BACKGROUND:Treatment that reduces systemic corticosteroid (SCS)-related adverse effects but maintains disease control is of broad public health importance. OBJECTIVE:To evaluate the effect of mepolizumab vs long-term SCS use on SCS-related adverse effects in patients with severe asthma. METHODS:This retrospective, longitudinal cohort study (GSK Identification: US 218950) used claims data from the Optum Clinformatics Data Mart database from November 2014 to December 2022. Eligible patients (aged ≥12 years with ≥2 asthma diagnostic claims), had at least 2 mepolizumab claims (mepolizumab-treated cohort) or at least 6 months of continuous SCS use (long-term SCS-treated cohort). Inverse probability of treatment weighting was used to balance cohort characteristics. The primary outcome was SCS-related adverse effects. The secondary outcomes included exacerbation frequency, SCS/oral corticosteroid use, healthcare resource utilization, and costs (excluding the cost of therapy). RESULTS:Overall, 1219 (mepolizumab-treated) and 835 (long-term SCS-treated) patients with severe asthma were included (median follow-up, 12 months). Cohorts were well-balanced after weighting (mean age, 63-65 years; 66% female). The mepolizumab-treated cohort had significant reductions in overall, acute, and long-term SCS-related adverse effects (rate ratio [CI] 0.80 [0.70-0.92], 0.63 [0.47-0.84], and 0.80 [0.70-0.92], respectively) vs the long-term SCS-treated cohort; SCS dose reduction of 4.7 mg/d corresponds to a 20% reduction in SCS-related adverse effects (P = .002). Similar trends were observed in exacerbation rates, healthcare resource utilization, and medical costs, although not all reached statistical significance. CONCLUSION:Mepolizumab treatment reduced acute and long-term corticosteroid effects in patients with severe asthma vs long-term SCS use, suggesting avoidance of corticosteroid use can lead to measurable regression of SCS-associated adverse effects and more favorable disease trajectory.

Background: Biologic therapy uptake for poorly controlled severe asthma is suboptimal despite guideline recommendations. Objectives: To evaluate real-world biologic initiation trends and predictors among patients with severe uncontrolled asthma (SUA) and SUA with eosinophilic phenotype (SUA-EP). Design: A retrospective real-world cohort study that used Komodo Health administrative claims to identify US patients with SUA (controller/rescue medication use and ⩾2 asthma exacerbations in a year) and a subgroup of patients with SUA-EP (blood eosinophil count ⩾150 cells/µL in the year pre- or post-exacerbation). Methods: Biologic initiation trends following first asthma exacerbation were assessed, and factors associated with lack of biologic initiation following second exacerbation (SUA-EP only) were identified using LASSO regression models; odds ratios (OR), 95% confidence intervals (CIs), and p -values were calculated using logistic regression. Results: Biologic initiation rates following the first exacerbation were low at 12.7% (4360/34,246) and 12.2% (309/2526) of patients with SUA and SUA-EP, respectively; mean time between second exacerbation and initiation was 13.4 and 11.9 months. Predictors of lack of biologic initiation included young age (12–17 years; OR (95% CI) 3.65 (1.69–7.89)), primary care physician specialty at index relative to respiratory specialist (2.89 (2.04–4.10)), and antibiotic use (2.29 (1.44–3.66); all p < 0.05), indicating that younger patients, those managed by primary care and those treated with antibiotics for exacerbations, were less likely to receive biologics. Biologic initiation was more likely among patients with a cumulative systemic corticosteroid dose ⩾500 mg (prednisone equivalent; 0.38 (0.25–0.57)), those using leukotriene modifiers (0.42 (0.28–0.62)) or single-inhaler triple therapy (0.06 (0.01–0.40)), and those with eosinophilic disorders (0.19 (0.07–0.52); all p < 0.05). Conclusion: Despite eligibility, most patients with SUA and SUA-EP did not receive any biologic; younger age and primary care management were predictors of lack of biologic initiation. This highlights the need for improved specialist referral and biologic uptake.

Background Evidence on real-world adherence to asthma biologic therapies and the relevance to clinical outcomes in asthma is limited. Objective To evaluate biologic use patterns and the relationships between adherence, clinical and healthcare resource utilization (HCRU) outcomes, and economic burden in patients with asthma. Methods This was a retrospective observational study using Optum’s de-identified Market Clarity Data (Optum® Market Clarity) from 2007–2023, in adults in the US with an asthma diagnosis in the 12 months prior to first biologic dose (index date) who had ≥12 months’ follow-up. Medication possession ratio (MPR; number of doses taken/dosing intervals) and group-based trajectory modeling (GBTM) identified distinct patient adherence patterns and assessed impact on exacerbations, HCRU and costs (all-cause/asthma-related). Results Overall, 10,088 eligible patients were included in the MPR analysis; 54.7% discontinued treatment, 5.2% were minimally adherent, 20.3% were partially adherent, and 19.8% were adherent. Of these, 9553 did not switch biologic during follow-up and were included in the GBTM analysis. For patients with ≥1 follow-up dose (n=8151), MPRs revealed suboptimal biologic adherence (average range: 40.6–64.0%). GBTM identified seven adherence clusters, with distinct adherence trajectories categorized from highest to lowest levels of biologic adherence. Patients with the highest adherence generally demonstrated the best outcomes. In patients in less adherent groups, increases were seen in exacerbations defined by asthma-related hospitalizations, all-cause HCRU, and all-cause healthcare costs. HCRU and asthma-related costs were generally lower for patients with the highest adherence. Conclusions Treatment adherence was consistently associated with better all-cause and asthma-related outcomes, highlighting the importance of biologic adherence in patients with asthma.

Background:Systemic corticosteroids (SCS) remain the cornerstone of eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES) therapy but are associated with substantial toxicity. Mepolizumab, an anti-interleukin-5 biologic, has demonstrated steroid-sparing effects in addition to EGPA and HES disease control, yet evidence of reductions in SCS-related complications is limited. Methods:This retrospective cohort study used US claims data from the Komodo Research Database to quantify SCS-related complications, healthcare resource utilization, and costs in patients with EGPA or HES treated with mepolizumab vs. chronic SCS. Patients were stratified as mepolizumab (300 mg) or chronic SCS users (≥6 months continuous SCS use with >7.5 mg/day for EGPA and >10 mg/day for HES) based on treatment received during a 6-month landmark period post-index (first claim of mepolizumab or SCS). An inverse probability of treatment weighting approach was applied to the cohorts to minimize confounding. Outcomes were assessed up to 12 months post-landmark. Results:578 patients with EGPA (305 mepolizumab users vs. 273 chronic SCS users) and 272 patients with HES (161 vs. 111) were included. In patients with EGPA, rates of any SCS-related complications were 39% lower with mepolizumab compared with chronic SCS (rate ratio [95% confidence interval]: 0.61 [0.49, 0.76], p < 0.001). Mepolizumab users had 57% lower rate of all-cause hospitalizations (0.43 [0.27, 0.69], p < 0.001), and lower outpatient and emergency department (ED) visits vs. chronic SCS. Patients with HES had significantly lower rates of any SCS-related complications with mepolizumab vs. chronic SCS (0.59 [0.42, 0.82], p = 0.002). Mepolizumab users had 66% lower rates of all-cause hospitalizations (0.34 [0.17, 0.65], p = 0.001), and lower outpatient visits relative to chronic SCS users. In EGPA and HES SCS-complication-related hospitalizations and ED visits were lower with mepolizumab compared with chronic SCS. SCS-complication-related medical costs per patient per year were $16,194 (p = 0.008) and $3,976 (p = 0.676) lower, in the mepolizumab vs. chronic SCS cohort of patients with EGPA and HES, respectively. Conclusion:This first of its kind study suggests that real-world mepolizumab use is associated with reduced SCS-related complications in EGPA and HES, reinforcing its clinical and economic steroid-sparing benefits in reducing healthcare burden among EGPA and HES populations.

Purpose:This study describes factors associated with biologic initiation and adherence, and impacts of adherence on exacerbations among US patients with severe asthma. Patients and Methods:This retrospective cohort study defined two populations, biologic-eligible patients and biologic users, using the Komodo Research Database of healthcare claims (2016-2024). The biologic-eligible cohort was defined as patients with severe asthma who had ≥2 exacerbations within 12 months, after the severe asthma index date. Severe asthma was defined as ≥3 month medium-to-high-dose inhaled corticosteroid use with ≥1 overlapping supply with controller therapy. The severe asthma index date was the first day of overlapping treatment supply. Biologic users were defined as patients with ≥2 dispensings of the same biologic and ≥2 asthma diagnoses in the year prior to biologic initiation. In the biologic-eligible cohort, biologic initiation was evaluated and compared between less- and more-favored social determinants of health (SDOH) areas (based on census-level quartiles). Adherence (assessed based on refills and treatment gaps) and exacerbations were assessed among biologic users in the 12 months following biologic initiation and compared between less- and more-favored SDOH areas. Results:Overall 29,652 patients had ≥2 years of follow-up in the biologic-eligible cohort. Of these, 11.3% (n=3362) initiated biologics. In total, 16,336 patients were included in the biologic-user cohort, among whom 62.6% were adherent, 12.1% partially adherent, 3.1% minimally adherent, and 22.3% discontinued treatment. Biologic initiation and adherence were lower in less- versus more-favored SDOH areas. Compared with adherent patients, those who were partially/minimally adherent or discontinued treatment in the 12 months following biologic initiation had significantly more exacerbations post-landmark period (+18% overall and +28% hospitalization-defined exacerbations). Conclusion:Disparities in biologic initiation and adherence exist between severe asthma populations with different characteristics and SDOH. Biologic adherence is associated with fewer exacerbations compared with partial adherence, minimal adherence, and treatment discontinuation.

Background:Hypereosinophilic syndromes (HES) are rare hematologic disorders characterized by hypereosinophilia and eosinophil-driven organ damage/dysfunction. The HES diagnostic and treatment journey is poorly understood. Objective:We sought to describe the experience and disease burden of HES from a patient perspective. Methods:An online cross-sectional survey was completed by US patients aged 18 years and older with self-reported HES or caregivers (recruited via the American Partnership for Eosinophilic Disorders). Data on symptoms, diagnosis process, treatment, health care resource utilization, quality of life, and support structure were collected. Results:The mean age of the respondents (HES, n = 53; caregiver, n = 1) was 43.6 years (80% White and 57% male). One-quarter (26%) received their HES diagnosis in less than 3 months from first symptoms; 30% waited 3 months to 1 year, 37% 1 to 5 years, and 7% more than 5 years. Almost half of the respondents (n = 26) required hospital care 1 to 3 times in the 12 months before diagnosis. Most common symptoms were fatigue (96%), general discomfort (85%), wheezing (80%), rash (78%), and dry cough (76%). The most burdensome symptoms included leg swelling (100%), sweating (78%), and shortness of breath (64%). Symptoms associated with HES end-organ damage (respiratory and hypercoagulability symptoms) were observed. HES substantially impacted quality of life including work quality/productivity, finances, and relationships. Patients additionally wished for their doctor to show more empathy for their symptom burden, pain, and long-term mental health impacts. Conclusions:People with HES face long diagnostic journeys. The findings in this study highlight the heterogeneous symptoms, challenges, and multifactorial burden they experience, providing a voice for patients with HES and enhancing physician awareness to support improved diagnostics and management.

Objective: Although the efficacy of mepolizumab in reducing exacerbations and oral corticosteroid (OCS) use in severe asthma is well-established, real-world long-term effectiveness data are limited. This study evaluated the real-world impact of mepolizumab treatment in patients with severe asthma over a 4-year follow-up period. Methods: This was a retrospective cohort study of patients with asthma initiating mepolizumab (index date: first claim, November 2015-September 2019) using the Merative MarketScan Commercial and Medicare Databases. Outcomes included asthma exacerbations, OCS use, and exacerbation-related healthcare resource utilization (HCRU) and costs, assessed 12-months pre-index (baseline) and annually during the 4-year follow-up period. Results: Among 189 eligible patients, mean asthma exacerbation rate (AER) declined progressively from baseline during follow-up: AER decreased by 53.8% at Year 1 and 73.8% by Year 4 (p < 0.001). The annual OCS prescription rate reduced from baseline by 41.1% at Year 1 and 62.2% at Year 4 (p < 0.001). The proportion of patients with both no exacerbations and no OCS use progressively increased from 6.4% at baseline to 18.5% at Year 1 and 41.8% at Year 4. Exacerbation-related HCRU including inpatient, emergency room, and outpatient office visits decreased from baseline (9.0%, 21.7%, and 78.8%, respectively), at Year 1 (3.2%, 12.2%, and 49.2%), and Year 4 (0.0%, 4.8%, and 31.8%). Exacerbation-related healthcare costs declined from $4,635 at baseline to $1,487 at Year 1 and $217 at Year 4 (p < 0.001). Conclusion: Patients treated with mepolizumab demonstrated progressive and sustained long-term, real-world reductions in exacerbation frequency, OCS dependency, and exacerbation-related HCRU and costs over 4 years.

Background: The risk of disease varies across populations based on factors like age, sex, race, ethnicity, socioeconomic status, and underlying medical conditions. Subgroup or subpopulation data are critical in planning, executing and evaluating public health interventions. However, most studies report the values for the overall (total) population with little or no information on the subgroups. As a result, finding subgroup specific data can be challenging. Objective: In this report, a set of formulae that can be used to calculate subgroup or subpopulation data using the overall estimates and the reported or assumed relative estimates were derived. Methods: A simple numerical example was used to illustrate the methodology. Next, symbolic formula for calculating the burden (e.g., incidence, prevalence, or average cost) for 3 (and extended to n number of) subgroups or subpopulations were derived. To account for uncertainty in the data, two statistical methods were used to estimate confidence intervals for the point estimates. Results: The derived formulae indicated that each subgroup or subpopulation's burden (incidence, prevalence, or average cost) can be calculated as the overall burden adjusted by the ratio of that subgroup or subpopulation's relative burden to the sum of the proportion-weighted relative burden (incidence, prevalence, or average cost) of all the subgroups or subpopulations within the population. Conclusion: These formulae can help to avoid or minimize potential quantitative and qualitative errors in subgroup or subpopulation disease burden estimates used for health research, interventions and/or policy analyses or deliberations.

Background: Data on the presentation and management of patients with eosinophilic granulomatosis with polyangiitis (EGPA) in private practice are limited. Objective: We sought to characterize the profiles and disease burden of patients with EGPA in a real-world private practice setting. Methods: This was a retrospective, noninterventional, longitudinal study (GSK ID: 217426) of US Allergy Partners network data. For patients with a diagnosis of EGPA, confirmed by 2 or more EGPA clinical features, index was defined as their first visit with an Allergy Partners physician (January 2007-June 2021); postindex lasted until loss of follow-up or study end (December 2021). Patient characteristics at index, physician characteristics at any time, symptoms, treatment characteristics, and clinical outcomes postindex were assessed. Results: Of 52 patients (median follow-up, 3.7 years), 75% were diagnosed with EGPA outside the Allergy Partners network. Each patient received care from a median (Q1-Q3) of 4.0 (3.0-5.0) physician specialties. Most had asthma (92%), rhinitis (75%), and sinusitis (62%) and experienced a mean +/- SD of 18.1 +/- 4.3 distinct self-reported symptoms. Most (85%) used oral corticosteroids, with 73% (32 of 44) on daily doses of more than 12 mg; 60% used mepolizumab. Overall, 75% of patients (39 of 52) achieved a response (improved/controlled symptoms); 46% (24 of 52) achieved controlled status after worsened, unchanged, or active symptoms, and of these 38% (9 of 24) relapsed. Conclusions: The complex private practice presentation of EGPA, with heterogeneous patient response to standard treatments, highlights a significant disease burden and continued need for optimized treatment strategies within a multidisciplinary team approach. (J Allergy Clin Immunol Global 2025;4:100437.)

Clinical remission (CR) is an ambitious and achievable treatment goal for many patients with severe asthma. This study evaluated real-life care of patients in the U.S. using CR criteria defined by the American Thoracic Society; American College of Allergy, Asthma, and Immunology; and American Academy of Allergy, Asthma Immunology. This retrospective cohort study (GSK ID: 219744) utilized data from the Mayo Clinic’s electronic health record database (January 1, 2014–March 31, 2023). Eligible adults had severe asthma, ≥ 1 respiratory biologic initiated, and ≥ 12 months of clinical activity post-index date. The primary objective quantified the proportion of patients with documented CR component criteria 12-months post-biologic initiation. Criteria included asthma exacerbations, systemic corticosteroid use for asthma, missed work/school due to asthma, ≥ 2 pulmonary function tests, controller medication use for asthma, ≥ 2 asthma control tests, and rescue medication use for asthma. Of 4623 patients receiving respiratory biologics, 707 were eligible. Documentation was available for ≥ 1 component in 94.2

Background: Real-world burden data on systemic corticosteroid (SCS) use in chronic rhinosinusitis with nasal polyps (CRSwNP) are limited. Objective: To describe the real-world burden of SCS in CRSwNP. Methods: This retrospective cohort study included commercial/Medicare Advantage with Part D health plan members from the Optum Research Database with a first medical claim (index) for CRSwNP (January 2015-July 2020). Primary outcomes/variables included SCS use, health care resource utilization, and costs during the 12-month follow-up period. Outcomes were analyzed overall (N = 21,172) and stratified by baseline comorbid asthma status and sinus surgeries during follow-up. Results: Overall, 64.7% and 41.0% of patients used all-cause and CRSwNP-related SCS, respectively, and 36.0% had >= 1 oral corticosteroid (OCS) burst (>= 20 mg for 3-28 days); SCS use was higher in patients with asthma and those with a NP-related surgery (1, 2, and >= 3) vs without. The mean (SD) all-cause cumulative oral corticosteroid dose was 303.3 (675.0) mg/year and 23.5% had a cumulative annual dose >= 400 mg; these values were higher (P < .001) in patients with vs without comorbid asthma (514.9 [956.1] vs 247.5 [567.0]; 36.9% vs 19.9%). All-cause and CRSwNP health care resource utilization and costs increased with increasing number of surgeries; mean (SD) all-cause total medical costs were $14,472 (38,915), $26,909 (40,800), $29,816 (41,677), and $31,558 (37,143) with 0, 1, 2, and >= 3 surgeries, respectively. Conclusion: These data highlight the significant burden of SCS use in CRSwNP, particularly in patients with comorbid asthma, and suggest a need to reduce SCS exposure. (c) 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Background:Real-world evidence on the effectiveness of mepolizumab in children and adolescents with severe asthma (SA) is limited. Objective:We sought to evaluate mepolizumab's impact on the clinical and health care resource utilization (HCRU) burden of SA in children and adolescents. Methods:A retrospective study (GSK ID: 218952) was conducted of US administrative claims for patients aged 6-17 years with SA who initiated mepolizumab (from October 1, 2016, to June 30, 2023), had continuous health plan enrollment for ≥12 months pre- and post-mepolizumab initiation, and had ≥1 additional mepolizumab dispensings/administrations ≤6 months from initiation. Rate ratios from Poisson regression models were used to compare asthma exacerbations, oral corticosteroid (OCS) dispensings and bursts, short-acting β2-agonist (SABA) canister use, and HCRU per patient-year (PPY) pre- and post-mepolizumab; risk ratios from log-binomial regression models compared proportions of patients with ≥1 OCS dispensings and ≥1 SABA canister dispensings between periods. Results:Of 580 patients, 47% were aged 6-11 years and 53% were aged 12-17 years. Mean OCS dispensings PPY decreased by 24% (P < .001) pre- versus post-mepolizumab initiation. Mean overall asthma exacerbations and OCS bursts PPY decreased by 34% and 29% (P < .001 each), respectively. The proportions of patients with ≥1 OCS dispensings and those using ≥1 SABA canisters decreased by 16% (P < .001) and 3% (P = .039), respectively. Asthma-related HCRU PPY decreased by 23% for inpatient visits (P = .031), 15% for emergency department visits (P = .021), and 26% for outpatient visits (P < .001). Conclusions:Mepolizumab initiation was associated with significant reductions in asthma exacerbations, OCS and SABA use, and HCRU in children and adolescents with SA, demonstrating real-world clinical benefit.

Background Systemic corticosteroid (SCS) use remains widespread among patients with severe asthma, despite associated complications. Objective Evaluate the association between cumulative SCS exposure and SCS-related complications in severe asthma. Methods This retrospective, longitudinal study used claims data from the Optum Clinformatics Data Mart database (GSK ID: 214469). Eligible patients (≥ 12 years old) had an asthma diagnosis and were divided into two cohorts: SCS use and non/burst-SCS use. Patients in the SCS use cohort had a claim for a daily prednisone-equivalent dose ≥ 5 mg SCS following ≥ 6 months of continuous SCS use; those in the non/burst-SCS cohort had no evidence of continuous SCS use and had a non-SCS controller/rescue medication initiation claim. For each cohort, the date of the qualifying claim was the index date. SCS users were further stratified by SCS use during each quarter of follow-up: low (≤ 6 mg/day), medium (> 6–12 mg/day), high (> 12 mg/day), and continuous high (≥ 20 mg/day for 90 days). SCS-related complications were evaluated in the quarter following SCS exposure. The adjusted odds ratios (OR) of experiencing SCS-related complications during follow-up in each of the SCS use groups versus the non/burst SCS cohort were calculated using generalized estimating equations models. Results SCS and non/burst-SCS use cohorts included 7473 and 89,281 patients (mean follow-up: 24.6 and 24.2 months), respectively. Compared with the non/burst-SCS use cohort, medium, high, and continuous high SCS use was associated with greater odds of any SCS-related complication (adjusted OR [95% confidence interval]: 1.30 [1.21, 1.39], 1.49 [1.35, 1.64] and 1.63 [1.40, 1.89], respectively) including increased acute gastrointestinal, cardiovascular, and immune system-related complications, and chronic cardiovascular, metabolic/endocrine, central nervous system, bone-/muscle-related, ophthalmologic, and hematologic/oncologic complications. Low-dose SCS use was also associated with significantly increased odds of acute gastrointestinal and immune system-related complications, and chronic bone-/muscle-related and hematologic/oncologic complications versus the non/burst-SCS use cohort. Conclusion SCS use, even at low doses, is associated with increased risk of SCS-related complications among patients with severe asthma.

This study evaluated the real-world impact of switching to mepolizumab (a first-in-class monoclonal antibody targeting IL-5) from other biologics on reducing asthma exacerbations and oral corticosteroid (OCS) use in severe asthma patients.