NEW YORK (Reuters Health)—Dose optimization of infliximab is needed much earlier in ulcerative colitis than in Crohn’s disease, a single-center retrospective study reveals.
“We compared the rates of dose increases over a fairly lengthy period of time,” said Dr. Mark Silverberg, the study’s senior author from the Mount Sinai Hospital in Toronto.
“Patients with ulcerative colitis needed dose optimization at seven months, compared with 27 months for Crohn’s disease,” he told Reuters Health. “The bottom line is that standard dosing regimens (for ulcerative colitis) are insufficient.”
As reported online June 26 in the Journal of Crohn’s and Colitis, the researchers reviewed all cases of maintenance infliximab therapy at their hospital to see whether dose optimization varied depending on whether patients had Crohn’s disease or ulcerative colitis. Dose adjustments had been up to the doctor’s discretion, with no standardized approach.
Using the hospital’s infusion center database, they identified 412 patients who had received at least four infusions of maintenance infliximab therapy for Crohn’s disease or ulcerative colitis between 2008 and 2014.
Overall, 52.7% needed dose optimization at least once. However, 67.2% of patients with ulcerative colitis had at least one dose optimization, compared with 46.3% of patients with Crohn’s disease.
Dr. Silverberg speculated on the mechanism, noting that the colon, at 90 cm, presents “a greater burden of disease than the smaller segmentary surface area inflamed by Crohn’s disease, as well as different drug metabolism.”
In email to Reuters Health, Dr. Stephen B. Hanauer, Medical Director of the Digestive Disease Center at Northwestern Medicine in Chicago, commented: “We are finding that UC often requires somewhat higher doses. The bottom line is that the overall inflammatory burden will dictate the need for dose optimization.”
“In hospitalized patients with UC, we usually start with 10 mg/kg,” Dr. Hanauer said. “Many patients need re-dosing within a week due to higher inflammatory burden and fecal losses of antibody.”
The authors—and Dr. Hanauer—pointed to two limitations of the Toronto study: its retrospective design and the absence of a standardized dose optimization method.
In a paper in the June print issue of Gastroenterology (published online in February), a separate team of researchers questions conventional infliximab dosing protocols, which are guided by symptoms. Instead, Dr. Niels Vande Casteele from University Hospitals, Leuven, Belgium and colleagues tested a strategy of adjusting infliximab dosing based on trough concentrations.
In the randomized TAXIT trial, during a lead-in optimization phase, drug levels in all patients – 178 with Crohn’s disease and 85 with ulcerative colitis – were titrated up or down if they were not in the range of 3-7 ug/mL. Then, in the maintenance phase of the trial, patients were assigned either to ongoing drug monitoring, with drug levels adjusted to reach target, or to dosing adjustment only for a clinical flare.
