TY - JOUR
T1 - Diagnostic Accuracy of Fecal Calprotectin Concentration in Evaluating Therapeutic Outcomes of Patients With Ulcerative Colitis
AU - Stevens, Toer W.
AU - Gecse, Krisztina
AU - Turner, Jerrold R.
AU - de Hertogh, Gert
AU - Rubin, David T.
AU - D'Haens, Geert R.
N1 - Funding Information: Funding All aspects of this study were funded by Shire , Inc. Medical writing support, under guidance of the authors, was provided by Joe Wilson of MedErgy, and funded by Shire , Inc, a Takeda company. Funding Information: Funding All aspects of this study were funded by Shire, Inc. Medical writing support, under guidance of the authors, was provided by Joe Wilson of MedErgy, and funded by Shire, Inc, a Takeda company. Conflicts of interest These authors disclose the following: Geert R. D'Haens has served as an advisor for AbbVie, Ablynx, Allergan, Amakem, Amgen, AM Pharma, Arena Pharmaceuticals, AstraZeneca, Avaxia, Biogen, Bristol Myers Squibb, Boerhinger Ingelheim, Celgene/Receptos, Celltrion, Cosmo, Covidien/Medtronics, Ferring, DrFALK Pharma, Eli Lilly, Engene, Galapagos, Genentech/Roche, Gilead, GlaxoSmithKline, Hospira/Pfizer, Immunic, Johnson & Johnson, Lycera, Medimetrics, Millenium/Takeda, Mitsubishi Pharma, Merck Sharp & Dome, Mundipharma, Nextbiotics, Novonordisk, Otsuka, Pfizer/Hospira, Photopill, Prometheus laboratories/Nestle, Progenity, Protagonist, Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Seres/Nestle, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant, and Vifor, and received speaker fees from AbbVie, Biogen, Ferring, Johnson & Johnson, Merck Sharp & Dome, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Millenium/Takeda, Tillotts, and Vifor; Krisztina Gecse has served as speaker and/or advisor for Amgen, AbbVie, Boehringer Ingelheim, Ferring, Hospira, MSD, Pfizer, Samsung Bioepis, Sandoz, Takeda, and Tigenix; Gert de Hertogh's institutions (KU Leuven, UZ Leuven) receive fees for his activities as a central pathology reviewer for Centocor and Takeda; and David T. Rubin has consulted for AbbVie, Abgenomics, Allergan, Inc, Amgen, Celgene Corporation, Forward Pharma, Genentech/Roche, Janssen Pharmaceuticals, Merck & Co, Inc, Miraca Life Sciences, Napo Pharmaceuticals, Pfizer, Salix Pharmaceuticals, Samsung Bioepis, Sandoz Pharmaceuticals, Shire, Takeda, and Target PharmaSolutions, and received grant support from AbbVie, Genentech/Roche, Janssen Pharmaceuticals, Prometheus Laboratories, Shire, Takeda, and UCB Pharma. The remaining authors disclose no conflicts. Publisher Copyright: © 2021 The Authors
PY - 2021/11
Y1 - 2021/11
N2 - Background & Aims: Histologic features of inflammation (histologic inflammation) are associated with clinical relapse in patients with ulcerative colitis (UC). Concentration of fecal calprotectin (FC) can be used to identify patients with mucosal inflammation. We aimed to assess the accuracy of FC measurements in identifying patients with histologic inflammation and to develop a model to predict outcomes of therapy. Methods: We performed a post hoc analysis of data from a phase 4 trial of the efficacy of multimatrix mesalamine in patients with mild to moderate UC (the MOMENTUM trial). We obtained clinical, endoscopic, and histologic data from week 8 (n = 639) and week 52 (n = 373) of the trial. We used area under the receiver operating characteristic curves to determine the accuracy and optimal cut-off values of FC in identifying patients with different therapeutic outcomes (clinical remission, endoscopic healing, deep remission, or histologic remission) at week 8 and week 52. We performed multivariable logistic regression analyses to identify factors associated with these outcomes. Results: Median FC concentrations were lower in patients who achieved outcomes of clinical remission, endoscopic healing, deep remission, or histologic remission vs patients who did not. FC concentrations identified patients with endoscopic healing and histologic remission with area under the receiver operating characteristic curve values of 0.77 and 0.76 at week 8, and 0.79 and 0.80 at week 52, respectively. The optimal FC cut-off concentrations for identification of patients with histologic remission were 75 μg/g at week 8 and 99 μg/g at week 52. In the subpopulation with an endoscopy score of 0, median FC concentrations were lower in patients with histologic remission than in patients with microscopic inflammation at week 8 (30 vs 140 μg/g; area under the receiver operating characteristic, 0.72) and week 52 (21.5 vs 134.5 μg/g; area under the receiver operating characteristic, 0.71). At both time points, the optimal FC cut-off concentration was approximately 75 μg/g. Our final prediction model for week 52 histologic remission comprised endoscopic score at week 8, FC concentration at week 8, and histologic activity at baseline and week 8. Conclusions: A post hoc analysis of data from a phase 4 trial found that, even in patients with complete endoscopic healing of UC, FC concentration can be used to discriminate patients with ongoing microscopic inflammation from patients with histologic remission. The optimal cut-off concentration of FC is between 75 and 100 μg/g. ClinicalTrials.gov no: NCT01124149.
AB - Background & Aims: Histologic features of inflammation (histologic inflammation) are associated with clinical relapse in patients with ulcerative colitis (UC). Concentration of fecal calprotectin (FC) can be used to identify patients with mucosal inflammation. We aimed to assess the accuracy of FC measurements in identifying patients with histologic inflammation and to develop a model to predict outcomes of therapy. Methods: We performed a post hoc analysis of data from a phase 4 trial of the efficacy of multimatrix mesalamine in patients with mild to moderate UC (the MOMENTUM trial). We obtained clinical, endoscopic, and histologic data from week 8 (n = 639) and week 52 (n = 373) of the trial. We used area under the receiver operating characteristic curves to determine the accuracy and optimal cut-off values of FC in identifying patients with different therapeutic outcomes (clinical remission, endoscopic healing, deep remission, or histologic remission) at week 8 and week 52. We performed multivariable logistic regression analyses to identify factors associated with these outcomes. Results: Median FC concentrations were lower in patients who achieved outcomes of clinical remission, endoscopic healing, deep remission, or histologic remission vs patients who did not. FC concentrations identified patients with endoscopic healing and histologic remission with area under the receiver operating characteristic curve values of 0.77 and 0.76 at week 8, and 0.79 and 0.80 at week 52, respectively. The optimal FC cut-off concentrations for identification of patients with histologic remission were 75 μg/g at week 8 and 99 μg/g at week 52. In the subpopulation with an endoscopy score of 0, median FC concentrations were lower in patients with histologic remission than in patients with microscopic inflammation at week 8 (30 vs 140 μg/g; area under the receiver operating characteristic, 0.72) and week 52 (21.5 vs 134.5 μg/g; area under the receiver operating characteristic, 0.71). At both time points, the optimal FC cut-off concentration was approximately 75 μg/g. Our final prediction model for week 52 histologic remission comprised endoscopic score at week 8, FC concentration at week 8, and histologic activity at baseline and week 8. Conclusions: A post hoc analysis of data from a phase 4 trial found that, even in patients with complete endoscopic healing of UC, FC concentration can be used to discriminate patients with ongoing microscopic inflammation from patients with histologic remission. The optimal cut-off concentration of FC is between 75 and 100 μg/g. ClinicalTrials.gov no: NCT01124149.
KW - Biomarker
KW - Histology
KW - Inflammatory Bowel Disease
KW - Prognostic
UR - http://www.scopus.com/inward/record.url?scp=85101337161&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.cgh.2020.08.019
DO - https://doi.org/10.1016/j.cgh.2020.08.019
M3 - Article
C2 - 32801008
SN - 1542-3565
VL - 19
SP - 2333
EP - 2342
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 11
ER -