Abstract

Background: Fecal calprotectin (FC) and serum C-reactive protein (CRP) are biomarkers of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC). We assessed FC, CRP, Harvey–Bradshaw index (HBi), partial Mayo Clinic Scoring (pMCS) and a cytokine panel during infliximab induction to predict therapy outcome.Methods: FC, CRP and clinical indices were evaluated in 123 (76 CD, 47 UC) patients before infliximab induction and after 12 weeks. Responders were monitored 48 weeks for an ‘incident’ (dosage increase, shortened dosage interval, surgery). Cutoff values for FC and CRP were obtained using receiver-operating characteristics (ROC). Disease progression was analyzed with Kaplan–Meier survivals, log-rank test and logistic regression for combined biomarkers. Cytokines were analyzed with Luminex multiplexing system.Results: Following infliximab, FC and CRP declined (p < .0001) along with HBi for CD and pMCS for UC. Simultaneously, IL-6 and TNF-α decreased, while IL-10 increased. Optimal FC ROC cutoff was 221 µg/g (sensitivity 66%, specificity 67%, AUC 0.71) and CRP ROC cutoff 2.1 mg/L (sensitivity 54%, specificity 60%, AUC 0.58). In CD, FC > 221 µg/g (p < .0001), but not CRP > 2.1 mg/L predicted an ‘incident’. However, combined FC and CRP also predicted an ‘incident’ (p < .042). In UC, both FC > 221 µg/g (p < .0005) and CRP > 2.1 mg/L (p = .0334) predicted ‘incident’, as did combined biomarkers (p < .005).Conclusions: Clinical disease activity is reduced by treatment with infliximab. In CD, persistently high FC, but not CRP, predict a treatment ‘incident’, whereas in UC both high FC and high CRP predict ‘incident’. Combined FC and CRP values also predict an ‘incident’.

Highlights

  • Long-term experience with standard therapies for inflammatory bowel disease (IBD) suggests diverse limitations and shortcomings as regards prediction of treatment response

  • Patients should be 18–75 years of age, diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) at least 1 year before study, maximum dosage of mesalazine up to 4.8 grams per day, devoid of glucocorticosteroids, receiving infliximab induction therapy according to the standard protocol at weeks 0, 2 and 6 at a dose of 5 mg/kg followed by maintenance therapy every 8 weeks

  • Our present study shows that patients responding to infliximab treatment, clinical indices, as well as Fecal calprotectin (FC) and C-reactive protein (CRP) levels all decreased significantly during the induction period

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Summary

Introduction

Long-term experience with standard therapies for inflammatory bowel disease (IBD) suggests diverse limitations and shortcomings as regards prediction of treatment response. The neutrophil-derived protein calprotectin is used as a fecal biomarker of inflammatory activity in CD and UC. In clinical practice, increased fecal calprotectin (FC) excretion is strongly correlated with intestinal inflammation [2], and is a useful marker of IBD [3]. Fecal calprotectin (FC) and serum C-reactive protein (CRP) are biomarkers of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC). We assessed FC, CRP, Harvey–Bradshaw index (HBi), partial Mayo Clinic Scoring (pMCS) and a cytokine panel during infliximab induction to predict therapy outcome. In UC, both FC > 221 mg/g (p < .0005) and CRP > 2.1 mg/L (p 1⁄4 .0334) predicted ‘incident’, as did combined biomarkers (p < .005). Conclusions: Clinical disease activity is reduced by treatment with infliximab. Combined FC and CRP values predict an ‘incident’

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