By Will Boggs MD
NEW YORK (Reuters Health) - 1/2/2019
As salvage therapy for acute severe ulcerative colitis refractory to corticosteroids, multiple infliximab doses are superior to a single dose for improving colectomy-free survival, according to a new systematic review and meta-analysis.
"On meta-analysis we found that induction with 2 or more 5 mg/kg doses of infliximab was significantly superior to single-dose 5 mg/kg induction," Dr. Peter P. De Cruz from Austin Health, in Heidelberg, Australia, told Reuters Health by email. "However, it was interesting that dose-intensification with either 10 mg/kg doses or accelerated schedules was not significantly different than 5 mg/kg standard induction at 3 months."
As many as 30% of patients with acute severe ulcerative colitis require emergency colectomy within three months of presentation, and about a third of patients do not respond to first-line therapy with corticosteroids. Infliximab has demonstrated efficacy as medical salvage therapy, but the optimal dosing strategy remains unclear.
Dr. De Cruz and colleagues used data from 2,158 patients across 41 separate study cohorts to examine the efficacy of infliximab induction in acute severe ulcerative colitis and the impact of dosage, dose number and dose intensification on colectomy-free survival.
They included three dose schedules: standard-schedule induction (three infliximab doses at weeks 0, 2, and 6); accelerated-schedule induction (three doses within four weeks); and dose-intensified induction (use of either multiple 10-mg/kg doses or an accelerated schedule with 5 mg/kg).
The overall pooled colectomy-free survival (CFS) following infliximab therapy was 85.7% at one month, 79.7% at three months and 69.8% at 12 months.
CFS at three months was higher with multiple 5-mg/kg doses of infliximab (89.4%) than with single 5-mg/kg doses (67.3%). Among comparative studies, this translated into 4.24-fold greater odds of colectomy at three months with the single-dose regimen (P<0.001).
Dose intensification did not differ significantly from standard induction in terms of one-, three-, or 12-month CFS, the researchers report in Inflammatory Bowel Diseases, online January 3.
In subanalyses, CFS did not differ significantly in comparisons of 5-mg/kg standard versus 5-mg/kg accelerated induction, 5-mg/kg standard versus 10-mg/kg standard induction, or 5-mg/kg standard induction versus 10-mg/kg accelerated dose.
"In clinical practice, physicians are increasingly turning to intensified and accelerated strategies based on limited evidence drawn from observational cohorts and case reports," Dr. De Cruz said. "However, such an approach risks over-treating patients who are destined for a favorable outcome at the expense of increased costs and potential morbidity."
"Whilst the optimal infliximab induction dosing regimen for acute severe ulcerative colitis remains unclear, hopefully we will be able to provide more clarity on the optimal dosing strategy with the PREDICT UC randomized controlled trial, which is currently underway in 17 centers in Australia," he said.
Six of the 13 authors have various relationships with manufacturers of infliximab.
SOURCE: https://bit.ly/2RoLCoq Inflamm Bowel Dis 2019.