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Background: Nasal polyps (NPs) are commonly associated with chronic rhinosinusitis (CRS). In keeping with the unified airway hypothesis, asthma and CRS with NP (CRSwNP) frequently co-occur, share a similar pathophysiology, and are often treated with oral corticosteroids (OCS); however, a need for alternative treatment options for patients with comorbid asthma and CRSwNP remains., Objective: To characterize the short- and long-term dual airway effectiveness of the anti-interleukin-5 monoclonal antibody, mepolizumab, in real-world patients with asthma and comorbid NP., Methods: Adult patients with CRSwNP who initiated mepolizumab from November 1, 2014, to September 30, 2021, were identified from 2 Merative MarketScan Research Databases. Outcomes were compared for the 12 months pre- and post-mepolizumab initiation and a variable follow-up period. Primary outcomes included the following: annual rate and proportion of patients with NP- and asthma-related exacerbations; NP surgery occurrences; all-cause OCS claims, number of OCS bursts, and daily OCS dose; all-cause and NP-related health care resource utilization., Results: During the 12 months post-index, patients experienced fewer NP- and asthma-related exacerbations, required fewer sinus surgeries, and reduced use of OCS, with fewer all-cause OCS claims and OCS bursts. Significant reductions in asthma exacerbation-related and NP-related health care resource utilization were also observed., Conclusion: This study illustrated the near- and long-term real-world effectiveness of mepolizumab treatment, with a focus on dual lower and upper airway benefit from single-agent add-on therapy. These results may aid physicians in clinical decision-making for patients with asthma and comorbid CRSwNP with complex care needs., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Trial data demonstrate that mepolizumab, a humanized anti-interleukin 5 monoclonal antibody, is effective for patients with severe asthma and comorbid chronic rhinosinusitis (CRS) with nasal polyps. This real-world, retrospective cohort study investigated mepolizumab for US patients with severe asthma and CRS with/without sinus surgery., Methods: IQVIA PharMetrics Plus claims data from baseline and follow-up (12 months before and after mepolizumab initiation) were used to analyze three patient cohorts: cohort 1 (severe asthma only); cohort 2 (severe asthma + comorbid CRS without sinus surgery); and cohort 3 (severe asthma+comorbid CRS+sinus surgery), allowing for cross-cohort comparisons., Results: The analysis included 495, 370, and 85 patients in cohort 1, cohort 2, and cohort 3, respectively. Systemic and oral corticosteroid use was lower for all cohorts after mepolizumab initiation. In cohort 3, asthma rescue inhaler and antibiotic use were lower during follow-up than baseline. Asthma exacerbations were reduced by 28% to 44% comparing follow-up versus baseline, with the largest reduction in cohort 3 (ratio of incidence rate ratio [RR] vs cohort 1: 0.76; p = 0.036). Reductions in oral corticosteroid claims were greater following mepolizumab initiation for cohort 3 versus cohort 1 (RR, 0.72; p = 0.011) and cohort 2 (RR, 0.70; p < 0.01). In cohorts 1 through 3, outpatient and emergency department visits were reduced by 1 to 2 and 0.4 to 0.6 visits annually, asthma-related and asthma exacerbation-related total costs were reduced by $387 to $2580 USD, and medical costs were reduced by $383 to $2438 USD during follow-up., Conclusions: Consistent with trial data, mepolizumab use in real-world practice shows benefits across comorbid patient cohorts with more a pronounced impact in those with severe asthma+comorbid CRS + sinus surgery., (© 2023 ARS-AAOA, LLC.)

Background/objective: Although the high disease burden associated with eosinophilic granulomatosis with polyangiitis (EGPA) has been established, the disease burden in patients initiating mepolizumab in real-world practice is poorly understood. This study aimed to assess characteristics and burden of real-world patients with EGPA initiating mepolizumab., Methods: This was a database study (GSK study ID: 214156) of US patients (≥12 years old) with EGPA and ≥1 mepolizumab claim (index date) identified from the Merative MarketScan Commercial and Medicare Supplemental Databases (November 1, 2015, to March 31, 2020). Outcomes assessed in the 12-month baseline period before index (inclusive) included patient characteristics, treatment use, EGPA relapses, asthma exacerbations, health care resource utilization, and costs., Results: In the 103 patients included (mean age, 51.1 years; 63.1% female), the most common manifestations were asthma (89.3%), chronic sinusitis (57.3%), and allergic rhinitis (43.7%). In total, 91.3% of patients had ≥1 oral corticosteroid (OCS) claim (median dose, 7.4 mg/d prednisone-equivalent), 45.6% were chronic OCS users (≥10 mg/d during the 90 days preindex), 99.0% had ≥1 EGPA-related relapse, and 62.1% ≥1 asthma exacerbation. During the baseline period, 26.2% and 97.1% of patients had EGPA-related inpatient admissions and office visits, respectively. Median all-cause total health care costs per patient were $33,298, with total outpatient costs ($16,452) representing the largest driver., Conclusions: Before initiating mepolizumab, a substantial real-world EGPA disease burden is evident for patients, with resulting impact on health care systems, and indicative of unmet medical needs. Mepolizumab treatment, with a demonstrated positive clinical benefit-risk profile may represent a useful treatment option for reducing EGPA disease burden., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The unified airway hypothesis proposes that upper and lower airway diseases reflect a single pathological process manifesting in different locations within the airway. Functional, epidemiological, and pathological evidence has supported this well-established hypothesis for some time. However, literature on the pathobiologic roles/therapeutic targeting of eosinophils and IL-5 in upper and lower airway diseases (including asthma, chronic rhinosinusitis with nasal polyps [CRSwNP], and nonsteroidal anti-inflammatory drug-exacerbated respiratory disease) has recently emerged. This narrative review revisits the unified airway hypothesis by searching the scientific literature for recent learnings and clinical trial/real-world data that provide a novel perspective on its relevance for clinicians. According to the available literature, eosinophils and IL-5 have important pathophysiological roles in both the upper and lower airways, although the impact of eosinophils and IL-5 may vary in asthma and CRSwNP. Some differential effects of anti-IL-5 and anti-IL-5-receptor therapies in CRSwNP have been observed, requiring further investigation. However, pharmaceutical targeting of eosinophils and IL-5 in patients with upper, lower, and comorbid upper and lower airway inflammation has led to clinical benefit, supporting the hypothesis that these are linked conditions manifesting in different locations. Consideration of this approach may improve patient care and aid clinical decision making., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess patient- and physician-reported reasons for discontinuing biologic therapy among patients with severe asthma from a real-world US cohort., Methods: This retrospective analysis surveyed US physicians and their patients with severe asthma who were receiving/had previously received biologic therapy between August and December 2019. Physicians managing ≥3 patients with asthma per month completed surveys on disease management, demographics, exacerbation history, and biologic adherence for eligible patients. Patients could voluntarily complete a questionnaire, providing perceptions of their disease and treatment., Results: 117 physicians completed case reports for 285 patients; 85 patients had discontinued biologic therapy. Physicians ( n  = 85) and patients ( n  = 64) reported patient request (28.2% and 46.9%), shortness of breath (45.9% and 23.4%), other chronic respiratory symptoms (29.4% and 10.9%), cost/reimbursement (17.7%/9.4% and 20.3%/7.8%), and exacerbations (25.9% and 10.9%) among the main reasons for biologic discontinuation. Patients who continued biologic therapy were older (mean age 47.6 years) than those who discontinued (43.8 years), and were more likely to have ≥2 exacerbations in the previous year (52.5% vs 35.3%), allergic rhinitis (70.0% vs 62.4%), or chronic rhinosinusitis (30.0% vs 12.9%). Side effects were cited as reasons by only 15.3% and 7.8% of physicians and patients, respectively., Conclusions: The most common reasons given for discontinuation of biologic therapy were lack of symptom control, exacerbations, cost, and patient request. These data highlight the complexity of care for this patient group and the need for ongoing, regular assessment of common challenges to biologic continuation and reasons for discontinuation, including both clinical and non-clinical factors.

Objective: Severe asthma is associated with substantial personal and economic burden; maintaining disease control is the key management goal. Increased understanding of asthma heterogeneity and development of type 2 (T2)-targeting biologics has substantially advanced disease management and outcomes; however, despite both being driven by T2 inflammation, allergic and eosinophilic asthma have different treatment recommendations. We sought to better understand the similarities and differences between allergic and eosinophilic asthma and highlight where misconceptions may arise., Data Sources: Published articles, pivotal trials, post hoc analyses, and asthma clinical guidelines sourced from PubMed., Study Selections: Sources reporting allergic and eosinophilic asthma classifications, disease mechanisms, and biomarkers associated with treatment response., Results: This review highlights that severe allergic and eosinophilic asthma are both driven by T2 inflammation with eosinophils playing a cardinal role. Despite this overlap, treatment recommendations differ based on asthma classification. T2 cytokine gene expression is a reasonably well-established research tool, but not a well-established biomarker in clinical practice, unlike blood eosinophil counts, fractional exhaled nitric oxide, and immunoglobulin E; the clinical relevance of immunoglobulin E as a predictive biomarker remains unclear., Conclusion: Asthma classifications that can be easily characterized at patient level to ensure accurate diagnosis, predict disease trajectory, and treatment response are required. The current dichotomy of allergic and eosinophilic asthma classifications is likely too simplistic, given the similar eosinophil-mediated disease pathophysiology in both classifications. Our results provide future directions to guide clinically meaningful interpretation of asthma endophenotypes, which may improve understanding of severe asthma characterization and aid future advances in defining responders more precisely with personalized medicine approaches., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Mepolizumab is a humanized anti-interleukin-5, monoclonal antibody approved for the treatment of patients with severe eosinophilic asthma (SEA). There is limited evidence that mepolizumab can reduce inhaled corticosteroid (ICS) use in these patients., Objective: To investigate changes in ICS use and clinical outcomes in patients with SEA who initiated mepolizumab treatment., Methods: This retrospective cohort study (GlaxoSmithKline identification: 212695/HO-20-19951) used administrative claims data from the IBM Watson Health MarketScan Database (identification period: November 2015 to March 2018). Eligible patients had SEA and were receiving high-dose ICS and mepolizumab. Use of ICS, oral corticosteroid (OCS), and short-acting β 2 -agonist and exacerbation frequency were analyzed quarterly during the 12-month follow-up period after mepolizumab initiation., Results: In total, 351 patients were included. The proportion of patients using high-dose ICS decreased in quarters 1 to 4 after mepolizumab initiation (79.8%, 74.6%, 68.9%, 65.5%, respectively); 49.0% of patients reduced or discontinued ICS for one or more quarter. Comparing patients who discontinued ICS vs those who remained on high-dose ICS, a lower proportion had chronic OCS use (3.4%-9.2% vs 13.9%-16.8%) and OCS burst use (15.4%-20.8% vs 19.7%-26.1%) in quarters 1 to 4; similarly in quarters 3 and 4, a lower proportion of patients had exacerbations (16.9% and 20.3% vs 27.2% and 27.7%) and short-acting β 2 -agonist claims (35.4% and 39.2% vs 43.3% and 49.0%, respectively)., Conclusion: In patients with SEA on high-dose ICS, a reduction in both ICS and OCS use was observed after initiating mepolizumab. These findings have important implications for clinical outcomes and follow-up care in this patient population., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Patients with life-threatening asthma typically experience recurrent exacerbations, are dependent on oral corticosteroids (OCSs), and have considerable asthma-related health care costs. Data on the impact of mepolizumab on exacerbations and OCS use in patients with life-threatening asthma in real-world clinical practice are limited. This study assessed the impact of mepolizumab on exacerbation rates and OCS use in patients with life-threatening asthma in a real-word setting., Methods: This retrospective study utilized data from US administrative claims from patients with life-threatening asthma. Eligible patients were treated between November 1, 2015, and December 31, 2017; were ≥12 years of age upon mepolizumab initiation (index date); and had undergone at least two mepolizumab administrations during the 6 months postindex. Data from the 12 months before (baseline) and after (follow-up) index were collected, with each patient serving as his or her own control. Life-threatening asthma was defined as at least three exacerbations and/or at least one asthma-related hospitalization during baseline, and/or a history of endotracheal intubation. Asthma exacerbation frequency and OCS use were assessed., Findings: The analysis included 327 patients who received a mean (SD) of 10.6 (4.3) mepolizumab doses during follow-up. The percentage of patients experiencing at least one exacerbation and the mean exacerbation rate were significantly reduced from baseline to follow-up with mepolizumab, from 94.5% to 67.9% (P < 0.001), and from 3.2 to 1.5 events per patient per year, corresponding to a 53.1% relative reduction (P < 0.001). The percentage of patients with OCS claims was reduced by 12.6%, from 99.1% to 86.5% (P < 0.001). Of the patients who had a reduction in mean daily OCS use, most (57.9%, 140/242) had a reduction in mean daily OCS use of at least 50%., Implications: These data from patients with life-threatening asthma in clinical practice demonstrated that asthma exacerbation and OCS use were significantly reduced with mepolizumab treatment., (Copyright © 2021. Published by Elsevier Inc.)

Background: Patients with severe asthma frequently have associated comorbidities, which can compound existing symptoms, complicating asthma management., Objective: To describe the real-world effectiveness of mepolizumab in patients with severe asthma stratified by common overlapping comorbidities., Methods: This was a retrospective analysis of patients with asthma from the MarketScan Commercial and Medicare Supplemental Database initiating mepolizumab treatment (index date). Eligible patients had more than or equal to 1 claim (excluding claims for diagnostic tests) with a diagnosis code for more than or equal to 1 of 7 comorbidities (atopic disease, nasal polyps, chronic sinusitis, obesity, respiratory infections, chronic obstructive pulmonary disease, and depression/anxiety) during the 12-month preindex baseline period; these were used to stratify patients into 7 nonmutually exclusive subgroups. Outcomes included asthma exacerbations and exacerbation-related health care resource utilization during the 12-month baseline and follow-up periods. Each patient acted as their own control., Results: Of the 639 patients included, the most common comorbidities were atopic diseases (73.2%), respiratory infections (55.6%), and chronic sinusitis (45.1%). Across all 7 comorbidity subgroups, there were significant (P < .05) reductions of 38% to 55% and 57% to 83% in exacerbations and exacerbations requiring hospitalization, respectively, during the follow-up vs baseline period, except for exacerbations requiring hospitalization in the nasal polyp subgroup, owing to the small subgroup sample size. During the follow-up vs baseline periods, mean number of oral corticosteroids claims was significantly (P < .001) reduced by 29% to 38%; 39% to 47% of patients achieved greater than or equal to 50% oral corticosteroids dose reduction. Significant reductions in exacerbation-related health care resource utilization were also observed., Conclusion: Mepolizumab treatment provided real-world clinical benefits in patients., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Real-world data on mepolizumab in patients with severe asthma and allergic and non-allergic phenotypes are limited. This study investigated the effectiveness of mepolizumab treatment in patients with severe asthma with allergic and non-allergic phenotypes. Patients and Methods: This retrospective cohort study (GSK ID: 214148) used administrative claims data from the Optum Research Database. Eligible patients were ≥ 6 years of age with asthma and had ≥ 2 mepolizumab claims post-index. Index date was the first mepolizumab claim/administration (January 2016–December 2018). Patients were divided into two cohorts: allergic and non-allergic asthma, based on diagnosis codes, medication use and lab test results. Outcomes included the rate of asthma-related exacerbations and oral corticosteroid (OCS) use during the 12 months before (baseline period) and 12 months after (follow-up period) mepolizumab initiation. Study ended in December 2019. Results: Overall, 240 (44.6%) and 298 (55.4%) patients were included in the allergic and non-allergic asthma cohorts, respectively. Mean (standard deviation [SD]) counts of asthma-related exacerbations were significantly reduced from baseline to follow-up in both the allergic and non-allergic asthma cohorts (3.2 [2.5] to 2.1 [2.1], p < 0.001 and 2.5 [2.2] to 1.7 [1.9], p < 0.001, respectively). The mean number of OCS pharmacy claims was significantly decreased by 33.3% and 41.4% from baseline to follow-up in the allergic and non-allergic cohorts, respectively (p < 0.001); mean daily OCS dose significantly decreased by 30.6% and 45.4%, respectively (p < 0.001) as well as the mean number of OCS bursts, which decreased by 44.9% and 41.8%, respectively (p < 0.001). No significant differences were observed between cohorts in reductions in asthma exacerbations, counts of OCS pharmacy claims or OCS bursts (baseline to follow-up). Conclusion: Mepolizumab significantly reduced asthma exacerbations and OCS use in patients with allergic and non-allergic asthma, suggesting that mepolizumab provides real-world benefit in severe asthma irrespective of whether a patient has an allergic phenotype. [ABSTRACT FROM AUTHOR]

Purpose: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with high healthcare resource utilization (HRU) and economic cost; however, heterogeneity of clinical burden among patients with differing clinical characteristics has not been fully elucidated. Here, an unsupervised machine learning approach supported by clinical validation identified distinct clusters of patients with CRSwNP and compared healthcare burden. Patients and Methods: This retrospective analysis identified adult patients with ≥ 2 claims for CRSwNP and date of first diagnosis (index date) between January 2015 and June 2019 from a healthcare database. Patients were required to have enrollment in the database 6-months pre- and 12-months post-index. Patients were assigned to clusters using latent class analysis. All-cause and nasal polyp (NP)-related HRU and costs were compared between clusters. Results: Among 12,807 patients, 5 clusters were identified: cluster 1: no surgery/low comorbidity/low medication use (n = 4076); cluster 2: no surgery/low comorbidity/high medication use (n = 2201); cluster 3: no surgery/high comorbidity/high medication use (n = 2093); cluster 4: surgery/low comorbidity/moderate medication use (n = 3168); cluster 5: surgery/high comorbidity/high medication use (n = 1269). All-cause HRU was similar across clusters. NP-related HRU was highest in the surgical clusters (clusters 4 and 5). All-cause costs were similar in clusters 1– 3 ($15,833–$17,461) and highest in clusters 4 ($31,083) and 5 ($31,103), driven by outpatient costs. Total NP-related costs were also highest for clusters 4 and 5 ($14,193 and $16,100, respectively). Conclusion: Substantial heterogeneity exists in clinical and economic burden among patients with CRSwNP. Machine learning offers a novel approach to better understand the diverse, complex burden of illness in CRSwNP. [ABSTRACT FROM AUTHOR]

Background: Patients with severe asthma often require oral corticosteroid (OCS) treatment. Clinical trials have demonstrated that mepolizumab can reduce OCS dependence, but real-world data are limited. Objective: To evaluate the impact of mepolizumab on OCS use, asthma exacerbations, and asthma exacerbation-related costs in a real-world setting. Methods: This retrospective cohort study (GSK ID: 209642; HO-19-19597) analyzed data from the MarketScan® Commercial database (identification period: November 2015–September 2017). Patients were ≥ 12 years old at mepolizumab initiation (index date), had a baseline asthma diagnosis, and received ≥ 2 mepolizumab administrations in the first 6 months of follow-up. OCS use, asthma exacerbation rate, and asthma exacerbation-related costs were assessed in the 12-months before (baseline) and 12-months after (follow-up) mepolizumab initiation. Results: Mepolizumab was associated with a 14.7% reduction in the proportion of patients with ≥ 1 OCS claim from baseline to follow-up (93.4% vs 79.7%; P< 0.001). The mean numbers of OCS claims/patient and OCS bursts (≥ 20 mg prednisone equivalents for 3‒28 days) between baseline and follow-up were also reduced by 29.1% (P< 0.001) and 36.8% (P< 0.001), respectively. Reductions in chronic OCS use were demonstrated during follow-up in patients with baseline mean OCS dose ≥ 5mg and those with a mean OCS dose ≥ 10mg 90 days before index; the proportion of patients with no OCS use also increased from 6.6% to 20.3% between baseline and follow-up. Conclusion: Our findings demonstrate that mepolizumab therapy is associated with reduced OCS use in patients treated in a real-world setting, potentially mitigating adverse health sequelae caused by OCS use in these patients. [ABSTRACT FROM AUTHOR]

B PURPOSE: b The MENSA (NCT01691521) and MUSCA (NCT02281318) trials showed that mepolizumab consistently reduced annualized asthma exacerbation rates in patients with severe eosinophilic asthma. B CONCLUSIONS: b Mepolizumab produced clinically relevant reductions in the exacerbation rate versus placebo in patients with severe eosinophilic asthma irrespective of baseline % predicted FEV1. [Extracted from the article]