Loss of response and need for adalimumab dose intensification in Crohn's disease: a systematic review

The objective of this study was to review loss of response and need for adalimumab dose intensification in adult and pediatric patients with Crohn's disease. Studies were identified through the electronic databases of MEDLINE and the annual meetings of Digestive Disease Week, of the United European Gastroenterology Week, and of the American College of Gastroenterology and the European Crohn's and Colitis Organization meetings. Studies evaluating loss of efficacy and/or need for dose intensification were included. Thirty-nine studies were included. The mean percentage of loss of response to adalimumab among primary responders was 18.2% and the annual risk was 20.3% per patient-year. The mean percentage of patients who required dose intensification among primary responders to adalimumab was 37% and the annual risk was 24.8% per patient-year. When considering initial responders and patients with primary non-response, the mean percentage of patients who needed an adalimumab dose escalation was 21.4% and the annual risk was 24.4% per patient-year. Pooled analysis showed that dose escalation permitted response to be regained in 71.4% and remission in 39.9% of patients. Predictors for loss of response or dose escalation were male gender, current/former smoker status, family history of inflammatory bowel disease, isolated colonic disease, extra-intestinal manifestations, 80/40  mg induction therapy, longer disease duration, greater baseline Crohn's Disease Activity Index, concomitant corticosteroid use, no deep remission at week 12, low serum trough concentrations of adalimumab, previous infliximab non-response and being previously treated with an anti-tumor necrosis factor agent. Overall, around one fifth of adult patients require dose intensification and experience a loss of response after initiation of adalimumab therapy. Adalimumab dose escalation permits response to be regained in the majority of patients.