P544. Does measuring IFX and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease impact clinical management? A Canadian experience
U. Chauhan1, U. Dutta2, D. Armstrong2, J. Marshall2, F. Tse2, E. Greenwald2, T. Xenodemetropoulos2, S. Halder2, 1McMaster University Medical Centre, Digestive Disease Speciality Adult Service, Hamilton ON, Canada, 2McMaster University, Division of Gastroenterology, Hamilton ON, Canada
Infliximab (IFX) is a chimeric (mouse/human) anti-Tumour Necrosis Factor alpha (anti-TNFa) therapy used for treatment of inflammatory bowel disease (IBD). Patients may become unresponsive to IFX or develop side effects. Reasons for this may be sub-therapeutic drug levels or development of Human Anti-Chimeric Antibodies (HACA). Objective assessment of these two parameters would help guide therapy in some complex patients. An HACA serum assay is commercially available through Prometheus Laboratories, Inc., San Diego, CA.
We conducted a retrospective chart review of adult patients with IBD in whom HACA and IFX trough levels were estimated, to determine whether these results impacted clinical management. The indications for these tests were recorded for each patient. Approval was sought from Ministry of Health and Long Term Care in Ontario for performing the test. Serum was collected 24 to 48 hours prior to the next IFX infusion.
Thirty-six patients with IBD (29 CD, 7 UC) had HACA and IFX levels estimated. The mean age (SD) was 32.5 (13) years and 56% were female. The mean disease duration (SD) was 10 (6) years and mean duration on IFX therapy (SD) was 4 (3) years. Indications for testing were diminished response to therapy in 80%, development of side effects in 14% and primary non-response in 6%. HACA was positive in 7 patients and IFX levels were undetectable in 9 patients. IFX levels were undetectable in all patients who were HACA positive except one. Based on these results, treatment was altered in 78% of the patients. Among the 7 HACA positive patients, 3 were switched biological therapy, 2 were switched to immunomodulators (endoscopy showed inactive disease), 2 were continued on IFX with increased frequency. Among 29 patients who were HACA negative, 9 had undetectable drug concentration. In them, frequency of infusion was increased in 6, dose was increased in 2 (10 mg/kg every 4 weeks), and one patient was switched to another biological agent. Among the remaining 20 patients with detectable drug levels (>6.25mcg/ml), only limited modifications were required. Of these, 8 were continued on the same treatment, 6 were switched to another biological agent; the IFX dose was increased in 3, immunomodulator therapy started in 2 and in one patient the dose of IFX was decreased.
Measurement of HACA and infliximab concentration impacts clinical management of patients with IBD. The use of these tests helps tailor therapy and optimises patient management.