Prior exposure to advanced therapy and timing of discontinuation and risk of serious infections in patients with inflammatory bowel disease initiating a new advanced therapy.

Abstract

Introduction: Despite regulatory mandates for advanced therapy (AT) washout periods of up to 5 drug half-lives before enrolling patients in inflammatory bowel disease (IBD) trials, the evidence base for these requirements is largely empirical, and whether shorter intervals independently increase the risk of serious infections in real-world practice remains unknown.

Methods: Using the OptumLabs Data Warehouse, we identified adult patients with IBD who initiated a new AT (tumor necrosis factor antagonists, vedolizumab, interleukin (IL)-12/23 or IL-23 antagonists, or Janus kinase inhibitors) between 2018 and 2023 using a class-specific new-user design. We examined whether exposure to AT within the preceding 12 months (vs no exposure to AT within that window) and timing of discontinuation (≤1 month, 1-<3 months, or 3-12 months) were associated with risk of serious infections using multivariable Cox proportional hazards regression.

Results: Among 21 564 AT initiators (47 ± 18 years; 52% female; 57% Crohn's disease), 7490 (34.7%) had AT exposure within the preceding 12 months. Over a mean follow-up of 1.6 ± 0.9 y, 1955 (9.1%) experienced a serious infection. Prior AT exposure was associated with higher infection risk (hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.07-1.33), consistent in inverse probability of treatment-weighted analyses (HR, 1.20 [1.06-1.37]). Among patients with prior exposure, timing of discontinuation was not associated with infection risk (HR, 1.17 [0.95-1.43] for ≤1 month vs 3-12 months; HR, 1.01 [0.83-1.22] for 1-<3 months), with no dose-response relationship on continuous modeling.

Discussion: AT exposure within the preceding 12 months is associated with modestly higher risk of serious infection after initiating a new AT in IBD, but timing of discontinuation does not independently influence this risk.