Infliximab Dosing in Ulcerative Colitis: Why Aggressive Strategies Yield No Extra Benefits

Infliximab Dosing in Ulcerative Colitis: Why Aggressive Strategies Yield No Extra Benefits

November 19, 2024 Catherine Williams Health

TOPLINE:

Intensified and accelerated infliximab dosing regimens perform similarly to standard dosing in patients with acute severe ulcerative colitis (ASUC) who do not respond to steroids.

METHODOLOGY:

  • Infliximab serves as a rescue therapy for steroid-refractory ASUC, but the best dosing strategy remains unclear.
  • The PREDICT-UC trial involved 138 patients (54% men) from 13 Australian hospitals. They were randomly assigned to either a first infliximab dose of 10 mg/kg or 5 mg/kg.
  • Those receiving 10 mg/kg had a second dose of 10 mg/kg on day 7 or sooner if needed (intensified strategy).
  • The 5 mg/kg group was further divided: one subgroup received doses of 5 mg/kg at weeks 0, 1, and 3 (with a potential increase on day 7), and the other received 5 mg/kg at weeks 0, 2, and 6 (also with potential increases as needed).
  • The primary outcome measured was clinical response by day 7, determined by changes in the Lichtiger score.

TAKEAWAY:

  • No significant difference in clinical response by day 7 was noted between initial doses of 10 mg/kg (65%) and 5 mg/kg (61%; P = .62).
  • Clinical response rates by day 14 and other outcomes, including remission and colectomy rates at 3 months, were also similar across all groups.
  • Continuing infliximab during maintenance treatment increased the likelihood of achieving combined clinical and endoscopic remission at 12 months (risk ratio, 1.95; P = .0014).
  • Rates of adverse events were similar across all dosing regimens, with no reported deaths.

IN PRACTICE:

The PREDICT-UC study may lead to reevaluation of intensified or accelerated dosing strategies for infliximab in ASUC, prompting consideration of new treatment methods, according to experts from the All India Institute of Medical Sciences.

SOURCE:

The study, led by Matthew C. Choy, PhD, was published in The Lancet Gastroenterology & Hepatology.

LIMITATIONS:

The open-label design may have introduced bias. There may be reduced estimates of treatment effects due to the intention-to-treat approach. The dosing intervals between groups could have impacted results. Pharmacokinetic and fecal biomarkers were not analyzed in this study.

DISCLOSURES:

This research received funding from several organizations, including the Australian National Health and Medical Research Council. Some authors have disclosed relationships with pharmaceutical companies, including Janssen Pharmaceuticals.