When Patients with Inflammatory Bowel Disease Have Suboptimal Response to Infliximab

Infliximab, a chimeric monoclonal antibody that acts against tumor necrosis factor (TNF), is effective for treating patients with inflammatory bowel disease (IBD; JW Gastroenterol Jan 3 2006 and JW Gastroenterol Jun 12 2002). However, clinical response to infliximab often declines. Such diminishing response is typically addressed empirically by increasing the infliximab dose, shortening the interval between dose administrations (sometimes in addition to increasing the dose), switching to another anti-TNF agent, or switching to a different class of immune modulators. Would measuring blood concentrations of infliximab and human antichimeric antibodies (HACAs) guide patient management more effectively?

To find out, investigators retrospectively analyzed data from 155 patients whose serum levels of infliximab and HACA had been measured primarily because of loss of response to infliximab (49% of patients) or partial response after treatment initiation (22%). Therapeutic levels of infliximab (defined as ≥12 µg/mL 4 weeks after infusion or >1.4 µg/mL at dosing trough) were identified in 51 patients (33%).

A total of 69 patients had subtherapeutic infliximab concentrations. In this group, among 29 whose infliximab doses were increased, 25 (86%) achieved a complete or partial response; among 6 patients who were switched to a different anti-TNF agent, 2 (33%) achieved a clinical response. A total of 35 patients had HACAs (and therefore undetectable infliximab levels as HACAs interfere with infliximab detection). In this group, among 12 who were switched to another anti-TNF agent, 11 (92%) experienced clinical responses; among 6 whose infliximab doses were increased, 1 (17%) experienced a clinical response.