From Pathogenesis to Treatment: Targeting Type-2 Inflammation in Eosinophilic Esophagitis
Abstract
:1. Introduction
2. Type 2 Inflammation: “Atopic March”—Common Pathogenesis between Atopic Dermatitis (AD), Asthma, Allergic Rhinitis (AR), Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), and EoE
3. Type 2 Inflammation Is Key in EoE Pathogenesis: Review of Molecular Mechanisms
4. Therapies Targeting Type 2 Inflammation: Evidence from Trials with Available Therapies and How They Target T2 Inflammation in EoE
4.1. Interleukin-4
4.2. Interleukin-5
4.3. Interleukin-13 (IL-13)
4.4. TSLP, Sialic Acid-Binding Immunoglobulin-like Lectin 8 (Siglec-8), and CRTH2 Receptor
4.5. Other Molecular Targets
5. Future Directions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Target | Rationale | Trials | NCTs | Drug | Pharmacodynamics | Approved |
---|---|---|---|---|---|---|
IL-4 |
| 5 |
| Dupilumab (5) | Anti IL-4Rα mAb | Yes (>12 years) |
IL-13 |
| 4 |
| Dectrekumab (1) Cendakimab (2) | IL-13Rα1–2 mAb | No |
IL-5 |
| 6 |
| Reslizumab (2) Mepolizumab (3) Benralizumab (1) | IL5Rα mAb (benralizumab) Anti-IL5 mAb (mepolizumab, reslizumab) | No |
TSLP |
| 1 |
| Tezepelumab (1) | Anti-TSLP mAb | No |
Siglec-8 |
| 1 |
| Lirentelimab (1) | Anti-Siglec-8 mAb | No |
CRTH2 |
| 1 |
| OC000459 (1) | Selective antagonist of CRTH2 receptor | No |
c-KIT |
| 1 |
| Barzolvolimab (1) | MCs anti-c-KIT mAb | No |
IL-15 |
| 1 |
| CALY-002 (1) | Anti-IL-15 mAb | No |
IgE |
| 1 |
| Omalizumab | Anti-IgE mAb | No |
TNFα |
| 1 |
| Infliximab (1) | Anti-TNFα mAb | No |
Cpn60.1 |
| 1 |
| IRL201104 (1) | Cpn60.1 peptide | No |
S1P |
| 1 |
| Etrasimod (1) | S1P-receptor modulator | No |
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Barchi, A.; Mandarino, F.V.; Yacoub, M.-R.; Albarello, L.; Massimino, L.; Savarino, E.V.; Ungaro, F.; Passaretti, S.; Masclee, G.M.C.; Danese, S.; et al. From Pathogenesis to Treatment: Targeting Type-2 Inflammation in Eosinophilic Esophagitis. Biomolecules 2024, 14, 1080. https://doi.org/10.3390/biom14091080
Barchi A, Mandarino FV, Yacoub M-R, Albarello L, Massimino L, Savarino EV, Ungaro F, Passaretti S, Masclee GMC, Danese S, et al. From Pathogenesis to Treatment: Targeting Type-2 Inflammation in Eosinophilic Esophagitis. Biomolecules. 2024; 14(9):1080. https://doi.org/10.3390/biom14091080
Chicago/Turabian StyleBarchi, Alberto, Francesco Vito Mandarino, Mona-Rita Yacoub, Luca Albarello, Luca Massimino, Edoardo Vincenzo Savarino, Federica Ungaro, Sandro Passaretti, Gwen M. C. Masclee, Silvio Danese, and et al. 2024. "From Pathogenesis to Treatment: Targeting Type-2 Inflammation in Eosinophilic Esophagitis" Biomolecules 14, no. 9: 1080. https://doi.org/10.3390/biom14091080