What bothers severe asthma patients most? A paired patient-clinician study across seven European countries

Introduction: Severe asthma is a complex, multi-dimensional disease. Optimal treatment adherence and outcomes require shared decision-making, rooted in mutual understanding between patient and clinician. This study used a novel, patient-centred approach to examine the most bothersome aspects of severe asthma to patients, as seen from both perspectives in asthma registries. Methods: Across seven countries, 126 patients with severe asthma completed an open-ended survey regarding most bothersome aspect(s) of their asthma. Patients’ responses were linked with their treating clinician who also completed free-text survey about each patient's most bothersome aspect(s). Responses were coded using content analysis, and patient and clinician responses were compared. Finally, asthma registries that are part of the SHARP Clinical Research Collaboration were examined to see the extent to which they reflected the most bothersome aspects reported by patients. Results: Eighty-eight codes and 10 themes were identified. Clinicians were more focused on direct physical symptoms and were less focused on ‘holistic’ aspects such as the effort required to self-manage their disease. Clinicians accurately identified a most bothersome symptom for 29% of patients. Agreement was particularly low in younger patients and those infrequently using oral corticosteroids. In asthma registries, patient aspects were predominantly represented in questionnaires. Conclusions: Results demonstrated different perspectives and priorities between patients and clinicians, with clinicians more focused on physical aspects. These differences must be considered when treating individual patients, and within multi-disciplinary treatment teams. The use of questionnaires that include multi-faceted aspects of disease may result in improved asthma research

The emergence of new biologics for severe asthma

Patients with severe asthma experience severe symptoms and frequent exacerbations despite intensive treatment with inhaled and oral glucocorticoids. Biologics for severe asthma aim to reduce asthma-related and glucocorticoid-induced morbidity. Recently, new biologics targeting interleukin (IL)-5, IL-5 receptor and IL-4/IL-13, which are all cytokines involved in so-called type 2 airway inflammation, were approved for severe asthma. They show a reduction in exacerbation rate and an oral glucocorticoid-sparing effect. Studies with upstream biologics targeting alarmin cytokines such as thymic stromal lymphopoietin (TSLP) and IL-33 are underway, and newly designed bispecific antibodies targeting more than one pathway are in early phases of development. Such pathway-targeted add-on treatments will soon become standard of care for all patients with severe asthma

Long-Term Therapy Response to Anti–IL-5 Biologics in Severe Asthma—A Real-Life Evaluation

Background: Patients with severe eosinophilic asthma show different responses to various anti–IL-5 biologics, ranging from super response to nonresponse. Residual disease manifestations observed in partial responders may prompt physicians to switch between biologics. More data on response, switches, and residual disease manifestations are needed to improve personalized treatment. Objective: To assess (1) prevalences and predictors of super, partial, and nonresponders to long-term anti–IL-5 treatment, (2) frequency and reasons for switches between anti–IL-5 biologics, and (3) nature of residual disease manifestations. Methods: In this 2-year follow-up study, patients with severe asthma were included who initiated an anti–IL-5 biologic (mepolizumab, reslizumab, benralizumab) (n = 114). Patient characteristics (clinical, functional, inflammatory) and comorbidities were collected at baseline and 2-year follow-up. “Super responders” showed no residual disease manifestations at 2-year follow-up, “partial responders” experienced residual disease manifestations, and “nonresponders” discontinued anti–IL-5 treatment after less than 2 years because of clinical worsening. Results: After 2-year anti–IL-5 treatment, 14% of patients were super responders, 69% partial responders, and 11% nonresponders. Super response was predicted by shorter asthma duration and higher FEV1, and tended to be associated with adult-onset asthma, absence of nasal polyps, and lower body mass index. Switches between anti–IL-5 biologics occurred frequently (41%). After 2-year treatment, most common residual disease manifestations included impaired lung function (59%), uncontrolled sinonasal disease (58%), and uncontrolled asthma symptoms (48%). Conclusions: After 2 years of anti–IL-5 treatment, a favorable response was found in 83% of patients with severe asthma, including a super response in 14%. Most partial responders show impaired lung function or uncontrolled sinonasal disease, causing physicians to switch between biologics

Poor outcome of SARS-CoV-2 infection in patients with severe asthma on biologic therapy

Background: It is unclear whether asthma and asthma medications increase or decrease the risk of severe COVID-19, and this is particularly true for patients with severe asthma receiving biologics. Objectives: The aim of this study was to assess incidence and disease course of COVID-19 in patients with severe asthma on biologic therapy (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab), as compared with COVID-19 data from the general Dutch population. Methods: COVID-19 cases were identified through a prospective ongoing survey between March 17 and April 30, 2020 among all severe asthma specialists from 15 hospitals of the Dutch Severe Asthma Registry RAPSODI. From these cases, data was collected on patient characteristics, including co-morbidities, COVID-19 disease progression and asthma exacerbations. Findings were then compared with COVID-19 data from the general Dutch population. Results: Of 634 severe asthma patients who received biologic therapy in RAPSODI, 9 (1.4%) were diagnosed with COVID-19. Seven patients (1.1%) required hospitalization for oxygen therapy, of which 5 were admitted to the intensive care for intubation and mechanical ventilation. One patient died (0.16%). All intubated patients had ≥1 co-morbidities. Odds (95%CI) for COVID-19 related hospitalization and intubations were 14 (6.6–29.5) and 41 (16.9–98.5) times higher, respectively, compared to the Dutch population. One patient presented with an asthma exacerbation. Conclusion: Patients with severe asthma using biologic therapy showed to have a more severe course of COVID-19 compared to the general population. This may be due to co-morbidities, the severity of asthmatic airway inflammation, the use of biologics, or a combination of these

What bothers severe asthma patients most?: a paired patient-clinician study across seven European countries

Introduction: severe asthma is a complex, multidimensional disease. Optimal treatment, adherence and outcomes require shared decision-making, rooted in mutual understanding between patient and clinician. This study used a novel, patient-centred approach to examine the most bothersome aspects of severe asthma to patients, as seen from both perspectives in asthma registries.Methods: across seven countries, 126 patients with severe asthma completed an open-ended survey regarding most the bothersome aspect(s) of their asthma. Patients’ responses were linked with their treating clinician who also completed a free-text survey about each patient's most bothersome aspect(s). Responses were coded using content analysis, and patient and clinician responses were compared. Finally, asthma registries that are part of the SHARP (Severe Heterogeneous Asthma Research collaboration, Patient-centred) Clinical Research Collaboration were examined to see the extent to which they reflected the most bothersome aspects reported by patients.Results: 88 codes and 10 themes were identified. Clinicians were more focused on direct physical symptoms and were less focused on “holistic” aspects such as the effort required to self-manage the disease. Clinicians accurately identified a most bothersome symptom for 29% of patients. Agreement was particularly low with younger patients and those using oral corticosteroids infrequently. In asthma registries, patient aspects were predominantly represented in questionnaires.Conclusions: results demonstrated different perspectives and priorities between patients and clinicians, with clinicians more focused on physical aspects. These differences must be considered when treating individual patients, and within multidisciplinary treatment teams. The use of questionnaires that include multifaceted aspects of disease may result in improved asthma research

Real-World Effectiveness of Reslizumab in Patients with Severe Eosinophilic Asthma - "First Initiators" and "Switchers"

BACKGROUND: Reslizumab, a biologic targeting interleukin-5 has been shown to reduce asthma exacerbations and maintenance oral corticosteroid (OCS) use in randomized controlled trials and pre-post studies in patients with severe eosinophilic asthma. However, real-world effectiveness data of reslizumab are scarce, and it is unknown whether reslizumab has added value after switching from another type-2 biologic. OBJECTIVE: To evaluate (1) real-world effectiveness of reslizumab on severe asthma exacerbations, maintenance OCS-use and overall treatment response, both in biologic naïve patients who initiated reslizumab, and in patients who switched from another type-2 biologic. (2) physicians experience with reslizumab treatment. METHODS: This observational real-world study evaluated data from 134 adults with severe eosinophilic asthma included in the Dutch severe asthma registry (RAPSODI) who initiated reslizumab treatment (4-weekly infusions, 0.3 mg/kg) before April 2020 and had follow-up data ≥6 months. Clinical asthma experts completed surveys on their experience with reslizumab treatment. RESULTS: Overall, reslizumab reduced exacerbation rate (OR(95%CI): 0.10(0.05-0.21), p<0.001), oral corticosteroid use (OR(95%CI) 0.2(0.0-0.5), p<0.001) and maintenance dose, median(CI): 5.0(0.0-10.0) to 0.0(0.0-5.0), p<0.001), with comparable results in biologic-naïve reslizumab initiators and switchers. The overall response to reslizumab was graded 'good' or 'excellent' in 59.2% of patients. The additive effectiveness of reslizumab after switching from another biologic was reflected in physicians' surveys. CONCLUSION: Real-world data show that reslizumab reduces severe asthma exacerbations and oral corticosteroid use in patients with severe eosinophilic asthma, both in biologic-naïve reslizumab initiators and in those who switched from another type-2 biologic. This additional value of reslizumab was recognized by clinical asthma experts