Fecal Calprotectin Levels Can Predict Pharmacokinetics of Anti-TNF Therapy

Abstract

Introduction: Even though anti-tumor necrosis factor (ATNF) agents have revolutionized the treatment of inflammatory bowel disease (IBD) many patients do not experience a benefit (primary nonresponse). This could be explained by insufficient drug, which is often seen in patients with severe intestinal disease. Fecal calprotectin is a novel marker of intestinal inflammation used to monitor patients with IBD, but it's role predicting the pharmacokinetics of ATNFs is not clear. The aim of this study was to assess if fecal calprotectin (FCP) pre-ATNF therapy can predict low drug levels and need for dose escalation. Methods: We designed a cohort study of patients 18 years or older with IBD who started infliximab (IFX) or adalimumab (ADA) at our tertiary IBD center. Predictive variables (before initiating ATNF therapy) included demographics, disease phenotype, FCP, C-Reactive protein (CRP), albumin and concomitant use of immunomodulators. The primary outcome was ATNF serum levels as a continuous and “adequate levels” as dichotomous variable (a threshold level of 3 and 5 mg/dL were used for IFX and ADA respectively as per current evidence). The secondary outcome was need for drug dose escalation.Table 2: Correlations of several measurements and anti-TNF levelsResults: 31 patients were included. Baseline characteristics of the study population are in Table 1. IFX levels were measured between weeks 14 and 22, while ADA levels were measured between weeks 12 and 36. Higher FCP levels predicted ATNF primary non response (ROC: 0.78, p=0.78). There was a negative correlation between pre-treatment FCP and drug levels and CRP, but only the former achieved statistical significance (rho: -0.5, p=0.0042 [Figure 1] and rho: -0.26, p=0.16). Concomitantly, there was a significant correlation between drug levels and pre-therapy serum albumin (rho: 0.38, p=0.035). Patients with a FCP ≥ 150 μg/g had an increased chance of requiring dose escalation (OR: 12 [95%CI: 1.2-117.4], p=0.03).Figure 1Table 1: Baseline characteristics of the study populationConclusion: Baseline FCP is correlated with drug levels achieved after starting ATNF therapy and those who require dose escalation. FCP can lead to more precise dosing of ATNF, decreasing the rate of primary non-responders by predicting the group of patients that may require higher induction/maintenance doses. Further, larger studies are warranted.