Remicade clearance predicted colectomy rates in severe UC
Patients’ clearance of Remicade was a ‘strong predictor’ of colectomy rates within 30 days, 6 months and 1 year of hospitalization for acute severe ulcerative colitis, according to data from Digestive Disease Week.
“Calculating infliximab drug clearance prior to treatment initiation was a strong predictor for colectomy in hospitalized acute severe UC patients,” Robert Battat, MD, of Weill Cornell Medicine, said during his recorded presentation. “In both univariable and multivariable analyses, the only factor that was associated with requiring colectomy was infliximab drug clearance.”
Battat and colleagues looked at 39 patients hospitalized for acute severe UC. In this group, the 1-month colectomy rate was 12.8%, 6-month colectomy rate was 25.6% and the 1-year rate was 30.8%.
He showed that the median Remicade (infliximab, Janssen) clearance was higher in patients who required colectomy at 6 months compared with those who did not require colectomy (0.733 L/d vs. 0.569 L/d; P = .005) and similarly the median infliximab clearance was higher in patients requiring colectomy at 1 year compared with those who did not require colectomy at 1 year (0.688 L/d vs. 0.569 L/d; P = .01).
Using a receiver operating characteristic curve analysis, Battat and colleagues found a threshold clearance of 0.627 L/d that had an 80% sensitivity and 82.8% specificity.
“In patients with an infliximab drug clearance that was greater than 0.627 liters per day, the 6-month colectomy rate was 61.5%, which was significantly higher than those who had a baseline clearance that was below 0.627 L/d,” he said. “Similarly, both 30-day and 1-year outcomes for colectomy were significantly higher in those who had clearances above these thresholds as compared to those who had clearance below this threshold of 0.627.”
At 30 days, the rate of colectomy was 30.7% in those above the threshold vs. 3.8% rate of colectomy in those below (P = .04). At 6 months, rates were 61.5% in those above vs. 7.7% in those below (P = .01). At 1 year, rates were 61.5% vs. 15.4% (P = .005).
Median infliximab dose was higher in patients who required colectomy than those who did not require colectomy in 30-day outcomes (21.8 mg/kg vs. 10.6 mg/kg; P = .01), 6-month outcomes (20.6 mg/kg vs. 10.4 mg/kg; P = .003)and 1-year outcomes (19.2 mg/kg vs. 10.4 mg/kg; P = .02)
“Those requiring colectomy received higher doses of infliximab, but we do not know of any data on whether accelerated dosing resulted in adequate drug concentration,” Battat said. “For this reason, there’s a need for pharmacokinetic models in acute severe UC to personalize dosing based on clearance and future trials in acute severe UC should compare clearance-based dosing to standard dosing.” – by Katrina Altersitz
Reference: Battat R, et al. Abstract 237. Presented at: Digestive Disease Week; May 2-5, 2020; Chicago (meeting canceled).
Disclosures: Battat reports no relevant financial disclosures. See abstract for full list of authors’ disclosures.