Real-World Study Reinforces Mepolizumab's Effectiveness in Severe Eosinophilic Asthma

Mepolizumab (Nucala; GSK) demonstrated efficacy in a real-world pooled analysis of patients with severe eosinophilic asthma (SEA), particularly those with comorbid chronic rhinosinusitis with nasal polyps (CRSwNP). The study, which was published in Allergy, included data from 5 European cohorts, provides a better understanding of the monoclonal antibody's effectiveness beyond the controlled clinical trial setting, showing significant and sustained improvements in asthma outcomes.¹

Previous randomized controlled trials have established mepolizumab’s efficacy, but the new study aimed to analyze its performance in a diverse, real-world patient population. | Image credit: luchschenF - stock.adobe.com

Mepolizumab is a humanized monoclonal antibody that targets interleukin-5 (IL-5), a key cytokine in type 2 inflammation that is a hallmark of SEA and CRSwNP. It was first approved by the FDA in 2015 and is now indicated for the treatment of SEA, CRSwNP, chronic obstructive pulmonary disease, eosinophilic granulomatosis with polyangiitis, and hypereosinophilic syndrome.²

Although previous randomized controlled trials have established mepolizumab’s efficacy, this new study aimed to analyze its performance in a diverse, real-world patient population.¹ The analysis included 1037 adult patients with SEA, with or without CRSwNP.

The study showed a substantial reduction in the annual rate of clinically significant asthma exacerbations (CSEs) at 12 months after mepolizumab initiation for both patient groups. Patients with SEA but no CRSwNP saw a 72.7% reduction in CSEs (95% CI, 67.8%-76.9%), while those with both conditions experienced an even greater reduction of 79.7% (95% CI, 74.4%-83.8%). Notably, this shows a 30% (95% CI, 18.0-40.3) incremental benefit for patients with the comorbid condition.

In addition to the drop in exacerbation rates, mepolizumab was associated with a significant reduction in the use of oral corticosteroids, which are often prescribed to manage severe asthma but carry a high risk of long-term adverse effects, at 6 and 12 months of treatment.

Mepolizumab also led to improvements in lung function, as measured by forced expiratory volume in 1 second (FEV₁). The mean (SD) difference in FEV₁ from baseline was 120.99 mL (95% CI, 74.10-167.88; 6.56% increase) at 6 months and 152.59 mL (95% CI, 96.09-209.08; 8.27% increase) at 12 months for patients with SEA and CRSwNP, with continued improvements at 18 and 24 months.

Patient-reported Asthma Control Test (ACT) scores also improved with mepolizumab at 6 and 12 months after initiation, with a mean difference of 5.50 (95% CI, 4.78-6.23; 40.78% increase) at 6 months and 6.02 (95% CI 5.15, 6.89; 44.64% increase) at 12 months in patients with SEA only. In patients with both conditions, the mean difference was 6.01 (95% CI, 5.28-6.74; 41.61% increase) at 6 months and 5.77 (95% CI, 4.54-7.00; 39.95% increase) at 12 months.

These positive outcomes were observed regardless of the patient's baseline blood eosinophil count.

The study was limited by missing data from existing cohorts that may limit additional analyses, such as the correlation between outcomes and comorbidities. Some of the cohorts also included more patients than others, and there were some differences in baseline characteristics between the existing cohorts, the authors noted. Missing or variable data could potentially limit the study’s generalizability to the overall patient population being treated with mepolizumab, they added. Still, the findings reinforce the therapy’s efficacy in patients with SEA with or without CRSwNP.

“A key strength of this study is that by pooling existing real-world data, a robust analysis on a large population of patients was feasible; furthermore, the use of health care records for at least 12 months prior to [the] index date provided internal validity, with patients acting as their own controls,” the authors wrote. “This methodology highlighted improvements in multiple end points post-mepolizumab initiation, reinforcing the real-world effectiveness of mepolizumab in patients with type 2 [inflammation]–driven diseases.”

References

1. Schleich F, Loukides S, Chaudhuri R, et al. Mepolizumab effectiveness in severe asthma with/without chronic rhinosinusitis with nasal polyps: real-world pooled analysis. Allergy. Published online July 1, 2025. doi:10.1111/all.16618

2. Nucala FDA approval history. Drugs.com. Updated May 26, 2025. Accessed September 12, 2025. https://www.drugs.com/history/nucala.html