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.