A Risk Stratification Tool for Relapse After Intravenous-to-Subcutaneous Switching of Infliximab in Patients with Inflammatory Bowel Diseases.

Abstract

Objectives: A subcutaneous formulation of infliximab was recently approved for maintenance therapy of inflammatory bowel disease (IBD). However, limited clinical experience, particularly with patients on escalated intravenous infliximab regimens, poses challenges for the transition to subcutaneous therapy. We investigated the pharmacokinetics and pharmacodynamics of subcutaneous infliximab to identify early predictors of relapse upon switching.

Methods: We repurposed data from a prospective, multicenter trial involving patients with IBD switching from intravenous to subcutaneous infliximab. We estimated each patient's infliximab clearance using Bayesian forecasting from a pre-switch sample and a population pharmacokinetics model. We performed pharmacodynamics modeling to evaluate pre-switch predictors of post-switch relapse. Relapse was defined as clinical recurrence (partial Mayo score >2 or Harvey-Bradshaw Index >4 leading to therapeutic escalation) or an increase in fecal calprotectin ≥150 μg/g upon switching.

Results: Using data from 98 patients with IBD, we identified infliximab clearance and fecal calprotectin as independent predictors of relapse. A two-item risk score stratified patients into low-risk (<19% probability of relapse; 75/98; 77%) and high-risk (≥19% probability of relapse; 23/98; 23%) groups (sensitivity 0.52 [95%CI 0.31-0.73], specificity 0.95 [95%CI 0.87-0.99], positive predictive value 75% [95%CI 48-93%], negative predictive value 87% [95%CI 77-93%]). Our pharmacokinetics-pharmacodynamics model classified patients with and without relapse (p <0.0001) with an area under the receiver operating characteristic curve of 0.83 (95%CI 0.71-0.93).

Conclusions: Pre-switch infliximab clearance and fecal calprotectin are accurate predictors of relapse after switching to subcutaneous infliximab. An interactive risk stratification tool facilitates confirmation of a stratified medicine approach to improve infliximab therapy in IBD.