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Review
. 2024 Jul 25;116(2):307-320.
doi: 10.1093/jleuko/qiae051.

Biologic therapy in rare eosinophil-associated disorders: remaining questions and translational research opportunities

Paneez Khoury  1 , Florence Roufosse  2 , Fei Li Kuang  3 , Steven J Ackerman  4 , Praveen Akuthota  5 , Bruce S Bochner  3 , Mats W Johansson  6 , Sameer K Mathur  6 , Princess U Ogbogu  7   8 , Lisa A Spencer  9   10 , Michael E Wechsler  11 , Nives Zimmermann  12   13 , Amy D Klion  1 ; International Eosinophil Society Clinical Research Interest Group
Collaborators, Affiliations
Review

Biologic therapy in rare eosinophil-associated disorders: remaining questions and translational research opportunities

Paneez Khoury et al. J Leukoc Biol. .

Abstract

Rare eosinophil-associated disorders (EADs), including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, and eosinophilic gastrointestinal disorders, are a heterogeneous group of conditions characterized by blood and/or tissue hypereosinophilia and eosinophil-related clinical manifestations. Although the recent availability of biologic therapies that directly and indirectly target eosinophils has the potential to dramatically improve treatment options for all EADs, clinical trials addressing their safety and efficacy in rare EADs have been relatively few. Consequently, patient access to therapy is limited for many biologics, and the establishment of evidence-based treatment guidelines has been extremely difficult. In this regard, multicenter retrospective collaborative studies focusing on disease manifestations and treatment responses in rare EADs have provided invaluable data for physicians managing patients with these conditions and helped identify important questions for future translational research. During the Clinical Pre-Meeting Workshop held in association with the July 2023 biennial meeting of the International Eosinophil Society in Hamilton, Ontario, Canada, the successes and limitations of pivotal multicenter retrospective studies in EADs were summarized and unmet needs regarding the establishment of guidelines for use of biologics in rare EADs were discussed. Key topics of interest included (1) clinical outcome measures, (2) minimally invasive biomarkers of disease activity, (3) predictors of response to biologic agents, and (4) long-term safety of eosinophil depletion. Herein, we report a summary of these discussions, presenting a state-of-the-art overview of data currently available for each of these topics, the limitations of the data, and avenues for future data generation through implementation of multidisciplinary and multicenter studies.

Keywords: eosinophilia; eosinophilic gastrointestinal disorders; eosinophilic granulomatosis with polyangiitis; hypereosinophilic syndrome.

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Conflict of interest statement

Conflict of interest statement. F.R. receives consultancy and/or speaker fees from GlaxoSmithKline, AstraZeneca, Menarini, and Merck. F.L.K. receives research funding from AstraZeneca and speaker fees from both AstraZeneca and GlaxoSmithKline. S.J.A. is the Chief Scientific Officer and an Executive Board member of EnteroTrack, LLC; a co-inventor and holds patents on the Esophageal String Test; and a consultant for Areteia Pharmaceuticals. P.A. has received consulting fees and research support from AstraZeneca, GlaxoSmithKline, and Sanofi and research support from Regeneron. B.S.B. receives remuneration for serving on the scientific advisory board of Allakos, Inc.; owns stock in Allakos; currently serves as a consultant for Third Harmonic Bio and Sanofi/Regeneron; receives publication-related royalty payments from Elsevier and UpToDate; is a co-inventor on existing Siglec-8–related patents and thus may be entitled to a share of royalties received by Johns Hopkins University during development and potential sales of such products; and is a co-founder of Allakos, which makes him subject to certain restrictions under university policy (the terms of this arrangement are being managed by Johns Hopkins University and Northwestern University in accordance with their conflict-of-interest policies). M.W.J. has received research funding from F. Hoffmann-La Roche. S.K.M. has received consulting, advisory, or speaking honoraria from AstraZeneca, Amgen, GlaxoSmithKline, Novartis, and Sanofi/Regeneron. P.O.B. receives research funding from GlaxoSmithKline, AstraZeneca, Blueprint, and DBV Technologies; and serves on advisory boards for AstraZeneca, Sanofi, Genentech, and Kalvista. M.E.W. has received consulting, advisory, or speaking honoraria from Amgen, Areteia Therapeutics, AstraZeneca, Avalo Therapeutics, Boehringer Ingelheim, Celldex, Cellergy Pharma, Cerecor, Cytoreason, Eli Lilly, Equillium, Glaxosmithkline, Incyte, Kinaset, Merck, Novartis, Om Pharma, Overtone Therapeutics/Foresite Labs, Phylaxis, Pulmatrix, Rapt Therapeutics, Regeneron, Roche/Genentech, Sanofi/Genzyme, Sentien, Sound Biologics, Tetherex Pharmaceuticals, Teva, Upstream Bio, and Verona Pharma. The other authors have no conflicts of interest to disclose.

Figures

Fig. 1.
Fig. 1.
Summary figure.
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References

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