Abstract
Background: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. Objective: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. Methods: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. Results: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. Conclusions: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.
Original language | English (US) |
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Pages (from-to) | 659-670 |
Number of pages | 12 |
Journal | Journal of Allergy and Clinical Immunology |
Volume | 149 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2022 |
Funding
Supported by grants from the Swiss National Science Foundation ( 32003B_160115/1 to A.M.S. and 32473B_185008 to E.S.), Switzerland. Supported by grants from the Swiss National Science Foundation (32003B_160115/1 to A.M.S. and 32473B_185008 to E.S.), Switzerland. Disclosure of potential conflict of interest: C. Ma reports consulting fees from AVIR Pharma and Alimentiv (formerly Robarts Clinical Trials). A. M. Schoepfer reports consulting fees, speaker fees, and/or research grants from Adare Pharmaceuticals, AstraZeneca (Switzerland), Aptalis Pharma, Celgene, Dr Falk Pharma (Germany), GlaxoSmithKline, Nestlé (Switzerland), Novartis (Switzerland), Receptos, and Regeneron Pharmaceuticals. E. S. Dellon reports research funding from Adare/Ellodi, Allakos, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Shire/Takeda; consulting fees from Abbott, Adare/Ellodi, Aimmune, Allakos, Amgen, Arena, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, GSK, Gossamer Bio, Parexel, Regeneron, Alimentiv, Salix, Sanofi, and Shire/Takeda; and educational grants from Allakos, Banner, and Holoclara. A. J. Bredenoord reports research funding from Nutricia, Norgine, SST, and Bayer; and received speaker and/or consulting fees from Laborie, Arena, EsoCap, Medtronic, Dr Falk Pharma, Calypso Biotech, Gossamer, Alimentiv, Reckett Benkiser, Regeneron, and AstraZeneca. M. Chehade reports research funding from Regeneron, Allakos, Shire, AstraZeneca, and Danone; consulting fees from Regeneron, Allakos, Adare, Shire/Takeda, AstraZeneca, Sanofi, and Bristol Myers Squibb; and lecture honoraria from Nutricia, Medscape, and Vindico. M. H. Collins is a consultant for Allakos, Arena, Astra Zeneca, Calypso, Esocap, GSK, Receptos/BMS, Regeneron, Shire/Takeda, and Alimentiv (formerly Robarts Clinical Trials); and reports research grants from Receptos/BMS, Regeneron, and Shire/Takeda. B. G. Feagan reports consulting fees from Allakos, Alimentiv (formerly Robarts Clinical Trials), Sanofi, and Bristol Myers Squibb. G. T. Furuta reports salary support from EnteroTrack. S. K. Gupta reports personal fees from Allakos, Abbott, Adare, Celgene, Gossamer Bio, QOL, Medscape, and Viaskin; research grants from Shire; and royalties from UpToDate. I. Hirano reports research funding from Adare, Allakos, GSK, Meritage, Celgene/Receptos, Regeneron, and Shire/Takeda; and consulting fees from Adare, Allakos, Arena, AstraZeneca, Celgene/Receptos, Eli Lilly, EsoCap, GSK, Gossamer Bio, Regeneron, and Shire/Takeda. V. Jairath reports consulting fees from Alimentiv (formerly Robarts Clinical Trials). D. A. Katzka reports consulting fees from Takeda, Sanofi, and Shire. R. K. Pai reports consulting fees from Eli Lilly, Genentech, Allergan, and Alimentiv (formerly Robarts Clinical Trials). M. E. Rothenberg reports personal fees from Celgene, Astra Zeneca, Arena Pharmaceuticals, Adare Pharmaceuticals, GlaxoSmithKline, Guidepoint, and Suvretta Capital Management; has an equity interest in Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, and Allakos; received royalties from Teva Pharmaceuticals (for reslizumab), Mapi Research Trust (for PEESSv2), and UpToDate; and is an inventor of patents owned by Cincinnati Children's Hospital. A. Straumann reports personal fees from Allakos, Astra-Zeneca, Calypso, EsoCap, Dr Falk Pharma, Gossamer, Nutricia, Pfizer, Receptos-Celgene, Regeneron-Sanofi, Roche-Genentec, Shire, and Tillotts. S. S. Aceves reports being a consultant for Regeneron, Astra-Zeneca, Astellos, and AImmune; and has a UCSD patent licensed to Shire/Takeda Pharma. J. A. Alexander reports personal fees or grants from Regeneron and Adare Pharmaceuticals and has equity interest in Meritage Pharmacia. L. Biedermann reports personal fees from Vifor, Dr Falk Pharma, Esocap, and Calypso. C. Blanchard is an employee of Société des produits Nestlé. C. Ciriza de los Rios reports consulting fees for Norgine and Allergan. C. M. Davis reports research grants from the National Institutes of Health/National Institute of Allergy and Infectious Disease (Consortium of Food Allergy Research/Consortium of Eosinophilic Gastrointestinal researchers), DBV Technologies, Aimmune Therapeutics, and Regeneron Pharmaceuticals; and owns stock in Moonlight Therapeutics. G. W. Falk reports grants and/or personal fees from Allakos, Shire/Takeda, ADARE/Ellodi, Regeneron, and Bristol Myers Squibb. R. M. Genta reports consulting fees from Allakos, Adare/Ellodi, and RedHill Pharma. N. Gonsalves reports consulting fees from Allakos, Astra-Zeneca, Nutricia, and Sanofi/Regeneron; and royalties from UpToDate. T. Greuter reports consulting contracts with Dr Falk Pharma and Sanofi-Aventis, and a research grant from Novartis. K. S. Hsu Blatman reports research funding from Shire/Takeda. H. M. Larsson reports consulting fees from EsoCap Biotech. F. J. Moawad reports personal fees from Takeda and Salix. A. V. A. Mukkada reports grants and/or personal fees from Shire Pharmaceutical. K. Peterson reports personal fees from Alladapt, Eli Lily, Medscape, Ellodi, Takeda, Allakos, AstraZeneca, and Regeneron-Sanofi; research funding or other research support from Astra Zeneca, Ellodi, Regeneron-Sanofi, Allakos, and Chobani; and owns stock in Nexeos. C. Schlag reports consulting fees, speaker fees, and/or research grants from Adare Pharmaceuticals, AstraZeneca, Calypso, EsoCap, Dr Falk Pharma, and Regeneron Pharmaceuticals. P. Schreiner reports consulting fees from Pfizer, Takeda, and Janssen-Cilag. T. J. M. Spergel reports grants and/or personal fees from DBV Technologies, End Allergy Together, Food Allergy Research Education, Aimmune Therapeutics, UpToDate, Regeneron, and Shire. T. H. Taft reports speaking fees from AbbVie and consulting fees from Healthline. T. Vanuytsel has served as a speaker for Abbott, Dr Falk Pharma, Fresenius Kabi, Kyowa Kirin and Menarini, Takeda, and Will Pharma; has served as a consultant and advisory board member for Baxter, Dr Falk Pharma, Takeda, Tramedico, Truvion, VectivBio, and Zealand Pharma; and has received research funding from Danone and MyHealth. C. Venter has provided and reviewed educational material for Danone, Reckitt Benckiser, Abbott Nutrition, DBV Technologies, and Nestlé Nutrition Institute; and has received research grants from the National Peanut Board and Reckitt Benckiser. M. C. Vieira reports speaker's fees from Danone Nutricia and Nestlé. M. Vieth reports speaker's fees from Dr Falk Pharma, Shire, and Menarini. U. von Arnim reports consulting fees from ESOCAP, AbbVie, MSD, Takeda, and Dr Falk Pharma. J. B. Wechsler reports consulting fees from Allakos and Regeneron. N. Zevit reports speaker's fees for Dr Falk Pharma; and is an advisory board member for Adare Pharmaceuticals. E. Safroneeva reports consulting fees from AVIR Pharma, Aptalis Pharma, Celgene, Novartis, and Regeneron Pharmaceuticals. The following authors declare that they have no relevant conflicts of interest: N. de Bortoli, D. Johnston, A. F. Kagalwalla, A. Ravelli, and B. Vlieg-Boerstra.
Keywords
- Eosinophilic esophagitis
- clinical trials
- end points
- endoscopy
- histology
- histopathology
- outcomes
- patient-reported outcomes
- quality of life
- symptoms
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology