A group of researchers developed and validated a clinical decision support tool that uses data on infliximab clearance and baseline patient and disease measures to identify patients most likely to have endoscopic healing with infliximab therapy. Their research was recently published in Clinical Gastroenterology and Hepatology.
“Response to [infliximab] therapy is highly variable among individuals. The rate of primary non-response to infliximab ranges from 8% - 42% and increases to 30% - 68% for primary non-remission,” Niels Vande Casteele, PharmD, PhD, University of California San Diego, and his colleagues wrote. “Of patients who initially respond, the yearly secondary loss of response rate is estimated to be approximately 13%. There are currently no tools available to predict the probability for endoscopic healing during the induction or maintenance periods at the patient level prior to initiation of infliximab therapy.”
Data from 484 patients with moderate-to-severe ulcerative colitis who participated in two double-blind, placebo-controlled, parallel group 54 and 30 week studies was used for the analysis. The trials had similar designs, with patients equally allocated to treatment with placebo, 5 mg/kg infliximab, or 10 mg/kg infliximab. Infusions occurred at week 0, 2, 6, and every 8 weeks thereafter.
For this study, endoscopic healing was defined as a Mayo endoscopic subscore (MES) less than or equal to 1. In the first trial, 142 (58.4%) patients had endoscopic healing at week 8 and 121 (49.8%) patients had endoscopic healing at week 30. In the second trial, 146 (60.6%) patients had endoscopic healing at week 8 and 121 (50.2%) patients had endoscopic healing at week 30.
The study 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 (MES ≤1) at weeks 8 and 30, using baseline variables. The clinical decision support tool (CDST) and calculator was developed to determine the probability of endoscopic healing in patients starting infliximab.
At week 8, higher baseline infliximab clearance, stool frequency, and rectal bleeding scores were negatively associated with endoscopic healing. In the validation set, a CDST score of 9 points or less identified patients without endoscopic healing at week 8 with 82% sensitivity (95% CI, 76%-88%). A CDST score of 16 points or more identified patients with endoscopic healing at week 8 with 87% specificity (95% CI, 81%-94%).
At week 30, higher baseline infliximab clearance, stool frequency score, white blood cell count, and lower body weight were negatively associated with endoscopic healing. In the validation set, CDST scores of 17 points or less identified patients without endoscopic healing at week 30 with 90% sensitivity (95% CI, 85%-95%). Scores greater than 22 points identified patients with endoscopic healing at week 30 with 80% specificity (95% CI, 73%-87%).
Casteele and his colleagues believe that the clinical decision support tool can “enable rapid control of symptoms and achievement of endoscopic remission to prevent unfavorable long-term disease outcomes and potentially avoid the use of costly ineffective medications, as well as the adverse disease outcomes and overall healthcare costs associated with their use.”