared to TNF Inhibitors in Individuals with Inflammatory Bowel Disease

Background: Vedolizumab, a monoclonal antibody targeting α4β7 integrin, has evolved into first-line therapy for managing moderate to severe active inflammatory bowel disease (IBD). Existing evidence of safety during pregnancy is mainly limited to data from registries and post-marketing surveillance.

Objectives: To compare the risk of pregnancy loss following prenatal exposure to vedolizumab versus tumor necrosis factor inhibitors (TNFi).

Methods: This retrospective cohort study used healthcare claims data from Merative MarketScan® Commercial Databases (2016-2023). We included pregnant persons aged 12 to 55 years with an IBD diagnosis and continuous insurance enrollment from 180 days preconception until 30 days after the end of pregnancy. Pregnancy episodes resulting in live delivery or pregnancy loss (i.e., spontaneous abortions or stillbirths) were identified using validated algorithms. Pregnancies with exposure to known teratogenic medications, chromosomal abnormalities, multiple gestation, and cancer were excluded. Exposures were defined as the use of vedolizumab versus a TNFi (adalimumab or infliximab) within up to 90 days before conception, assuming that effects last through conception, given their long half-lives. Study covariates included demographics, comorbidities, IBD severity, and healthcare utilization. We matched the treatment groups up to 1:2 on the propensity score and included unbalanced variables in the outcome model. We estimated the adjusted odds ratio (aOR) of pregnancy loss and its 95% CI via conditional logistic regression.

Results: The cohort included 360 vedolizumab-exposed (mean [SD] maternal age: 32.5 [4.9] years) and 1,638 TNFi-exposed (31.9 [5.0] years) pregnancies. Vedolizumab users were more likely to have ulcerative colitis compared to TNFi users (48.9% vs. 31.6%). 3.9% of the vedolizumab group had an autoimmune condition other than IBD, compared to 5.4% of the TNFi group. Other characteristics more prevalent in the vedolizumab group included anxiety (22.2% vs. 16.8%), immunization/screening for infectious disease (33.1% vs. 26.7%), and preconception mesalamine use (20.3% vs. 15.4%). The risk of pregnancy loss was 26.7% for vedolizumab and 23.0% for TNFi (OR, 1.221; 95% CI, 0.941-1.584). After matching, the risk was 26.6% among 357 vedolizumab pregnancies, compared to 23.3% among 692 TNFi pregnancies (aOR, 1.206; 95% CI, 0.889-1.636).

Conclusions: This study did not find a significant increase in the risk of pregnancy loss associated with vedolizumab compared to TNFi after adjusting for confounding factors. Future studies and continued surveillance are needed to provide more precise risk estimates as additional data become available.