Aggressive Infliximab Dosing Shows No Added Benefit in UC

TOPLINE:
Aggressive infliximab dosing regimens – intensified induction or accelerated induction – show similar clinical responses and remission rates as the standard infliximab dosing approach in patients with acute severe ulcerative colitis (ASUC) that is steroid refractory.
METHODOLOGY:
Infliximab is a commonly used rescue therapy in patients with ASUC; however, its optimal dosing strategy in steroid-refractory ASUC is unknown.
This open-label PREDICT-UC trial included 138 patients with steroid-refractory ASUC (54% men) recruited from 13 Australian tertiary hospitals who were randomly assigned (1:2) to a first infliximab dose of 10 mg/kg (intensified dose) or 5 mg/kg.
Patients in the initial 10 mg/kg dosing group received a second dose of 10 mg/kg infliximab on day 7 or earlier if they didn’t respond (intensified induction strategy).
Those in the 5 mg/kg group were randomly assigned (1:1) to receive either an accelerated induction strategy (5 mg/kg infliximab at weeks 0, 1, and 3, with the week 1 dose increased to 10 mg/kg between day 3 and day 7 in cases of nonresponse) or a standard induction strategy (5 mg/kg infliximab at weeks 0, 2, and 6, with an extra 5 mg/kg dose between day 3 and 7 in cases of nonresponse).
The primary outcome was achieving a clinical response by day 7, defined as a reduction in the Lichtiger score to < 10 with a decrease of ≥ 3 points from baseline, improvement in rectal bleeding, and decreased stool frequency to ≤ 4 per day. The secondary outcomes were time to clinical response, change in the Lichtiger score, colectomy rates, and adverse events up to 3 months.
TAKEAWAY:
No statistically significant difference in clinical response by day 7 was found between patients receiving infliximab 10 mg/kg or 5 mg/kg as the first dose (65% vs 61%; P = .62). The time to clinical response, change in the Lichtiger score, and rates of colectomy within the first 7 days also were comparable between the dosing regimens.
There was no significant difference in the proportion of patients achieving a clinical response on day 14 or in the proportion of patients with clinical remission, steroid-free remission, endoscopic remission, and colectomy at 3 months between the standard, intensified, and accelerated induction strategy groups.
Continuing infliximab as maintenance was associated with an increased probability of being in combined clinical and endoscopic remission at 12 months (risk ratio, 1.95; P = .0014).
The aggressive infliximab dosing regimens did not lead to a greater number of adverse events. No deaths occurred in this study.
IN PRACTICE:
“The PREDICT-UC study potentially signals the end of accelerated or intensified dosing strategies for infliximab as rescue therapy for ASUC, which should prompt new strategic approaches,” experts from the Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, wrote in an accompanying editorial.
SOURCE:
The study, led by Matthew C. Choy, PhD, Department of Gastroenterology, Austin Health, Melbourne, Australia, was published online in The Lancet Gastroenterology & Hepatology.
LIMITATIONS:
The open-label design of the study might have introduced bias. Overall estimates of treatment effects are likely to have been reduced due to the intention-to-treat approach. The large time gap in infliximab dosing between the intensified and accelerated induction strategy groups compared with the standard induction strategy group could have affected outcomes. Infliximab pharmacokinetic and fecal biomarker data were not collected in this study.
DISCLOSURES:
This study was funded by the Australian National Health and Medical Research Council, Gastroenterology Society of Australia, Gandel Philanthropy, Janssen Pharmaceuticals-Cilag, and an Australian Postgraduate Award. Some authors declared relationships with various pharmaceutical companies, including Janssen Pharmaceuticals.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 
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