Infliximab Exposure-Response Relationship and Thresholds Associated With Endoscopic Healing in Patients With Ulcerative Colitis.

Background & Aims: Therapeutic drug monitoring might be used to personalize infliximab treatment of patients with ulcerative colitis (UC), although exposure thresholds associated with endoscopic healing are uncertain. We aimed to determine infliximab concentration thresholds associated with endoscopic outcomes during induction and maintenance therapy for patients with UC.

Methods: We analyzed data from 484 patients with active UC included in 2 randomized controlled trials of infliximab vs placebo. Mayo endoscopic scores (MES) were available from weeks 0, 8, and 30. A 2-compartment population pharmacokinetic model was used to calculate infliximab clearance at baseline. We tested the linear trend between baseline infliximab clearance and MES at week 8. Receiver operating curve analysis identified infliximab clearance and concentration thresholds with a maximum Youden index corresponding to a MES of 0 or ≤1.

Results: We found a linear relationship between baseline infliximab clearance and week 8 MES (P < .001); a threshold of <0.397 L/d was associated with week 8 MES ≤1. Infliximab concentrations ≥18.6 μg/mL at week 2, ≥10.6 μg/mL at week 6, and ≥34.9 μg/mL at week 8 were associated with a week 8 MES of ≤1. Infliximab concentrations ≥5.1 μg/mL at week 14 and ≥2.3 μg/mL at week 30 were associated with a week 30 MES of ≤1. Infliximab concentrations ≥6.7 μg/mL at week 14 and ≥3.8 μg/mL at week 30 were associated with a week 30 MES of 0.

Conclusions: Baseline clearance of infliximab and drug concentrations during induction and maintenance infliximab therapy are associated with short- and long-term endoscopic healing. Interventional studies that incorporate individualized dosing based on these parameters are required to show improved patient outcomes.