Measurement of infliximab and anti-infliximab antibody levels can help distinguish maintenance versus loss of response.

Inflammatory bowel disease (IBD), comprised primarily of Crohn’s disease (CD) and ulcerative colitis (UC), is estimated to affect approximately 1 million individuals in the United States alone, with approximately 30,000 new cases diagnosed annually.1 A hallmark of this disease is chronic inflammation of the intestinal mucosa, which results in part from production of the tumor necrosis factor–α (TNF-α) cytokine. Understanding of this pathogenesis has been exploited for treatment purposes, and antibodies directed against TNF-α have proven to be highly effective for the induction and maintenance of remission in both CD and UC. Infliximab (Remicade, Janssen Biotech) was the first anti–TNF-α biologic therapy approved for the treatment of both CD and UC, based on clinical trial data showing robust efficacy in these conditions.2-6 Despite its proven efficacy, a subset of patients do not respond to infliximab (and other anti–TNF-α agents).2 Additionally, some patients achieve an initial response to induction therapy but lose this response over time with maintenance treatment. The reasons for these therapeutic failures remain a matter of debate. One possibility is that loss of response is due to an immunologic mechanism, whereby the patient mounts an immune response to infliximab, thus forming anti-infliximab antibodies. Multiple studies in CD patients have linked the development of anti-infliximab antibodies with loss of treatment response and shorter duration of response.7-10 Another possibility is that loss of response to infliximab is pharmacologic in nature; under this mechanism, individuals’ differing pharmacokinetic or pharmacodynamic profiles may contribute to their inability to maintain a therapeutic serum level of infliximab. Indeed, low serum infliximab concentrations have been linked to a lack of clinical response in both CD and UC.7,11-14 Therapeutic failures with infliximab, and the underlying reasons for these failures, pose a significant challenge for clinicians who manage patients with IBD. There are no standard guidelines defining a therapeutic strategy among this patient subset, although treatment algorithms have been proposed.15,16 The lack of such guidance is primarily due to a paucity of data demonstrating clinically relevant threshold levels of infliximab and/or anti-infliximab antibodies. Further, clinicians do not yet know whether the use of such threshold levels, if identified, would aid in the discrimination of responding versus nonresponding patients. These knowledge gaps led to the design of the recent study by Steenholdt and colleagues, published in the Scandinavian Journal of Gastroenterology, which is the first study to establish threshold values for clinically relevant concentrations of circulating serum levels of both infliximab and antiinfliximab antibodies in IBD patients.17