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Observational Study
. 2024 Nov;41(11):4008-4031.
doi: 10.1007/s12325-024-02967-x. Epub 2024 Aug 31.

Real-World Effectiveness of Mepolizumab in Severe Asthma: Results from the Multi-country, Self-controlled Nucala Effectiveness Study (NEST)

Riyad Omar Al-Lehebi  1   2 , Mona Al Ahmad  3 , Venkata Nagarjuna Maturu  4 , Alejandra Galeano Mesa  5 , Bassam Mahboub  6 , Elizabeth Garcia  7 , Patricia Fernandez  8 , Claudia Soares  9 , Gabriela Abreu  9 , Debora Dos Santos  9 , Juliana Queiroz  9 , Alejandro Raimondi  10 , Maria Laucho-Contreras  11   12 , Saeed Noibi  13 , Gur Levy  14 , Sevim Bavbek  15
Affiliations
Observational Study

Real-World Effectiveness of Mepolizumab in Severe Asthma: Results from the Multi-country, Self-controlled Nucala Effectiveness Study (NEST)

Riyad Omar Al-Lehebi et al. Adv Ther. 2024 Nov.

Abstract

Introduction: The Nucala Effectiveness Study (NEST) assessed the effectiveness of mepolizumab in patients with severe asthma (SA) in countries previously underrepresented in real-world studies.

Methods: A multi-country, bi-directional, self-controlled, observational cohort study conducted in Colombia, Chile, India, Türkiye, Saudi Arabia, United Arab Emirates, Kuwait, Oman, and Qatar. Historical and/or prospective data from patients with SA were assessed 12 months pre- and post-mepolizumab initiation.

Primary endpoint: incident rate ratio (IRR) of clinically significant exacerbations (CSEs). Key secondary endpoints: healthcare resource utilisation (HCRU), oral corticosteroid (OCS) use, lung function and symptom control (Asthma Control Test [ACT] scores).

Results: Overall, 525 patients with SA burden pre-initiation (geometric mean blood eosinophil count [BEC] 490.7 cells/µl; 31.4% prior biologic use; 37.3% obese) received at least one dose of mepolizumab 100 mg subcutaneously. Post-initiation, a significant reduction in CSEs was observed (76% [p < 0.001]; IRR [95% confidence interval] 0.24 [0.19-0.30]); 72.0% of patients had no CSEs. Mepolizumab treatment led to a reduction in OCS use (52.8% pre-initiation vs. 16.6% post-initiation) and a mean (standard deviation [SD]) change in OCS dose of - 18.1 (20.7) mg post-initiation; 36.1% of patients became OCS-free. Fewer patients were hospitalised post-initiation (22.5% pre-initiation vs. 6.9% post-initiation). Improvements in mean (SD) forced expiratory volume in 1 s (62.8 [20.2]% pre-initiation vs. 73.0 [22.7]% post-initiation) and ACT scores (15.0% pre-initiation vs. 64.5% of patients post-initiation with well-controlled asthma) were observed. Proportion of patients with BEC ≥ 500 cells/µl decreased from 84.4% pre-initiation to 18.1% post-initiation.

Conclusion: Mepolizumab was effective in reducing the burden of SA by significantly reducing CSEs, reducing OCS use and HCRU, and improving lung function and asthma control, which could translate to improvements in health-related quality of life in patients with SA and high OCS dependency in the countries studied. A graphical abstract is available with this article.

Keywords: Antibodies; Asthma; Biological therapy; Corticosteroids; Interleukin-5; Low-middle-income countries; Mepolizumab; Monoclonal.

Plain language summary

Severe asthma occurs when asthma symptoms remain uncontrolled despite optimised treatment. In many low-middle income countries, and in some countries in the Middle East, Asia, Latin America and the Arab Gulf, the management and treatment of patients with severe asthma remain poor, with many patients having unscheduled hospital visits or admission, and use of steroids for a prolonged period. Mepolizumab is an injectable monoclonal antibody approved as an add-on treatment for severe asthma in patients ≥ 6 years of age. In clinical trials, mepolizumab has demonstrated reductions in the risk of clinically significant exacerbations (CSE; an asthma exacerbation that requires systemic corticosteroids and/or an emergency room visit and/or hospitalisation) and the need for oral corticosteroid (OCS) treatment in patients with severe asthma by reducing inflammation caused by eosinophil (a type of white blood cell) production. The Nucala Effectiveness Study (NEST) was performed to observe the effectiveness of mepolizumab in people with severe asthma in Colombia, Chile, India, Turkey, Saudi Arabia, United Arab Emirates, Kuwait, Oman and Qatar. The frequency of CSEs and other outcomes was compared 12 months pre- and post-mepolizumab initiation. Post-initiation, the risk of CSEs was significantly reduced by 76% (p < 0.001), and 72% of patients had no CSEs. Fewer patients were dependent on OCS, with 36.1% of patients not using OCS at all, and fewer patients were hospitalised. Lung function and asthma control also improved. NEST shows that mepolizumab could benefit people with severe asthma living in countries where disease-related burden and OCS use remain high.

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Conflict of interest statement

Riyad Omar Al-Lehebi has given lectures at meetings supported by AstraZeneca, Boehringer Ingelheim, GSK and Sanofi, and received advisory board fees from GSK. Mona Al Ahmad received lecture and advisory board honoraria from Sanofi, GSK and AstraZeneca. Venkata Nagarjuna Maturu has given lectures at meetings supported by AstraZeneca, GSK, Novartis, Sun Pharma, Cipla and Lupin, and participated in advisory boards with AstraZeneca and GSK. Alejandra Galeano Mesa has no conflicts of interest to report. Bassam Mahboub is a speaker for AstraZeneca, GSK and Sanofi. Elizabeth Garcia reports having been a speaker for Sanofi, Novartis, and Pfizer and received advisory board fees from GSK, Sanofi and Novartis. Patricia Fernandez reports having been a speaker for AstraZeneca, GSK, Sanofi and Teva, and participated in advisory boards with AstraZeneca, GSK and Sanofi. Claudia Soares, Alejandro Raimondi, Maria Laucho-Contreras, Saeed Noibi and Gur Levy are employed by GSK and hold financial equities in GSK. Gabriela Abreu and Juliana Queiroz are complementary employees of GSK and do not hold financial equities in GSK. Debora dos Santos was a complementary worker of GSK at the time of the study analysis. Debora dos Santos’ current affiliation is a postdoctoral fellowship at University of Brasilia under the Program of Collective Health. Sevim Bavbek has given lectures at meetings supported by AstraZeneca, GSK and Novartis, and reports receipt of advisory board fees from AstraZeneca, GSK and Novartis.

Figures

Fig. 1
Fig. 1
Study design. Mo month
Fig. 2
Fig. 2
Distribution of CSEs pre- vs. post-mepolizumab initiation. Data available for 472 patients pre-mepolizumab initiation and 493 patients in the post-mepolizumab initiation; proportions calculated with appropriate denominator. CSE clinically significant exacerbation
Fig. 3
Fig. 3
CSEs that required hospitalisation (i) and length of hospital stay (ii). Values displayed as text in the graphs are (i) the proportion of patients and (ii) the mean length of hospital stay. CSE clinically significant exacerbation, SD standard deviation
Fig. 4
Fig. 4
Proportion of patients who used OCS (i) and the changes in OCS usage (ii) pre- vs. post-mepolizumab initiation. OCS oral corticosteroid
Fig. 5
Fig. 5
Pre-bronchodilator FEV1 and pre-bronchodilator FVC pre- vs. post-mepolizumab initiation. FEV1 data only available for 129 and 87 patients pre- and post-mepolizumab initiation, respectively. FVC data only available for 131 and 88 patients pre- and post-mepolizumab initiation, respectively. FEV1 forced expiratory volume in one second, FVC forced vital capacity, SD standard deviation
Fig. 6
Fig. 6
ACT scores pre- vs. post-mepolizumab initiation. Results from patients that received 12 doses of mepolizumab 100 mg over the 12-month period post-mepolizumab initiation (data available for: pre-mepolizumab initiation, n = 240; post-mepolizumab initiation, n = 172); proportions calculated with appropriate denominator. ACT Asthma Control Test
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