Development and Validation of a Clinical Decision Support Tool That Incorporates Pharmacokinetic Data to Predict Endoscopic Healing in Patients Treated With Infliximab.

ABSTRACT

BACKGROUND & AIMS: Infliximab is an effective treatment for moderate to severe ulcerative colitis (UC). Little is known about patient-related factors that might be used to predict endoscopic healing with infliximab therapy. METHODS: We analyzed data from 484 patients included in the randomized trials of the effects of infliximab therapy for patients with UC (Active Ulcerative Colitis Trials [ACT]-1 and ACT-2). We used a 2-compartment population pharmacokinetic model to calculate baseline infliximab clearance. Two multivariable regression models were derived and validated for their ability to identify patients with endoscopic healing (Mayo endoscopic score, ≤1) at weeks 8 and 30, using only baseline variables. We developed a clinical decision support tool (CDST) and calculator to determine the probability of endoscopic healing in patients starting infliximab. RESULTS: Higher baseline infliximab clearance, stool frequency, and rectal bleeding scores were associated negatively with endoscopic healing at week 8. In the validation set, a CDST score of 9 points or fewer identified patients without endoscopic healing at week 8 with 82% sensitivity (95% CI, 76%-88%), whereas a CDST score of 16 points or more identified patients with endoscopic healing at week 8 with 87% specificity (95% CI, 81%-94%). Higher baseline infliximab clearance, stool frequency score, white blood cell count, and lower body weight were associated negatively with endoscopic healing at week 30. In the validation set, CDST scores of 17 points or fewer identified patients without endoscopic healing at week 30 with 90% sensitivity (95% CI, 85%-95%), whereas scores greater than 22 points identified patients with endoscopic healing at week 30 with 80% specificity (95% CI, 73%-87%). External validation models had a modest predictive value, with an area under of the curve of 0.67 (95% CI, 0.61-0.74). Patient-level probabilities of endoscopic healing at weeks 8 or 30 can be calculated online (www.premedibd.com). CONCLUSIONS: Using data from 2 clinical trials of patients receiving infliximab therapy for UC, we developed and validated the CDST, which uses data on infliximab clearance and baseline patient and disease measures to identify patients most likely to have endoscopic healing. This tool will facilitate therapy decision making and precision medicine.