A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions

Evan S. Dellon; Paneez Khoury; Amanda B. Muir; Chris A. Liacouras; Ekaterina Safroneeva; Dan Atkins; Margaret H. Collins; Nirmala Gonsalves; Gary W. Falk; Jonathan M. Spergel; Ikuo Hirano; Mirna Chehade; Alain M. Schoepfer; Calies Menard-Katcher; David A. Katzka; Peter A. Bonis; Albert J. Bredenoord; Bob Geng; Elizabeth T. Jensen; Robert D. Pesek; Paul Feuerstadt; Sandeep K. Gupta; Alfredo J. Lucendo; Robert M. Genta; Girish Hiremath; Emily C. McGowan; Fouad J. Moawad; Kathryn A. Peterson; Marc E. Rothenberg; Alex Straumann; Glenn T. Furuta; Seema S. Aceves

doi:10.1016/j.jaci.2022.03.015

A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions

Evan S. Dellon^*, Paneez Khoury, Amanda B. Muir, Chris A. Liacouras, Ekaterina Safroneeva, Dan Atkins, Margaret H. Collins, Nirmala Gonsalves, Gary W. Falk, Jonathan M. Spergel, Ikuo Hirano, Mirna Chehade, Alain M. Schoepfer, Calies Menard-Katcher, David A. Katzka, Peter A. Bonis, Albert J. Bredenoord, Bob Geng, Elizabeth T. Jensen, Robert D. PesekPaul Feuerstadt, Sandeep K. Gupta, Alfredo J. Lucendo, Robert M. Genta, Girish Hiremath, Emily C. McGowan, Fouad J. Moawad, Kathryn A. Peterson, Marc E. Rothenberg, Alex Straumann, Glenn T. Furuta, Seema S. Aceves

^*Corresponding author for this work

Medicine, Gastroenterology Division

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Background & Aims: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. Methods: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. Results: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system—the Index of Severity for Eosinophilic Esophagitis (I-SEE)—that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. Conclusions: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated “I-SEE” to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.

Original language	English (US)
Pages (from-to)	33-47
Number of pages	15
Journal	Journal of Allergy and Clinical Immunology
Volume	150
Issue number	1
DOIs	https://doi.org/10.1016/j.jaci.2022.03.015
State	Published - Jul 2022

Funding

This article is based on a virtual conference sponsored solely by the American Gastroenterological Association (AGA), with the support of independent medical education grant from Takeda Pharmaceuticals USA, Inc. Takeda Pharmaceuticals USA, Inc was not involved with the virtual conference and its content or with the development of this article. No authors received funding from Takeda Pharmaceuticals USA, Inc as part of this effort. Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR; U54 AI117804) is part of the Rare Disease Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences (NCATS), and is funded through collaboration among the National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases, and NCATS, and in part by the Division of Intramural Research, NIAID/National Institutes of Health. CEGIR is also supported by patient advocacy groups, including American Partnership for Eosinophilic Disorders, Campaign Urging Research for Eosinophilic Diseases, and Eosinophilic Family Coalition. As a member of the RDCRN, CEGIR is also supported by its Data Management and Coordinating Center (U2CTR002818). The authors are grateful for the contributions of the participants in the August 13, 2021 conference, who are listed, together with affiliations, in the Appendix. In addition, the authors acknowledge Dr Terra Ziporyn, medical editor, for her assistance with the manuscript and Alissa Effland for her assistance with the manuscript's graphics. Author contributions: All co-authors served as faculty in a day-long web-based conference aimed at defining EoE clinical severity, designing a tool to measure severity, and identifying future research directions. Drs Dellon, Furuta, and Aceves served on the conference steering committee, led the conference, and were involved in both project conception and drafting, critical revision, and final approval of the resulting paper. Drs Aceves, Collins, Falk, Gonsalves, Hirano, Chehade, Menard-Katcher, Katzka, and Spergel served as conference presenters and, together with session chairs Drs Khoury, Liacouras, and Atkins, contributed to manuscript drafting, critical revision, and final approval. Drs Bonis, Bredenoord, Feuerstadt, Geng, Genta, Hiremath, Jensen, Lucendo, McGowan, Moawad, Pesek, Peterson, Rothenberg, Schoepfer, and Straumann participated as conference faculty and provided critical revisions and final approval to the manuscript. This virtual conference was sponsored solely by the American Gastroenterological Association (AGA), with the support of independent medical education grants from Takeda Pharmaceuticals USA, Inc. Takeda Pharmaceuticals USA, Inc was not involved with the virtual conference and its content or with the development of this article. This conference was also funded in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases/National Institutes of Health, and supported by the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR; U54 AI117804). All activities and products resulting from this conference were independently developed with no involvement or input from the funder. All intellectual property has been created and developed on behalf of the AGA and is public domain. Writing assistance: Terra Ziporyn, PhD, provided writing assistance with funding from Knighten Health, LLC. These authors disclose the following: Evan S. Dellon: Research funding: Adare/Ellodi, Allakos, Arena, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Shire/Takeda; Consultant: Abbott, Abbvie, Adare/ Ellodi, Aimmune, Allakos, Amgen, Arena, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, GSK, Gossamer Bio, InveniAI, Landos, LucidDx, Morphic, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, TargetRWE; Educational grant: Allakos, Banner, Holoclara. Amanda B. Muir: Research funding: Morphic. Ekaterina Safroneeva: Speaker fees: Alimentiv, Inc, Avir Pharma, Inc; Consulting fees: Sanofi Genzyme Inc. Margaret H. Collins: Research funding: AstraZeneca, Meritage Pharma Inc, Receptos/Celgene, Regeneron Pharmaceuticals, and Shire, a Takeda company; Consultant: Allakos, Arena Pharmaceuticals, AstraZeneca, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene, Regeneron Pharmaceuticals, Robarts Clinical Trials Inc/Alimentiv, Inc, and Shire, a Takeda company. Nirmala Gonsalves: Consultant: Regeneron, Allakos, AstraZeneca, Abbvie, Knopp, Nutricia; Speakers bureau: Takeda; Royalties: UpToDate. Gary W. Falk: Research funding: Adare/Ellodi, Allakos, Arena, Celgene/BMS, Lucid, Regeneron/Sanofi, Shire/Takeda; Consultant: Adare/Ellodi, Allakos, Celgene/BMS, Lucid, Phathom, Regeneron/Sanofi, Shire/Takeda. Mirna Chehade: Consultant: Regeneron, Allakos, Adare/Ellodi, Shire/Takeda, AstraZeneca, Sanofi, Bristol Myers Squibb, Phathom; Research funding: Regeneron, Allakos, Shire/Takeda, AstraZeneca, Adare/Ellodi, Danone. Alain M. Schoepfer: Research funding: AstraZeneca, GSK, Celgene/Receptos/BMS, Dr Falk Pharma, Regeneron, Pfizer; Consultant: Abbvie, Adare/Ellodi, Amgen, AstraZeneca, Celgene/Receptos/BMS, Dr Falk Pharma, GSK, Gossamer Bio, Janssen-Cilag, MSD, Mylan, Regeneron, Sanofi, Takeda, Tillotts. Albert J. Bredenoord: Research funding: Nutricia, Norgine, Thelial, SST, and Bayer; Speaker and/or consulting fees: Laborie, Arena, EsoCap, Medtronic, Dr. Falk Pharma, Calypso Biotech, Alimentiv, Sanofi, Reckett, Regeneron, and AstraZeneca. Bob Geng: Consultant: Regeneron, Sanofi, and Takeda. Robert D. Pesek: Consultant: Takeda. Paul Feuerstadt: Consultant/Speakers Bureau: Takeda Pharmaceuticals; Research support: Adare Pharmaceuticals. Sandeep K. Gupta: Consultant Abbott, Gossamer Bio, QOL, Shire, MedScape, ViaSkin, UpToDate; Research funding: National Institutes of Health, Ellodi, and Allakos. Alfredo J. Lucendo: Research Funding: Dr. Falk Pharma, Adare/Ellodi, Regeneron/Sanofi, EsoCap; Consultant: Dr. Falk Pharma. Robert M. Genta: Consultant: Allakos, Adare/Ellodi Pharmaceuticals. Emily C. McGowan: Research funding: Regeneron. Kathryn A. Peterson: Consultant/Advisory: AGA, Alladapt, AstraZeneca, Allakos, Bistol Meyers Squibb, Ellodi, Lucid, Medscape, Peerview, Regeneron, Takeda; Speaker: Regeneron, Peerview, Takeda, Allakos, Medscape; Equity: Nexeos Bio. Marc E. Rothenberg: Consultant: Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Celgene, Astra Zeneca, Adare/Ellodi Pharma, GlaxoSmith Kline, Regeneron/Sanofi, Revolo Biotherapeutics, and Guidepoin; Equity interest in the first 6 listed, and royalties from reslizumab (Teva Pharmaceuticals), Pediatric Eosinophilic Esophagitis Symptom Scores, version 2 (Mapi Research Trust) and UpToDate. Alex Straumann: Consultant; Astra-Zeneca, Calypso, EsoCap, Falk Pharma, Gossamer, Receptos-Celgene, Regeneron-Sanofi, Roche-Genentec, Shire. Glenn T. Furuta: LaCache Chair in Gastrointestinal Allergic and Immunologic Diseases Children's Hospital Colorado; Founder EnteroTrack; Research Funding: Holoclara, Arena. Seema S. Aceves: Co-Inventor oral viscous budesonide, UCSD patent, Takeda license; Consultant: Regeneron, AstraZeneca; Speaker: MedScape/WebMD; Author for UptoDate. The remaining authors disclose no conflicts. This article is based on a virtual conference sponsored solely by the American Gastroenterological Association (AGA), with the support of independent medical education grant from Takeda Pharmaceuticals USA, Inc. Takeda Pharmaceuticals USA, Inc was not involved with the virtual conference and its content or with the development of this article. No authors received funding from Takeda Pharmaceuticals USA, Inc as part of this effort. Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR; U54 AI117804) is part of the Rare Disease Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences (NCATS), and is funded through collaboration among the National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases, and NCATS, and in part by the Division of Intramural Research, NIAID/National Institutes of Health. CEGIR is also supported by patient advocacy groups, including American Partnership for Eosinophilic Disorders, Campaign Urging Research for Eosinophilic Diseases, and Eosinophilic Family Coalition. As a member of the RDCRN, CEGIR is also supported by its Data Management and Coordinating Center (U2CTR002818). The authors are grateful for the contributions of the participants in the August 13, 2021 conference, who are listed, together with affiliations, in the Appendix . In addition, the authors acknowledge Dr Terra Ziporyn, medical editor, for her assistance with the manuscript and Alissa Effland for her assistance with the manuscript's graphics. Author contributions: All co-authors served as faculty in a day-long web-based conference aimed at defining EoE clinical severity, designing a tool to measure severity, and identifying future research directions. Drs Dellon, Furuta, and Aceves served on the conference steering committee, led the conference, and were involved in both project conception and drafting, critical revision, and final approval of the resulting paper. Drs Aceves, Collins, Falk, Gonsalves, Hirano, Chehade, Menard-Katcher, Katzka, and Spergel served as conference presenters and, together with session chairs Drs Khoury, Liacouras, and Atkins, contributed to manuscript drafting, critical revision, and final approval. Drs Bonis, Bredenoord, Feuerstadt, Geng, Genta, Hiremath, Jensen, Lucendo, McGowan, Moawad, Pesek, Peterson, Rothenberg, Schoepfer, and Straumann participated as conference faculty and provided critical revisions and final approval to the manuscript. This virtual conference was sponsored solely by the American Gastroenterological Association (AGA), with the support of independent medical education grants from Takeda Pharmaceuticals USA, Inc. Takeda Pharmaceuticals USA, Inc was not involved with the virtual conference and its content or with the development of this article. This conference was also funded in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases/National Institutes of Health, and supported by the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR; U54 AI117804). All activities and products resulting from this conference were independently developed with no involvement or input from the funder. All intellectual property has been created and developed on behalf of the AGA and is public domain. Writing assistance: Terra Ziporyn, PhD, provided writing assistance with funding from Knighten Health, LLC.

Keywords

Eosinophilic esophagitis
complications
endoscopy
histology
severity
symptoms

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/j.jaci.2022.03.015

Cite this

Dellon, E. S., Khoury, P., Muir, A. B., Liacouras, C. A., Safroneeva, E., Atkins, D., Collins, M. H., Gonsalves, N., Falk, G. W., Spergel, J. M., Hirano, I., Chehade, M., Schoepfer, A. M., Menard-Katcher, C., Katzka, D. A., Bonis, P. A., Bredenoord, A. J., Geng, B., Jensen, E. T., ... Aceves, S. S. (2022). A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions. Journal of Allergy and Clinical Immunology, 150(1), 33-47. https://doi.org/10.1016/j.jaci.2022.03.015

@article{b11f989a892b41b1bb034eeaf17130a1,

title = "A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions",

abstract = "Background & Aims: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. Methods: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. Results: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system—the Index of Severity for Eosinophilic Esophagitis (I-SEE)—that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. Conclusions: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated “I-SEE” to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.",

keywords = "Eosinophilic esophagitis, complications, endoscopy, histology, severity, symptoms",

author = "Dellon, {Evan S.} and Paneez Khoury and Muir, {Amanda B.} and Liacouras, {Chris A.} and Ekaterina Safroneeva and Dan Atkins and Collins, {Margaret H.} and Nirmala Gonsalves and Falk, {Gary W.} and Spergel, {Jonathan M.} and Ikuo Hirano and Mirna Chehade and Schoepfer, {Alain M.} and Calies Menard-Katcher and Katzka, {David A.} and Bonis, {Peter A.} and Bredenoord, {Albert J.} and Bob Geng and Jensen, {Elizabeth T.} and Pesek, {Robert D.} and Paul Feuerstadt and Gupta, {Sandeep K.} and Lucendo, {Alfredo J.} and Genta, {Robert M.} and Girish Hiremath and McGowan, {Emily C.} and Moawad, {Fouad J.} and Peterson, {Kathryn A.} and Rothenberg, {Marc E.} and Alex Straumann and Furuta, {Glenn T.} and Aceves, {Seema S.}",

note = "Publisher Copyright: {\textcopyright} 2022 AGA Institute",

year = "2022",

month = jul,

doi = "10.1016/j.jaci.2022.03.015",

language = "English (US)",

volume = "150",

pages = "33--47",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

number = "1",

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Dellon, ES, Khoury, P, Muir, AB, Liacouras, CA, Safroneeva, E, Atkins, D, Collins, MH, Gonsalves, N, Falk, GW, Spergel, JM, Hirano, I, Chehade, M, Schoepfer, AM, Menard-Katcher, C, Katzka, DA, Bonis, PA, Bredenoord, AJ, Geng, B, Jensen, ET, Pesek, RD, Feuerstadt, P, Gupta, SK, Lucendo, AJ, Genta, RM, Hiremath, G, McGowan, EC, Moawad, FJ, Peterson, KA, Rothenberg, ME, Straumann, A, Furuta, GT & Aceves, SS 2022, 'A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions', Journal of Allergy and Clinical Immunology, vol. 150, no. 1, pp. 33-47. https://doi.org/10.1016/j.jaci.2022.03.015

TY - JOUR

T1 - A Clinical Severity Index for Eosinophilic Esophagitis

T2 - Development, Consensus, and Future Directions

AU - Dellon, Evan S.

AU - Khoury, Paneez

AU - Muir, Amanda B.

AU - Liacouras, Chris A.

AU - Safroneeva, Ekaterina

AU - Atkins, Dan

AU - Collins, Margaret H.

AU - Gonsalves, Nirmala

AU - Falk, Gary W.

AU - Spergel, Jonathan M.

AU - Hirano, Ikuo

AU - Chehade, Mirna

AU - Schoepfer, Alain M.

AU - Menard-Katcher, Calies

AU - Katzka, David A.

AU - Bonis, Peter A.

AU - Bredenoord, Albert J.

AU - Geng, Bob

AU - Jensen, Elizabeth T.

AU - Pesek, Robert D.

AU - Feuerstadt, Paul

AU - Gupta, Sandeep K.

AU - Lucendo, Alfredo J.

AU - Genta, Robert M.

AU - Hiremath, Girish

AU - McGowan, Emily C.

AU - Moawad, Fouad J.

AU - Peterson, Kathryn A.

AU - Rothenberg, Marc E.

AU - Straumann, Alex

AU - Furuta, Glenn T.

AU - Aceves, Seema S.

PY - 2022/7

Y1 - 2022/7

N2 - Background & Aims: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. Methods: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. Results: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system—the Index of Severity for Eosinophilic Esophagitis (I-SEE)—that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. Conclusions: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated “I-SEE” to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.

AB - Background & Aims: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. Methods: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. Results: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system—the Index of Severity for Eosinophilic Esophagitis (I-SEE)—that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. Conclusions: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated “I-SEE” to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.

KW - Eosinophilic esophagitis

KW - complications

KW - endoscopy

KW - histology

KW - severity

KW - symptoms

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A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions

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