Prognostic Value of Fecal Calprotectin to Inform Treat-to-Target Monitoring in Ulcerative Colitis

Parambir S. Dulai; Brian G. Feagan; Bruce E. Sands; Jingjing Chen; Karen Lasch; Richard A. Lirio

doi:10.1016/j.cgh.2022.07.027

Prognostic Value of Fecal Calprotectin to Inform Treat-to-Target Monitoring in Ulcerative Colitis

Parambir S. Dulai^*, Brian G. Feagan, Bruce E. Sands, Jingjing Chen, Karen Lasch, Richard A. Lirio

^*Corresponding author for this work

Medicine, Gastroenterology Division

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Background & Aims: We evaluated the value of post-induction fecal calprotectin (FCP) concentration as a biomarker in patients with ulcerative colitis (UC) treated with a biologic. Methods: This post hoc analysis of the GEMINI 1/GEMINI LTS (N = 620) and VARSITY (N = 771) trials evaluated the cross-sectional accuracy of post-induction FCP in identifying endoscopic activity and histologic inflammation, and the prognostic performance of FCP in identifying patients most likely to achieve endoscopic and histologic remission or require colectomy and UC-related hospitalization. Results: The cross-sectional accuracy of FCP in identifying endoscopic activity and histologic inflammation was modest (63%–79%). However, a post-induction FCP concentration of ≤250 μg/g vs >250 μg/g was associated with a substantially higher probability of achieving clinical remission (odds ratio [OR], 4.03; 95% confidence interval [CI], 2.78–5.85), endoscopic remission (OR, 4.26; 95% CI, 2.83–6.40), and histologic remission (Robarts Histopathology Index: OR, 5.54; 95% CI, 3.77–8.14; Geboes grade: OR, 6.42; 95% CI, 4.02–10.26) at week 52 and a lower probability of colectomy over 7 years (hazard ratio, 0.296; 95% CI, 0.130–0.677) and UC-related hospitalization (hazard ratio, 0.583; 95% CI, 0.389–0.874). The association with colectomy was significant even among patients in symptomatic remission or with endoscopic improvement post-induction, and among patients with elevated FCP at baseline. Conclusions: Although FCP had only modest cross-sectional accuracy in identifying disease activity, an FCP concentration of ≤250 μg/g vs >250 μg/g was associated with increased probability of achieving long-term clinical, endoscopic, and histologic remission, and reduced probability of colectomy and UC-related hospitalization (ClinicalTrials.gov: NCT00783718, NCT00790933, NCT02497469).

Original language	English (US)
Pages (from-to)	456-466.e7
Journal	Clinical Gastroenterology and Hepatology
Volume	21
Issue number	2
DOIs	https://doi.org/10.1016/j.cgh.2022.07.027
State	Published - Feb 2023

Funding

Funding Medical writing support was provided by Peggy Robinet, Pharm D, PhD, of ProEd Communications, Inc and Cerys Evans, PhD, of PharmaGenesis Cardiff, Cardiff, UK, and was funded by Takeda Pharmaceuticals U.S.A. Inc.The authors thank Ding Feng, Sharon Hunter, Ellen Xiao, Decai Deng, and the Takeda statistical programming team for data analysis support. The datasets, including the redacted study protocol, redacted statistical analysis plan, and individual participants data supporting the results reported in this article, will be available 3 months from initial request, to researchers who provide a methodologically sound proposal. The data will be provided after its de-identification, in compliance with applicable privacy laws, data protection and requirements for consent and anonymization. Parambir S Dulai, MD (Formal analysis: Supporting; Investigation: Lead; Methodology: Lead; Supervision: Equal; Writing – original draft: Supporting; Writing – review & editing: Supporting), Brian G. Feagan (Formal analysis: Supporting; Methodology: Supporting; Supervision: Supporting; Writing – review & editing: Equal), Bruce E. Sands (Methodology: Supporting; Writing – review & editing: Equal), Jingjing Chen (Formal analysis: Lead; Investigation: Equal; Methodology: Equal), Karen Lasch (Data curation: Supporting; Formal analysis: Supporting; Funding acquisition: Lead; Investigation: Equal; Methodology: Equal; Project administration: Supporting; Resources: Supporting; Supervision: Supporting; Visualization: Supporting; Writing – original draft: Supporting; Writing – review & editing: Equal), Richard A. Lirio (Data curation: Equal; Formal analysis: Equal; Investigation: Equal; Supervision: Equal; Writing – original draft: Supporting; Writing – review & editing: Equal) Conflicts of interest The authors disclose the following: Parambir S. Dulai has received consulting fees from Johnson and Johnson, Gilead, Lily, BMS, Novartis, Pfizer, and Takeda; financial support for research from Takeda and Pfizer; stock options for DigbiHealth; and licensing royalties from PreciDiag. Brian G. Feagan has received consulting fees from Abbott/AbbVie, ActoGeniX, Akros, Albireo Pharma, Amgen, AstraZeneca, Avaxia Biologics Inc, Avir Pharma, Axcan, Baxter Healthcare Corp, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, enGene, Ferring Pharma, gIcare Pharma, Gilead, Given Imaging Inc, GSK, Ironwood Pharma, Janssen Biotech (Centocor), Johnson & Johnson/Janssen, Kyowa Hakko Kirin Co, Ltd, Lexicon, Lilly, Lycera Biotech, Merck, Mesoblast Pharma, Millennium, Nektar, Nestlé, Novartis, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist, Receptos, Roche/Genentech, Salix Pharmaceuticals, Serono, Shire, Sigmoid Pharma, Synergy Pharmaceuticals Inc, Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharmaceuticals, VHsquared Ltd, Warner Chilcott, Wyeth, Zealand, and Zyngenia; and financial support for research from Abbott/AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen Biotech (Centocor), Johnson & Johnson/Janssen, Millennium, Pfizer, Receptos, Roche/Genentech, Sanofi, Santarus, Tillotts, and UCB Pharma. Bruce E. Sands has received consulting fees from AbbVie, Abivax, Alimentiv, Allergan, Amgen, Arena Pharmaceuticals, AstraZeneca, Bacainn Therapeutics, Baxalta Bioscience India, Boehringer Ingelheim, Boston Pharmaceuticals, Calibr, Capella BioScience, Celgene, Celltrion Healthcare, ClostraBio, F. Hoffmann-La Roche, Galapagos, Gilead, Gossamer Bio, Immunic, InDex Pharmaceuticals, Innovation Pharmaceuticals, Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Lilly, Morphic Therapeutic, Oppilan Pharma, OSE Immunotherapeutics, Otsuka, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, RedHill Biopharma, Rheos Medicines, Salix Pharmaceuticals, Seres Therapeutics, Shire, Surrozen, Takeda, Target RWE, Theravance Biopharma R&D, USWM Enterprises, and Vivelix Pharmaceuticals. Jingjing Chen is an employee of Takeda Pharmaceuticals USA, Inc and has stock or stock options. Karen Lasch and Richard A. Lirio are ex-employees of Takeda Pharmaceuticals USA, Inc. and have stock or stock options; they were employed by the company when this analysis was conducted. Funding Medical writing support was provided by Peggy Robinet, Pharm D, PhD, of ProEd Communications, Inc and Cerys Evans, PhD, of PharmaGenesis Cardiff , Cardiff , UK , and was funded by Takeda Pharmaceuticals U.S.A. Inc.

Keywords

Fecal Calprotectin
Histology
Mucosal Healing
Treat-To-Target

ASJC Scopus subject areas

Gastroenterology
Hepatology

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10.1016/j.cgh.2022.07.027

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title = "Prognostic Value of Fecal Calprotectin to Inform Treat-to-Target Monitoring in Ulcerative Colitis",

abstract = "Background & Aims: We evaluated the value of post-induction fecal calprotectin (FCP) concentration as a biomarker in patients with ulcerative colitis (UC) treated with a biologic. Methods: This post hoc analysis of the GEMINI 1/GEMINI LTS (N = 620) and VARSITY (N = 771) trials evaluated the cross-sectional accuracy of post-induction FCP in identifying endoscopic activity and histologic inflammation, and the prognostic performance of FCP in identifying patients most likely to achieve endoscopic and histologic remission or require colectomy and UC-related hospitalization. Results: The cross-sectional accuracy of FCP in identifying endoscopic activity and histologic inflammation was modest (63%–79%). However, a post-induction FCP concentration of ≤250 μg/g vs >250 μg/g was associated with a substantially higher probability of achieving clinical remission (odds ratio [OR], 4.03; 95% confidence interval [CI], 2.78–5.85), endoscopic remission (OR, 4.26; 95% CI, 2.83–6.40), and histologic remission (Robarts Histopathology Index: OR, 5.54; 95% CI, 3.77–8.14; Geboes grade: OR, 6.42; 95% CI, 4.02–10.26) at week 52 and a lower probability of colectomy over 7 years (hazard ratio, 0.296; 95% CI, 0.130–0.677) and UC-related hospitalization (hazard ratio, 0.583; 95% CI, 0.389–0.874). The association with colectomy was significant even among patients in symptomatic remission or with endoscopic improvement post-induction, and among patients with elevated FCP at baseline. Conclusions: Although FCP had only modest cross-sectional accuracy in identifying disease activity, an FCP concentration of ≤250 μg/g vs >250 μg/g was associated with increased probability of achieving long-term clinical, endoscopic, and histologic remission, and reduced probability of colectomy and UC-related hospitalization (ClinicalTrials.gov: NCT00783718, NCT00790933, NCT02497469).",

keywords = "Fecal Calprotectin, Histology, Mucosal Healing, Treat-To-Target",

author = "Dulai, {Parambir S.} and Feagan, {Brian G.} and Sands, {Bruce E.} and Jingjing Chen and Karen Lasch and Lirio, {Richard A.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

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doi = "10.1016/j.cgh.2022.07.027",

language = "English (US)",

volume = "21",

pages = "456--466.e7",

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T1 - Prognostic Value of Fecal Calprotectin to Inform Treat-to-Target Monitoring in Ulcerative Colitis

AU - Dulai, Parambir S.

AU - Feagan, Brian G.

AU - Sands, Bruce E.

AU - Chen, Jingjing

AU - Lasch, Karen

AU - Lirio, Richard A.

PY - 2023/2

Y1 - 2023/2

N2 - Background & Aims: We evaluated the value of post-induction fecal calprotectin (FCP) concentration as a biomarker in patients with ulcerative colitis (UC) treated with a biologic. Methods: This post hoc analysis of the GEMINI 1/GEMINI LTS (N = 620) and VARSITY (N = 771) trials evaluated the cross-sectional accuracy of post-induction FCP in identifying endoscopic activity and histologic inflammation, and the prognostic performance of FCP in identifying patients most likely to achieve endoscopic and histologic remission or require colectomy and UC-related hospitalization. Results: The cross-sectional accuracy of FCP in identifying endoscopic activity and histologic inflammation was modest (63%–79%). However, a post-induction FCP concentration of ≤250 μg/g vs >250 μg/g was associated with a substantially higher probability of achieving clinical remission (odds ratio [OR], 4.03; 95% confidence interval [CI], 2.78–5.85), endoscopic remission (OR, 4.26; 95% CI, 2.83–6.40), and histologic remission (Robarts Histopathology Index: OR, 5.54; 95% CI, 3.77–8.14; Geboes grade: OR, 6.42; 95% CI, 4.02–10.26) at week 52 and a lower probability of colectomy over 7 years (hazard ratio, 0.296; 95% CI, 0.130–0.677) and UC-related hospitalization (hazard ratio, 0.583; 95% CI, 0.389–0.874). The association with colectomy was significant even among patients in symptomatic remission or with endoscopic improvement post-induction, and among patients with elevated FCP at baseline. Conclusions: Although FCP had only modest cross-sectional accuracy in identifying disease activity, an FCP concentration of ≤250 μg/g vs >250 μg/g was associated with increased probability of achieving long-term clinical, endoscopic, and histologic remission, and reduced probability of colectomy and UC-related hospitalization (ClinicalTrials.gov: NCT00783718, NCT00790933, NCT02497469).

AB - Background & Aims: We evaluated the value of post-induction fecal calprotectin (FCP) concentration as a biomarker in patients with ulcerative colitis (UC) treated with a biologic. Methods: This post hoc analysis of the GEMINI 1/GEMINI LTS (N = 620) and VARSITY (N = 771) trials evaluated the cross-sectional accuracy of post-induction FCP in identifying endoscopic activity and histologic inflammation, and the prognostic performance of FCP in identifying patients most likely to achieve endoscopic and histologic remission or require colectomy and UC-related hospitalization. Results: The cross-sectional accuracy of FCP in identifying endoscopic activity and histologic inflammation was modest (63%–79%). However, a post-induction FCP concentration of ≤250 μg/g vs >250 μg/g was associated with a substantially higher probability of achieving clinical remission (odds ratio [OR], 4.03; 95% confidence interval [CI], 2.78–5.85), endoscopic remission (OR, 4.26; 95% CI, 2.83–6.40), and histologic remission (Robarts Histopathology Index: OR, 5.54; 95% CI, 3.77–8.14; Geboes grade: OR, 6.42; 95% CI, 4.02–10.26) at week 52 and a lower probability of colectomy over 7 years (hazard ratio, 0.296; 95% CI, 0.130–0.677) and UC-related hospitalization (hazard ratio, 0.583; 95% CI, 0.389–0.874). The association with colectomy was significant even among patients in symptomatic remission or with endoscopic improvement post-induction, and among patients with elevated FCP at baseline. Conclusions: Although FCP had only modest cross-sectional accuracy in identifying disease activity, an FCP concentration of ≤250 μg/g vs >250 μg/g was associated with increased probability of achieving long-term clinical, endoscopic, and histologic remission, and reduced probability of colectomy and UC-related hospitalization (ClinicalTrials.gov: NCT00783718, NCT00790933, NCT02497469).

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Prognostic Value of Fecal Calprotectin to Inform Treat-to-Target Monitoring in Ulcerative Colitis

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