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Background: Dupilumab, a human monoclonal antibody, blocks the shared receptor component for interleukins‐4/13, key and central drivers of type 2 inflammation. The TRAVERSE (NCT02134028) open‐label extension study demonstrated the long‐term safety and efficacy of dupilumab in patients ≥12 years who completed a previous dupilumab asthma study. The safety profile was consistent with that observed in the parent studies. Here, we assess whether dupilumab sustains long‐term efficacy in patients regardless of inhaled corticosteroid (ICS) dose at parent study baseline (PSBL). Methods: Patients from phase 2b (NCT01854047) or phase 3 (QUEST; NCT02414854) studies receiving high‐ or medium‐dose ICS at PSBL and enrolled in TRAVERSE were included. We analyzed unadjusted annualized severe exacerbation rates, change from PSBL in pre‐bronchodilator (BD) forced expiratory volume in 1 second (FEV1), 5‐item asthma control questionnaire, and type 2 biomarkers in patients with type 2 asthma at baseline (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide [FeNO] ≥25 ppb), and subgroups defined by baseline blood eosinophils or FeNO. Results: Of patients with type 2 asthma (n = 1666), 891 (53.5%) were receiving high‐dose ICS at PSBL. In this subgroup, unadjusted exacerbation rates for dupilumab versus placebo were 0.517 versus 1.883 (phase 2b) and 0.571 versus 1.300 (QUEST) over the parent study (52 weeks) and remained low throughout TRAVERSE (0.313–0.494). Improvements in pre‐BD FEV1 were sustained throughout TRAVERSE. Similar clinical efficacy was observed among patients receiving medium‐dose ICS at PSBL and biomarker subgroups. Conclusions: Dupilumab showed sustained efficacy for up to 3 years in patients with uncontrolled, moderate‐to‐severe type 2 asthma on high‐ or medium‐dose ICS. [ABSTRACT FROM AUTHOR]

Background: Severe asthma exacerbations increase the risk of accelerated lung function decline. This analysis examined the effect of dupilumab on forced expiratory volume in 1 s (FEV1) in patients with moderate‐to‐severe asthma and elevated type 2 biomarkers from phase 3 LIBERTY ASTHMA QUEST (NCT02414854). Methods: Changes from baseline in pre‐ and post‐bronchodilator (BD) FEV1 and 5‐item Asthma Control Questionnaire (ACQ‐5) scores were assessed in patients with elevated type 2 biomarkers at baseline (type 2–150/25: eosinophils ≥150 cells/μl and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb; type 2–300/25: eosinophils ≥300 cells/μl and/or FeNO ≥25 ppb), stratified as exacerbators (≥1 severe exacerbation during the study) or non‐exacerbators. Results: In exacerbators and non‐exacerbators, dupilumab increased pre‐BD FEV1 by Week 2 vs placebo; differences were maintained to Week 52 (type 2–150/25: LS mean difference (LSMD) vs placebo: 0.17 L (95% CI: 0.10–0.24) and 0.17 L (0.12–0.23); type 2–300/25: 0.22 L (0.13–0.30) and 0.21 L (0.15–0.28)), in exacerbators and non‐exacerbators, respectively (p <.0001). Similar trends were seen for post‐BD FEV1. Dupilumab vs placebo also showed significantly greater improvements in post‐BD FEV1 0–42 days after first severe exacerbation in type 2–150/25 (LSMD vs placebo: 0.13 L [0.06–0.20]; p =.006) and type 2–300/25 (0.14 L [0.06–0.22]; p =.001) patients. ACQ‐5 improvements were greater with dupilumab vs placebo in both groups. Conclusion: Dupilumab treatment led to improvements in lung function independent of exacerbations and appeared to reduce the impact of exacerbations on lung function in patients who experienced a severe exacerbation during the study. [ABSTRACT FROM AUTHOR]

A significant number of patients with asthma remain uncontrolled despite treatment with inhaled corticosteroids (ICS) and long‐acting β2 adrenergic bronchodilators (LABA). The addition of long‐acting antimuscarinic agents (LAMA) can improve the management of asthma in these patients. Recently, three novel triple therapy (ICS/LABA/LAMA) formulations in a single‐inhaler device (SITT) have been investigated in patients with uncontrolled asthma despite ICS/LABA treatment. Here, we review systematically the evidence available to date in relation to SITT in patients with uncontrolled asthma despite ICS‐LABA treatment and conclude that SITT is a safe and effective therapeutic alternative in these patients. We also discuss how to position this new therapeutic alternative in their practical clinical management as well as the opportunities and challenges that it may generate for patients, physicians, and payers. [ABSTRACT FROM AUTHOR]

Effective treatment of inflammatory diseases is often challenging owing to their heterogeneous pathophysiology. Understanding of the underlying disease mechanisms is improving and it is now clear that eosinophils play a complex pathophysiological role in a broad range of type 2 inflammatory diseases. Standard of care for these conditions often still includes oral corticosteroids (OCS) and/or cytotoxic immune therapies, which are associated with debilitating side effects. Selective, biological eosinophil‐reducing agents provide treatment options that improve clinical symptoms associated with eosinophilic inflammation and reduce OCS use. Mepolizumab is a humanized monoclonal antibody that binds to and neutralizes interleukin‐5, the major cytokine involved in eosinophil proliferation, activation, and survival. Mepolizumab is approved for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Additionally, the efficacy of add‐on mepolizumab has been observed in patients with severe chronic rhinosinusitis with nasal polyposis and chronic obstructive pulmonary disease with an eosinophilic phenotype. Here, we review the development, approval, and real‐world effectiveness of mepolizumab for the treatment of patients with severe eosinophilic asthma, from the DREAM to REALITI‐A studies, and describe how knowledge from this journey extended to the use of mepolizumab and other biologics across a broad spectrum of eosinophilic diseases. [ABSTRACT FROM AUTHOR]

Rescue ICS/SABA (under development as a single inhaler8 with favourable results of the pivotal studies just announced)9 would address many of these limitations as it could be used to overcome the current barriers to the ICQ generalizability at all treatment steps, irrespective of the type of background maintenance asthma therapy (if any). Anti-inflammatory treatment is the pharmacological cornerstone of asthma management. [Extracted from the article]

All centres have been contacted and inquired to report confirmed or highly suspect cases of COVID-19 (ie, patients with symptoms, laboratory findings and lung imaging typical of COVID-19 but without access to nasopharyngeal or oropharyngeal swab specimens because of clinical contingencies/emergency) among their cohorts of severe asthma. The total number of patients with severe asthma for each single region is reported under the each region name gl Nine (34.6%) infected patients experienced worsening of asthma during the COVID-19 symptomatic period; four of them needed a short course of oral corticosteroids for controlling asthma exacerbation symptoms. This is in line with the under-reported asthma cases among patients with COVID-19 patients.3 The COVID-19 related mortality rate in our cohort of patients was 7.7%, lower than in the general population (14.5% in Italy1). Since the end of February 2020, Italy, first non-Asian Country, has reported an ever increasing number of COronaVIrus Disease 19 (COVID-19) patients, which has reached over 200 000 confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected subjects, resulting in more than 34 000 deaths (data updated to June 19th, 20201). [Extracted from the article]

Background: Dupilumab blocks the shared receptor component for interleukin (IL)‐4/IL‐13, key drivers of type 2 inflammation. In phase 2b (NCT01854047) and phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add‐on dupilumab 200/300 mg every 2 weeks (q2w) reduced severe exacerbations, improved prebronchodilator (pre‐BD) forced expiratory volume in 1 second (FEV1) and quality of life measures, and it was generally well tolerated in patients with uncontrolled, persistent (phase 2b), or moderate‐to‐severe (phase 3) asthma. Methods: In patients on high‐dose inhaled corticosteroids (ICS) with type 2‐high asthma (subgroups including baseline blood eosinophils ≥150/300 cells/µL and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb), annualized severe exacerbation rates over the treatment period, changes from baseline in pre‐BD FEV1 and asthma control (5‐item asthma control questionnaire [ACQ‐5]) were analyzed. Results: In high‐dose ICS type 2‐high subgroups, dupilumab 200/300 mg q2w vs placebo in the phase 2b (24 weeks) and phase 3 (52 weeks) studies significantly reduced severe exacerbations by 55%‐69%/57%‐60% (all P<.05) and 53%‐69%/48%‐66% (all P <.001), respectively, except in patients with ≥ 300 eosinophils/µL in phase 2b study (24%/50% (P =.52/0.15). Across subgroups, pre‐BD FEV1 improved by 0.18‐0.22 L/0.19‐0.24 L (all P <.05) and 0.23‐0.36 L/0.15‐0.25 L (all P <.01) and ACQ‐5 scores were reduced by 0.46‐0.55/0.47‐0.85 (all P <.05) and 0.38‐0.50/0.24‐0.30 (all P <.05), respectively, except dupilumab 200 mg q2w in phase 2b in patients with FeNO ≥ 25 ppb (0.41; P =.09). Dupilumab was also effective in patients taking medium‐dose ICS. Conclusion: Dupilumab significantly reduced severe exacerbations and improved lung function and asthma control in patients with type 2‐high asthma on high‐dose ICS at baseline. [ABSTRACT FROM AUTHOR]

Moreover, Chhiba et al did not found significant difference in risk of hospitalization or mortality due to COVID-19 in patients with or without asthma, even after adjusting for covariates or the level of asthma treatment. Are severe asthma patients at higher risk of developing severe outcomes from COVID-19? REFERENCES 1 Kow CS, Capstick T, Hasan SS. Are severe asthma patients at higher risk of developing severe outcomes from COVID-19?. [Extracted from the article]

Severe asthma imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of severe asthma, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include selection of a certain biological (as they all target overlapping disease phenotypes), the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based) and its cost-effectiveness. The EAACI Guidelines on the use of biologicals in severe asthma follow the GRADE approach in formulating recommendations for each biological and each outcome. In addition, a management algorithm for the use of biologicals in the clinic is proposed, together with future approaches and research priorities., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)