Comparison of fecal calprotectin and serum C-reactive protein in early prediction of outcome to infliximab induction therapy

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’.

Keywords:

• Biomarker
• cytokines
• IBD clinical
• induction therapy
• outcome

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Disclosure statement

No conflicts to declare by any of the authors.

Author contributions

J.E.: data collection, data analysis and writing up of the second draft of manuscript; M.L.: data collection, data analysis and writing up of first draft of manuscript; R.B.: patient recruitment; T.L.: study design, data analysis and critical review of manuscript; H.D-T.: data collection and analysis; M.H.: study design, data analysis, critical review of manuscript; P.M.H.: study design, data analysis, critical review, final writing and submission of manuscript.

Additional information

Funding

The study was supported by the Swedish Research Council 2017-02243, Swedish Society of Medicine, Karolinska Institutet and Uppsala University.