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A Study to Evaluate Safety and Efficacy of Mepolizumab in Patients with Moderate Persistent Asthma

¹ Royal Gwent Hospital, Newport, Wales, United Kingdom; ² Allergy and Asthma Clinical Research Unit, University of Wisconsin-Madison, Madison, Wisconsin; ³ Respiratory and Inflammation Discovery Medicine, GlaxoSmithKline, Greenford, United Kingdom; ⁴ National Heart and Lung Institute, Imperial College London, London, United Kingdom; ⁵ National Jewish Medical and Research Center, Denver, Colorado; and ⁶ London Chest Hospital, London, United Kingdom

Correspondence and requests for reprints should be addressed to N. C. Barnes, F.R.C.P., London Chest Hospital, Bonner Road, London E2 9JX, UK. E-mail: neil.barnes{at}bartsandthelondon.nhs.uk

Rationale: Accumulation of eosinophils in the bronchial mucosa of individuals with asthma is considered to be a central event in the pathogenesis of asthma. In animal models, airway eosinophil recruitment and airway hyperresponsiveness in response to allergen challenge are reduced by specific targeting of interleukin-5. A previous small dose-finding study found that mepolizumab, a humanized anti–interleukin-5 monoclonal antibody, had no effect on allergen challenge in humans.

Objectives: To investigate the effect of three intravenous infusions of mepolizumab, 250 or 750 mg at monthly intervals, on clinical outcome measures in 362 patients with asthma experiencing persistent symptoms despite inhaled corticosteroid therapy (400–1,000 µg of beclomethasone or equivalent).

Methods: Multicenter, randomized, double-blind, placebo-controlled study.

Measurements and Main Results: Morning peak expiratory flow, forced expiratory volume in 1 second, daily ₂-agonist use, symptom scores, exacerbation rates, and quality of life measures. Sputum eosinophil levels were also measured in a subgroup of 37 individuals. Mepolizumab was associated with a significant reduction in blood and sputum eosinophils in both treatment groups (blood, P < 0.001 for both doses; sputum, P = 0.006 for 250 mg and P = 0.004 for 750 mg). There were no statistically significant changes in any of the clinical end points measured. There was a nonsignificant trend for decrease in exacerbation rates in the mepolizumab 750-mg treatment group (P = 0.065).

Conclusions: Mepolizumab treatment does not appear to add significant clinical benefit in patients with asthma with persistent symptoms despite inhaled corticosteroid therapy. Further studies are needed to investigate the effect of mepolizumab on exacerbation rates, using protocols specifically tailored to patients with asthma with persistent airway eosinophilia.

Key Words: anti–interleukin-5 • asthma • eosinophils • mepolizumab • monoclonal antibodies

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject IL-5 is believed to be a key cytokine in eosinophil function at sites of allergic inflammation. A previous small dose-finding study found the humanized anti–IL-5 monoclonal antibody mepolizumab had no effect on allergen challenge in humans. What This Study Adds to the Field Mepolizumab treatment does not appear to add significant clinical benefit in patients with asthma with persistent symptoms despite inhaled corticosteroid therapy.

 

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The Demise of Anti–IL-5 for Asthma, or Not

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