Reviews
14 October 2025

Evolving role of the Interleukin-5 antagonist mepolizumab for hypereosinophilic syndrome: pathogenesis and advances in therapy - A narrative review

Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
0
Views
0
Downloads

Authors

Hypereosinophilic syndrome (HES) is a rare blood disorder characterized by hypereosinophilia greater than 1,500/μL on at least two separate occasions with some degree of associated end-organ damage and exclusion of other identifiable causes of hypereosinophilia. The systemic effects and damage seen in HES can be extensive, resulting in a variety of clinical presentations, but most commonly the affected organs include the lungs, heart, skin, and the gastrointestinal tract. After FDA-approval in 2020, mepolizumab (trade name Nucala) an interleukin-5 (IL-5) antagonist monoclonal antibody, is considered an effective treatment for HES given its ability to lower absolute eosinophil counts, improve the symptomatic burden, reduce the number of HES flares experienced, and limit the need for corticosteroids as a primary therapy. Also of benefit, Nucala has been shown to have a positive safety profile with limited adverse effects and no notable contraindications to treatment.

Altmetrics

Downloads

Download data is not yet available.

Citations

1. Dispenza MC, Bochner BS. Diagnosis and novel approaches to the treatment of hypereosinophilic syndromes. Curr Hematol Malig Rep 2018;13:191-201. DOI: https://doi.org/10.1007/s11899-018-0448-8
2. Valent P, Klion AD, Roufosse F, et al. Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes. Allergy 2023;78:47-59.
3. Pavord ID, Bel EH, Bourdin A, et al. From DREAM to REALITI‐A and beyond: Mepolizumab for the treatment of eosinophil‐driven diseases. Allergy 2022;77:778-97. DOI: https://doi.org/10.1111/all.15056
4. GlaxoSmithKline LLC. Nucala Drug Label. 2022. Accessed: 26 Apr 2023. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761122s008,125526s019lbl.pdf
5. Rothenberg ME, Klion AD, Roufosse FE, al. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med 2008;358:1215-28. DOI: https://doi.org/10.1056/NEJMoa070812
6. Roufosse FE, Kahn JE, Gleich GJ, et al. Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes. J Allergy Clin Immunol 2013;131:461-7.e1-5. DOI: https://doi.org/10.1016/j.jaci.2012.07.055
7. Roufosse F, Kahn JE, Rothenberg ME, et al. Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial. J Allergy Clin Immunol 2020;146:1397-405. DOI: https://doi.org/10.1016/j.jaci.2020.08.037
8. Kuang FL, Fay MP, Ware J, et al. Long-term clinical outcomes of high-dose mepolizumab treatment for hypereosinophilic syndrome. J Allergy Clin Immunol Pract 2018;6:1518-27.e5. DOI: https://doi.org/10.1016/j.jaip.2018.04.033
9. Shomali W, Gotlib J. World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management. Am J Hematol 2024;99:946-68 DOI: https://doi.org/10.1002/ajh.27287
10. Klion A. Hypereosinophilic syndrome: approach to treatment in the era of precision medicine. Hematol Am Soc Hematol Educ Program 2018;2018:326-31. DOI: https://doi.org/10.1182/asheducation-2018.1.326
11. Roufosse FE, Goldman M, Cogan E. Hypereosinophilic syndromes. Orphanet J Rare Dis 2007;2:37. DOI: https://doi.org/10.1186/1750-1172-2-37
12. Choy MS, Dixit D, Barna Bridgeman M. Mepolizumab (Nucala) for severe eosinophilic asthma. P.T. 2016:41:619-22.
13. Smith DA, Minthorn EA, Beerahee M, et al. Pharmacokinetics and pharmacodynamics of mepolizumab, an anti-Interleukin-5 monoclonal antibody. Clin Pharmacokinet 2011;50:215-27. DOI: https://doi.org/10.2165/11584340-000000000-00000
14. Gupta A, Ikeda M, Geng B, et al. Long-term safety and pharmacodynamics of mepolizumab in children with severe asthma with an eosinophilic phenotype. J Allergy Clin Immunol 2019;144:1336-42.e7. DOI: https://doi.org/10.1016/j.jaci.2019.08.005
15. Gleich GJ, Roufosse F, Chupp G, et al. Safety and efficacy of mepolizumab in hypereosinophilic syndrome: an open-label extension study. J Allergy Clin Immunol Pract 2021;9:4431-40.e1.
16. Valent P, Klion AD, Roufosse F, et al. Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes. Allergy 2022;78:47-59. DOI: https://doi.org/10.1111/all.15544
17. Sekar N, Umakanth M. A diagnosis of idiopathic hypereosinophilic syndrome with skin involvement in a patient presenting with lymphadenopathy and rash. Cureus 2022;14:e23580. DOI: https://doi.org/10.7759/cureus.23580
18. Wechsler ME, Akuthota P, Jayne D, et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med 2017;376:1921-32. DOI: https://doi.org/10.1056/NEJMoa1702079
19. Bettiol A, Urban ML, Dagna L, et al. Mepolizumab for eosinophilic granulomatosis with polyangiitis: A European multicenter observational study. Arthritis Rheumatol 2022;74:295-306. DOI: https://doi.org/10.1002/art.41943
20. Ogbogu PU, Bochner BS, Butterfield JH, et al. Hypereosinophilic syndrome: A multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol 2009;124:1319-25.e3. DOI: https://doi.org/10.1016/j.jaci.2009.09.022
21. Jin JJ, Butterfield JH, Weiler CR. Hematologic malignancies identified in patients with hypereosinophilia and hypereosinophilic syndromes. J Allergy Clin Immunol Pract 2015;3:920-5. DOI: https://doi.org/10.1016/j.jaip.2015.06.009
22. Wei L, MacDonald TM, Walker BR. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med 2004;141:764-70. DOI: https://doi.org/10.7326/0003-4819-141-10-200411160-00007
23. Wang H, Zhou J, Guo X, et al. Use of glucocorticoids in the management of immunotherapy‐related adverse effects. Thorac Cancer 2020;11:3047-52. DOI: https://doi.org/10.1111/1759-7714.13589
24. Podjasek JC, Butterfield JH. Mortality in hypereosinophilic syndrome: 19 years of experience at Mayo Clinic with a review of the literature. Leuk Res 2013;37:392–5. DOI: https://doi.org/10.1016/j.leukres.2012.12.016
25. Pane F, Lefevre G, Kwon N, et al. Characterization of disease flares and impact of mepolizumab in patients with hypereosinophilic syndrome. Front Immunol 2022;13:935996. DOI: https://doi.org/10.3389/fimmu.2022.935996
26. Gleich GJ, Roufosse F, Chupp G, et al. Safety and efficacy of mepolizumab in hypereosinophilic syndrome: an open-label extension study. J Allergy Clin Immunol Pract 2021;9:4431-40.e1.
27. Roufosse F, Butterfield J, Steinfeld J, et al. Mepolizumab therapy improves the most bothersome symptoms in patients with hypereosinophilic syndrome. Front Med (Lausanne) 2023;10:1035250. DOI: https://doi.org/10.3389/fmed.2023.1035250
28. Roufosse F, de Lavareille A, Schandené L, et al. Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant hypereosinophilic syndrome. J Allergy Clin Immunol 2010;126:828-35.e3. DOI: https://doi.org/10.1016/j.jaci.2010.06.049

How to Cite



1.
Askins DH, Bobo EW, Chacko BJ, Mansourian KA, McDonough SR, Jean Baptiste C, et al. Evolving role of the Interleukin-5 antagonist mepolizumab for hypereosinophilic syndrome: pathogenesis and advances in therapy - A narrative review. Adv Health Res [Internet]. 2025 Oct. 14 [cited 2025 Oct. 15];2(1). Available from: https://www.ahr-journal.org/site/article/view/29