Background: Mepolizumab and benralizumab are monoclonal antibodies directed against anti-IL-5 and anti-IL5R, respectively, and their use reduces the exacerbation rate and maintains oral corticosteroid requirements in severe eosinophilic asthma. Previous studies have tested the therapeutic switch between two biologics with excellent results, further demonstrating the heterogeneity of asthmatic disease and the complexity of the therapeutic choice. It remains unclear if such patients may improve following a switch from mepolizumab to benralizumab. Aims: Within a multicentre real-life setting, we decided to evaluate the potential effectiveness of a therapeutic switch to benralizumab in patients with severe eosinophilic asthma initially treated with mepolizumab, who experienced sub-optimal responses. The secondary aim was to identify the clinical factors associated with a better response to benralizumab. Methods: We retrospectively assessed patients with severe eosinophilic asthma treated at six Italian specialist centres, who were switched from mepolizumab to benralizumab following a sub-optimal response, defined as a partial or total lack of clinical remission (i.e., frequent severe exacerbations and/or poorly controlled symptoms and/or higher OCS daily use in patients with a poor or moderate response in the global evaluation of treatment effectiveness scale), after at least 12 months of treatment. Results: Twenty-five patients were included in the analysis (mean age 56.76 ± 11.97 years, 65% female). At 6 months of treatment with benralizumab, the ACT score was significantly higher than the ACT score with mepolizumab (20.24 ± 3.38 vs. 16.77 ± 3.48, p < 0.0001); the mean number of daily SABA inhalations was significantly lower after 6 months and 12 months of treatment with benralizumab than that after treatment with mepolizumab; OCS intake and the prednisone median dosage at 6 months of treatment with benralizumab were significantly lower than those with mepolizumab. Benralizumab treatment resulted in a marked improvement in asthma control, suppressed blood eosinophil levels and reduction in the number of exacerbations in the subgroup of patients with severe eosinophilic asthma and nasal polyposis. Conclusions: Patients diagnosed with severe eosinophilic asthma who experience a partial response to mepolizumab could benefit from switching to benralizumab, and even more those who have nasal polyposis.

Background: Omalizumab is the best treatment for patients with chronic spontaneous urticaria (CSU). Machine learning (ML) approaches can be used to predict response to therapy and the effectiveness of a treatment. No studies are available on the use of ML techniques to predict the response to Omalizumab in CSU. Methods: Data from 132 CSU outpatients were analyzed. Urticaria Activity Score over 7 days (UAS7) and treatment efficacy were assessed. Clinical and demographic characteristics were used for training and validating ML models to predict the response to treatment. Two methodologies were used to label the data based on the response to treatment (UAS7 ≥ 6): (A) at 1, 3 and 5 months; (B) classifying the patients as early responders (ER), late responders (LR) or non-responders (NR) (ER: UAS 7 ≥ 6 at first month, LR: UAS 7 ≥ 6 at third month, NR: if none of the previous conditions occurred). Results: ER were predominantly characterized by hypertension, while LR mainly suffered from asthma and hypothyroidism. A slight positive correlation (R² = 0.21) was found between total IgE levels and UAS7 at 1 month. Variable Importance Analysis (VIA) reported D-dimer and C-reactive proteins as the key blood tests for the performance of learning techniques. Using methodology (A), SVM (specificity of 0.81) and k-NN (sensitivity of 0.8) are the best models to predict LR at the third month. Conclusion: k-NN plus the SVM model could be used to identify the response to treatment. D-dimer and C-reactive proteins have greater predictive power in training ML models.

Background: Biological therapies, such as mepolizumab, have transformed the treatment of severe eosinophilic asthma. While 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 REMI-M is a retrospective, real-world, multicenter study that analyzed 303 severe eosinophilic asthma patients 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 corticosteroids (OCS) use, and good asthma control with or without assessment of lung function parameters, were adopted. 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% to 29%. Factors associated with the likelihood of achieving clinical remission included the presence of aspirin-exacerbated respiratory disease, better lung function, male sex, absence of anxiety/depression, gastro-esophageal 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. HIGHLIGHTS BOX: What is already known about this topic?: Mepolizumab, an anti-IL-5 monoclonal antibody, has been shown to induce clinical remission after 12 months of treatment. However, long-term evidence remains limited. What does this article add to our knowledge?: The REMI-M study investigated the effectiveness of mepolizumab in achieving clinical and sustained remission over 24 months. How does this study impact current management guidelines?: Mepolizumab can elicit long-term clinical and sustained remission in a conspicuous proportion of patients with severe eosinophilic asthma, supporting its role as a possible disease-modifying agent. Management of comorbidities and timely identification of patients who may benefit from biological treatment are crucial for optimizing long-term outcomes.