Fecal Calprotectin Pretreatment and Induction Infliximab Levels for Prediction of Primary Nonresponse to Infliximab Therapy in Crohn's Disease

Introduction: The association between infliximab (IFX) and fecal calprotectin (FC) levels on one hand, and the clinical and endoscopic response of patients with inflammatory bowel disease on the other, is well established. Objective and Methods: To investigate the association between inflammatory biochemical parameters and serum concentrations of IFX during induction treatment with a primary nonresponse in a prospective cohort of Crohn's disease (CD) patients. Results: Of the 35 patients included, 8 (22.8%) had primary nonresponse at the end of induction. Induction IFX levels were lower among primary nonresponders at weeks 6 and 14 (week 6: median IFX level 7.3 vs. 11.2 mu g/mL, respectively, p = 0.090; week 14: median IFX level 1.5 vs. 4.7 mu g/mL, respectively, p = 0.020). FC levels were higher in patients with primary nonresponse versus primary response at weeks 0, 6, and 14 (week 0: median FC level 1,830 vs. 410 mu g/g, respectively, p = 0.030; week 6: median FC level 1,150 vs. 230 mu g/g, respectively, p = 0.074; week 14: median FC level 1,210 vs. 208 mu g/g, respectively, p = 0.060). For the multivariate analysis, the median IFX level at week 14 and median FC level at week 0 were independently associated with primary nonresponse. A significant inverse correlation was determined between FC level at week 0 and IFX level at week 14 (Spearman's rho correlation, 0.440; p < 0.05). Conclusions: IFX levels (at week 14) and baseline FC levels could predict primary nonresponse after induction IFX therapy in patients with CD. A high baseline inflammatory load might modify the pharmacokinetic processes of anti-tumor necrosis factor drugs. Drug level monitoring and measurement of baseline inflammatory parameters could improve the efficacy of IFX in the induction therapy of patients with active CD. (C) 2018 S. Karger AG, Basel