What to Do When Biologic Agents Are Not Working in Inflammatory Bowel Disease Patients

Abstract

Anti-tumor necrosis factor α and anti-integrin biologic therapies are effective for induction and maintenance of remission in moderate to severe ulcerative colitis and Crohn's disease. However, clinicians face many challenges in determining the best course of action when a patient does not respond or loses response to a biologic therapy. When patients are found to have continued active inflammation despite having undergone biologic therapy, the first determination should be whether this represents a primary nonresponse to the drug's mechanism of action or a secondary loss of response due to inadequate drug levels and/or antibody formation to the drug. Primary nonresponders may respond to a drug with a different mechanism of action. Secondary loss of response may be addressed through strategies such as dose escalation or addition of an immunosuppressant. Future options may include changing to a therapy targeting other mechanisms of immune modulation.

Keywords: Crohn’s disease; Inflammatory bowel disease; anti-integrin; anti—tumor necrosis factor α; biologic therapy; ulcerative colitis.

Figure 1

An algorithm for the evaluation and dose adjustment of infliximab in an inflammatory bowel disease patient with continued inflammation. ATI, antibodies to infliximab; TNF, tumor necrosis factor.

Figure 2

An algorithm for the management of patients with inflammatory bowel disease in whom biologic agents are not working. *Other causes of symptoms can include celiac disease, small intestinal bacterial overgrowth, or irritable bowel syndrome.