P089 - Results from a prospective study combining infliximab, surgery, and methotrexate in severe fistulising ano-perineal Crohn's disease

Abstract

Background: Treatment with infliximab (IFX) can result in immunogenicity through the formation of human anti-chimeric antibodies (HACAs). These antibodies are associated with a decreased duration of response, whereas therapeutic levels of IFX are associated with durable clinical response. We evaluated the clinical utility of measuring serum IFX and HACA levels. Methods: We retrospectively reviewed charts of patients with inflammatory bowel disease who had IFX drug and HACA levels measured over a three-year period from 2005-2008. The clinical utility of these tests was assessed by determining whether the result affected clinical management. The management and subsequent clinical response to therapeutic changes based on test results was evaluated. Fisher's exact test and log-rank test for discontinuation were used for statistical analysis. Results: One hundred and fifty-five patients underwent IFX level and HACA status testing. The median time to initial testing after IFX initiation was 50 weeks (IQR: 22.7-120). The main indications for testing were: loss of response to IFX (50.3%), partial response after initiation of IFX (22.6%) and possible autoimmune/delayed hypersensitivity reaction (14.8%). HACAs were identified in 35 patients (22.6%) and therapeutic IFX levels were found in 51 (32.9%). Of 177 total tests assessed, the results impacted treatment decisions in 73.4% (95% CI: 66-80%). In those with positive HACAs, change to another anti-TNF was associated with a complete or partial response in 91.6% of patients whereas increasing the dose had a response of 16.7% (p<0.004). In those with sub-therapeutic levels, increasing the dose was associated with complete or partial clinical response in 86.2% of patients while changing to another anti-TNF resulted in a response of 40% (p<0.048). Patients with clinical symptoms and therapeutic IFX levels were: continued at the same dose 70.8% of the time (95% CI: 49-87%) and had no evidence of active inflammation by endoscopic/radiographic assessment 61.9 % of the time (95% CI, 38-82%). In patients with therapeutic IFX levels who continued the same dose and those with non-therapeutic levels who were dose-escalated, the median time to discontinuation of IFX after the test date was similar at 51 weeks (IQR: 45-92). Conclusions: Measurement of IFX level and HACA status impacts management and is clinically useful. Increasing the IFX dose in patients who have HACAs is ineffective, whereas in patients with non-therapeutic IFX levels, this strategy may be more effective than changing to another anti-TNF agent. Changing treatment based on clinical symptoms alone may lead to inappropriate management.