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.