Anti-tumor necrosis factor therapy with adalimumab is an effective therapy for the induction and maintenance of remission in moderate to severe Crohn's disease. Although a large proportion of patients show a favorable clinical response to adalimumab, therapy failure is common. In this review, we provide a practical overview of adalimumab therapy in patients with Crohn's disease, with a specific focus on the clinical management of adalimumab failure. In the case of inadequate efficacy, a thorough assessment is required to confirm inflammatory disease activity and rule out noninflammatory causes. Evaluation may include biomarkers (fecal calprotectin and serum C-reactive protein), colonoscopy, and/or magnetic resonance enterography/enteroclysis. Furthermore, adalimumab trough levels and antibodies to adalimumab are informational after the confirmation of active inflammation. In the case of low or undetectable adalimumab trough levels, dose escalation to 40 mg weekly is recommended, whereas high antibody titers or adverse events frequently require switching to an alternative anti-TNF agent such as infliximab. Active inflammation despite therapeutic adalimumab trough levels requires alternative strategies such as switching to drugs with a different mode of action or surgical intervention.
Keywords: anti-TNF; biological; inflammatory bowel disease; infliximab; loss of response.