Mepolizumab Effectiveness In Asthma, Rhinosinusitis, and Sinus Surgery Patients
Overview
In this retrospective cohort study utilizing IQVIA PharMetrics Plus claims data, the effectiveness of mepolizumab, a humanized anti-interleukin 5 monoclonal antibody, was explored in a real-world setting for U.S. patients with severe asthma and comorbid chronic rhinosinusitis (CRS) with or without sinus surgery. The analysis involved three patient cohorts: cohort 1 (severe asthma only), cohort 2 (severe asthma with comorbid CRS without sinus surgery), and cohort 3 (severe asthma with comorbid CRS and sinus surgery), facilitating cross-cohort comparisons.
The study, including 495, 370, and 85 patients in cohorts 1, 2, and 3, respectively, revealed reduced systemic and oral corticosteroid use across all cohorts following mepolizumab initiation. Notably, in cohort 3, there was a decrease in asthma rescue inhaler and antibiotic use during follow-up compared to baseline. Asthma exacerbations demonstrated a reduction ranging from 28% to 44% in follow-up versus baseline, with the most significant decrease observed in cohort 3 (ratio of incidence rate ratio [RR] vs cohort 1: 0.76; p = 0.036). Furthermore, the study found greater reductions in oral corticosteroid claims following mepolizumab initiation for cohort 3 compared to cohorts 1 and 2.
Across cohorts 1 to 3, outpatient and emergency department visits were annually reduced by 1 to 2 and 0.4 to 0.6 visits, respectively. Moreover, asthma-related and asthma exacerbation–related total costs were decreased by $387 to $2580 USD, while medical costs were reduced by $383 to $2438 USD during follow-up.
The study concludes that mepolizumab, consistent with trial data, exhibits benefits in real-world practice across comorbid patient cohorts, with a more pronounced impact observed in individuals with severe asthma, comorbid CRS, and sinus surgery. These findings suggest the potential positive effects of mepolizumab in improving outcomes and reducing healthcare utilization and costs in patients with severe asthma and CRS in various clinical scenarios.
Introduction
This article addresses the frequent co-occurrence of asthma and chronic rhinosinusitis (CRS) in patients, indicating a shared inflammatory pathway in the upper and lower airways. The unified airway concept underscores the interconnectedness of these conditions, and studies have shown that treating one can positively impact the other. Sinus surgery is considered for CRS patients not responding to standard medical management, particularly for those with persistent symptoms after surgery, necessitating repeat procedures in a significant percentage.
Mepolizumab, an anti–interleukin 5 (IL-5) monoclonal antibody, known for its efficacy in severe eosinophilic asthma, is explored for its potential benefits in patients with comorbid asthma and CRS, especially those who have undergone sinus surgery. The drug inhibits IL-5, disrupting eosinophil activity and survival. While established as effective in clinical trials, real-world data on mepolizumab’s impact, particularly in patients with both asthma and CRS, are limited.
The study aims to fill this gap by retrospectively analyzing the real-world effectiveness of mepolizumab in a U.S. setting. Specifically, it investigates the drug’s influence on asthma exacerbations and the use of oral/systemic corticosteroids (OCS/SCS) in patients with asthma and comorbid CRS, including those with a history of sinus surgery. The focus on real-world scenarios aims to provide insights beyond clinical trial limitations, shedding light on the drug’s practical outcomes in diverse patient populations.
Method
In this retrospective cohort study (GSK ID: 214151), health plan claims data from the IQVIA PharMetricsR Plus database were utilized to assess patients initiating mepolizumab treatment between November 4, 2016, and March 1, 2019. The study aimed to explore the real-world effectiveness of mepolizumab in patients with severe asthma and comorbid chronic rhinosinusitis (CRS). The IQVIA database, comprising fully adjudicated medical and pharmacy claims, represented over 210 million unique enrollees, providing a comprehensive view of the commercially insured U.S. national record for patients that are aged 65 years and above.
Patients included in the study were aged ≥18 years, with continuous enrollment for ≥12 months during both baseline and follow-up periods. The cohorts were defined based on the presence of severe asthma, CRS, and sinus surgery. Cohort 1 consisted of patients with severe asthma only, while Cohort 2 involved those with severe asthma and comorbid CRS without sinus surgery. Cohort 3 included patients with severe asthma and comorbid CRS with sinus surgery. Subgroups within Cohorts 2 and 3 were further categorized into CRSwNP (with nasal polyps) and CRSsNP (without nasal polyps).
Outcomes and assessments covered patient demographics, clinical characteristics, medication use, asthma exacerbations, oral/systemic corticosteroid (OCS/SCS) use, healthcare resource utilization (HRU), and healthcare costs. Asthma exacerbations were defined as inpatient admissions or outpatient/emergency department claims with asthma diagnosis and corticosteroid prescription within a specific timeframe. OCS claims and HRU were quantified, and healthcare costs were analyzed, distinguishing asthma-related and asthma exacerbation–related costs. All costs were adjusted to 2020 Q1 in U.S. dollars.
The study utilized a robust methodology to analyze real-world data, providing valuable insights into the outcomes of mepolizumab treatment in diverse patient cohorts with severe asthma and comorbid CRS.
Statistical Analysis
In the study, a sample size calculation based on one-way analysis of variance determined that 62 patients in each cohort were needed to achieve 80% power for rejecting the null hypothesis. The null hypothesis posited no difference in the change in exacerbation rate across the three cohorts, assuming a type I error rate of 0.05 and attributing 5% of the total variation in the outcome to the cohort effect.
Patient demographics and clinical characteristics were reported as mean and standard deviation for continuous variables and counts and percentages for categorical variables. Statistical comparisons within cohorts or across cohorts during baseline and follow-up periods employed standardized differences, where a difference exceeding 20% indicated a meaningful imbalance. Comparisons within each cohort for asthma exacerbation rates, OCS claims per patient-year, and asthma-related or asthma exacerbation–related HRU utilized generalized linear models with a log link function and Poisson distribution. Incidence rate ratios (IRRs), corresponding 95% confidence intervals (CIs), and p-values were calculated using robust standard errors, and repeated measures were adjusted using generalized estimating equations.
Univariable generalized linear models were employed to compare asthma-related and asthma exacerbation–related costs per patient per year before and after mepolizumab initiation. Covariance among repeated measures was considered with an unstructured type, and 95% CIs and p-values were reported using robust standard errors.
For cross-cohort comparisons, asthma exacerbation rates, OCS claims, and asthma-related or asthma exacerbation–related HRU per patient-year before and after mepolizumab were compared between cohorts using univariable and multivariable generalized linear models for repeated measurements. Multivariable models were adjusted for baseline characteristics with standardized differences exceeding 20% between cohorts and other known confounders. Ratio of IRRs (RRs) between two cohorts, 95% CIs, and p-values were reported using robust standard errors.
Within cohort 2 and 3, patients were categorized into subgroups of CRSwNP and CRSsNP, and outcomes of interest before and after mepolizumab initiation were compared. Asthma-related and asthma exacerbation–related costs per person per year were compared across patient cohorts using univariable and multivariable generalized linear models, adjusting for baseline characteristics exceeding 20% standardized difference and other known confounders. Covariance among repeated measures was considered with an unstructured type, and 95% CIs and p-values were reported using robust standard errors.
Result
The retrospective cohort study involved 6,033,859 asthma patients, with 1124 meeting inclusion criteria. The three cohorts analyzed were: severe asthma only (495 patients, cohort 1), severe asthma with comorbid CRS without sinus surgery (370 patients, cohort 2), and severe asthma with comorbid CRS and sinus surgery history (85 patients, cohort 3). Mepolizumab use was similar across cohorts during the 12-month follow-up.
Baseline demographics differed, with cohort 3, particularly those with sinus surgery history, being younger, having more male patients, greater commercial insurance, and higher prevalence of allergic rhinitis and gastroesophageal reflux disease.
Regarding medication use, rescue inhaler and antibiotic use reduced during follow-up in cohort 3 with sinus surgery history. OCS and SCS use decreased in all cohorts during follow-up.
Asthma exacerbations decreased by 28-44% across cohorts during follow-up. In cohort 3 without nasal polyps, the reduction was greatest (49%). Cross-cohort comparisons showed a significantly greater reduction in asthma exacerbations for cohort 3 with sinus surgery compared to cohort 1 (severe asthma only).
OCS use reduced by 30-52%, with the greatest reduction in cohort 3 without nasal polyps (57%). Cross-cohort comparisons demonstrated significantly greater OCS reduction in cohort 3 with sinus surgery compared to both cohort 1 and cohort 2.
Healthcare resource utilization (HRU) decreased during follow-up for inpatient, ED, and outpatient visits in all cohorts. Asthma-related total costs and asthma exacerbation–related costs decreased across cohorts during follow-up, primarily driven by reduced outpatient costs.
In conclusion, mepolizumab demonstrated efficacy in reducing asthma exacerbations, OCS use, and HRU across diverse comorbid cohorts, with a more pronounced impact in severe asthma patients with comorbid CRS and sinus surgery history.
Conclusion
The retrospective cohort study underscores the clinical benefits of mepolizumab for patients with severe asthma and comorbid chronic rhinosinusitis (CRS), revealing reductions in asthma exacerbation rates, oral corticosteroid (OCS) use, asthma-related healthcare resource utilization (HRU), and costs. The study, inclusive of three cohorts with severe asthma, highlights the most significant improvements in asthma exacerbations and OCS reductions within the subgroup of patients with severe asthma and comorbid CRS who underwent sinus surgery before initiating mepolizumab.
The findings indicate that mepolizumab, evaluated through real-world data, provides meaningful insights into the typical patient experience in daily U.S. clinical practice, extending beyond the more controlled environments of randomized controlled trials. The study complements previous analyses, revealing enhanced clinical benefits of mepolizumab for patients with asthma and concomitant upper airway conditions like CRS, emphasizing improvements in asthma exacerbations, lung function, CRS symptoms, and health-related quality of life.
The enhanced efficacy observed in patients with severe asthma, CRS, and sinus surgery history may be attributed to the presence of robust characteristics of IL-5–associated disease and eosinophilia. Despite variations in cohorts, mepolizumab demonstrated benefits, suggesting that T2 inflammation and IL-5 play significant roles in severe asthma, irrespective of CRS and sinus surgery status. Additionally, the unified airway model, indicating shared pathological processes between upper and lower airway diseases, is supported by the study.
The study emphasizes the multidisciplinary approach required for patients with severe asthma and CRS, involving specialists such as allergists, pulmonologists, and ear, nose, and throat specialists. The consideration of mepolizumab as part of the therapeutic continuum, alongside sinus surgery, is underscored, raising interest in future studies examining mepolizumab’s impact on the need for subsequent sinus surgery.
The study’s strengths lie in its utilization of a large database of adjudicated U.S. medical and pharmacy claims, providing a representative view of commercially insured Americans aged ≤65 years. However, limitations include potential data quality issues, the absence of a control group, and the retrospective nature, relying on physician-diagnosed asthma. Despite these limitations, the findings support mepolizumab as an effective real-world treatment for severe asthma with comorbid respiratory conditions, offering valuable insights for physicians managing patients with complex upper and lower respiratory diseases.
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