Open AccessAssociation of Biomarker Cutoffs and Endoscopic Outcomes in Crohn’s Disease: A Post Hoc Analysis From the CALM Study
Author(s) -
Walter Reinisch,
Remo Panaccione,
Peter Bossuyt,
Filip Baert,
Alessandro Armuzzi,
Xavier Hébuterne,
Simon Travis,
Silvio Danese,
William J. Sandborn,
Stefan Schreiber,
Sofie Berg,
Qian Zhou,
Kristina Kligys,
Ezequiel Neimark,
Ahmed A. Suleiman,
Geert R. D’Haens,
Jean–Frédéric Colombel
Publication year - 2020
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1093/ibd/izaa025
Subject(s) - calprotectin , medicine , biomarker , gastroenterology , post hoc analysis , c reactive protein , randomization , crohn's disease , area under the curve , randomized controlled trial , disease , inflammatory bowel disease , inflammation , biochemistry , chemistry
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.