Loss of response and requirement of infliximab dose intensification in Crohn's disease: a review

Am J Gastroenterol. 2009 Mar;104(3):760-7. doi: 10.1038/ajg.2008.88. Epub 2009 Jan 27.

Abstract

Objectives: To review the frequency with which infliximabloses its effect and dose "intensification" is required for Crohn's disease treatment.

Methods: Bibliographical searches were performed in MEDLINE, and European (ECCO) and American (DDW) Congresses. Studies evaluating loss of efficacy and requirement of infliximab dose intensification-defined either as an increase of the infliximab dose (generally from 5 mg/kg to 10 mg/kg) or as a decrease in the frequency of infusion (to as often as every 4 weeks)-in Crohn's disease patients were included.

Results: Sixteen studies evaluating the incidence of loss of response to infliximab in Crohn's disease patients were found. A total of 2,236 patients were included (the majority of them receiving a three-dose induction regimen at weeks 0, 2, and 6, followed by maintenance therapy every 8 weeks), providing 6,284 patient-years of follow-up. The mean percentage of patients with loss of infliximab response was 37%. However, as the follow-up time varied markedly among studies, the risk of losing response to infliximab is better expressed as the incidence of this complication per patient-year of follow-up. Therefore, the annual risk for loss of infliximab response was calculated to be 13% per patient-year.

Conclusions: A variable but relevant proportion of Crohn's disease patients on long-term infliximab treatment lose response. This may be interpreted in two different but compatible ways: a positive view, highlighting that infliximab therapy is relatively durable, with the majority of patients predicted to continue infliximab treatment at least during the first year; or a negative view, interpreting that a significant proportion of Crohn's disease patients-more than 10% per patient-year of infliximab treatment-on long term will lose response and will require an increase in dose and/or decrease in infusion interval.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Inflammatory Agents / administration & dosage*
  • Antibodies, Monoclonal / administration & dosage*
  • Crohn Disease / drug therapy
  • Drug Tolerance
  • Gastrointestinal Agents / administration & dosage*
  • Humans
  • Infliximab

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Gastrointestinal Agents
  • Infliximab