Infliximab Dose Escalation as an Effective Strategy for Managing Secondary Loss of Response in Ulcerative Colitis

Dig Dis Sci. 2015 Oct;60(10):3075-84. doi: 10.1007/s10620-015-3735-4. Epub 2015 Jun 5.

Abstract

Background: The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluated.

Aims: To assess the short- and long-term outcomes of infliximab dose escalation in a cohort of patients with UC.

Methods: This was a multicenter, retrospective, cohort study. All consecutive UC patients who had lost response to infliximab maintenance infusions and who underwent infliximab dose escalation were included. Post-escalation short-term clinical response and remission were evaluated. In the long term, the cumulative probabilities of infliximab failure-free survival and colectomy-free survival were calculated. Predictors of short-term response and event-free survival were estimated using logistic regression analysis and Cox proportional hazard regression analysis.

Results: Seventy-nine patients were included. Fifty-four patients (68.4%) achieved short-term clinical response and 41 patients (51.9%) entered in clinical remission. After a median follow-up of 15 months [interquartile range (IQR) 8-26], 33 patients (41.8%) had infliximab failure. Patients with short-term response had a significantly lower adjusted rate of infliximab failure [hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.12-0.49; p < 0.001]. During a median follow-up of 24 months (IQR 13-34), 9 patients (11.4%) needed colectomy. Short-term response was identified as a predictor of colectomy avoidance (HR 0.14; 95% CI 0.03-0.69; p < 0.007).

Conclusions: In UC patients who lost response to infliximab during maintenance, infliximab dose escalation enabled recovery of short-term response in nearly 70% of patients. In the long term, 58% of patients maintained sustained clinical benefit, and 9 of 10 avoided colectomy. Short-term response was associated with an 86% reduction in the relative risk of colectomy.

Keywords: Cohort study; Colectomy; Dose escalation; Dose optimization; Infliximab; Ulcerative colitis.

Publication types

  • Comparative Study
  • Evaluation Study
  • Multicenter Study

MeSH terms

  • Adult
  • Cohort Studies
  • Colectomy / statistics & numerical data
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / mortality
  • Colitis, Ulcerative / surgery
  • Confidence Intervals
  • Disease Progression
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Infliximab / adverse effects
  • Infliximab / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Recurrence
  • Remission Induction
  • Retrospective Studies
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome

Substances

  • Gastrointestinal Agents
  • Infliximab