Development and validation of a novel Endoscopic ulcer Activity Score for Evaluation of Crohn's Disease (EASE-CD) using data from two randomised controlled trials

Christopher Ma¹, Reena Khanna², Bryan R Maguire³, Guangyong Zou⁴, Brian Bressler⁵, Pieter Hindryckx⁶, Mahmoud Mosli⁷, Miles P Sparrow⁸, Ailsa L Hart⁹, Rupert W Leong¹⁰, David T Rubin¹¹, Julie Rémillard³, Lisa M Shackelton³, Geert R D'Haens¹², Silvio Danese¹³, Laurent Peyrin-Biroulet¹⁴, Bruce E Sands¹⁵, Remo Panaccione¹⁶, Brian G Feagan¹⁷, Vipul Jairath¹⁷

Affiliations

¹ Division of Gastroenterology & Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AL, Canada; Department of Community Health Sciences, University of Calgary, Calgary, AL, Canada; Alimentiv, London, ON, Canada. Electronic address: christopher.ma@ucalgary.ca.
² Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
³ Alimentiv, London, ON, Canada.
⁴ Alimentiv, London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada; Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
⁵ Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada; St Paul's Hospital, Vancouver, BC, Canada.
⁶ Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium.
⁷ Department of Medicine, Division of Gastroenterology, King Abdulaziz University, Jeddah, Saudi Arabia.
⁸ Department of Gastroenterology, Alfred Health and Monash University, Melbourne, VIC, Australia.
⁹ St Mark's Hospital, Inflammatory Bowel Disease Unit, London, UK.
¹⁰ Concord Clinical School, University of Sydney, Sydney, NSW, Australia; Department of Gastroenterology, Concord Repatriation General Hospital, Sydney, NSW, Australia.
¹¹ University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA.
¹² Alimentiv, London, ON, Canada; Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Academic Medical Centre, Amsterdam, Netherlands.
¹³ Department of Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milano, Italy; Division of Immunology, Transplantation and Infectious Disease, IRCCS Ospedale San Raffaele, Milano, Italy.
¹⁴ University of Lorraine, CHRU-Nancy, Department of Gastroenterology, Nancy, France.
¹⁵ The Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁶ Division of Gastroenterology & Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AL, Canada.
¹⁷ Alimentiv, London, ON, Canada; Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.

PMID: 40505666
DOI: 10.1016/S2468-1253(25)00093-7

Clinical Trial

Development and validation of a novel Endoscopic ulcer Activity Score for Evaluation of Crohn's Disease (EASE-CD) using data from two randomised controlled trials

Christopher Ma et al. Lancet Gastroenterol Hepatol. 2025 Aug.

. 2025 Aug;10(8):746-756.

doi: 10.1016/S2468-1253(25)00093-7. Epub 2025 Jun 9.

Authors

Affiliations

¹ Division of Gastroenterology & Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AL, Canada; Department of Community Health Sciences, University of Calgary, Calgary, AL, Canada; Alimentiv, London, ON, Canada. Electronic address: christopher.ma@ucalgary.ca.
² Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
³ Alimentiv, London, ON, Canada.
⁴ Alimentiv, London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada; Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
⁵ Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada; St Paul's Hospital, Vancouver, BC, Canada.
⁶ Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium.
⁷ Department of Medicine, Division of Gastroenterology, King Abdulaziz University, Jeddah, Saudi Arabia.
⁸ Department of Gastroenterology, Alfred Health and Monash University, Melbourne, VIC, Australia.
⁹ St Mark's Hospital, Inflammatory Bowel Disease Unit, London, UK.
¹⁰ Concord Clinical School, University of Sydney, Sydney, NSW, Australia; Department of Gastroenterology, Concord Repatriation General Hospital, Sydney, NSW, Australia.
¹¹ University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA.
¹² Alimentiv, London, ON, Canada; Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Academic Medical Centre, Amsterdam, Netherlands.
¹³ Department of Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milano, Italy; Division of Immunology, Transplantation and Infectious Disease, IRCCS Ospedale San Raffaele, Milano, Italy.
¹⁴ University of Lorraine, CHRU-Nancy, Department of Gastroenterology, Nancy, France.
¹⁵ The Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁶ Division of Gastroenterology & Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AL, Canada.
¹⁷ Alimentiv, London, ON, Canada; Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.

PMID: 40505666
DOI: 10.1016/S2468-1253(25)00093-7

Abstract

Background: Endoscopy is essential for measuring luminal disease activity in Crohn's disease. Existing indices for evaluating endoscopic Crohn's disease activity are only modestly correlated with clinical disease activity, contain items with ambiguous definitions and poor interobserver reliability, and do not have validated thresholds for defining clinically relevant changes. To address these issues, we conducted a multiphase study to develop and validate a novel endoscopic index for Crohn's disease.

Methods: Paired baseline and post-induction ileocolonoscopy videos from a phase 3b adalimumab trial (NCT00348283) and phase 2 risankizumab trial (NCT02031276) were assessed by multiple central readers using candidate endoscopic items with face validity derived using modified RAND/UCLA appropriateness methods. The four readers were masked to all clinical information, including treatment assignment and patient symptom scores. A total of 112 and 99 paired ileocolonoscopy videos with treatment assignment were available from the adalimumab trial and risankizumab trial, respectively; after the four readers assessed the 112 videos, two readers then reassessed 44 post-treatment videos to assess inter-rater reliability in index development. Items with acceptable inter-rater reliability (with an intraclass correlation coefficient [ICC] of ≥0·41) and responsiveness (win probability [WinP], the probability that a patient receiving active treatment has a better endoscopy score than a patient receiving placebo, of ≥0·56) were included as covariables in regression for model building with internal validation with bootstrapping. External validation was conducted using the paired videos from the risankizumab trial.

Findings: Ten endoscopic items met ICC and WinP thresholds and were considered for novel index development. They included items from the SES-CD (presence and size of ulcers, extent of ulcerated surface, and extent of affected surface) and CDEIS (percentage of surface involved by Crohn's disease, percentage of ulcerated surface, deep ulceration, and superficial ulceration) and exploratory items (presence of Crohn's disease-related lesions, Crohn's disease-related lesion severity, and Crohn's disease-related lesion involvement). The final model, Endoscopic ulcer Activity Score for Evaluating CD (EASE-CD), included the presence and size of ulcerations measured on an ordinal scale of 0 (none), 1 (ulcers <5 mm), 2 (ulcers between 5 mm and 20 mm), and 3 (ulcers >20 mm); the presence or absence of deep ulcerations measured dichotomously, with 0 for absent and 1 for present; and the proportion of ulcerated surface area, expressed as a continuous proportion from 0-1, with each item evaluated and averaged across visualised bowel segments. The total score ranges from 0-100 with higher scores indicating greater endoscopic activity. The r² and optimism adjusted r² of EASE-CD in internal validation were 0·608 and 0·554, and the index was well calibrated with a slope of 0·983. In external validation, the adjusted r² was 0·565 and the calibration slope was 0·997. EASE-CD also demonstrated substantial inter-rater reliability (ICC 0·798 [95% CI 0·711-0·836]) and a large degree of responsiveness (WinP 0·769 [95% CI 0·658-0·851], p<0·001) in external validation. A 10-point reduction in EASE-CD had 82·4% specificity (95% CI 78·6-86·0) and 69·9% sensitivity (63·3-76·4) for endoscopic response, defined by at least 50% reduction in SES-CD or CDEIS. Ulcer-free endoscopic remission results in EASE-CD score of 0.

Interpretation: EASE-CD is a novel, internally and externally validated continuous measure of endoscopic ulcer activity in Crohn's disease that is reliable and responsive to treatment.

Funding: None.

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Conflict of interest statement

Declaration of interests CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences, Roche, Sanofi, Takeda, and Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi, and Takeda; royalties from Springer Publishing; and research support from AbbVie, Ferring, and Pfizer. RK reports research grants from Roche/Genentech; consulting fees from AbbVie, Amgen, BMS, Innomar, Gilead, Janssen, Jamp, Lilly, Merck, Pendopharm, Pfizer, and Roche/Genetech; and speaker fees from AbbVie, Amgen, BMS, Gilead, Jamp, Lilly, Merck, Pendopharm, Pfizer, Roche/Genetech, Shire, and Takeda. GZ has received consulting fees from Alimentiv. BB reports consulting fees from Janssen, AbbVie, Takeda, Pfizer, BMS, Merck, Celltrion, Alimentiv, Eli Lilly, and Eupraxia. PH reports consulting fees and grant support from Boston Scientific. MM has served on advisory boards and received speaker and consultation fees from AbbVie, Takeda, Janssen, Lilly, Ferring, Falk, Sandoz, Sanofi, Hikma, Pfizer, BMS, and Organon; and has received research funding from Celgene, Pfizer, and Takeda. MPS reports consulting fees from Janssen, Takeda, Pfizer, Celgene, AbbVie, MSD, Emerge Health, Gilead, BMS, Celltrion, Eli-Lilly, and Alimentiv; speaker fees from Janssen, AbbVie, Ferring, Takeda, Pfizer, Shire, Celltrion, Eli-Lilly, and Dr Falk Pharma; and support for attending meetings or travel from Pfizer, and Dr Falk Pharma. ALH reports consulting and speakers fees from AbbVie, Abivax, BMS, Celltrion, Falk, GSK, Eli Lilly, J&J, Pfizer, and Takeda; and support for attending meetings or travel from AbbVie, Abivax, BMS, Celltrion, Falk, Eli Lilly, J&J, Pfizer, and Takeda. DTR reports grant support from Takeda, AbbVie, Abivax, Eli Lilly, Iterative Health, Johnson & Johnson Pharmaceuticals, and Pfizer; and consulting fees from Altrubio, Avalo Therapeutics, Bausch Health, Bristol-Myers Squibb, Buhlmann Diagnostics, Celltrion, Clostrabio, Connect BioPharma, Douglas Pharmaceuticals, Foresee, Genentech, Image Analysis Group, InDex Pharmaceuticals, Odyssey Therapeutics, Sanofi, Throne, and Vedanta. LMS has received consulting fees from Alimentiv. GRD'H reports research grants from Pfizer, Takeda, AbbVie, Eli Lilly, BMS, and Alimentiv; consulting fees from AbbVie, Agomab, Alimentiv, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Exeliom Biosciences, Index Pharmaceuticals, GlaxoSmithKline, Pfizer, J&J, Polpharma, Procise Diagnostics, Prometheus laboratories, Prometheus Biosciences, and Ventyx; speaker fees from AbbVie, Arena, Boehringer Ingelheim, BMS, Celltrion, Eli Lilly, J&J, Pfizer, and Takeda; support for attending meetings or travel from Eli Lilly and Pfizer; and participation on advisory boards for Galapagos, AstraZeneca, and Seres Health. SD reports consulting fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB, Vial, and Vifor; lecture fees from AbbVie, Amgen, Ferring Pharmaceuticals, Gilead, Janssen, Mylan, Pfizer, and Takeda. LP-B reports grants support from Celltrion, Fresenius Kabi, Medac, MSD, Takeda; consulting fees from AbbVie, Abivax, Adacyte, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, BMS, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Eli Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par' Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx, and Ysopia; lecture fees from AbbVie, Alfasigma, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Janssen, Kern Pharma, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots, and Viatris; support for attending meetings or travel from AbbVie, Alfasigma, Amgen, Celltrion, Connect Biopharm, Ferring, Galapagos, Genentech, Gilead, Gossamer Bio, Janssen, Eli Lilly, Medac, Morphic, MSD, Pfizer, Sandoz, Takeda, Thermo Fischer, Tillots; and participation on advisory board for AbbVie, Alfasigma, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Janssen, Kern Pharma, Eli Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots, and Viatris. BES reports research grants from Janssen and Bristol Myers Squibb; consulting fees from AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Ensho Therapeutics, Equillium, Eli Lilly, Enthera, Enveda Biosciences, Evommune, Ferring, Fzata, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Kallyope, Merck, Microba, Microbiotica, Mitsubishi Tanabe Pharma, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Immunyx Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Palisade Bio, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biotherapeutics, Sorriso Pharmaceuticals, Spyre Therapeutics, Surrozen, Target RWE, Takeda, Teva, Theravance Biopharma, TLL Pharmaceutical, TR1X, Union Therapeutics, and Ventyx Biosciences; lecture fees from AbbVie, Abivax, Bristol Myers Squibb, Celltrion, Eli Lilly, Janssen, Mitsubishi Tanabe Pharma, Pfizer, and Takeda; support for attending meetings or travel from Eli Lilly, Janssen, and Takeda; participation on advisory board for Agomab and Amgen; stock or stock options from Ventyx Biosciences; and medical writing or editorial support for AbbVie, Abivax, Bristol Myers Squibb, Celltrion, Eli Lilly, Janssen, Merck, Pfizer, Ventyx Biosciences, Morphic Therapeutics, Takeda, and Alimentiv. RP reports research grants, consulting, and speaker fees from AbbVie. BGF reports consulting fees from AbbVie, Abivax, Adiso, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Arena Pharma, Avoro Capital Advisors, Atomwise, BioJamp, Biora Therapeutics, Blackbird Laboratories, Boehringer-Ingelheim, Boxer Capital, Celsius Therapeutics, Celgene/BMS, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, Forbion, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer Pharma, GSK, Hinge Bio, Index Pharma, Imhotex, Immunic Therapeutics, Intercept, JAKAcademy, Janssen, Japan Tobacco, Kaleido Biosciences, Klick Health, Landos Biopharma, Lenczner Slaght, LifeSci Capital, Lument, Mage Biologics, Mestag, Millennium, MiroBio, Monte Rose, Morgan Lewis, Morphic Therapeutics, Mylan, Nexys Therapeutics, Nimbus Therapeutics, OM Pharma, OrbiMed Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics (Merck), Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Roivant/Televant, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Sobi, Spyre Therapeutics, Surrozen, Synedgen, Takeda, Teva, Thelium, Tigenix, Tillotts, Triastek, and Ventyx; lecture fees from Takeda, Janssen, and AbbVie; participation on advisory board for AbbVie, AnaptysBio, Boehringer-Ingelheim, Celgene/BMS, Eli Lilly, Genentech/Roche, Janssen, Merck, MiroBio, Origo BioPharma, Pfizer, REDX Pharma, Sanofi, Takeda, Teva, Ecor1Capital, Morphic, and GSK; and stock or stock options from Evida, EnGene, and Connect Biopharma. VJ reports consulting fees and participation on advisory board for AbbVie, Alimentiv, Altrubio, Amgen, AnaptysBio, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, AstraZeneca, BiomeBank, Boehringer Ingelheim, Bristol Myers Squibb, Calluna Pharma, Celltrion, Eli Lilly, Endpoint Health, Ensho Therapeutics, Enthera, Exeliom Biosciences, Ferring, Flagship Pioneering, Fresenius Kabi, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, MRM Health, Nxera Therapeutics, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Roivant, Sandoz, Sanofi, Second Genome, Sorriso, Spyre Therapeutics, Takeda, Teva, Tillotts, Ventyx, Vividion; and speaker fees from AbbVie, Ferring, Bristol Myers Squibb, Galapagos, Janssen, Pfizer, Takeda, Tillotts, and Fresenius Kabi. BRM, JR, and RWL have nothing to disclose.

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Development and validation of a novel Endoscopic ulcer Activity Score for Evaluation of Crohn's Disease (EASE-CD) using data from two randomised controlled trials

Affiliations

Development and validation of a novel Endoscopic ulcer Activity Score for Evaluation of Crohn's Disease (EASE-CD) using data from two randomised controlled trials

Authors

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Abstract

Conflict of interest statement

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