BACKGROUND:Systemic corticosteroids (SCS) effectively control acute asthma exacerbations. However, repeated use of SCS causes significant adverse effects, necessitating escalation to steroid-sparing biologics. OBJECTIVE:To assess SCS utilization patterns in patients with moderate-to-severe asthma in real-world settings. METHODS:Patients with asthma initiating biologics between January 1, 2023, and December 31, 2024, were identified from the Komodo Health database. The index date was defined as the date of the first biologic claim. Patients (≥12 years) with 1 or more asthma diagnosis claims within 90 days preindex or at index and no biologic claim in the 12-month preindex period were included. Patients with other indications requiring SCS during the 12-month preindex period were excluded. The SCS utilization patterns were assessed within the 12-month preindex period. The utilization of SCS was also assessed in patients with uncontrolled moderate-to-severe asthma but who had not initiated biologics. RESULTS:Overall, 30,652 patients initiated biologics. During the 12-month preindex period, 63.9% (mean: 5.0 fills) of patients received at least 2 SCS prescriptions, with 36.3% receiving 2 to 4 and 27.6% (mean: 7.7 fills) receiving 5 or more prescriptions. The mean (SD) cumulative SCS dosage was 1100.4 (862.3) mg and 1709.0 (933.6) mg, respectively; the corresponding SCS days covered were 38.3 (30.3) and 58.9 (32.8) days in patients with 2 or more and 5 or more prescriptions, respectively. Consistent SCS utilization patterns were observed in patients who had not initiated biologics. CONCLUSION:This analysis reveals that a substantial proportion of patients with moderate-to-severe asthma receive frequent SCS prescriptions, necessitating continued education on guideline-recommended steroid-sparing strategies to achieve asthma control without SCS bursts.

Background: Asthma characterization using blood eosinophil count (BEC) (among other biomarkers and clinical indices) is recommended in severe asthma (SA), but the masking effect of oral corticosteroids (OCS), makes this challenging. Aim: Our aim was to explore the effect of OCS use (both intermittent [iOCS] and long-term [LTOCS]) prior to biologic initiation on SA phenotype and biomarker profile in real-life and to characterize the burden of SA among patients prescribed LTOCS by biomarker profile. Methods: This was a registry-based cohort study, including data from 23 countries collected between 2003 and 2023 and shared with the Internatonal Severe Asthma Registry (ISAR). Patients with SA were categorized into 3 cohorts, those with: (i) no prescription for OCS, (ii) prescription(s) for iOCS (ie, ≤90 days in previous 12-months, usually short courses for exacerbations), and (iii) prescriptions for LTOCS (ie, >90 days in previous 12-months). Biomarker distribution (ie, BEC, fractional exhaled nitric oxide [FeNO], and total Immunoglobulin E [IgE]) were quantified in the year prior to biologic initiation in patients with SA according to OCS prescription pattern. Phenotypes were characterized for those prescribed LTOCS according to BEC cut-off (<150 and ≥ 150 cells/μL). Results: Of 4305 patients included, 5.0% (n = 215), 54.1% (n = 2330) and 40.9% (n = 1760) were prescribed no OCS, iOCS, and LTOCS, respectively. The BEC distribution varied by prescription pattern and LTOCS dose (<5 mg to ≥20 mg/day); BEC was <150 cells/μL in 28.6% (n = 369/1288) of LTOCS patients, compared to 19.5% (n = 284/1460) of iOCS patients and 14.0% (n = 21/150) of those in the no OCS group. Median BEC was also significantly lower in the LTOCS versus the iOCS group (310 vs 400 cells/μL; p < 0.001). A similar pattern was noted for IgE, but not FeNO. Among LTOCS patients with BEC <150 cells/μL, 39.9% experienced ≥4 exacerbations, 75.1% had uncontrolled asthma symptoms and 55.9% had evidence of persistent airflow obstruction (compared with 40.9%, 76.2% and 59.5% of those with BEC ≥150 cells/μL, respectively). Conclusions: OCS, whether prescribed intermittently or long term, affect BEC distribution potentially leading to heightened risk of phenotype misclassification and influencing subsequent treatment decisions. FeNO appears to be less susceptible to OCS-induced suppression. Disease burden was high for those in the LTOCS group and was high independent of dose and BEC. Our findings highlight the importance of considering OCS use, even intermittent use, when characterizing SA, and suggests the need for earlier phenotyping and alternative treatment strategies for LTOCS patients with low BEC.

BACKGROUND:Asthma with low levels of type 2 (T2) biomarkers is poorly understood. OBJECTIVE:To characterize severe asthma phenotypes and compare changes in asthma outcomes from pre- to postbiologic treatment along a gradient of T2 involvement. METHODS:This was a registry-based cohort study including data from 24 countries. Biomarker distribution (blood eosinophil count, fractional exhaled nitric oxide, and IgE) was quantified before biologic initiation. Clusters were identified using a 5-component Gaussian finite mixture model and phenotypically characterized. Changes in asthma and health care utilization outcomes between 1-year pre- and postbiologic initiation were compared between clusters and by biologic class. RESULTS:Among 3675 patients, 5 biomarker clusters were identified along a gradient of T2 involvement: cluster A with the lowest T2 involvement (16.4%), cluster B (20.4%), cluster C (22.9%), cluster D (30.3%), and cluster E with the highest T2 involvement (10.0%). In multivariable analysis, biologic use was associated with improved outcomes in all clusters but tended to be better at the higher end of the T2 spectrum. For example, patients in cluster C had a significantly greater increase in forced expiratory volume in 1 second compared with cluster A (difference 0.16 L [95% confidence interval: 0.08, 0.25]; P < .001). The odds of uncontrolled asthma were approximately 0.6 for all clusters compared with cluster A. Overall, exacerbation rates were lower, and greater improvements in lung function and asthma control were noted for anti-IL-5/5 receptor (R) (but not anti-IgE or anti-IL-4Rα) for all clusters compared with cluster A. CONCLUSION:T2-targeting biologics have utility in the management of asthma with low T2 involvement, but more effective therapies are needed. Further research is warranted to identify specific pathogenic pathways at the lower end of the T2 spectrum that can be effectively targeted by biologics.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

Rationale: Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes. Objective: To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. Methods: This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom). For biologic initiators, the index date was the date of biologic initiation. For noninitiators, it was the date of enrollment (for ISAR) or a random medical appointment date (for OPCRD). Inverse probability of treatment weighting was used to improve comparability between groups, and weighted Cox proportional hazard models were used to estimate the hazard ratios (HRs) of developing OCS-related adverse outcomes for up to 5 years from the index date. Measurements and Main Results: A total of 42,908 patients were included. Overall, 27.3% and 4.7% of biologic initiators and noninitiators were long-term OCS users (daily intake ⩾90 consecutive days in year before the index date), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared with noninitiators, biologic initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% confidence interval (CI)]: 0.82 [0.72-0.93]; P = 0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; P = 0.006), major cardiovascular events (0.65 [0.44-0.97]; P = 0.034), and anxiety and/or depression (0.68 [0.55-0.85]; P = 0.001). There were no significant differences in the rates of new-onset cataract (HR, 0.77 [95% CI, 0.47-1.25]), sleep apnea (HR, 0.82 [95% CI, 0.78-1.41]), or other OCS-related adverse outcomes assessed (e.g., osteoporosis). The results were consistent across both datasets. Conclusions: Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.

RATIONALE: Use of oral corticosteroids (OCS), both as maintenance treatment and for exacerbations, is associated with serious adverse effects (AEs). Biologic use decreases the need for OCS in patients with severe asthma and therefore could reduce the risk of OCS-related AEs. Exploring this relationship could inform treatment decisions and highlight the benefits of biologics beyond asthma control. METHODS: Longitudinal data from adult patients with severe asthma were pooled from two real-world data sources: the International Severe Asthma Registry (ISAR, 16 countries) and the Optimum Patient Care Research Database (OPCRD, the United Kingdom). For biologic initiators, the index date was date of biologic initiation. For non-initiators, the index date was the date of enrollment into the registry for ISAR and a random medical appointment date for OPCRD. Index dates and end of follow-up spanned from 2008 to 2024. We compared the risk of developing type-2 diabetes mellitus, a major cardiovascular event (heart failure, myocardial infarction, or cerebrovascular accident), sleep apnea, pulmonary embolism, anxiety/depression, osteoporosis, renal failure, peptic ulcer, cataract, glaucoma, and pneumonia between biologic initiators and non-initiators. Time at risk was censored at 5 years. We used inverse probability for treatment weighting to improve the balance between comparison groups for potential confounders. Weighted Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of being diagnosed with new-onset OCS-related AEs. RESULTS: The study population included 5,690 biologic initiators and 37,218 non-initiators, followed for a median of 2.1 years (interquartile range: 1.0-3.9). The proportions of long-term OCS users (daily intake for ≥90 consecutive days in the year preceding index date) were 27.3% and 4.7% in biologic initiators and non-initiators, with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. The risk of any AE was lower in biologic initiators than in non-initiators (HR=0.82, 95% CI: 0.72-0.93) (Figure). This overall risk reduction was mainly driven by a reduction in the risk of diabetes (HR=0.62, 0.45-0.87), major cardiovascular events (HR=0.65, 0.44-0.97), and anxiety/depression (HR=0.68, 0.55-0.85). We did not detect an association between initiating biologics and the risk of osteoporosis (HR=0.96, 0.65-1.42), sleep apnea (HR=0.82, 0.58-1.15), pneumonia (HR=1.05, 0.78-1.40), or less frequent AEs included in our analysis (renal failure, peptic ulcer, cataract, and glaucoma). CONCLUSIONS: Initiation of biologics in patients with severe asthma was associated with reduction in their risk of new-onset OCS-related AEs, including diabetes, anxiety/depression, and major cardiovascular events.

Plain Language SummaryWhat is this summary about?This is a summary of an article originally published in the European Respiratory Journal, which presented combined results from five retrospective real-world studies (i.e., studies looking at data collected during historical medical appointments) that each took place in a different country and which, together, formed the XALOC-1 study programme. XALOC-1 looked at how effective benralizumab injections were in real-world clinical practice at treating a type of asthma called 'severe eosinophilic asthma'.What were the main results of the XALOC-1 study programme?Patients with severe eosinophilic asthma treated with benralizumab in the real world had a reduction in the number of asthma attacks, a reduction in their dose of steroid tablets (sometimes to zero), and improved lung function and asthma symptom control. This was true regardless of whether patients had or had not responded well to other biologic therapies before starting benralizumab. Patients who had nasal polyps or signs of allergy-related asthma also benefitted from treatment with benralizumab.What do the results of XALOC-1 mean?In real-world clinical practice (during medical appointments, rather than a specially designed clinical study), patients with severe eosinophilic asthma treated with benralizumab have reduced symptom severity and improved quality of life.This is an abstract of the Plain Language Summary of Publication article.View the full Plain Language Summary PDF of this article to read the full-text AcknowledgmentsAstraZeneca would like to thank the XALOC-1 study participants and their family members and carers. They would also like to thank the investigators and staff at the study centres who cared for the participants in the studies. Prof. Parmeswaran Nair (McMaster University, Hamilton, McGill University, Montreal and St Joseph's Healthcare Hamilton, Canada) acted as an author for the manuscript on which this summary is based, providing valuable inputs and assistance. Laurence Alexander (Toronto, ON, Canada) reviewed this piece from a patient perspective. Anna Mett and Lucy Cooper, of inScience Communications, Springer Healthcare, UK, provided medical writing support, which was funded by AstraZeneca in accordance with the Good Publication Practice 2022 guidelines.Disclosure statementDavid J. Jackson has received consultancy fees and speakers' fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Sanofi Regeneron,and research grants from AstraZeneca. Girolamo Pelaia has received lecture fees and advisory board fees from AstraZeneca, Boehringer Ingelheim, Chiesi,GlaxoSmithKline, Guidotti, Insmed, Lusofarmaco, Menarini, Neopharmed Gentili, Novartis, Sanofi and Zambon. Benjamin Emmanuel, Trung N. Tran, David Cohen,Sheena Kayaniyil and Silvia Boarino, are employees of, and may own stock in, AstraZeneca. At the time of writing, Anat Shavit and Douglas Arbetter were employees of, and may own stock in, AstraZeneca. Marisa Pardal, Javier Nuevo and Michael Watt are employees of AstraZeneca. Vivian H. Shih, Rohit Katial, Adrian Paul J. Rabe and Esther Garcia-Gil were previously employees of AstraZeneca. Claudia Chaves Loureiro has received consultancy fees and speakers' fees from AstraZeneca,Chiesi, GlaxoSmithKline, Sanofi Regeneron and Teva, and research grants from GlaxoSmithKline. Alicia Padilla-Galo reports grants, personal fees and non-financial support from AstraZeneca and Sanofi; personal fees and non-financial support from Chiesi, GlaxoSmithKline, Novartis and Teva; and personal fees from ALK, Bial and FAES, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Anna Mett, PhD and Lucy Cooper, MSc, of inScience Communications, Springer Healthcare, UK, provided medical writing support, which was funded by AstraZeneca in accordance with the Good Publication Practice 2022 guidelines.Patient reviewers on this PLSP have received honoraria from Immunotherapy for their review work but have no other relevant financial relationships to disclose.FundingThis manuscript was funded by AstraZeneca, whose input was important to the design, collection and interpretation of data from the XALOC studies, the decision to publish this data, and the preparation of this manuscript.

Background: Eosinophilic esophagitis (EoE) is characterized by eosinophil infiltration into the esophageal tissue and esophageal dysfunction. In the United States, EoE has an estimated prevalence of 26–163 cases per 100,000 people. Real-world data concerning the clinical burden of EoE and treatment patterns in the United States are limited. Objectives: To describe the demographics, clinical characteristics, symptoms, comorbidities, treatment pathways, and healthcare resource utilization (HCRU) and costs among patients with EoE in the United States. Design: Retrospective analysis. Methods: A study of pediatric and adult patients diagnosed with incident EoE (full incident EoE cohort) using Merative™ MarketScan ® health insurance claims data between January 1, 2017, and June 30, 2020. A subset of patients (matched incident EoE cohort) was matched with patients without EoE for age, sex, and payor (matched control cohort). Follow-up was 12 months after the EoE diagnosis date. All statistics are descriptive. Results: The full incident EoE cohort included 20,290 patients (62.61% were male; median (range) age was 38 (1–93) years); 13,710 patients (matched incident EoE cohort) were matched to 54,727 patients without EoE (matched control cohort). During baseline in the full incident EoE cohort, the most common comorbidities within the Charlson Comorbidity Index (CCI) were chronic pulmonary disease (19.79%), hypertension (15.77%), and depression (9.71%); the most common non-CCI comorbidities were reflux esophagitis (38.84%), allergic rhinitis (19.14%), and depression/anxiety (19.07%). During follow-up, the most frequently reported symptoms were acid reflux/heartburn (56.02%), dysphagia (51.89%), and abdominal pain (30.50%). The most common medications first observed were proton pump inhibitors (42.51%) and oral corticosteroids (12.26%). Overall, a larger proportion of the matched incident EoE cohort had visits to any healthcare setting during baseline and follow-up than the matched control cohort. Correspondingly, the annualized, all-cause healthcare costs per patient were higher in the matched incident EoE cohort than in the matched control cohort at baseline (mean (standard deviation), $10,185 ($29,455); median, $3248 vs $4906 ($20,601); $632) and during follow-up ($15,103 ($35,484); $6708 vs $5200 ($21,314); $651). Conclusion: Considerable disease burden is experienced by patients with EoE (before and after diagnosis), which contributes to a high level of HCRU and increased costs.

Asthma and rhinitis are interlinked conditions. Despite skin testing being pivotal for evaluating allergy, U.S. data on ST reactivity patterns in asthmatics remains sparse. The purpose of this study is to elucidate these patterns and their relationship with asthma severity and onset.

Background Pivotal phase 3 trials and real-world studies have demonstrated benralizumab's ' s overall efficacy and safety in severe eosinophilic asthma (SEA). Additional large-cohort data are needed to confirm its real-world effectiveness in SEA according to previous biologic use and key baseline characteristics important for treatment selection. Methods XALOC-1 is a large, multinational, retrospective, observational, real-world study programme of benralizumab in adults with SEA. This 48-week integrated analysis assessed annualised exacerbation rate (AER), maintenance oral corticosteroid (mOCS) use, asthma symptom control and lung function during a 12-month baseline period and up to 48 weeks after benralizumab initiation. Subgroup analyses were based on previous biologic use and key baseline clinical characteristics (mOCS use, blood eosinophil count, exacerbation history, age at asthma diagnosis, fractional exhaled nitric oxide level and presence of atopy and chronic rhinosinusitis with nasal polyps). Results Out of 1002 patients analysed, 380 were biologic-experienced. At week 48, 71.3% were exacerbation-free ( versus 17.2% at baseline); relative reduction in AER was 82.7% overall and 72.9% in biologic-experienced patients; rates were maintained across all key clinical characteristic subgroups. Of patients using mOCS at baseline (n=274), 47.4% (130 out of 274) eliminated their use by week 48; the mean reduction from baseline in daily dose was 51.2% and, notably, 34.9% in biologic-experienced patients (n=115). Clinically significant improvements in asthma symptom control and lung function were observed. Conclusion In this large, real-world programme, SEA patients treated with benralizumab had substantial improvements in clinical outcomes irrespective of previous biologic use and key clinical characteristics important to therapeutic decision-making in clinical practice.

As the number of biologics available for asthma treatment continues to grow, the ability to target clinical remission becomes an increasingly attainable goal. Ultimately, the aim should be to tailor therapy to high-risk patients earlier in their disease course in order to prevent long-term lung damage and airway remodeling. Aiming for clinical remission early in life could improve overall asthma outcomes and increase the proportion of patients who are able to achieve and maintain clinical remission leading to decreased morbidity and improved quality of life. Establishing a consensus definition thus becomes crucial as it will move us closer to a "treat-to-target" approach that strives for the absence of disease activity and symptoms.