Early infliximab TDM & ASUC outcomes

August 25, 2025

Issue 17

Clinical Question

Do early infliximab levels and clearance predict clinical outcomes in acute severe ulcerative colitis?

Editor’s Bottom Line

Infliximab pharmacokinetics are highly variable among patients with acute severe ulcerative colitis and appear to predict response to therapy. Measurement of serum and fecal infliximab levels may be informative in this high-risk population.

Reference

Li Wai Suen CFD, Choy MC, Con D, et al. Early Infliximab Levels and Clearance Predict Outcomes After Infliximab Rescue in Acute Severe Ulcerative Colitis: Results From PREDICT-UC. Gastroenterol. Epub ahead of print August 16, 2025. https://www.gastrojournal.org/article/S0016

Synopsis

This prospective observational study examined whether early infliximab therapeutic drug monitoring predicts clinical outcomes in patients with acute severe ulcerative colitis (ASUC). Researchers analyzed serum and fecal samples from 135 patients enrolled in the PREDICT-UC randomized controlled trial, which compared intensified versus standard infliximab dosing strategies in steroid-refractory ASUC.

Infliximab levels were measured in 681 serum and 198 fecal samples collected at multiple timepoints after infliximab administration. Pharmacokinetic modeling was used to calculate infliximab clearance, and these parameters were correlated with clinical outcomes including day 7 response, day 14 infliximab failure (defined as a Lichtiger score ≥10) and three-month colectomy rates.

Analysis showed that lower day 3 serum infliximab levels were significantly associated with an increased risk of infliximab failure at day 14 (p=0.043) and colectomy by three months (p=0.0027).

A day 3 serum infliximab threshold of ≤57.9 μg/mL was the optimal cutoff for predicting colectomy by three months, with 83% sensitivity, 67% specificity, 24% positive predictive value and 97% negative predictive value. The optimal threshold for day 14 infliximab failure was ≤53.6 μg/mL (50% sensitivity, 75.6% specificity, 42.4% PPV and 80.8% NPV).

Infliximab clearance was highest in the first 3 days and gradually decreased over time. Patients with high early clearance (≥0.62 L/day) were more likely to respond to an initial 10 mg/kg dose versus a 5 mg/kg infliximab dose (Risk Ratio [RR]: 1.50; 95% Confidence Interval [CI], 1.01–2.23) and had higher colectomy risk if they received the 5 mg/kg dose, compared to the 10 mg/kg dose (Hazard Ratio: 4.81; 95% CI, 1.09–21.37). Among high-clearance patients who did not respond to the first dose, day 14 response rates were higher with a second 10 mg/kg dose versus another 5 mg/kg dose (38% vs. 11%; RR: 3.43; 95% CI, 1.05–11.19).

Fecal infliximab levels correlated with endoscopic severity and inflammatory markers. Day 3 fecal infliximab levels were associated with day 7 nonresponse (p=0.016), and lower day 1 fecal levels predicted both Mayo endoscopic remission and combined clinical-endoscopic remission at month 3.

Early infliximab clearance was higher in men, correlated with weight and baseline C-reactive protein, and was inversely correlated with albumin levels.

Details

Study Design: Prospective observational cohort
Funding: Janssen-Cilag investigator-initiated study grant
Allocation: Not applicable
Setting: Multicenter
Level of Evidence: 2b