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Original article
Development of an index to define overall disease severity in IBD
  1. Corey A Siegel1,
  2. Cynthia B Whitman2,
  3. Brennan M R Spiegel2,
  4. Brian Feagan3,
  5. Bruce Sands4,
  6. Edward V Loftus Jr5,
  7. Remo Panaccione6,
  8. Geert D'Haens7,
  9. Charles N Bernstein8,
  10. Richard Gearry9,
  11. Siew C Ng10,
  12. Gerassimos J Mantzaris11,
  13. Balfour Sartor12,
  14. Mark S Silverberg13,
  15. Robert Riddell13,
  16. Ioannis E Koutroubakis14,
  17. Colm O'Morain15,
  18. Peter L Lakatos16,
  19. Dermot P B McGovern17,
  20. Jonas Halfvarson18,
  21. Walter Reinisch19,
  22. Gerhard Rogler20,
  23. Wolfgang Kruis21,
  24. Curt Tysk18,
  25. Stefan Schreiber22,
  26. Silvio Danese23,
  27. William Sandborn24,
  28. Anne Griffiths25,
  29. Bjorn Moum26,
  30. Christoph Gasche27,
  31. Francesco Pallone28,
  32. Simon Travis29,
  33. Julian Panes30,
  34. Jean-Frederic Colombel4,
  35. Stephen Hanauer31,
  36. Laurent Peyrin-Biroulet32
  1. 1Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
  2. 2Department of Health Services, Cedars-Sinai Medical Center, Los Angeles, California, USA
  3. 3Robarts Clinical Trials, London, Ontario, Canada
  4. 4Icahn School of Medicine at Mount Sinai, New York, New York, USA
  5. 5Mayo Clinic, Rochester, Minnesota, USA
  6. 6University of Calgary, Calgary, Alberta, Canada
  7. 7Academic Medical Center, Amsterdam, Netherlands
  8. 8University of Manitoba, Winnipeg, Manitoba, Canada
  9. 9University of Otago, Christchurch, New Zealand
  10. 10Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  11. 11Evangelismos-PolyCliniki-Ophthalmiatreion Hospital, Athens, Greece
  12. 12University of North Carolina, Chapel Hill, North Carolina, USA
  13. 13Mount Sinai Hospital, Toronto, Ontario, Canada
  14. 14University Hospital Heraklion, Crete, Greece
  15. 15Faculty of Health Sciences Trinity College Dublin, Dublin, Ireland
  16. 16Semmelweis University, Budapest, Hungary
  17. 17Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
  18. 18Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
  19. 19McMaster University, Hamilton, Ontario, Canada
  20. 20University Hospital of Zuürich, Zurich, Switzerland
  21. 21University of Cologne, Koln, Germany
  22. 22University Hopital Schleswig Holstein, Kiel, Germany
  23. 23Humanitas University, Milan, Italy
  24. 24UCSD, San Diego, California, USA
  25. 25Hospital for Sick Children, Toronto, Ontario, Canada
  26. 26Oslo University Hospital and University Oslo, Oslo, Norway
  27. 27Medical University and General Hospital Vienna, Vienna, Austria
  28. 28University of Rome Tor Vergata, Rome, Italy
  29. 29Oxford University Hospital, Oxford, UK
  30. 30Hospital Clinic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
  31. 31Northwestern Feinberg School of Medicine, Chicago, Illinois, USA
  32. 32Inserm U954 and CHU de Nancy, Lorraine University, Nancy, France
  1. Correspondence to Dr Corey A Siegel, Inflammatory Bowel Disease Center, Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA; corey.a.siegel{at}hitchcock.org

Abstract

Background and aim Disease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC.

Methods Using a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute.

Results For CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities.

Conclusions Based on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD.

  • IBD
  • CROHN'S DISEASE
  • ULCERATIVE COLITIS

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Footnotes

  • Contributors CAS (study design, analysis and interpretation, manuscript development and writing). CBW (study design, analysis and interpretation, manuscript development and writing). BMRS (panel moderator, manuscript review). BF, BS, EVL, RP, GD, CNB, RG, SN, GJM, BS, MSS, RR, IK, COM, PLK, DPBM, JH, WR, GR, WK, CT, SS, SD, WS, AG, BM, CG, FP, ST, JP, JFC, SH (panellist, manuscript review). LPB (study design, analysis and interpretation, manuscript development and writing).

  • Funding AbbVie (Unrestricted educational grant), Tillotts (Unrestricted educational grant).

  • Competing interests Phase 1 was funded thanks to an unrestricted educational grant to IOIBD from AbbVie and Tillotts. CAS has served as a consultant on advisory boards for AbbVie, Amgen, Lilly, Janssen, Sandoz, Pfizer, Prometheus, Takeda, Theradiag and UCB; as a speaker for American Regent, AbbVie, Janssen, Pfizer and Takeda; and receives grant support from AbbVie, Janssen and Takeda. BMRS has research grants from Shire and Takeda. BF has served as a consultant for Abbott/AbbVie, Actogenix, Akros, Albireo Pharma, Amgen, Astra Zeneca, Avaxia Biologics, Avir Pharma, Axcan, Baxter Healthcare, Biogen Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, GiCare Pharma, Gilead, Given Imaging, GSK, Ironwood Pharma, Janssen Biotech (Centocor), JnJ/Janssen, Kyowa Kakko Kirin Co., Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nektar, Nestles, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist, Receptos, Salix Pharma, Serono, Shire, Sigmoid Pharma, Synergy Pharma, Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, VHsquared, Warner-Chilcott, Wyeth, Zealand and Zyngenia; has been a speaker for Abbott/AbbVie, JnJ/Janssen, Takeda, Warner-Chilcott and UCB Pharma; has served on advisory boards for Abbott/AbbVie, Amgen, Astra Zeneca, Avaxia Biologics, Bristol-Myers Squibb, Celgene, Centocor, Elan/Biogen, Ferring, JnJ/Janssen, Merck, Nestles, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Takeda, Teva, TiGenix, Tillotts Pharma AG and UCB Pharma; receives research funding from Abbott/AbbVie, Amgen, Astra Zeneca, Bristol-Myers Squibb (BMS), Janssen Biotech (Centocor), JnJ/Janssen, Roche/Genentech, Millennium, Pfizer, Receptos, Santarus, Sanofi, Tillotts and UCB Pharma; and serves on the board of directors for Robarts Clinical Trials. BS has served as a consultant for AbbVie, Celgene, Janssen Biotech, MedImmune, Takeda, Pfizer, TiGenix, Bristol-Myers Squibb, Receptos, Akros Pharma, Arena Pharmaceuticals, Theravance Biopharma R&D, Boehringer-Ingelheim, Synergy Pharmaceuticals, Toplvert Pharma, UCB and Lilly; has served on scientific advisory boards for Celgene, Janssen Biotech, MedImmune, Takeda, Pfizer, TiGenix and Lily; and he receives research funding from Celgene, Janssen Biotech, MedImmune, Takeda and Pfizer. EVL has consulted for UCB Pharma, Takeda, Janssen, AbbVie, Genentech, Celgene, Amgen, Mesoblast, Theradiag, Sun Pharma and Seres Health; has received research support from UCB Pharma, Takeda, Janssen, AbbVie, Genentech, Celgene, Amgen, Pfizer, Receptos, Gilead and Robarts Clinical Trials. RP has served as a consultant for Abbvie/Abbott, Amgen, Aptalis, AstraZeneca, Baxter, Eisai, Ferring, Janssen, Merck, Schering-Plough, Shire, Centocor, Elan, Glaxo-Smith Kline, UCB, Pfizer, Bristol-Myers Squibb, Warmer Chilcot, Takeda, Cubist and Celgene; on speaker's bureaus for Abbvie/Abbott, AstraZeneca, Janssen, Schering-Plough, Shire, Centocor, Elan, Prometheus, Warner Chilcott and Takeda; on advisory boards for Abbvie/Abbott, Amgen, Aptalis, AstraZeneca, Baxter, Eisai, Ferring, Genentech, Janssen, Merck, Schering-Plough, Shire, Centocor, Elan, Glaxo-Smith Kline, UCB, Pfizer, Bristol-Myers Squibb, Warner Chilcott, Takeda, Cubist, Celgene and Salix; and receives research/educational support from Abbvie, Abbott, Ferring, Janssen, Schering-Plough, Centocor, Millenium, Elan, Proctor and Gamble and Bristol-Myers Squibb. GD has served as advisor for Abbvie, Ablynx, Amakem, AM Pharma, Avaxia, Biogen, Bristol-Meyers Squibb, Boerhinger Ingelheim, Celgene, Celltrion, Cosmo, Covidien, Ferring, DrFALK Pharma, Engene, Galapagos, Gilead, Glaxo Smith Kline, Hospira, Johnson & Johnson, Medimetrics, Millenium/Takeda, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Novonordisk, Pfizer, Prometheus laboratories/Nestle, Receptos, Robarts Clinical Trials, Salix, Sandoz, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant and Vifor; and received speaker fees from Abbvie, Ferring, Johnson & Johnson, Merck Sharp Dome, Mundipharma, Norgine, Pfizer, Shire, Millenium/Takeda, Tillotts and Vifor. CNB is supported in part by the Bingham Chair in Gastroenterology. He has served on advisory boards to Abbvie Canada, Janssen Canada, Shire Canada, Takeda Canada and Pfizer Canada and has consulted to Mylan Pharmaceuticals; he has received unrestricted educational grants from Abbvie Canada, Janssen Canada, Shire Canada and Takeda Canada. RG has received consulting and speaking fees from AbbVie, Janssen, MSD, Ferring, Takeda and Baxter; and research grants from AbbVie. GJM has served as speaker or advisory board member for AbbVie, Angelini, Astellas, Danone, MSD, Falk Pharma, Ferring, Hospira, Janssen, Omega Pharma, Otsuka, Pharmacosmos, Pfizer, Sandoz and Takeda; as consultant for Janssen, MSD, Takeda and Omega Pharma; and has received research grants in the last 3 years from Menarini, AbbVie, and MSD. BS has served on advisory boards for Dann and Yakult North American Probiotic Council, Second Genome, Lilly and Enterome; and receives grant support from Janssen, Salix and GSK. MSS has received consulting and speaker fees from AbbVie, Amgen, Ferring, Janssen, Merck, Pfizer, Prometheus, Shire and Takeda; and research funding from AbbVie, Janssen, Prometheus and Takeda. IEK has served as a consultant and on advisory boards for AbbVie and MSD. CO is the principal investigator for Redhill Pharma. DPBM is a consultant for UCB, Jannsen, Merck and Second Genome. WR has served as a speaker for Abbott Laboratories, Abbvie, Aesca, Aptalis, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, Schering-Plough, Shire, Takeda, Therakos, Vifor and Yakult; as a consultant for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Bioclinica, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, 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, Robarts Clinical Trial, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Vifor, Zyngenia and 4SC; as an 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, 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, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zyngenia and 4SC; and has received research funding from Abbott Laboratories, Abbvie, Aesca, Centocor, Falk Pharma GmbH, Immundiagnsotik and MSD. GR has consulted to Abbot, Abbvie, Augurix, Boehringer, Calypso, FALK, Ferring, Fisher, Genentech, Essex/MSD, Novartis, Pfizer, Phadia, Roche, UCB, Takeda, Tillots, Vifor, Vital Solutions and Zeller; has received speaker's honoraria from Astra Zeneca, Abbott, Abbvie, FALK, MSD, Phadia, Tillots, UCB and Vifor; has received educational grants and research grants from Abbott/Abbvie, Ardeypharm, Augurix, Calypso, Essex/MSD, FALK, Flamentera, Novartis, Roche, Takeda, Tillots, UCB and Zeller. WK has received fees for advising from Dr. Falk Pharma GmbH, Ferring International, GA-Analysis; support for research from Dr. Falk Pharma GmbH and GA-Analysis; grants for lectures from Abbvie, Ardeypharm, Falk Foundation, Ferring Arzneimittel, GA-Analysis, Institut Allergosan, Nikkiso, Otsuka and Recordati. CT has served as a speaker for Dr. Falk Pharma, Tillotts Pharma, Ferring, MSD and AstraZeneca. SS has received consulting fees from AbbVie, Boehringer; Celltrion/Mundipharma, Jansen, Novartis, Merck, Pfizer/Hospira, Sanofi, Takeda and UCB; and speaking fees from AbbVie Ferring, Falk, Merck, Takeda and Shire. SD has served as a speaker, a consultant and an advisory board member for Abbvie, Ferring, Hospira, Johnson & Johnson, Merck, Millennium Takeda, Mundipharma, Pfizer, Tigenix, UCB Pharma and Vifor. WS reports grant support from Receptos, Exact Sciences, Amgen, the American College of Gastroenterology and the Broad Foundation; grant support and personal fees from Prometheus Laboratories, AbbVie, Boehringer Ingelheim, Takeda, Atlantic Pharmaceuticals, Janssen, Bristol-Myers Squibb, Genentech, Pfizer and Nutrition Science Partners; and personal fees from Kyowa Hakko Kirin, Millennium Pharmaceuticals, Celgene Cellular Therapeutics, Santarus, Salix Pharmaceuticals, Catabasis Pharmaceuticals, Vertex Pharmaceuticals, Warner Chilcott, Gilead Sciences, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Sigmoid Biotechnologies, Tillotts Pharma, Am Pharma BV, Dr. August Wolff, Avaxia Biologics, Zyngenia, Ironwood Pharmaceuticals, Index Pharmaceuticals, Nestle, Lexicon Pharmaceuticals, UCB Pharma, Orexigen, Luitpold Pharmaceuticals, Baxter Healthcare, Ferring Research Institute, Amgen, Novo Nordisk, Mesoblast, Shire, Ardelyx, Actavis, Seattle Genetics, MedImmune (AstraZeneca), Actogenix NV, Lipid Therapeutics Gmbh, Eisai, Qu Biologics, Toray Industries, Teva Pharmaceuticals, Eli Lilly, Chiasma, TiGenix, Adherion Therapeutics, Immune Pharmaceuticals, Celgene, Arena Pharmaceuticals, Ambrx, Akros Pharma, Vascular Biogenics, Theradiag, Forward Pharma, Regeneron, Galapagos, Seres Health, Ritter Pharmaceuticals, Theravance, Palatin, Biogen and the University of Western Ontario (owner of Robarts Clinical Trials). AG has served as a consultant for AbbVie, Janssen, Merck and Takeda; a speaker for Janssen; and received research and clinical programme support from AbbVie and Janssen. ST has received Grants/Research Support from AbbVie, IOIBD, Lilly, UCB, Vifor and Norman Collison Foundation; consulting fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chemocentryx, Cosmo, Ferring, Giuliani SpA, GlaxoSmithKline, Lilly, MSD, Neovacs, NovoNordisk, Norman Collison Foundation, Novartis, NPS Pharmaceuticals, Pfizer, Proximagen, Receptos, Shire, Sigmoid Pharma, Takeda, Topivert, UCB, VHsquared and Vifor; speaker fees from AbbVie, Ferring and Takeda. JP has received consultant fees from Abbvie, Boehringer Ingelheim, Celltrion, Galapagos, Genentech-Roche, Janssen, Pfizer, Takeda, TiGenix and Topivert; speaker fees from Abbvie, Celltrion, Janssen, MSD and Pfizer. JFC has served as a consultant or advisory board member for AbbVie, Amgen, Boehringer-Ingelheim, Celgene Corporation, Celltrion, Enterome, Ferring, Genentech, Janssen and Janssen, Medimmune, Merck & Co., Pfizer, Protagonist, Second Genome, Seres, Takeda and Theradiag; a speaker for AbbVie, Ferring, Takeda and Shire; receives research support from Abbvie, Janssen and Janssen, Genentech and Takeda; and has stock options for Intestinal Biotech Development and Genfit. SH is a consultant for AbbVie, Actavis, Amgen, Arena, Astellas Pharma Global, Astra Zeneca, Baxter, Boehringer Ingelheim, Bristol Myers Squibb, Catabasis, Cellgene, Celltrion, Cubist, Ferring, Forest Labs, Genentech, Glenmark, GSK, Hospira, Janssen, Lilly, Lutipold/American Regent, Meda, Nestle, Novartis, Novo Nordisk, Pfizer, Prometheus, Receptos, Salix, Sanofi-Avantis, Seattle-Genetics, Seres Health, Shire, Takeda, Theradiag, Tigenex, UCB Pharma and VHsquared; does clinical research with Abbvie, Amgen, Genentech, GSK, Janssen, Lilly, Lutipold/American Regent, Novartis, Novo Nordisk, Pfizer, Prometheus, Receptos, Sanofi-Avantis, Takeda and UCB Pharma; is a speaker for AbbVie, Janssen and Takeda; and serves on a DSMB for Bristol Myers Squibb. LPB reports consulting fees from Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, Therakos, Pharmacosmos, Pilège, BMS, UCB-pharma, Hospira, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, Pfizer, HAC-Pharma, Index Pharmaceuticals, Amgen, Sandoz, Forward Pharma GmbH, Celgene, Biogen, Lycera and Samsung Bioepis; and lecture fees from Merck, Abbvie, Takeda, Janssen, Takeda, Ferring, Norgine, Tillots, Vifor, Therakos, Mitsubishi and HAC-pharma.

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

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