Infliximab Therapeutic Drug Monitoring in Clinical Practice: Indications and Utility

Abstract

Purpose: Infliximab (IFX) is effective for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Measurement of serum IFX levels and antibodies to infliximab (ATI) have shown utility in the management of inflammatory bowel disease (IBD) patients with inadequate/loss of response (LOR) to IFX or infusion reactions. Evolving evidence suggests additional indications for therapeutic drug monitoring using IFX and ATI concentrations in patients without specific response-related issues, and in patients restarting IFX after drug holiday, may help predict and optimize response to IFX. Here, we report the spectrum of use of IFX and ATI testing at an academic IBD Center, including novel indications such as reintroduction of IFX and therapeutic drug monitoring. Methods: We conducted a retrospective review of the electronic medical records of all IBD patients at our institution who underwent IFX/ATI testing between January 1, 2010 and December 31, 2012. The testing date, results, indication for testing, and clinical management based on test results were obtained. Results: One hundred forty two IBD patients (83 with CD, 58 with UC, one with indeterminate colitis) underwent 205 IFX/ATI tests. Sixty-one percent (87/142) of patients received concomitant immunosuppression (IS). The most common indications for testing were inadequate/LOR (50%) and therapeutic drug monitoring (19%). Of 49 patients with confirmed LOR, 50% (25/49) had non-therapeutic IFX levels, and additional 16% (8/49) had detectable ATI with undetectable IFX levels. Thirty-eight patients underwent testing for therapeutic drug monitoring: 16% (6/38) had nontherapeutic IFX levels, 3% (1/38) had detectable ATI, and 3% (1/38) had measurable IFX with detectable ATI. Of seven patients tested prior to reintroduction of IFX, 43% (3/7) were found to have detectable ATI. Of 11 patients tested after re-challenge with IFX, 55% (6/11) had nontherapeutic IFX concentrations, and 36% (4/11) had detectable ATI. Concomitant IS therapy was significantly associated with negative ATI status (p=0.0026). Non-therapeutic IFX concentration was associated with higher C-reactive protein (p<0.0001). Testing resulted in changes in therapy in 67% of patients with LOR, and 21% of patients undergoing routine therapeutic drug monitoring. Conclusion: The measurement of IFX and ATI concentrations in IBD patients receiving IFX can aid decision-making in multiple clinical scenarios and frequently results in changes in clinical care. Disclosure - Dr. Sandborn - Consultant and Grant/Research Support: Janssen Biotech, Inc, Consultant: P rometheus Laboratories, Inc.; Dr. Levesque - Consultant: Prometheus Laboratories, Inc.