Current and emerging biologic therapies targeting eosinophilic disorders

Eosinophilic disorders include a wide array of conditions in which eosinophils play a primary pathophysiologic role. While historically treated with corticosteroids and immunosuppressants, knowledge of eosinophil biology has led to the development of several biologics targeting eosinophils. In this review, we discuss the current US Food and Drug Administration (FDA) approved eosinophil-specific biologics targeting IL-5 (mepolizumab and reslizumab) and IL-5R (benralizumab) along with biologics under investigation targeting siglec-8 (lirentelimab). We discuss efficacy and safety data from trials of these medications in conditions including eosinophilic asthma, hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), and eosinophilic gastrointestinal disease (EGID). Additionally, we discuss case reports utilizing these medications in conditions including drug reaction with eosinophilia and systemic symptoms (DRESS), allergic bronchopulmonary aspergillosis (ABPA), and eosinophilic pneumonia, among others. While eosinophilic targeting biologic therapy has been successful in eosinophilic asthma, HES, EGPA, and CRSwNP leading to FDA approval for these conditions, trials treating EoE and EGID have been disappointing to date. Given the increasing number of trials utilizing these biologics, it will be imperative for the allergist-immunologist to stay up to date on the latest treatment options to provide the most optimal care for eosinophilic disorders.

• Publication year

  2022

• Venue

  The World Allergy Organization Journal

• Publication date

  2022-07-31

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.waojou.2022.100676PMID 35983569PMCID 9356173
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Integrated Safety and Efficacy Among Patients Receiving Benralizumab for Up to Five Years.

  2021cited by this paper
• Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial.

  2021influential reference
• Oral corticosteroid elimination via a personalised reduction algorithm in adults with severe, eosinophilic asthma treated with benralizumab (PONENTE): a multicentre, open-label, single-arm study.

  2021cited by this paper
• Efficacy and Safety of Benralizumab in Chronic Rhinosinusitis with Nasal Polyps: A Randomized, Placebo-controlled Trial.

  2021influential reference
• Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial

  2020influential reference
• Mepolizumab as Possible Treatment for Allergic Bronchopulmonary Aspergillosis: A Review of Eight Cases

  2020cited by this paper
• Severe eosinophilic asthma and aspirin-exacerbated respiratory disease associated to eosinophilic gastroenteritis treated with mepolizumab: a case report

  2020influential reference
• Eosinophilic bronchiolitis successfully treated with mepolizumab.

  2020cited by this paper
• Real-Life Study of Mepolizumab in Idiopathic Chronic Eosinophilic Pneumonia

  2020cited by this paper
• Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis.

  2020influential reference
• Benralizumab for severe DRESS in two COVID-19 patients

  2020cited by this paper
• Benefit of benralizumab treatment in a patient with chronic symptomatic dermographism

  2019cited by this paper
• Benralizumab for PDGFRA‐Negative Hypereosinophilic Syndrome

  2019influential reference
• Increasing Rates of Diagnosis, Substantial Co-Occurrence, and Variable Treatment Patterns of Eosinophilic Gastritis, Gastroenteritis, and Colitis Based on 10-Year Data Across a Multicenter Consortium.

  2019cited by this paper
• Eosinophilic Gastrointestinal Disorders

  2019cited by this paper
• Anti–IL‐5 treatments in patients with severe asthma by blood eosinophil thresholds: Indirect treatment comparison

  2019influential reference
• Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial.

  2019cited by this paper
• Two-Year Integrated Efficacy And Safety Analysis Of Benralizumab In Severe Asthma

  2019cited by this paper
• Long-term Safety and Clinical Benefit of Mepolizumab in Patients With the Most Severe Eosinophilic Asthma: the COSMEX Study.

  2019influential reference
• Siglec-8 antibody reduces eosinophil and mast cell infiltration in a transgenic mouse model of eosinophilic gastroenteritis.

  2019cited by this paper
• Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma

  2019cited by this paper
• Long-term safety and pharmacodynamics of mepolizumab in children with severe asthma with an eosinophilic phenotype.

  2019cited by this paper
• World Health Organization‐defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management

  2019cited by this paper
• AK002, a Humanized Sialic Acid-Binding Immunoglobulin-Like Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell-Mediated Anaphylaxis in Mice

  2019cited by this paper
• Sialic acid-binding immunoglobulin-like lectin (Siglec) 8 in patients with eosinophilic disorders: Receptor expression and targeting using chimeric antibodies.

  2019cited by this paper
• Hypereosinophilic syndrome: approach to treatment in the era of precision medicine.

  2018cited by this paper
• Eosinophilic gastrointestinal diseases beyond eosinophilic esophagitis.

  2018cited by this paper
• Diagnosis and Novel Approaches to the Treatment of Hypereosinophilic Syndromes

  2018cited by this paper
• Targeting the Interleukin-5 Pathway for Treatment of Eosinophilic Conditions Other than Asthma

  2018cited by this paper
• Benefit of mepolizumab treatment in a patient with chronic spontaneous urticaria

  2018cited by this paper
• Benefit from reslizumab treatment in a patient with chronic spontaneous urticaria and cold urticaria

  2018cited by this paper
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome successfully treated with mepolizumab.

  2017cited by this paper
• Oral Glucocorticoid–Sparing Effect of Benralizumab in Severe Asthma

  2017influential reference
• Safety and Efficacy of Reslizumab for Children and Adolescents With Eosinophilic Esophagitis Treated for 9 Years

  2017cited by this paper
• Pharmacokinetic/pharmacodynamic drug evaluation of benralizumab for the treatment of asthma

  2017cited by this paper
• Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis

  2017influential reference
• Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial.

  2016cited by this paper
• Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study.

  2016influential reference
• Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies.

  2016cited by this paper
• Reslizumab for Inadequately Controlled Asthma With Elevated Blood Eosinophil Levels: A Randomized Phase 3 Study.

  2016influential reference
• Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers.

  2016cited by this paper
• Reslizumab: First Global Approval

  2016cited by this paper
• Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial.

  2016cited by this paper
• Phase 3 Study of Reslizumab in Patients With Poorly Controlled Asthma: Effects Across a Broad Range of Eosinophil Counts.

  2016influential reference
• Eosinophilic Endotype of Asthma.

  2016cited by this paper
• Revised International Chapel Hill Consensus Conference nomenclature of vasculitides

  2016cited by this paper
• Novel Therapies for Eosinophilic Disorders.

  2015cited by this paper
• Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials.

  2015influential reference
• Hypereosinophilic Syndrome

  2015cited by this paper
• Mepolizumab: First Global Approval

  2015cited by this paper
• Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma.

  2014influential reference
• Mepolizumab treatment in patients with severe eosinophilic asthma.

  2014influential reference
• Differences in Initial Immunoprofiles between Recurrent and Nonrecurrent Chronic Rhinosinusitis with Nasal Polyps

  2014cited by this paper
• Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes.

  2013influential reference
• 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.

  2013cited by this paper
• Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial.

  2012cited by this paper
• Management of eosinophilic esophagitis from childhood to adulthood.

  2012cited by this paper
• Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions.

  2012cited by this paper
• Workshop report from the National Institutes of Health Taskforce on the Research Needs of Eosinophil-Associated Diseases (TREAD).

  2012cited by this paper
• Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial.

  2012influential reference
• Increased production of IL-5 and dominant Th2-type response in airways of Churg-Strauss syndrome patients.

  2012cited by this paper
• Heterogeneity of bronchitis in airway diseases in tertiary care clinical practice.

  2011cited by this paper
• An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis.

  2011influential reference
• MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function.

  2010cited by this paper
• Siglec‐8 on human eosinophils and mast cells, and Siglec‐F on murine eosinophils, are functionally related inhibitory receptors

  2009cited by this paper
• Treatment of patients with the hypereosinophilic syndrome with mepolizumab.

  2008influential reference
• The eosinophil.

  2006cited by this paper
• IL-5 synthesis is upregulated in human nasal polyp tissue.

  1997cited by this paper
• Characterization of the human IL-5 receptors on eosinophils.

  1991cited by this paper
• Clinical Reviews in Allergy and Immunology Eosinophilic Esophagitis: Updated Consensus Recommendations for Children and Adults

  year unknowncited by this paper

• Progress in research on predictors of adverse outcomes in patients with nasal inflammatory diseases

  2026cites this paper
• Peripheral blood eosinophils increase the risk on the occurrence of acute rhinosinusitis and transition to chronic rhinosinusitis: A Mendelian randomization study

  2026cites this paper
• Outcomes in eosinophilic esophagitis: current understanding and future directions

  2025cites this paper
• Long Short-term Memory-enhanced Haematology Signal Analysis for Dynamic Eosinophil Activation Profiling in Eosinophilic Otitis Media Diagnosis

  2025cites this paper
• Eosinophilic gastroduodenitis: a pediatric perspective

  2025cites this paper
• Paradoxical Use of Benralizumab in Reactive Hypereosinophilia from Toxocariasis and Tuberculosis Co-Infection—Case Report and Literature Review

  2025cites this paper
• Enhanced Siglec-8 and HLA-DR and Reduced CRTH2 Surface Expression, Highlight a Distinct Phenotypic Signature of Circulating Eosinophils in Atopic Dermatitis.

  2025cites this paper
• Refractory Atopic Dermatitis: A Case With a Missing Bridge Between Dermatology and Hematology

  2025cites this paper
• Mouse Models of Eosinophilic Esophagitis: Molecular and Translational Insights.

  2025cites this paper
• Mepolizumab in chronic rhinosinusitis with nasal polyps: Real life data in a multicentric Sicilian experience.

  2025cites this paper
• Advances in Biologic Therapies for Allergic Diseases: Current Trends, Emerging Agents, and Future Perspectives

  2025cites this paper
• Remarkable increase in Interleukin-5 receptor expression beyond tissue eosinophils in inflammatory bowel disease

  2025cites this paper
• Inhibition of EETosis with an anti-citrullinated histone antibody: a novel therapeutic approach for eosinophilic inflammatory disorders

  2025cites this paper
• Comparative Insights on IL-5 Targeting with Mepolizumab and Benralizumab: Enhancing EGPA Treatment Strategies

  2025cites this paper
• Efficacy and safety of benralizumab in eosinophilic granulomatosis with polyangiitis: A meta‐analysis of eight studies

  2024cites this paper
• Targeted inhibition of the IL5 axis for immune checkpoint inhibitors eosinophilic-induced adverse events

  2024cites this paper
• Fasciite à éosinophiles traitée par anti-IL5

  2024cites this paper
• Vectorized Human Antibody-Mediated Anti-Eosinophil Gene Therapy

  2024cites this paper
• Optimizing Siglec-8-Directed Immunotherapy for Eosinophilic and Mast Cell Disorders

  2024cites this paper
• Monocentric study of IL-5 monoclonal antibody induction therapy for eosinophilic granulomatosis with polyangiitis.

  2024cites this paper
• An update on Eosinophilic Esophagitis.

  2024cites this paper
• Moderate-High Blood Eosinophilia Is Associated with Increased Hospitalization and Other Asthma Comorbidities

  2024influential citation
• Monoclonal antibodies in idiopathic chronic eosinophilic pneumonia: a scoping review

  2024cites this paper
• Results of omalizumab treatment in chronic eosinophilic pneumonia: Real-life data

  2024cites this paper
• Clinical and Therapeutic Intervention of Hypereosinophilia in the Era of Molecular Diagnosis

  2024cites this paper
• Management of patients with chronic rhinosinusitis with nasal polyps (CRSwNP): Results from a survey among allergists and clinical immunologists of the North-west and Center Italy Inter-Regional Sections of SIAAIC and otorhinolaryngologists of National IAR

  2024cites this paper
• Effectiveness and safety profile of mepolizumab in chronic rhinosinusitis with nasal polyps: Real life data in a tertiary care.

  2024cites this paper
• scRNA-seq profiling of human granulocytes reveals expansion of developmentally flexible neutrophil precursors with mixed neutrophil and eosinophil properties in asthma.

  2024cites this paper
• Treatment-Refractory Eosinophilic Esophagitis Successfully Managed with benralizumab: A Case Presentation and literature review

  2024cites this paper
• Anti-IL-5 Pathway Agents in Eosinophilic-Associated Disorders Across the Lifespan

  2024cites this paper
• Single‐cell RNA sequencing of human blood eosinophils reveals plasticity and absence of canonical cell subsets

  2024cites this paper
• Idiopathic hypereosinophilic syndromes and rare dysimmune conditions associated with hyper-eosinophilia in practice: An innovative multidisciplinary approach

  2024cites this paper
• Biological drugs in the treatment of atopic diseases in pediatric patients

  2023cites this paper
• Acute Versus Chronic Eosinophilic Pneumonia: A Case Report

  2023cites this paper
• Review of Non-Eosinophilic Esophagitis-Eosinophilic Gastrointestinal Disease (Non-EoE-EGID) and a Case Series of Twenty-Eight Affected Patients

  2023cites this paper
• How should we interpret the data of eosinophilic esophagitis patients from an academic institution?

  2023cites this paper
• Renal Manifestations of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome: A Systematic Review of 71 Cases

  2023cites this paper
• Dupilumab in chronic rhinosinusitis with nasal polyposis: current status, challenges, and future perspectives

  2023cites this paper
• Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome

  2023cites this paper
• The Role of Benralizumab in Eosinophilic Immune Dysfunctions: A Case Report-Based Literature Review

  2023cites this paper
• Biologic Therapies Targeting Eosinophilic Gastrointestinal Diseases

  2023cites this paper
• Food Allergy and Eosinophilic Gastrointestinal Diseases-The Next 10 Years.

  2022cites this paper
• An allergist's approach to food poisoning.

  2022cites this paper