Baseline Clearance and Early Troughs Identify Candidates for Early Therapeutic Drug Monitoring During Infliximab Induction in Inflammatory Bowel Disease

Abstract

ABSTRACT Background and Aims The value of therapeutic drug monitoring during infliximab induction remains uncertain. We evaluated whether baseline infliximab clearance and early exposure metrics identify candidates for potential early proactive therapeutic drug monitoring during induction in inflammatory bowel disease. Methods We analysed a multicenter Phase 4 study in which adults with Crohn's disease and ulcerative colitis initiated standard infliximab therapy (5 mg/kg at Weeks 0, 2, 6, 14, 22 and 30) with predefined peak, intermediate and trough sampling. A population pharmacokinetic model characterized disposition and covariates. Logistic regression assessed exposure–response relationships. The primary outcome was week‐30 combined remission (Crohn's disease: Harvey–Bradshaw Index ≤ 4; ulcerative colitis: Partial Mayo score ≤ 2; with faecal calprotectin < 100 μg/g and C‐reactive protein ≤ 5 mg/L). Results Seventy‐five participants (33 female; median age 39 years, interquartile range 28–52) contributed pharmacokinetic data. Sixty‐three were evaluable for exposure–response analyses. Twelve participants (19%) achieved combined remission (7/35 Crohn's disease; 5/28 ulcerative colitis). Lower serum albumin, higher body weight, and antibodies to infliximab increased clearance. In ulcerative colitis, baseline clearance and model‐predicted week‐6 trough concentration showed strong discrimination for combined remission (area under the receiver operating characteristic curve 0.88, 95% confidence interval 0.75–1.00; and 0.86, 0.69–1.00, respectively). Baseline clearance > 0.28 L/day and week‐6 trough ≤ 21.6 mg/L identified high‐risk subgroups with few remissions (0/18 and 1/20, respectively, p < 0.05). No robust predictors were identified in Crohn's disease. Conclusions A pragmatic, risk‐stratified, model‐informed approach centered on baseline clearance and early troughs may guide personalized infliximab induction in ulcerative colitis. External validation is warranted. Trial Registration EudraCT number: 2015‐004618‐10