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Review
. 2023 Mar;151(3):595-606.
doi: 10.1016/j.jaci.2023.01.007.

The role of biologics in pediatric food allergy and eosinophilic gastrointestinal disorders

Sayantani B Sindher  1 , Suzanne Barshow  1 , Jyothi Tirumalasetty  1 , Stefania Arasi  2 , Dan Atkins  3 , Maureen Bauer  3 , Philippe Bégin  4 , Margaret H Collins  5 , Antoine Deschildre  6 , Alfred D Doyle  7 , Alessandro Fiocchi  2 , Glenn T Furuta  3 , Maria Garcia-Lloret  8 , Maurizio Mennini  2 , Marc E Rothenberg  9 , Jonathan M Spergel  10 , Julie Wang  11 , Robert A Wood  12 , Benjamin L Wright  7 , Torsten Zuberbier  13 , Andrew R Chin  1 , Andrew Long  1 , Kari C Nadeau  1 , R Sharon Chinthrajah  14
Affiliations
Review

The role of biologics in pediatric food allergy and eosinophilic gastrointestinal disorders

Sayantani B Sindher et al. J Allergy Clin Immunol. 2023 Mar.

Abstract

Continuing insight into the molecular mechanisms of atopic disorders has enabled the development of biologics to precisely target these diseases. Food allergy (FA) and eosinophilic gastrointestinal disorders (EGIDs) are driven by similar inflammatory molecular mechanisms and exist along the same atopic disease spectrum. Therefore, many of the same biologics are being investigated to target key drivers of mechanisms shared across the disease states. The enormous potential of biologics for the treatment of FA and EGIDs is highlighted by the significant increases in the number of ongoing clinical trials (more than 30) evaluating their use in these disease states, as well as by the recent US Food and Drug Administration approval of dupilumab for the treatment of eosinophilic esophagitis. Here we discuss past and current research into the use of biologics in FA and EGIDs and their potential role in improving treatment options in the future, with the need to have biologics widely clinically available.

Keywords: Food allergy; biologics; eosinophilic colitis; eosinophilic enteritis; eosinophilic esophagitis; eosinophilic gastritis; eosinophilic gastrointestinal disorders; oral immunotherapy.

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Conflict of interest statement

Conflicts of interest

SBS reports grants from NIH, Regeneron, DBV Technologies, Aimmune, Novartis, CoFAR, and FARE. She is an Advisory member at Genentech and DBV Technologies. SA reports participation as an advisory board member, and/or consultant, and/or speaker for Novartis, and Ulrich outside the submitted work. MB has received consulting fees from Sanofi and GLG consulting. ADe reports grants from Fondation du Souffle; Conseil Régional Hauts-de-France; consulting fees or honoraria from Novartis, ALK, GSK, Sanofi, Regeneron, AstraZeneca, Boehringer Ingelheim, Aimmune Therapeutics, DBV Technologies, Nestlé Health Science; participation in data safety monitoring board for BOOM study, outside the submitted work. GTF is a- Chief Medical Officer at EnteroTrack, and reports research grants from NIH, Holocalara, and Arena]. AL reports consultant fees from COUR Pharmaceuticals. KCN reports gr ants from National Institute of Allergy and Infectious Diseases (NIAID), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Environmental Health Sciences (NIEHS), and Food Allergy Research & Education (FARE); stock options from IgGenix, Seed Health, ClostraBio, and ImmuneID; is Director of the World Allergy Organization Center of Excellence for Stanford, Advisor at Cour Pharma, Consultant for Excellergy, Red tree ventures, Eli Lilly, and Phylaxis, Co-founder of Before Brands, Alladapt, Latitude, and IgGenix; and National Scientific Committee member at Immune Tolerance Network (ITN), and National Institutes of Health (NIH) clinical research centers, outside the submitted work; patents include, “Mixed allergen composition and methods for using the same,” “Granulocyte-based methods for detecting and monitoring immune system disorders,” and “Methods and Assays for Detecting and Quantifying Pure Subpopulations of White Blood Cells in Immune System Disorders.”. MER is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Nextstone One, Bristol Myers Squibb, Astra Zeneca, Ellodi Pharma, GlaxoSmith Kline, Regeneron/Sanofi, Revolo Biotherapeutics, and Guidepoint and has an equity interest in the first seven listed, and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust) and UpToDate. M.E.R. is an inventor of patents owned by Cincinnati Children’s Hospital. JMS has grant support from Regeneron/Sanofi, NIH. Consultant agreements with Regeneron/Sanofi, Allakos, and Celgene, Royalties from Uptodate. PB reports personal fees from Novartis, Pfizer, Sanofi-Genzyme, Bausch Health, Astra Zenaca, ALK and Aralez, as well as grants from DBV technologies, Regeneron, Novartis and Sanofi outside the submitted work. MHC has received research funding from AstraZeneca, Ception, GSK, Meritage Pharma Inc., Receptos/Celgene/BMS, Regeneron Pharmaceuticals and Shire, a Takeda company, and is a consultant for Allakos, Arena Pharmaceuticals, AstraZeneca, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene/BMS, Regeneron Pharmaceuticals, Robarts Clinical Trials Inc./Alimentiv, Inc. and Shire, a Takeda company. AD has received fees for lectures and honoraria for attending advisory boards from Novartis, GSK, Sanofi, Regeneron, AstraZeneca, Aimmune Therapeutics, DBV Technologies, Nestlé Health Science, ALK, Stallergènes-Greer outside the submitted work; participates in data safety monitoring board for BOOM study, outside the submitted work.. JW receives research support from National Institute of Allergy and Infectious Diseases, Aimmune, DBV Technologies, and Regeneron, and consultancy fees from ALK Abello and Jubilant HollisterStier. BLW reports research support from the National Institute of Allergy and Infectious Disease. RAW receives research support from NIH, Aimmune, DBV, Genentech, Novartis, Regeneron, FARE, and Siolta, and royalties from Up To Date. TZ reports industry consulting, research grants and/or honoraria from AImmune, Ajanta Pharma, AstraZeneca, AbbVie, ALK, Almirall, Astellas, Bayer Health Care, Bencard, Berlin Chemie, Bio Cryst, Celldex, FAES, HAL, Henkel, Kryolan, Leti, Lofarma, L’Oreal, Meda, Medi Wound, Menarini, Merck, MMV Medicines for Malaria Venture, MSD, Novartis, PCM Scientific, Pfizer, Sanofi, Sanoflore, Stallergenes, Takeda, Teva, and UCB. He is a committee member of WHO-Initiative “Allergic Rhinitis and its Impact on Asthma” (ARIA), Member of the Board for German Society for Allergy and Clinical Immunology (DGAKI), Chairman of the Board for European Centre for Allergy Research Foundation (ECARF), President of Global Allergy and Asthma European Network (GA2LEN), and member of Committee on Allergy Diagnosis and Molecular Allergology for World Allergy Organisation (WAO). RSC receives grant support from the Consortium for Food Allergy Research (CoFAR), National Institute of Allergy and Infectious Disease (NIAID), Food Allergy Research & Education (FARE), Aimmune, DBV Technologies, Astellas, Novartis, Regeneron, and Astra Zeneca, and is an advisory board member for Alladapt Immunotherapeutics, Novartis, Sanofi, Allergenis, Intrommune Therapeutics, and Genentech. All other authors indicate no conflicts of interest.

Figures

FIG1.
FIG1.
Biologics targeting key allergic pathways. Schematic of major allergic pathways that drive FA and EGIDs highlighting pathways that are targeted by biologics (red boxes) to treat these diseases.
FIG2.
FIG2.
FDA approval of biologics that are used or are under investigation for the treatment of FA and/or EGIDs. Most biologics being investigated for use in FA and/or EGIDs have been approved for use in other atopic diseases. Recent years have seen an explosion of FDA approvals for the use of these biologics for several different diseases. Each tick in the timeline represents 1 year.
FIG3.
FIG3.
Impaired skin barrier in EoE and AD. Several genetic and environmental factors lead to the disruption of the epithelial skin barrier. This disrupted barrier initiates downstream signaling pathways that drive EoE and AD.
See this image and copyright information in PMC

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