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Over the last two decades, we have witnessed great advancements in our understanding of the immunological pathways of asthma, leading to the development of targeted therapies, such as biologic drugs, that have radically and definitively changed the clinical outcomes of severe asthma. Despite the numerous therapeutic options available, ~4-10% of all people with asthma have severe or uncontrolled asthma, associated with an increased risk of developing chronic oral corticosteroid use, fixed airflow limitation, exacerbations, hospitalization and, finally, increased healthcare costs. The new concept of disease modification in asthma comes from the evolution of asthma management, which encompasses phenotyping patients with different inflammatory endotypes characterizing the disease, followed by the advent of more effective therapies capable of targeting the proximal factors of airway inflammation. This treat-to-target approach aims to achieve remission of the disease. Because the novel treatment paradigm for severe asthma with the advent of biologic therapies is no longer clinical control but rather clinical remission - a step closer to the concept of cure - a deeper and more accurate understanding of the critical causal mechanisms and endotypes of asthma is necessary to achieve the goal of clinical remission, which has the potential to generate real life-changing benefits for patients. This review aims to frame the evolution of the debated concept of clinical remission and provide clinicians with insights that may be helpful in achieving remission in the greatest number of patients., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2024/09/dic.2024-7-2-COI.pdf, (Copyright © 2024 Bosi A, Lombardi C, Caruso C, Cottini M, Baglivo I, Colantuono S, Menzella F.)

Background: Patients with severe asthma are often dependent on oral corticosteroids (OCS) and have frequent exacerbations. This article aims to report very long-term data of patients with severe eosinophilic asthma assessing asthma control, lung function, inhaled corticosteroid (ICS) dose reduction, and clinical and biological parameters of patients treated with mepolizumab., Methods: Four cases of adult patients with severe eosinophilic asthma who were treated for 60 months or more with mepolizumab 100 mg/4 weeks, leading to the stable discontinuation of OCS, are presented. ICS dose, OCS dose and withdrawal date, lung function, eosinophil count, fractional exhaled nitric oxide, and asthma control test were recorded as well as exacerbations in the 12 months before commencing mepolizumab and in the 12 months before the last follow-up visit., Results: Three of the patients were men, median age was 52.5 years (range 79-53), median length of asthma before mepolizumab start was 67.5 months (range 24-240), three had chronic rhinosinusitis without nasal polyposis and two were atopic. All had eosinophil counts >300 cells/μL at baseline. The median follow-up was 73.5 months (range 71-74), and OCS withdrawal from baseline occurred after a median of 13 months of mepolizumab treatment (range 12-39). A substantial reduction of ICS treatment was registered as well as improvement in asthma control test, fractional exhaled nitric oxide and functional parameters, and a significant reduction of exacerbations in the last 12 months before last visit was observed as compared to the 12 months before baseline (from a median of 4 (range 3-6) to 0; p =0.0286)., Conclusions: Mepolizumab could be a 'disease-modifying' agent, with high tolerability and a good efficacy profile in the long term., Competing Interests: Disclosure and potential conflicts of interest: CL has received lecture fee and advisory board fees from GlaxoSmithKline (GSK), AstraZeneca, Chiesi, Boehringer Ingelheim, Mylan, Mundipharma and Sanofi. FM participated in contracted research and clinical trials for Novartis and Sanofi, and has received lecture fees and advisory board fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma and Novartis. AB has received lecture fees and advisory board fees from GSK and Medscape. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2024/07/dic.2024-4-2-COI.pdf, (Copyright © 2024 Lombardi C, Menzella F, Berti A.)

Type 2 inflammation is a heterogeneous condition due to the complex activation of different immunological pathways. Rapid progress in research to evaluate the efficacy of biologics for chronic rhinosinusitis with nasal polyps and asthma has led to the availability of effective therapeutic options. These drugs are safe, but temporary iatrogenic hypereosinophilia may sometimes be associated with clinical symptoms or organ damage. Here, we describe a case of severe hypereosinophilia in a patient with chronic rhinosinusitis with nasal polyps and asthma treated with dupilumab and a subsequent therapeutic shift to mepolizumab that led to maintenance of symptom control and concomitant normalization of blood eosinophil count., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2024/05/dic.2024-3-5-COI.pdf, (Copyright © 2024 Munari S, Ciotti G, Cestaro W, Corsi L, Tonin S, Ballarin A, Floriani A, Dartora C, Bosi A, Tacconi M, Gialdini F, Gottardi M, Menzella F.)

At the end of December 2019, a novel coronavirus, the severe acute respiratory syndrome coronavirus 2, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China and then the entire world, forcing the World Health Organization to make the assessment that the coronavirus disease (COVID-19) can be characterized as a pandemic, the first ever caused by a coronavirus. To date, clinical evidence and guidelines based on reliable data and randomized clinical trials for the treatment of COVID-19 are lacking. In the absence of definitive management protocols, many treatments for COVID-19 are currently being evaluated and tested worldwide. Some of these options were soon abandoned due to ineffectiveness, while others showed promising results. The basic treatments are mainly represented by antiviral drugs, even if the evidence is not satisfactory. Among the antivirals, the most promising appears to be remdesivir. Corticosteroids and tocilizumab seem to guarantee positive results in selected patients so far, although the timing of starting therapy and the most appropriate therapeutic schemes remain to be clarified. Efficacy of the other drugs is still uncertain, and they are currently used as a cocktail of treatments in the absence of definitive guidelines. What will represent the real solution to the enormous problem taking place worldwide is the identification of a safe and effective vaccine, for which enormous efforts and investments are underway., Competing Interests: Disclosure and potential conflicts of interest: Francesco Menzella participated in contracted research and clinical trials for Novartis and Sanofi. He has received lecture fees and advisory board fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mundipharma, and Novartis. The other authors report no conflicts of interest in this work. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2020/05/dic.2020-4-6-COI.pdf, (Copyright © 2020 Menzella F, Biava M, Barbieri C, Livrieri F, Facciolongo N.)

Recent research in the field of bronchial asthma has mainly focused on eosinophilic disease phenotype. Several trials proved the efficacy and safety profile of eosinophils and interleukin (IL)-5 targeting molecules, currently approved for severe asthma and available on the market. They include mepolizumab and reslizumab, IL-5 blocking molecules, and benralizumab, targeting the IL-5 receptor and eliciting a NK cell-mediated antibody-dependent cellular cytotoxicity against eosinophils. Eosinophilic inflammation represents the common pathophysiological background of several conditions, providing the rationale for the use of the same biologics beyond asthma. Although with different evidence grade, from clinical trials to case reports, anti-IL-5 biologics have been investigated in eosinophilic granulomatosis with polyangitis, allergic bronchopulmonary aspergillosis, chronic eosinophilic pneumonia, nasal polyposis, hypereosinophilic syndrome, and eosinophilic esophagitis. However, non-negligible differences between asthma and other eosinophilic diseases, particularly in eosinophils homing (blood and/or tissues), target organs and thus clinical features, probably account for the different response to the same drug in different clinical conditions and highlights the need for tailoring the therapeutic approach by modulating the drug dose and/or by combination therapy with multiple drugs. The optimal safety and tolerability profile of anti-IL-5 drugs warrants further and larger experimental and real-life investigations, which are needed especially in the field of non-asthma eosinophilic diseases. This review aims at summarizing the rationale for the use of biologics in eosinophilic diseases and their mechanisms of action. The current efficacy and safety evidence about eosinophils and IL-5 targeting molecules in asthma and in eosinophilic conditions beyond bronchi is also discussed., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at https://www.drugsincontext.com/wp-content/uploads/2019/07/dic.212587-COI.pdf

Severe refractory asthma is characterized by a higher risk of asthma-related symptoms, morbidities, and exacerbations. This disease also determines much greater healthcare costs and deterioration in health-related quality of life (HR-QoL). Another concern, which is currently much discussed, is the high percentage of patients needing regular use of oral corticosteroids (OCS), which can lead to several systemic side effects. Airway eosinophilia is present in the majority of asthmatic patients, and elevated levels of blood and sputum eosinophils are associated with worse control of asthma. Regarding severe refractory eosinophilic asthma, interleukin-5 (IL-5) plays a fundamental role in the inflammatory response, due to the profound effect on eosinophils biology. The advent of the biological therapies provided an effective strategy, even if the increased number of molecules with different targets raised the challenge of choosing the right therapy and avoid overlapping. When considering severe refractory eosinophilic asthma and anti-IL-5 treatments, it is not easy to define which drug to choose between mepolizumab, reslizumab, and benralizumab. In this article, we carried out an indirect comparison among literature data, especially between OCS reduction studies (ZONDA-SIRIUS) and pivotal studies (SIROCCO-MENSA), evaluating whether the clinical efficacy and the steroid-sparing effect of benralizumab may represent an advantage over other compounds. This data could help the clinician in the decision process of treatment choice, within the different available therapeutic options for eosinophilic refractory severe asthma., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that there is no conflict of interest in preparing this article. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors are available for download at http://www.drugsincontext.com/wp-content/uploads/2019/03/dic.212580-COI.pdf

Patients with severe asthma have a greater risk of asthma-related symptoms, morbidities, and exacerbations. Moreover, healthcare costs of patients with severe refractory asthma are at least 80% higher than those with stable asthma, mainly because of a higher use of healthcare resources and chronic side effects of oral corticosteroids (OCS). The advent of new promising biologicals provides a unique therapeutic option that could achieve asthma control without OCS. However, the increasing number of available molecules poses a new challenge: the identification and selection of the most appropriate treatment. Thanks to a better understanding of the basic mechanisms of the disease and the use of predictive biomarkers, especially regarding the Th2-high endotype, it is now easier than before to tailor therapy and guide clinicians toward the most suitable therapeutic choice, thus reducing the number of uncontrolled patients and therapeutic failures. In this review, we will discuss the different biological options available for the treatment of severe refractory asthma, their mechanism of action, and the overlapping aspects of their usage in clinical practice. The availability of new molecules, specific for different molecular targets, is a key topic, especially when considering that the same targets are sometimes part of the same phenotype. The aim of this review is to help clarify these doubts, which may facilitate the clinical decision-making process and the achievement of the best possible outcomes., Competing Interests: Disclosure and potential conflicts of interest: Francesco Menzella participated in contracted research and clinical trials for Novartis and Sanofi, he has received lecture fees and advisory board fees from AstraZeneca, BoehringerIngelheim, Chiesi, GlaxoSmithKline, Mundipharma and Novartis. The other authors report no conflicts of interest in this work. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors are available for download at http://www.drugsincontext.com/wp-content/uploads/2018/11/dic.212561-COI.pdf