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Enabling reductions in maintenance ICS/LABA therapy using as needed anti-inflammatory reliever for patients with severe eosinophilic asthma controlled with benralizumab: SHAMAL phase IV clinical study. Finally, although all patients were prescribed the highest licensed dose of their ICS baseline, we did not record which patients received which ICS, and thus cannot comment on whether choice of ICS could have influenced outcomes. Asthma is a common inflammatory airways disorder for which inhaled corticosteroids (ICS) are the cornerstone of treatment.1 Whilst the majority of patients can be successfully managed by optimization of ICS therapy, some require frequent courses of systemic corticosteroids or indeed maintenance oral corticosteroids (mOCS), leading to significant OCS-related morbidity.2 Biologic agents targeting type-2 inflammatory pathways facilitate reduced OCS exposure in the treatment of severe eosinophilic asthma (SEA). [Extracted from the article]

Mepolizumab and benralizumab are monoclonal antibodies (mAb) directed against anti-IL-5 and anti-IL5R, respectively, and their use reduces exacerbation rate and maintenance oral corticosteroid (mOCS) requirements in severe eosinophilic asthma (SEA).1-4 We recently reported that a minority of patients treated with mepolizumab experience a sub-optimal response including those with a higher baseline ACQ and mOCS requirement.1 It remains unclear if such patients may improve following a switch to benralizumab which provides a more complete depletion of airway eosinophils.5,6 We retrospectively assessed patients with SEA treated at our specialist centre, who were switched from mepolizumab to benralizumab following a sub-optimal response defined as failing to achieve either: >=50% reduction in mOCS dose; >=50% reduction in annualized exacerbation rate (AER);and an ongoing requirement of >=7.5 mg prednisolone/day or an AER of >=3. In essence this notion is no different from the reality that within severe eosinophilic asthma, some patients require low dose maintenance oral steroids, whilst others require a higher dose to adequately suppress their airways inflammation. Our results appear to support this possibility and suggest that a more profound depletion in airway eosinophilia as occurs with benralizumab may offer additional clinical benefit in patients with particularly severe eosinophilic asthma. Role of local eosinophilopoietic processes in the development of airway eosinophilia in prednisone-dependent severe asthma. [Extracted from the article]

Background: Benralizumab is an IL5-receptor monoclonal antibody licensed for the treatment of severe eosinophilic asthma (SEA). It has demonstrated efficacy in clinical trials in reducing asthma exacerbation rates and maintenance oral corticosteroids (mOCSs).Research Question: What is the real-world effectiveness of benralizumab and what baseline characteristics are associated with response to therapy?Study Design and Methods: We assessed outcomes in all SEA patients who began benralizumab treatment at our specialist center. At each dosing visit, exacerbation history, mOCS dose, spirometry, and Asthma Control Questionnaire (ACQ6) and Mini-Asthma Quality of Life Questionnaire (mAQLQ) scores were recorded. Response to treatment was defined as a reduction of ≥ 50% in annualized exacerbation rate (AER) or in mOCS dose after 48 weeks of treatment. Super response was defined as zero exacerbations and no mOCSs for asthma.Results: One hundred thirty patients were included in the analysis. At 48 weeks, a 72.8% reduction in AER was noted, from 4.92 ± 3.35 per year in the year preceding biologic treatment to 1.34 ± 1.71 per year (P < .001), including 57 patients (43.8%) who were exacerbation-free with benralizumab. In those receiving mOCSs (n = 74 [56.9%]), the median daily prednisolone dose fell from 10 mg (interquartile range, 5-20 mg) to 0 mg (interquartile range, 0-5 mg; P < .001), and 38 of 74 patients (51.4%) were able to discontinue mOCS therapy. Clinically and statistically significant improvements were found in ACQ6 scores, mAQLQ scores, and FEV1. Overall, 51 patients (39%) met the super responder definition and 112 patients (86%) met the responder definition. The optimal regression model of super responders vs other responders included baseline characteristics associated with a strongly eosinophilic phenotype and less severe disease. Eighteen patients (13.8%) were nonresponders to benralizumab. Evidence of chronic airway infection was observed in 6 of 18 patients, and an increase in the blood eosinophil count consistent with the development of anti-drug antibodies was observed in 5 of 18 patients.Interpretation: In a large real-world SEA cohort, benralizumab led to significant improvements in all clinical outcome measures. A lack of response was seen in a minority of patients and should be a focus for future investigation. [ABSTRACT FROM AUTHOR]

Background: Mepolizumab was the first licensed anti-IL5 monoclonal antibody for severe eosinophilic asthma (SEA). To date there are few data to confirm its efficacy in the real-world setting or assessment of baseline characteristics associated with response.Research Question: How do patients with severe eosinophilic asthma respond to mepolizumab in the real world setting and which characteristics are associated with a super-response to this therapy?Study Design and Methods: We conducted a retrospective review of all patients who received at least 16 weeks of treatment with mepolizumab (100 mg subcutaneously) for SEA at our regional asthma center in the United Kingdom. Clinical data were collected at each 4-week visit. At 16, 24, and 52 weeks, patients were classified as "responders" or "nonresponders." A response was defined as ≥50% reduction in exacerbations; for patients whose condition requires maintenance oral corticosteroids (mOCS), a response was defined as ≥50% reduction in prednisolone dose. Super responders were defined as exacerbation-free and off mOCS at one year.Results: Ninety-nine patients were included in the analysis. Asthma exacerbations decreased from a baseline of 4.04 ± 2.57 to 1.86 ± 2.17 per year at one year (54% reduction; P < .001). Sixty-eight patients were receiving mOCS at the time of commencing mepolizumab. By one year, the daily median dose fell from 10 mg (interquartile range, 10 to 15) to 0 mg (interquartile range, 0 to 10; P < .001). Fifty-seven percent of them were able to discontinue mOCS; 72.7% (95% CI, 63.0 to 80.7) of the patients were classified as responders, and 28.3% (95% CI, 20.2 to 38.0) of the patients were classified as super responders. Baseline characteristics associated with responder and super responder status included the presence of nasal polyposis (P = .012), lower baseline Asthma Control Questionnaire 6 (P = .006), a lower BMI (P = .014), and, in those patients receiving mOCS, a significantly lower prednisolone dose at baseline (P = .005). At 16 weeks, the one-year responder status was correctly identified in 80.8% patients; by 24 weeks, this status rose to 92.9%.Interpretation: In a real-world SEA cohort, treatment with mepolizumab reduced exacerbation frequency and mOCS requirements. Nasal polyposis, a lower BMI, and a lower maintenance prednisolone requirement at baseline were associated with better outcomes. Twelve-month response was identifiable in >90% of patients by week 24. [ABSTRACT FROM AUTHOR]

Background: Chronic cough in interstitial lung disease (ILD) causes significant impairment in quality of life. Effective treatment approaches are needed for cough associated with ILD.Methods: This systematic review asked: Is there evidence of clinically relevant treatment effects for therapies for cough in ILD? Studies of adults aged > 18 years with a chronic cough ≥ 8 weeks' duration were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using CHEST guideline methodology.Results: Eight randomized controlled trials and two case series (≥ 10 patients) were included that reported data on patients with idiopathic pulmonary fibrosis, sarcoidosis, and scleroderma-related ILD who received a variety of interventions. Study quality was high in all eight randomized controlled trials. Inhaled corticosteroids were not supported for cough associated with sarcoidosis. Cyclophosphamide and mycophenolate were not supported for solely treating cough associated with scleroderma-associated ILD. A recommendation for thalidomide to treat cough associated with idiopathic pulmonary fibrosis did not pass the panel vote. In view of the paucity of antitussive treatment options for refractory cough in ILD, the guideline panel suggested that the CHEST unexplained chronic cough guideline be followed by considering options such as the neuromodulator gabapentin and speech pathology management. Opiates were also suggested for patients with cough refractory to alternative therapies.Conclusions: The evidence supporting the management of chronic cough in ILD is limited. This guideline presents suggestions for managing and treating cough on the best available evidence, but future research is clearly needed. [ABSTRACT FROM AUTHOR]

Cough is one of the most common reasons that patients seek medical attention. Cough guidelines from numerous countries and societies are available to assist the clinician to investigate and manage patients with cough. We review some of the recent progress in the field of cough that may lead to revision of these guidelines. In adults with chronic cough, new causes such as obstructive sleep apnoea have been identified. A new terminology, cough hypersensitivity syndrome (CHS), has been proposed for patients with chronic cough, which emphasises cough reflex hypersensitivity as a key feature. New therapeutic options are now available, particularly for patients with refractory or idiopathic chronic cough, which include gabapentin, speech pathology management and morphine. There has been great progress in the assessment of cough with the development of validated quality of life questionnaires and cough frequency monitoring tools. In children, common aetiologies differ from adults and those managed according to guidelines have better outcomes compared to usual care. New diagnostic entities such as protracted bacterial bronchitis have been described. Paediatric-specific cough assessment tools such as the Parent/Child Quality of Life Questionnaire will help improve the assessment of patients. Further research is necessary to improve the evidence base for future clinical guideline recommendations. Guidelines in future should also aim to reach a wider audience that includes primary care physicians, non-specialists and patients. [ABSTRACT FROM AUTHOR]