676 Infliximab Trough Level or Combination Immunomodulator Therapy: Which Correlates Best With Mucosal Healing in IBD?

Abstract

INTRODUCTION: Combination immunomodulator (IMM) with infliximab (IFX) has been shown to be superior to IFX monotherapy therapy in the management of inflammatory bowel disease (IBD). It is unclear if this is related to IMM solely or higher IFX trough level (IFX-TL). The aims of this study are to examine the correlation of IFX-TL with clinical outcomes of IBD patients and to evaluate whether IFX-TL or combination IMM therapy correlate best with mucosal healing (MH). METHODS: This is a retrospective study of consecutive IFX treated IBD patients undergoing drug monitoring with liquid chromatography-tandem mass spectrometry (LC-MS/MS). IMM included either thiopurines or methotrexate. Primary analyses included: comparing IFX-TL with clinical remission, MH (absence of mucosal ulcers in Crohn's disease (CD) and Mayo endoscopic score ≤1 for ulcerative colitis (UC)) and normal c-reactive protein (CRP ≤8 mg/L). Secondary analyses included determining an IFX-TL cut off to achieve MH and evaluating the predictors of MH (IMM vs. IFX-TL). RESULTS: A total of 151 patients were included (67% CD, 24% UC, 6% indeterminate colitis, 3% pouchitis) (Table 1). The median IFX-TL was 7 mcg/mL (IQR: 1.3, 19.4). The distribution of IFX-TL was not significantly different between patients in clinical remission, response and no response (median: 5.7 vs. 8.4 vs. 2.3 mcg/mL, respectively; P = 0.46). The median IFX-TL was significantly higher in patients who had a normal CRP (11.1 vs. 1.4 mcg/mL; P < 0.001) and in those who achieved MH (13.1 mcg/mL vs. 3.9 mcg/mL; P = 0.01). An IFX-TL ≥7.5 mcg/mL predicted MH with a sensitivity of 67% and specificity of 64% (AUC = 0.67; Figure 1). Combination therapy was associated with higher IFX-TL (median: 15.8 vs. 4.6 mcg/mL; P < 0.001). In a multivariable model to predict MH based on IFX-TL (continuously), combination therapy (yes vs no), dosing frequency (≥8 vs <8 weeks), and albumin (<3.5 vs ≥3.5), higher IFX-TL was associated with higher likelihood of MH (OR for 5-mcg/mL increase: 1.18, 95% CI 1.01-1.39; P = 0.04). In this model, IMM combination was not significant (OR: 0.79, P = 0.66), neither was dosing frequency (OR: 1.44, P = 0.48). Low albumin showed lower likelihood of MH, but this was not statistically significant (OR 0.14, 95% CI: 0.02-1.16, P = 0.07). CONCLUSION: IFX-TL was associated with normal CRP and MH but not clinical remission in this cohort of IBD patients. IFX-TL and not combination IMM therapy was independently associated with MH.