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Biomedicines
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Molecular Targets for Biological Therapies of Severe Asthma: Second Edition
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Molecular Targets for Biological Therapies of Severe Asthma: Second Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (28 February 2025) | Viewed by 2564

Special Issue Editor

Prof. Dr. Girolamo Pelaia

E-Mail Website
Guest Editor
Department of Health Sciences, University “Magna Græcia” of Catanzaro, 88100 Catanzaro, Italy
Interests: COPD; eosinophilic asthma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Asthma is a heterogeneous respiratory disease characterized by usually reversible bronchial obstruction, which is clinically expressed by different phenotypes driven by complex pathobiological mechanisms (endotypes). Within this context, in recent years, several molecular effectors and signalling pathways have emerged as suitable targets for biological therapies of severe asthma, refractory to standard treatments. Indeed, various therapeutic antibodies currently allow one to intercept at different levels the chain of pathogenic events leading to type 2 (T2) airway inflammation. In addition to pro-allergic immunoglobulin E (IgE), which chronologically represents the first molecule against which an anti-asthma monoclonal antibody (omalizumab) was developed, today, other targets are successfully being exploited by biological treatments of severe asthma. In particular, pro-eosinophilic interleukin 5 (IL-5) can be targeted by mepolizumab or reslizumab, whereas benralizumab is a selective blocker of IL-5 receptor. Moreover, dupilumab behaves as a dual receptor antagonist of pleiotropic interleukins 4 (IL-4) and 13 (IL-13). Besides these drugs, which are already available in medical practice, other biologics are under clinical development such as those targeting innate cytokines, including the alarmin thymic stromal lymphopoietin (TSLP), which plays a key role in the pathogenesis of type 2 asthma. Therefore, ongoing and future biological therapies are significantly changing severe asthma management on a global level. These new therapeutic options make it possible to implement phenotype/endotype-specific treatments, which are delineating personalized approaches precisely addressing the individual traits of asthma pathobiology. Such tailored strategies are thus allowing one to successfully target the immune-inflammatory responses underlying uncontrolled T2-high asthma.

Prof. Dr. Girolamo Pelaia
Guest Editor

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Keywords

  • IgE
  • IL-5
  • IL-4
  • IL-13
  • cytokine receptors
  • TSLP
  • monoclonal antibodies
  • omalizumab
  • mepolizumab
  • reslizumab
  • benralizumab
  • dupilumab
  • tezepelumab

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Published Papers (3 papers)

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Research

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16 pages, 1942 KiB  
Article
Pathway to Remission in Severe Asthma: Clinical Effectiveness and Key Predictors of Success with Benralizumab Therapy: A Real-Life Study
by Piotr Damiański, Adam Jerzy Białas, Marta Kołacińska-Flont, Anna Elgalal, Katarzyna Jarmakowska, Dorota Kierszniewska, Michał Panek, Grzegorz Kardas, Piotr Kuna and Maciej Kupczyk
Biomedicines 2025, 13(4), 887; https://doi.org/10.3390/biomedicines13040887 - 6 Apr 2025
Viewed by 377
Abstract
Introduction: Recent data indicate that approximately 10–20% of patients with severe asthma (SA) receiving benralizumab (BENRA) do not achieve the desired outcomes. Emerging evidence suggests that clinical remission (CRem) is possible with biologics, warranting investigations into predictive factors. Methods: In this retrospective, single-center [...] Read more.
Introduction: Recent data indicate that approximately 10–20% of patients with severe asthma (SA) receiving benralizumab (BENRA) do not achieve the desired outcomes. Emerging evidence suggests that clinical remission (CRem) is possible with biologics, warranting investigations into predictive factors. Methods: In this retrospective, single-center study, we analyzed 103 SA patients treated with BENRA for 12 months. CRem was defined as meeting four criteria: no exacerbations requiring oral corticosteroids (OCSs), discontinuation of chronic OCS therapy, improvement in FEV1 ≥100 mL, and an ACQ score < 1.5. Logistic regression identified predictors of remission. Results: After 12 months, 33% of patients achieved CRem, while 10% discontinued treatment due to lack of improvement. BENRA reduced the annual exacerbation rate from a median of 2 to 0 (p < 0.0001) and eliminated OCS use in 80% of patients. Lung function improved significantly, with a +13.5% predicted increase in FEV1 (p < 0.0001). Asthma control also improved, with ACQ scores decreasing from 3.2 to 1.5 (p < 0.0001) and mini-AQLQ scores increasing from 3.4 to 5.0 (p < 0.0001). Key predictors of remission included baseline eosinophil count ≥740 × 103/μL (OR = 3.91, p = 0.02), SA duration (OR = 0.90, p = 0.02), baseline quality of life (OR = 2.18, p = 0.04), and pre-treatment FEV1 (OR = 1.07, p = 0.005). The logistic regression model for these parameters showed strong predictive accuracy (AUC = 0.855, 95% CI 0.78–0.93). Importantly, the SA phase, rather than total asthma duration, was the critical factor, with each additional year reducing the odds of remission by ~10%. Conclusion: Clinical remission is a realistic goal in severe asthma, and early initiation of biologic therapy is vital for improving remission rates and long-term outcomes. Full article
(This article belongs to the Special Issue Molecular Targets for Biological Therapies of Severe Asthma: Second Edition)
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Review

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17 pages, 268 KiB  
Review
Severe Asthma and Active SARS-CoV-2 Infection: Insights into Biologics
by Sara Manti, Michela Leotta, Federica D’Amico, Simone Foti Randazzese, Giuseppe Fabio Parisi and Salvatore Leonardi
Biomedicines 2025, 13(3), 674; https://doi.org/10.3390/biomedicines13030674 - 10 Mar 2025
Viewed by 633
Abstract
Since the onset of the COVID-19 pandemic, managing asthma has become significantly more challenging. Both national and international guidelines emphasize the importance of continuing prescribed medications to maintain asthma control and prevent exacerbations. However, the emergence of SARS-CoV-2 infection has raised concerns about [...] Read more.
Since the onset of the COVID-19 pandemic, managing asthma has become significantly more challenging. Both national and international guidelines emphasize the importance of continuing prescribed medications to maintain asthma control and prevent exacerbations. However, the emergence of SARS-CoV-2 infection has raised concerns about the safety of biologic therapies during acute COVID-19 episodes, necessitating a careful and individualized approach to their use. Biologic therapies, including omalizumab, dupilumab, mepolizumab, reslizumab, benralizumab, and tezepelumab, which target specific pathways in severe asthma, have revolutionized asthma management by improving symptom control and reducing exacerbation rates. Despite their proven benefits, the intersection of biologic therapy and active SARS-CoV-2 infection has prompted questions regarding potential immunomodulatory effects and risks. This review aimed to synthesize the current literature on the antiviral effects and safety of biologic drugs in severe asthmatic patients with active SARS-CoV-2 infection, encompassing both pediatric and adult populations. Full article
(This article belongs to the Special Issue Molecular Targets for Biological Therapies of Severe Asthma: Second Edition)
14 pages, 1018 KiB  
Review
Connections and Unmet Needs: Severe Asthma Biologics and Osteoporosis
by Fabiana Furci, Marco Umberto Scaramozzino, Giuseppe Rocco Talesa and Corrado Pelaia
Biomedicines 2025, 13(1), 197; https://doi.org/10.3390/biomedicines13010197 - 15 Jan 2025
Cited by 1 | Viewed by 982
Abstract
Asthma is a chronic inflammatory disease with the main anti-inflammatory drugs for better disease control being steroids or corticosteroids. The use of steroids in asthma patients, in particular in uncontrolled asthma patients, is associated with an increased risk of osteoporosis and fragility fractures. [...] Read more.
Asthma is a chronic inflammatory disease with the main anti-inflammatory drugs for better disease control being steroids or corticosteroids. The use of steroids in asthma patients, in particular in uncontrolled asthma patients, is associated with an increased risk of osteoporosis and fragility fractures. A single oral corticosteroid course increases the risk of osteoporosis and the continual use of inhaled corticosteroids is correlated over time to an increased risk for both bone conditions. With the use of new, available biologic therapies for asthma, perhaps even anticipating the times of their use in therapeutic management, in the current guidelines and with targeted strategies of prevention it may be possible to improve asthma management, preventing some comorbidities, such as osteoporosis. Full article
(This article belongs to the Special Issue Molecular Targets for Biological Therapies of Severe Asthma: Second Edition)
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