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Original research
Predicting endoscopic remission in Crohn’s disease by the modified multiplier SES-CD (MM-SES-CD)
  1. Neeraj Narula1,
  2. Emily C L Wong1,
  3. Jean-Frederic Colombel2,
  4. William J Sandborn3,
  5. John Kenneth Marshall1,
  6. Marco Daperno4,
  7. Walter Reinisch5,
  8. Parambir S Dulai3
  1. 1Department of Medicine (Division of Gastroenterology), McMaster University, Hamilton, Ontario, Canada
  2. 2Department of Medicine (Division of Gastroenterology), Mount Sinai School of Medicine, New York, New York, USA
  3. 3Department of Medicine (Division of Gastroenterology), University of California San Diego School of Medicine, La Jolla, California, USA
  4. 4Department of Internal Medicine (Division of Gastroenterology), Azienda Ospedaliera Ordine Mauriziano di Torino, Torino, Piemonte, Italy
  5. 5Department of Internal Medicine III (Division of Gastroenterology and Hepatology), Medical University of Vienna, Wien, Austria
  1. Correspondence to Dr Neeraj Narula, Department of Medicine (Division of Gastroenterology), McMaster University, Hamilton, Canada; neeraj.narula{at}medportal.ca

Abstract

Background and aims The Simple Endoscopic Score for Crohn’s disease (SES-CD) is the primary tool for measurement of mucosal inflammation in clinical trials but lacks prognostic potential. We set to develop and validate a modified multiplier of the SES-CD (MM-SES-CD), which takes into consideration each individual parameter’s prognostic value for achieving endoscopic remission (ER) while on active therapy.

Methods In this posthoc analysis of three CD clinical trial programmes (n=350 patients, baseline SES-CD ≥ 3 with confirmed ulceration), data were pooled and randomly split into a 70% training and 30% testing cohort. The MM-SES-CD was designed using weights for individual parameters as determined by logistic regression modelling, with 1-year ER (SES-CD < 3) being the dependent variable. A cut point score for low and high probability of ER was determined by using the maximum Youden Index and validated in the testing cohort.

Results Baseline ulcer size, extent of ulceration and presence of non-passable strictures had the strongest association with 1-year ER as compared with affected surface area, with differential weighting of individual parameters across disease segments being observed during logistic regression. The MM-SES-CD was generated using this weighted regression model and demonstrated strong discrimination for ER in the training dataset (area under the receiver operator curve (AUC) 0.83, 95% CI 0.78 to 0.94) and in the testing dataset (AUC 0.82, 95% CI 0.77 to 0.92). In comparison to the MM-SES-CD scoring model, the original SES-CD score lacks accuracy (AUC 0.60, 95% CI 0.55 to 0.65) for predicting the achievement of ER.

Conclusions We developed and internally validated the MM-SES-CD as an endoscopic severity assessment tool to predict one-year ER in patients with CD on active therapy.

  • crohn's disease
  • inflammatory bowel disease
  • endoscopy

Data availability statement

Data may be obtained from a third party and are not publicly available. This study, carried out under YODA Project # 2020-4363, used data obtained from the Yale University Open Data Access Project, which has an agreement with JANSSEN RESEARCH & DEVELOPMENT, L.L.C. The interpretation and reporting of research using this data are solely the responsibility of the authors and does not necessarily represent the official views of the Yale University Open Data Access Project or JANSSEN RESEARCH & DEVELOPMENT, L.L.C. This publication (Vivli protocol #00005567) is based on research using data from AbbVie that has been made available through Vivli, Inc. Vivli has not contributed to or approved, and is not in any way responsible for, the contents of this publication.

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Data availability statement

Data may be obtained from a third party and are not publicly available. This study, carried out under YODA Project # 2020-4363, used data obtained from the Yale University Open Data Access Project, which has an agreement with JANSSEN RESEARCH & DEVELOPMENT, L.L.C. The interpretation and reporting of research using this data are solely the responsibility of the authors and does not necessarily represent the official views of the Yale University Open Data Access Project or JANSSEN RESEARCH & DEVELOPMENT, L.L.C. This publication (Vivli protocol #00005567) is based on research using data from AbbVie that has been made available through Vivli, Inc. Vivli has not contributed to or approved, and is not in any way responsible for, the contents of this publication.

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Footnotes

  • WR and PSD are joint senior authors.

  • Correction notice This article has been corrected since it published Online First. The senior authorship statement has been added and corrections to the Modified SES-CD scoring method section has been updated.

  • Contributors NN: study concept and design; acquisition and compilation of data; statistical analysis; data interpretation; drafting of the manuscript. ECLW: acquisition and compilation of data; statistical analysis; drafting of the manuscript. J-FC: study design; drafting of the manuscript. WJS: study design; drafting of the manuscript. JKM: study design; drafting of the manuscript. MD: study design; drafting of the manuscript. WR: study concept and design; acquisition and compilation of data; data interpretation; drafting of the manuscript. PD: study concept and design; statistical analysis; data interpretation; drafting of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests NN holds a McMaster University Department of Medicine Internal Career Award. NN has received honoraria from Janssen, Abbvie, Takeda, Pfizer, Merck, Sandoz, Novartis and Ferring. J-FC reports receiving research grants from AbbVie, Janssen Pharmaceuticals and Takeda; receiving payment for lectures from AbbVie, Amgen, Allergan, Inc. Ferring Pharmaceuticals, Shire and Takeda; receiving consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene Corporation, Celltrion, Eli Lilly, Enterome, Ferring Pharmaceuticals, Genentech, Janssen Pharmaceuticals, Landos, Ipsen, Medimmune, Merck, Novartis, Pfizer, Shire, Takeda, Tigenix, Viela bio and hold stock options in Intestinal Biotech Development and Genfit. WJS is supported in part by the NIDDK-funded San Diego Digestive Diseases Research Center (P30 DK120515) grant. He has received: research grants from Abbvie, Abivax, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Genentech, Gilead Sciences, Glaxo Smith Kline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Takeda, Theravance Biopharma; consulting fees from Abbvie, Abivax, Admirx, Alfasigma, Alimentiv (Robarts Clinical Trials, owned by Health Academic Research Trust (HART)), Alivio Therapeutics, Allakos, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Bausch Health (Salix), Beigene, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Meyers Squibb, Celgene, Celltrion, Cellularity, Cosmo Pharmaceuticals, Escalier Biosciences, Equillium, Forbion, Genentech/Roche, Gilead Sciences, Glenmark Pharmaceuticals, Gossamer Bio, Immunic (Vital Therapies), Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyverna Therapeutics, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pandion Therapeutics, Pfizer, Progenity, Prometheus Biosciences, Protagonists Therapeutics, Provention Bio, Reistone Biopharma, Seres Therapeutics, Shanghai Pharma Biotherapeutics, Shire, Shoreline Biosciences, Sublimity Therapeutics, Surrozen, Takeda, Theravance Biopharma, Thetis Pharmaceuticals, Tillotts Pharma, UCB, Vendata Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals, Vivreon Biosciences, Zealand Pharma; and stock or stock options from Allakos, BeiGene, Gossamer Bio, Oppilan Pharma, Prometheus Biosciences, Progenity, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences. Spouse: Iveric Bio—consultant, stock options; Progenity—stock; Oppilan Pharma—consultant, stock options; Prometheus Biosciences—employee, stock options; Ventyx Biosciences—stock options; Vimalan Biosciences—stock options. JKM has received honoraria from Janssen, AbbVie, Allergan, Bristol-Meyer-Squibb, Ferring, Janssen, Lilly, Lupin, Merck, Pfizer, Pharmascience, Roche, Shire, Takeda and Teva. MD served as a speaker, consultant and advisory board member for AbbVie, Takeda, Janssen, Norgine, Pfizer, MSD, Celltrion, Roche, Gilead, Bioclinica, Ferring, SOFAR, Chiesi, Zambo. WR has received support for the following: speaker for Abbott Laboratories, Abbvie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering-Plough, Shire, Takeda, Therakos, Vifor, Yakult, Consultant for Abbott Laboratories, Abbvie, Aesca, Algernon, Amgen, AM Pharma, AMT, AOP Orphan, Arena Pharmaceuticals, Astellas, Astra Zeneca, Avaxia, Roland Berger GmBH, Bioclinica, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, DSM, Elan, Eli Lilly, Ernest & Young, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, LivaNova, Mallinckrodt, Medahead, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nash Pharmaceuticals, Nestle, Nippon Kayaku, Novartis, Ocera, OMass, Otsuka, Parexel, PDL, Periconsulting, Pharmacosmos, Philip Morris Institute, Pfizer, Procter & Gamble, Prometheus, Protagonist, Provention, Robarts Clinical Trial, Sandoz, Schering-Plough, Second Genome, Seres Therapeutics, Setpointmedical, Sigmoid, Sublimity, Takeda, Therakos, Theravance, Tigenix, UCB, Vifor, Zealand, Zyngenia and 4SC, Advisory board member for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, DSM, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Sandoz, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zealand, Zyngenia and 4SC. PD is supported by a Digestive Diseases Research Center grant NIH DK120515 and a Research Scholar Award from the American Gastroenterology Association. PD has received research support and consulting for Takeda, Abbvie, Janssen, Pfizer.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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