Loss of Response and Requirement of Infliximab Dose Intensification in Crohn's Disease: A Review

OBJECTIVES: To review the frequency with which infliximab loses 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.