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Inflammatory bowel disease
Original article
Development and validation of a histological index for UC
  1. Mahmoud H Mosli1,2,3,
  2. Brian G Feagan1,2,4,
  3. Guangyong Zou1,4,
  4. William J Sandborn1,5,
  5. Geert D'Haens1,6,
  6. Reena Khanna1,2,
  7. Lisa M Shackelton1,
  8. Christopher W Walker1,
  9. Sigrid Nelson1,
  10. Margaret K Vandervoort1,
  11. Valerie Frisbie1,
  12. Mark A Samaan1,
  13. Vipul Jairath1,7,8,
  14. David K Driman9,
  15. Karel Geboes10,
  16. Mark A Valasek11,
  17. Rish K Pai12,
  18. Gregory Y Lauwers13,14,
  19. Robert Riddell15,
  20. Larry W Stitt1,4,
  21. Barrett G Levesque1,5
  1. 1Robarts Clinical Trials, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada
  2. 2Department of Medicine, University of Western Ontario, London, Ontario, Canada
  3. 3Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
  4. 4Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
  5. 5Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA
  6. 6Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands
  7. 7Nuffield Department of Medicine, University of Oxford, Oxford, UK
  8. 8Oxford Clinical Trials Research Unit, University of Oxford, Oxford, UK
  9. 9Department of Pathology, University of Western Ontario, London, Ontario, Canada
  10. 10Department of Pathology, University Hospital of KU Leuven and UZ Gent, Leuven, Belgium
  11. 11Department of Pathology, University of California, San Diego, USA
  12. 12Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, USA
  13. 13Massachusetss General Hospital, Boston, USA
  14. 14Department of Pathology, Harvard Medical School, Boston, USA
  15. 15Department of Pathology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Dr Barrett G Levesque, Division of Gastroenterology, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA; bglevesque{at}ucsd.edu

Abstract

Objective Although the Geboes score (GS) and modified Riley score (MRS) are commonly used to evaluate histological disease activity in UC, their operating properties are unknown. Accordingly, we developed an alternative instrument.

Design Four pathologists scored 48 UC colon biopsies using the GS, MRS and a visual analogue scale global rating. Intra-rater and inter-rater reliability for each index and individual index items were measured using intraclass correlation coefficients (ICCs). Items with high reliability were used to develop the Robarts histopathology index (RHI). The responsiveness/validity of the RHI and multiple histological, endoscopic and clinical outcome measures were evaluated by analyses of change scores, standardised effect size (SES) and Guyatt's responsiveness statistic (GRS) using data from a clinical trial of an effective therapy.

Results Inter-rater ICCs (95% CIs) for the total GS and MRS scores were 0.79 (0.63 to 0.87) and 0.80 (0.69 to 0.87). The correlation estimates between change scores in RHI and change score in GS and MRS were 0.75 (0.67 to 0.82) and 0.84 (0.79 to 0.88), respectively. The SES and GRS estimates for GS, MRS and RHI were: 1.87 (1.54 to 2.20) and 1.23 (0.97 to 1.50), 1.29 (1.02 to 1.56) and 0.88 (0.65 to 1.12), and 1.05 (0.79 to 1.30) and 0.88 (0.64 to 1.12), respectively.

Conclusions The RHI is a new histopathological index with favourable operating properties.

  • ULCERATIVE COLITIS
  • HISTOPATHOLOGY

https://doi.org/10.1136/gutjnl-2015-310393

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    Footnotes

    • Contributors Guarantor of the article: BGL. Development of study concept and design: MHM, BGF, WJS, GD'H, RK, DKD, LMS, SN, MKV, KG, MAV, RKP, RR, LWS, GZ, BGL. Study supervision: MHM, BGF, WJS, GD'H, RK, MKV, KG, BGL. Acquisition, analysis and interpretation of data: MHM, BGF, WJS, GD'H, RK, DKD, LMS, MAS, MKV, KG, MAV, RKP, GL, RR, LWS, GZ, BGL. Statistical analysis: LWS, GZ. Drafting of the manuscript: MHM, BGF, LMS, LWS, GZ, BGL. Critical revision of the manuscript for important intellectual content: MHM, BGF, WJS, GD'H, RK, DKD, LMS, SN, MKV, KG, MAV, RKP, GL, RR, LWS, GZ, BGL.

    • Funding Robarts Clinical Trials, University of Western Ontario, London, Ontario, Canada (Central Reading, Database Management).

    • Ethics approval Research Ethics Board at the University of Western Ontario.

    • Competing interests MHM, LMS, CWW, SN, MKV and GZ are employees of Robarts Clinical Trials, which was the research organisation that conducted this study. BGF reports personal fees from Robarts Clinical Trials. Grants from AbbVie, Amgen, Astra Zeneca, Bristol Myers Squibb, Janssen/JnJ—Canada, USA and Global, Biotech/Centocor, Roche/Genentech, Millennium, Pfizer, Receptos, Santarus, Sanofi, Tillotts Pharma AG, UCB, personal fees from AbbVie—Canada, USA and Global, Actogenix, Akros, Albireo, Amgen, Astra Zeneca, Avaxia Biologics Avir, Axcan, Baxter Healthcare, Biogen Idec, Boehringer-Ingelheim, Bristol Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring, Roche/Genentech, GiCare, Gilead, Given Imaging, GSK, Ironwood, Janssen/JnJ/Biotech, Kyowa Kakko Kirin, Lexicon, Lilly, Lycera Biotech, Merck, Millennium, Nestle, Novo Nordisk, Pfizer, Prometheus Therapeutics & Diagnostics, Protagonist, Receptos Salix, Serono, Shire, Sigmoid, Synergy, Takeda—Canada, USA and Global, Teva, TiGenix, Tillotts, UCB, Vertex, VHsquared, Warner-Chilcott, Wyeth, Zealand and Zyngenia, outside the submitted work. WJS reports personal fees from Robarts Clinical Trials, has received consulting fees from Abbott, ActoGeniX NV, AGI Therapeutics, Alba Therapeutics, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys, Atlantic Healthcare, Aptalis, BioBalance, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, EnGene, Eli Lilly, Enteromedics, Exagen Diagnostics, Ferring Pharmaceuticals, Flexio Therapeutics, Funxional Therapeutics, Genzyme, Gilead Sciences, Given Imaging, GSK, Human Genome Sciences, Ironwood Pharmaceuticals, KaloBios Pharmaceuticals, Lexicon Pharmaceuticals, Lycera, Meda Pharmaceuticals, Merck Research Laboratories, Merck Serono, Millennium Pharmaceuticals, Nisshin Kyorin Pharmaceuticals, Novo Nordisk, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics, PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb, Purgenesis Technologies, Relypsa, Roche, Salient Pharmaceuticals, Salix Pharmaceuticals, Santarus, Schering Plough, Shire Pharmaceuticals, Sigmoid Pharma, Sirtris Pharmaceuticals, SLA Pharma UK, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics, Warner Chilcott UK and Wyeth; research grants from Abbott, Bristol Myers Squibb, Genentech, GSK, Janssen, Milennium Pharmaceuticals, Novartis, Pfizer, Procter and Gamble, Shire Pharmaceuticals and UCB Pharma; payments for lectures/speakers bureaux from Abbott, Bristol Myers Squibb and Janssen; and holds stock/stock options in Enteromedics. GD’H reports grants and personal fees from Abbvie, Ferring, Glaxo SmithKline, Jansen Biologics, Hospira, Takeda, Merck Sharp Dome, Prometheus Labs, Robarts Clinical Trials, Tillotts, personal fees from Ablynx, Amakem, Amgen, AM Pharma, Boehringer Ingelheim, Bristol Myers Squibb, Cosmo, Celgene, Celtrion, Galapagos, Covidien, Engene, Medimetrics, Mitsubishi, Mundipharma, Novonordisk, Pfizer, Receptos, Salix, Sandoz, Setpoint, Shire, Teva, Tigenix, Topivert, Versant and Vifor, grants from Photopill and Dr Falk Pharma, outside the submitted work. RK reports fees from Janssen, AbbVie and Takeda, Canada, outside the submitted work and is an employee of Robarts Clinical Trials which was the research organisation that conducted this study. VF, LWS report receiving personal fees from Robarts Clinical Trials. MAS has nothing to disclose. VJ reports personal fees from Robarts Clinical Trials. Salary is partially funded by the UK National Institute for Health Research, has received scientific advisory board fees from AbbVie. RKP reports personal fees from Robarts Clinical Trials, during the conduct of the study. BGL reports personal fees from Takeda, Prometheus Labs, Nestle Health Sciences, Abbvie and Robarts Clinical Trials, outside the submitted work.

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