The outcome of infliximab dose doubling in 157 patients with ulcerative colitis after loss of response to infliximab

Aliment Pharmacol Ther. 2015 Nov;42(10):1192-9. doi: 10.1111/apt.13393. Epub 2015 Sep 10.

Abstract

Background: Optimising infliximab therapy is recommended in inflammatory bowel disease (IBD) patients who lose response to infliximab; however, there are no data on the outcome of ulcerative colitis (UC) patients after doubling the dose.

Aim: To determine the efficacy and safety of infliximab dose doubling in UC patients with a loss of response to infliximab.

Methods: From January 2006 to May 2013, we retrospectively reviewed the outcome of the consecutive UC patients who were treated with infliximab dose doubling (10 mg/kg) for loss of response in four French academic centres. The clinical response and remission were assessed. A composite event-free survival analysis was performed using the log-rank test and the Cox model.

Results: One hundred and fifty-seven patients [84 males; median age 37. 6 (IQR 28.2-49.4) years] were included. The median follow-up after infliximab dose doubling was 1.8 (1.0-3.1) years. At weeks 8 and 24, 55% and 43% of the patients achieved a clinical response respectively. The probabilities of the event-free survival were 71%, 61% and 55% at 6 months, 1 year and 2 years respectively. In the multivariate analysis, the predictors of infliximab dose doubling failure were the absence of the introduction of an immunomodulator concomitantly to dose doubling, a partial Ulcerative Colitis Disease Activity Index >6, a C-reactive protein level >10 mg/L, a leucocyte count >8000/mm(3) and a haemoglobin level <12.5 g/dL. Adverse events were reported in 12 patients (8%).

Conclusions: Infliximab dose doubling led to short- and long-term event-free survival in UC patients, who had a loss of response to infliximab, in greater than 50% of the cases. The benefits of such a strategy were significantly improved by adding a concomitant immunomodulator.

MeSH terms

  • Adult
  • C-Reactive Protein / metabolism
  • Colitis, Ulcerative / drug therapy*
  • Disease-Free Survival
  • Female
  • Humans
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / therapeutic use
  • Infliximab / administration & dosage*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Immunologic Factors
  • C-Reactive Protein
  • Infliximab