Association of Higher Infliximab Drug Levels with Response Rates of Perianal Crohnʼs Disease

Abstract

Introduction: Perianal fistulas are a common complication of Crohn's disease (CD) that significantly impair quality of life. The efficacy of infliximab (IFX) for treatment of perianal fistulas is well established. Recent studies have demonstrated an association between IFX trough levels and fistula healing. One of the challenges encountered in these studies is the heterogeneity of the assays used to monitor IFX levels. The aim of this study was to determine the association between IFX levels, exclusively measured using the LabCorp electrochemiluminescence (ECLIA) assay and fistula response. Methods: CD patients with known perianal fistulas and treated with IFX between 2009 and 2015 were identified. Patients who had IFX drug levels measured using the LabCorp assay were further selected. The primary outcome of interest was perianal fistula response, which was defined as partial for decrease in drainage or pain, and complete for cessation of drainage and pain. Results: 37 patients were identified. 15, 15, and 7 patients had a complete, partial and no response respectively. Mean IFX level was higher in patients with complete response compared to those with partial response and no response (13.1 mcg/ml, 7.65 mcg/ml, 3.62 mcg/ml respectively). However, the difference in mean IFX level was significant only for the comparison between patients with complete response versus no response (p=0.003). Amongst responders to IFX, there was no difference in mean IFX level in patients on concomitant immunosuppressants compared to those that were not (10.1 mcg/ml versus 10.7 mcg/ml, p=0.838). 8 patients were treated with fecal diversion in addition to IFX. There was no difference in mean IFX level among patients with diversion compared to those in continuity (7.7 mcg/ml, 11.4 mcg/ml, p=0.21). Conclusion: In CD patients with perianal fistulas treated with IFX, a higher IFX level is associated with complete fistula response. These findings are consistent with prior studies that demonstrated incremental gains in fistula healing with increased IFX levels. With exclusive use of the LabCorp ECLIA assay to measure IFX levels, the results of this study further address the inherent variability encountered with use of multiple assays. Further studies are required to determine the optimal IFX levels to which therapy for perianal fistulas can be targeted. Furthermore, prospective studies are needed to determine if treating to a target IFX level improves outcomes in patients with perianal CD.