Reinisch W¹, Panaccione R², Bossuyt P³, Baert F⁴, Armuzzi A⁵, Hébuterne X⁶, Travis S⁷, Danese S⁸, Sandborn WJ⁹, Schreiber S¹⁰, Berg S¹¹, Zhou Q¹², Kligys K¹², Neimark E¹³, Suleiman AA¹⁴, D'Haens G¹⁵, Colombel JF¹⁶. Inflamm Bowel Dis. 2020 Feb 27. pii: izaa025. doi: 10.1093/ibd/izaa025. [Epub ahead of print]

Author information

1 Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

2 Inflammatory Bowel Disease Unit, Department of Medicine, University of Calgary, AB, Canada.

3 Imelda General Hospital, Bonheiden, Belgium.

4 AZ Delta, Roeselare-Menen, Belgium.

5 Presidio Columbus, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

6 Inflammatory Bowel Disease Center, University of Nice-Sophia Antipolis, CHU of Nice, Nice, France.

7 Translational Gastroenterology Unit, National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK.

8 Department of Biomedical Sciences, Humanitas University, Milan, Italy.

9 Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA, USA.

10 Department of Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany.

11 Global Medical Affairs, AbbVie AB, Solna, Sweden.

12 AbbVie Inc., North Chicago, IL, USA.

13 Research and Development, Gastroenterology/Immunology, AbbVie Inc., Worcester, MA, USA.

14 Clinical Pharmacology and Pharmacometrics, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen am Rhein, Germany.

15 Academic Medical Center, Amsterdam, Netherlands.

16 Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Abstract

BACKGROUND: CALM was a randomized phase 3 trial in patients with Crohn's disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone. The purpose of this post hoc analysis of CALM was to identify drivers of treatment escalation and evaluate the association between biomarker cutoff concentrations and endoscopic end points.

METHODS: The proportion of patients achieving CD Endoscopic Index of Severity (CDEIS) <4 and no deep ulcers 48 weeks after randomization was evaluated according to CRP <5 mg/L or ≥5 mg/L and FC <250 μg/g or ≥250 μg/g. Subgroup analyses were performed according to disease location, and sensitivity analyses were conducted in patients with elevated CRP and/or FC at baseline. The association between endoscopic end points and biomarker cutoffs was performed using χ?2 test.

RESULTS: The proportion of patients who achieved the primary end point CDEIS <4 and no deep ulcers was significantly greater for those with FC <250 µg/g (74%; P < 0.001), with an additive effect for CRP <5 mg/L. The association of FC <250 µg/g with improved endoscopic outcomes was independent of disease location, although the greatest association was observed for ileocolonic disease. Fecal calprotectin <250 µg/g, CRP <5 mg/L, and CDAI <150 gave a sensitivity/specificity of 72%/63% and positive/negative predictive values of 86%/42% for CDEIS <4 and no deep ulcers 48 weeks after randomization.

CONCLUSION: This post hoc analysis of CALM demonstrated that a cutoff of FC <250 µg/g is a useful surrogate marker for mucosal healing in CD.