Severe Asthma Remissions Induced by Biologics Targeting IL5/IL5r: Results from a Multicenter Real-Life Study.

Add-on biological therapy has proven to be effective in many patients with severe eosinophilic asthma. In this observational multicenter retrospective study, we report the results obtained with mepolizumab and benralizumab in severe asthmatics treated for 12 months in a real-life setting. In these patients, peripheral eosinophil levels, pulmonary function trends, exacerbation rates, systemic corticosteroid use, and symptom control were evaluated during the observation period, to understand which patients met all the criteria in order to be considered in disease remission. The percentage of remittent patients was 30.12% in the mepolizumab-treated subgroup, while in the benralizumab-treated subgroup, patients in complete disease remission were 40%, after 12 months. The results of this study confirm the efficacy of anti-IL-5 biologic drugs in the treatment of severe eosinophilic asthma in a real-life setting.

Long-Term Clinical and Sustained REMIssion in Severe Eosinophilic Asthma Treated With Mepolizumab: The REMI-M Study.

BACKGROUND: Biological therapies, such as mepolizumab, have transformed the treatment of severe eosinophilic asthma. Although mepolizumab's short-term effectiveness is established, there is limited evidence on its ability to achieve long-term clinical remission. OBJECTIVE: To evaluate the long-term effectiveness and safety of mepolizumab, explore its potential to induce clinical and sustained remission, and identify baseline factors associated with the likelihood of achieving remission over 24 months. METHODS: The REMIssion in Severe Eosinophilic Asthma Treated with Mepolizumab (REMI-M) is a retrospective, real-world, multicenter study that analyzed 303 patients with severe eosinophilic asthma who received mepolizumab. Clinical, demographic, and safety data were collected at baseline, 3, 6, 12, and 24 months. The most commonly used definitions of clinical remission, which included no exacerbations, no oral corticosteroid (OCS) use, and good asthma control with or without assessment of lung function parameters, were assessed. Sustained remission was defined as reaching clinical remission at 12 months and maintaining it until the end of the 24-month period. RESULTS: Clinical remission rates ranged from 28.6% to 43.2% after 12 months and from 26.8% to 52.9% after 24 months based on the different remission definitions. The proportion of patients achieving sustained remission varied between 14.6% and 29%. Factors associated with the likelihood of achieving clinical remission included the presence of aspirin-exacerbated respiratory disease, better lung function at baseline, male sex, absence of anxiety/depression, gastroesophageal reflux disease, bronchiectasis, and reduced OCS consumption. Adverse events were infrequent. CONCLUSIONS: This study demonstrates the real-world effectiveness of mepolizumab in achieving clinical remission and sustained remission in severe eosinophilic asthma over 24 months. The identification of distinct factors associated with the likelihood of achieving clinical remission emphasizes the importance of comprehensive management of comorbidities and timely identification of patients who may benefit from biologics.

Effectiveness of Benralizumab in OCS-Dependent Severe Asthma: The Impact of 2 Years of Therapy in a Real-Life Setting.

Patients with severe OCS-dependent asthma can be considered a subgroup of asthma patients with severe disease and great risk of complications, related to chronic OCS use. The introduction of biological drugs has represented a turning point in the therapeutic strategy for severe asthma, offering a valid alternative to OCS. Benralizumab, like other anti-IL-5 agents, has been shown to reduce exacerbations and OCS intake/dosage and improve symptom control and lung function. While these findings have also been confirmed in real-life studies, data on long-term efficacy are still limited. METHODS: In this retrospective study, we evaluated the effects of 2 years of treatment with benralizumab on 44 patients with OCS-dependent severe asthma by analyzing clinical, biological and functional data. RESULTS: After 2 years of benralizumab, 59.4% discontinued OCS and patients who continued to use OCS had their mean dose reduced by approximately 85% from baseline. Meanwhile, 85% of patients had their asthma well-controlled (ACT score > 20) and had no exacerbations, and 41.6% had normal lung function. CONCLUSIONS: Our findings support the long-term effectiveness of benralizumab in severe OCS-dependent asthma in a real-life setting, suggesting potential reductive effects on costs and complications such as adverse pharmacological events.

Eosinophilic inflammation: An Appealing Target for Pharmacologic Treatments in Severe Asthma.

Severe asthma is characterized by different endotypes driven by complex pathologic mechanisms. In most patients with both allergic and non-allergic asthma, predominant eosinophilic airway inflammation is present. Given the central role of eosinophilic inflammation in the pathophysiology of most cases of severe asthma and considering that severe eosinophilic asthmatic patients respond partially or poorly to corticosteroids, in recent years, research has focused on the development of targeted anti-eosinophil biological therapies; this review will focus on the unique and particular biology of the eosinophil, as well as on the current knowledge about the pathobiology of eosinophilic inflammation in asthmatic airways. Finally, current and prospective anti-eosinophil therapeutic strategies will be discussed, examining the reason why eosinophilic inflammation represents an appealing target for the pharmacological treatment of patients with severe asthma.