Fecal Calprotectin Predicts Mucosal Healing in Patients With Ulcerative Colitis Treated With Biological Therapies: A Prospective Study

Lorenzo Bertani, Corrado Blandizzi, Maria Gloria Mumolo, Linda Ceccarelli, Eleonora Albano, Gherardo Tapete, Giovanni Baiano Svizzero, Federico Zanzi, Francesca Coppini, Nicola de Bortoli, Massimo Bellini, Riccardo Morganti, Santino Marchi, Francesco Costa, Lorenzo Bertani, Corrado Blandizzi, Maria Gloria Mumolo, Linda Ceccarelli, Eleonora Albano, Gherardo Tapete, Giovanni Baiano Svizzero, Federico Zanzi, Francesca Coppini, Nicola de Bortoli, Massimo Bellini, Riccardo Morganti, Santino Marchi, Francesco Costa

Abstract

Introduction: Biological therapies are widely used for the treatment of ulcerative colitis. However, only a low proportion of patients achieve clinical remission and even less mucosal healing. There is currently scarce knowledge about the early markers of therapeutic response, with particular regard to mucosal healing. The aim of this prospective study was to evaluate the role of fecal calprotectin (FC) as early predictor of mucosal healing.

Methods: A prospective observational study was conducted on patients with ulcerative colitis, who started biological therapy with infliximab, adalimumab, golimumab, or vedolizumab at our center. All patients underwent colonoscopy, performed by 2 blinded operators, at baseline and week 54 or in case of therapy discontinuation because of loss of response. FC was assessed at baseline and week 8 and evaluated as putative predictor of mucosal healing at week 54.

Results: We enrolled 109 patients, and 97 were included in the analysis. Twenty-six patients (27%) experienced loss of response. Over 71 patients (73%) with clinical response at week 54, clinical remission was obtained in 60 patients (61.9%) and mucosal healing in 45 patients (46.4%). After 8 weeks of treatment, FC predicted mucosal healing at week 54 (P < 0.0001). Sensitivity, specificity, positive predictive value, and negative predictive value were estimated to be 75%, 88.9%, 86.6%, and 75.5%, respectively, based on a cutoff of 157.5 mg/kg.

Discussion: The present study suggests that FC assessment after 8 weeks of treatment with all the biological drugs could represent a promising early marker of response to therapy in terms of mucosal healing.

Conflict of interest statement

Guarantor of the article: Lorenzo Bertani, MD.

Specific author contributions: L.B.: study concept and design, data collection, writing of the manuscript, and approving final version; C.B.: writing of the manuscript and approving the final version; M.G.M., L.C., E.A., G.T., G.B.S., F.Z., and F.C.: data collection and approving the final version; N.d.B. and M.B.: writing of the manuscript and approving the final version; R.M.: statistical analysis and approving the final version; S.M.: writing of the manuscript and approving the final version; and F.C.: study concept and design, writing of the manuscript, and approving the final version.

Financial support: This paper has not required funding in terms of grants, equipment, and drugs. No supportive foundations have funded this article.

Potential competing interests: F.C. received board membership honoraria from Takeda, Janssen, and Amgen and lecture fees from Abbvie, Takeda, Zambon, Ferring, Diasorin, Otsuka, and MSD; none of these honoraria had influence on this paper. All other authors have no potential conflict of interest in presenting this paper.

Figures

Figure 1.
Figure 1.
Receiver operating characteristic curve analysis of fecal calprotectin levels at week 8 for the prediction of mucosal healing at week 54. At the cutoff ≤157.5 mg/kg, sensitivity was 75%, specificity 88.9%, positive predictive value 86.6%, and negative predictive value 75.5%.

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