BACKGROUND:Exacerbation frequency strongly influences treatment choices in patients with severe asthma. RESEARCH QUESTION:What is the extent of the variability of exacerbation rate across countries and its implications in disease management? STUDY DESIGN AND METHODS:We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naive model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. RESULTS:The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39). INTERPRETATION:Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies.

Introduction and Objectives Benralizumab is an anti-interleukin-5 receptor α monoclonal antibody indicated as an add-on maintenance treatment in adult patients with severe eosinophilic asthma (SEA). Herein we present real-world data from the Benralizumab Patient Access Programme (BPAP) for a subgroup of patients with SEA and concomitant nasal polyposis (SEAwNP) after 2 years of treatment with benralizumab for SEA. Methods The BPAP study is a multi-centre, retrospective, observational study of patients with SEA from eight UK centres. Data were collected from the medical records of patients receiving their first benralizumab dose between April 2018 and November 2019. Outcomes were assessed using descriptive statistics, with patients censored when treatment was discontinued. Results Within the BPAP cohort of 276 patients, 57 (21%) patients had SEAwNP and were included in this subgroup analysis. The mean age was 50.9 (standard deviation [SD] 13.5); 46% (26/57) were female; mean BMI was 30.2 (SD 5.7); 61% (35/57) of patients were receiving maintenance oral corticosteroids (mOCS) at baseline. Clinical outcomes for the overall BPAP cohort and SEAwNP subgroup are shown in the table 1. Patients with SEAwNP had a mean annualised exacerbation rate (AER) of 3.8 (95% confidence interval [CI] 3.1–4.5) at baseline (n=56), decreasing to 0.8 (95% CI 0.5–1.1) at Year 2 (n=48); a relative reduction of 79%, with 44% of patients being exacerbation free over 2 years. For patients with SEAwNP on mOCS at baseline, 57% were off mOCS for asthma after 2 years, with 77% achieving a dose reduction of ≥50%. At baseline, mean asthma control questionnaire (ACQ-6) score was 2.9 (SD 1.5, n=55); this reduced to 1.3 (SD 1.5. n=30) at 2 years. The proportion of patients with SEAwNP achieving an improvement of ≥0.5 was 71% (20/28); 63% (19/30) had an ACQ-6 score of <1.5. Clinical outcomes in the overall BPAP cohort and SEAwNP subgroup were comparable (table 1). Conclusions This analysis in a subgroup of patients with SEAwNP shows that patients who were treated with benralizumab had clinically relevant and sustained improvements in clinical outcomes comparable to the overall cohort, including improved exacerbation rates, mOCS use and asthma symptom control. Please refer to page A291 for declarations of interest related to this abstract.

Introduction Benralizumab is an anti-interleukin-5 receptor α monoclonal antibody indicated as an add-on maintenance therapy in adult patients with severe eosinophilic asthma (SEA). Herein we present real-data from the Benralizumab Patient Access Programme (BPAP) on the asthma-related, hospital healthcare resource utilisation (HCRU) in patients with severe asthma. Methods The BPAP study is a multi-centre, retrospective chart review study of patients with SEA from eight severe asthma centres in the UK. Data were collected from the medical records of patients receiving their first benralizumab dose between April 2018 and November 2019. Outcomes were assessed using descriptive statistics. HCRU including hospitalisations and emergency department (ED) visits related to exacerbations were described in the 12 months prior to benralizumab initiation (baseline), 1- and 2-years post benralizumab initiation. Patients remaining on treatment were included at each timepoint. Results A total of 276 patients were included. During baseline, 42% of patients had ≥1 asthma-related ED attendance; this proportion decreased to 23% at Year 2. Mean (SD) ED attendances reduced from 1.2 (2.2) at baseline to 0.4 (1.0) at Year 2, a relative reduction of 67%. The proportion of patients with ≥1 hospitalisation was 39% at baseline, falling to 18% in Year 2. Mean (SD) hospitalisations reduced from 1.0 (1.8) at baseline to 0.4 (1.0) at Year 2, a relative reduction of 70%. For patients with inpatient hospitalisations during the baseline with a recorded length of stay (n=50), median (IQR) length of stay was 6.5 (3.0–17.3) days; this decreased to 2.5 (0.0–8.3) days (n=38) at Year 2; a relative reduction of 62%. There was also a reduction in intensive care admissions from 16/241 (7%) at baseline to 5/209 (2%) at year 2. Conclusions The results show that patients with SEA treated with benralizumab experienced clinically meaningful and sustained reductions in un-scheduled hospital HCRU. Treatment with benralizumab may be associated with >60% reduction in ED visits, hospitalisation and length of stay across all sites. This would reduce pressures on acute services and further work is warranted to investigate the overall economic impact of reduced HCRU. Please refer to page A295 for declarations of interest related to this abstract.

Introduction and Objectives Benralizumab is indicated as an add-on maintenance treatment in adult patients with severe eosinophilic asthma (SEA) that is inadequately controlled despite high-dose inhaled corticosteroids plus long-acting β-agonists. Real-world clinical outcomes following 1-year of treatment with benralizumab in the United Kingdom (UK) have been previously described in the Benralizumab Patient Access Programme (BPAP) study; however, longer-term outcomes are unknown. Herein we report results from an extended follow-up period of two years for the BPAP study cohort. Methods The BPAP study is a multi-centre, retrospective, observational study of patients with SEA from eight UK centres. Data were collected between May 2019 and October 2021 from the medical records of patients receiving their first benralizumab dose between April 2018 and November 2019. Outcomes were assessed using descriptive statistics at baseline, 1 year and 2 years post-benralizumab initiation. Results A total of 276 patients were included: 62% (171/276) were female and mean (SD) age at asthma onset was 31.4 (18.5) years. In total, 49% (134/276) of patients had atopic asthma, 75% (104/138) had adult-onset asthma, and 21% (57/276) had nasal polyposis. At baseline, the median (IQR) FeNO count was 65.0 (36.0–99.0) ppb and the median (IQR) peak EOS count was 500.0 (300.0–800.0) cells/mcL. The mean (95%CI) annualised exacerbation rate (AER) reduced from baseline by 79% from 5.3 (4.8–5.7) to 1.1 (0.9–1.2) exacerbations/patient/year, with 34% (72/209) of patients totally exacerbation-free at 2 years. At baseline, 63% (174/276) of patients were on maintenance oral corticosteroids (mOCS) for asthma. Of these, 55% (70/127) were mOCS-free at 2 years. Mean (SD) asthma control (ACQ-6) improved from 3.0 (1.5) to 1.6 (1.5) at 2 years with 70% (89/128) achieving the MCID of 0.5. Quality of life [AQLQ] improved from a mean (SD) of 3.4 (1.4) to 4.8 (1.5) at 2 years with 72% of patients achieving the MCID of 0.5 or more. 76% of patients remained on benralizumab at 2 years. Key results are summarised in table 1. Conclusions Clinical outcomes up to 2 years post-benralizumab treatment suggest a sustained improvement in all clinical measures including exacerbations, mOCS use, asthma control and health-related quality of life. Please refer to page A213 for declarations of interest related to this abstract.

Introduction: Real-world evidence on the effectiveness of therapeutic antibodies (“biologics”) in patients with asthma is limited. Aim: To examine the effectiveness of initiating biologics in a large, international, real-world cohort of adult patients with severe asthma (SA) and high oral corticosteroid (OCS) exposure. Methods: Patients with SA on long-term (maintenance) OCS or ≥4 courses of rescue OCS within a 12-month period were identified (January 2015-February 2021) from the International Severe Asthma Registry (http://isaregistries.org/). Biologic initiators were identified and matched 1:1, using propensity scores, with non-initiators. The impact of biologic initiation (first 365 days) on asthma exacerbations, OCS dose (both total and long-term) and healthcare resource utilization were assessed using generalized linear models. Results: Among 996 matched pairs, at 365 days of follow-up, biologic initiation was associated with a 69.2% reduction in the number of exacerbations relative to non-initiators (0.64 vs 2.06, p=0.019). Biologic initiators were also 2.20 times more likely than non-initiators to have daily long-term OCS dose below 5 mg (p=0.002) and inclined to be more likely to achieve a high reduction (>75%) in total OCS dose (4.01 times, p=0.063). Initiation of biologics reduced the frequency of asthma-related hospitalizations (reduction: 57.3%, p=0.006) and had a trend towards reduction for emergency department visits (52.2%, p=0.054). Conclusions: Real-world initiation of biologics is associated with reduced exacerbation rate, OCS exposure, and healthcare resource utilization in patients with severe asthma and high OCS.

Introduction/Background: Biomarker-defined clusters of severe asthma patients were previously identified via hierarchical cluster analysis; a cluster of older females with low-to-medium Type 2 (T2) biomarkers was characterized (Denton, E. et al. J Allergy Clin Immunol Pract 2021;9:2680-8.e7). Aims and Objectives: To describe biomarker-defined clusters (blood eosinophil counts [BEC], FeNO, and serum IgE [IgE]) in severe asthma patients, and characterize T2-low asthma using a model-based approach to clustering. Methods: Patients in the International Severe Asthma Registry (ISAR) with biomarker data were included, regardless of biologic use. A Gaussian finite mixture model was used to perform cluster analyses using BEC, FeNO and IgE standardized by z score. The prespecified thresholds for low biomarkers were BEC <300cells/µL, FeNO <25ppb and IgE <75 IU/mL. Results: Of 4459 patients, five clusters were identified. Cluster 1 had females with low T2 biomarkers. Cluster 2 had high BEC and FeNO; Cluster 3, triple T2 biomarker high; Cluster 4, high BEC; Cluster 5, high IgE. Figure: Median (IQR) biomarker levels and characteristics of clusters Conclusions: In line with previous findings, a cluster with females and low biomarkers suggested low T2 involvement. The other 4 clusters varied in biomarker elevations, highlighting the complexity of T2 inflammatory involvement in severe asthma.

Introduction/Background: Biologics (Bx) are known to decrease specific biomarker levels: anti-IL5 reduces blood eosinophils (BEC) and anti-IgE slightly reduces FeNO. Anti-IL5 and anti-IgE are thought to have limited effect on total IgE (IgE). Aims and Objectives: To assess the proportions of severe asthma patients whose biomarkers (BEC, FeNO, and serum IgE) decrease following anti-IL5 and anti-IgE initiation. Methods: Patients in the International Severe Asthma Registry (ISAR) with biomarker and Bx data were included. From pre-Bx baseline to the post-Bx time period, the median (IQR) change in biomarker level and the proportion of patients with >25% decrease in biomarkers were determined. Results: At 2-3 years from Bx initiation, BEC decreased by >25% in 80.7% of anti-IL5 and 41.6% of anti-IgE patients. FeNO decreased by >25% in 41.6% of anti-IL5 and 47.8% of anti-IgE patients. IgE decreased by >25% in 41.7% of anti-IL5 and 15.6% of anti-IgE patients (Figure). Figure: Median (IQR) biomarker changes and patient proportions with decreased biomarkers in response to Bx. Conclusions: Anti-IL5 was superior in decreasing BEC and both Bx classes decreased FeNO to a limited extent. The lower proportion of anti-IgE patients with IgE reduction could be attributed to serum total IgE (not free IgE) measurement. Apart from anti-IL5’s effect on BEC, <50% patients had decreased biomarkers; the clinical implications should be explored.

Introduction A Virtual Covid-19 Follow-up Clinic was designed in response to the need to review a large number of in-patients, at a large hospital trust, recovering from Covid-19 but without any significant increase in resources Methods Patients complete a structured online/telephone symptom and psychological health questionnaire and have a chest x-ray 12 weeks after their illness These results, and their medical records, are reviewed asynchronously by the medical team in a virtual clinic Patients are then triaged to further virtual review, telephone review, face to face review, or are discharged All patients receive comprehensive written information to aid their recovery Results During the first 8 weeks of the service, 388 patients have completed the questionnaire (63% online) and been reviewed Current symptoms are shown in figure 1 The questionnaire has identified the holistic needs of patients and allowed triaged follow-up with 122 discharged and 53 urgent face-to-face review appointments completed 25 CT pulmonary angiogram scans were arranged for patients with typical symptoms of pulmonary emboli;no thromboembolic disease was identified Conclusion This early experience of a new service has highlighted 5 learning points: