Although optimal medical management of acute severe ulcerative colitis (UC) is ill-defined, infliximab has become a standard of care.
Accumulating evidence suggests an increased rate of infliximab clearance in patients with acute severe UC, and a reduced colectomy rate with an intensified infliximab induction regimen.
Dr Brian Feagan and colleagues from Canada assessed the strength of the current evidence for the relationship between infliximab pharmacokinetics, dosing strategies and disease behaviour in patients with acute severe UC.
The team systematically searched MEDLINE and conference proceedings from 2000 to 2016 for relevant articles describing the pharmacokinetics of infliximab in acute severe UC, and/or infliximab dose intensification strategies in acute severe UC.
|The first 3 weeks of treatment could reduce the early colectomy rate by up to 80%|
|Alimentary Pharmacology & Therapeutics|
Eligible articles described randomized controlled trials, and cohort, cross-sectional, and case–controlled studies.
Of 400 citations identified, the team found that 76 studies were eligible.
The researchers found that increased infliximab clearance occurs in patients with acute severe UC, and is driven by the total inflammatory burden and leakage of drug into the colonic lumen.
Several cohort studies suggest that infliximab dose intensification is beneficial to at least 50% of acute severe UC patients and the results of case–controlled studies indicate that an intensified infliximab dosing regimen with 1–2 additional infusions in the first 3 weeks of treatment could reduce the early colectomy rate by up to 80%, although these data require prospective validation.
Dr Feagan's team concludes, "Uncontrolled studies suggest a benefit for infliximab dose optimisation in patients with acute severe UC."
"A randomized controlled trial in acute severe UC patients comparing a personalized infliximab dose-optimisation strategy with conventional dosing is a research priority."