{rfName}
Eo

Indexed in

License and use

Icono OpenAccess

Altmetrics

Grant support

CIBER Respiratorio.

Analysis of institutional authors

Sastre JAuthorDel Pozo VAuthor

Share

May 10, 2022
Publications
>
Review

Eosinophilia Induced by Blocking the IL-4/IL-13 Pathway: Potential Mechanisms and Clinical Outcomes

Publicated to:JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY. 32 (3): 165-180 - 2022-01-01 32(3), DOI: 10.18176/jiaci.0823

Authors: Olaguibel JM, Sastre J, Rodríguez JM, Del Pozo V

Affiliations

Allergy Service, Fundación Jiménez Díaz. CIBER de Enfermedades Respiratorias (CIBERES). Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain. - Author
CIBER de Enfermedades Respiratorias (CIBERES) and Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain. - Author
CIBER Enfermedades Resp CIBERES, Madrid, Spain - Author
Department of Immunology, IIS-Fundación Jiménez Díaz and CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain. - Author
Hosp Univ Navarra, Serv Alergol, CIBER Enfermedades Resp CIBERES, Pamplona, Spain - Author
IIS Fdn Jimenez Diaz, Dept Immunol, Madrid, Spain - Author
Servicio de Alergología, Hospital Universitario de Navarra. CIBER de Enfermedades Respiratorias (CIBERES). Pamplona, Spain. - Author
Univ Autonoma Madrid, CIBER Enfermedades Resp CIBERES, Madrid, Spain - Author
Univ Autonoma Madrid, Sch Med, CIBER Enfermedades Resp CIBERES, Allergy Dept,Fdn Jimenez Diaz, Madrid, Spain - Author
Univ Autonoma Madrid, Sch Med, Madrid, Spain - Author
See more

Abstract

Five biological drugs are currently marketed for treatment of uncontrolled severe asthma. They all block type 2 inflammatory pathways by targeting IgE (omalizumab), the IL-5 pathway (mepolizumab, reslizumab, benralizumab), or the IL-4/IL-13 pathway (dupilumab). Hypereosinophilia has been observed in 4%-25% of patients treated with dupilumab and is transient in most cases, although there have been reports of persistent cases of symptomatic hypereosinophilia consistent with eosinophilic granulomatosis with polyangiitis (EGPA), eosinophilic pneumonia, eosinophilic vasculitis, and sudden worsening of asthma symptoms. Cases of EGPA have been reported with all biologics, including anti???IL-5 agents, and with leukotriene receptor antagonists in publications or in the EudraVigilance database. In many cases, EGPA appears during tapering of systemic corticosteroids or after switching from an anti???IL-5 biologic to dupilumab, suggesting that systemic corticosteroids or the anti???IL-5 agent were masking vasculitis. This review investigates plausible mechanisms of dupilumab-induced hypereosinophilia and review cases of symptomatic hypereosinophilia associated with dupilumab. Blockade of the IL-4/IL-13 pathway reduces eosinophil migration and accumulation of blood by inhibiting eotaxin-3, VCAM-1, and TARC without simultaneously inhibiting eosinophilopoiesis in bone marrow. When choosing the optimal biologic, it seems necessary to consider the presence of hypereosinophilia (>1500/??L), in which case an anti???IL-5/IL-5R agent is preferable. Furthermore, when switching from an anti???IL-5/5R to an anti???IL-4/13R agent, blood eosinophils and clinical progress should be closely monitored. Nevertheless, dual therapy with anti???IL-5/5R and anti???IL4/IL-13R agents may be needed for optimal control, since both the IL-5 and the IL-4/IL-13 pathways can simultaneously contribute to airway inflammation. This approach can prevent the development of EGPA and other types of symptomatic hypereosinophilia while maintaining control of nasal polyposis. In the near future, it will be possible to use a new generation of biological therapies for the treatment of severe asthma. These act at a higher level of the inflammatory cascade, as is the case of the antialarmins tezepelumab and itepekimab.

Keywords

alpha-chainbindingbiologic treatmentcellsdupilumabeosinophil granulomatosis with polyangiitiseosinophiliaexpressiongranulomatosisil-4interleukin-13severe asthmaAsthmaBiologic treatmentChurg-strauss-syndromeEosinophil granulomatosis with polyangiitisEosinophilia

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 5/28, thus managing to position itself as a Q1 (Primer Cuartil), in the category Allergy.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 5.13. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 5.61 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 40.49 (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-09, the following number of citations:

  • WoS: 23
  • Scopus: 37

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-09:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 67.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 80 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.25.
  • The number of mentions on the social network X (formerly Twitter): 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: Last Author (DEL POZO ABEJON, MARIA VICTORIA).