An evaluation of mepolizumab for the treatment of severe asthma

ABSTRACT

Introduction: Asthma is considered one of the most common chronic conditions globally, characterized by variable airflow obstruction and symptoms. Severe asthma is diagnosed when asthma control requires high-intensity therapy or continues to remain uncontrolled despite treatment. Eosinophilic inflammation is known to be perpetuated by the activity of IL-5 in a proportion of severe asthma subjects, and targeting IL-5 may offer a therapeutic option.

Areas covered: In this review, we discuss the role and pathogenesis of IL-5 and eosinophils in asthma and rationale of antagonizing IL-5 in severe eosinophilic asthma. Mepolizumab is the first of three anti-IL-5 biologics licensed in 2015 for use in this subgroup of patients. We discuss clinical and real-life studies leading up to its approval and post-marketing outcomes in terms of efficacy and safety to-date, as well as its pros and cons.

Expert opinion: IL-5 antagonism has paved the way for an additional personalized therapeutic opportunity for use in severe asthma with eosinophilic inflammation, though there is limited evidence on the long-term implications of suppressing/depleting eosinophils and the duration for which they should be administered.

Trial registration: ClinicalTrials.gov identifier: NCT02555371.

Trial registration: ClinicalTrials.gov identifier: NCT01290887.

Trial registration: ClinicalTrials.gov identifier: NCT02452190.

KEYWORDS:

• Severe asthma
• eosinophilic asthma
• anti-Il-5 therapies
• biologics
• mepolizumab

Box 1. Drug summary

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Article highlights

• Severe asthma is a challenging condition to manage with a considerable social economic impact.

• Patients with severe asthma and eosinophilia (in blood and sputum) are associated with having poor control of their condition as well as prone to severe exacerbations.

• Anti-IL-5 agents have been licensed for use in severe eosinophilic asthma with significant improvements in subjective parameters as well as exacerbations rates.

• Mepolizumab, one of the earliest licensed anti-IL-5 biologic, has been demonstrated to not only be efficacious but also safe in this subgroup of severe asthma patients in clinical as well as real-life studies.

This box summarizes key points contained in the article.

Declaration of interest

JB Morjaria has received honoraria for speaking and financial support to attend meetings/advisory boards from Wyeth, Chiesi, Pfizer, MSD, Boehringer Ingelheim, Teva, GlaxoSmithKline, Napp, Almirall, AstraZeneca, Trudell Medical International and Novartis Pharmaceuticals UK. R Polosa has received grant support from CV Therapeutics, NeuroSearch A/S, Sandoz, Merck Sharp & Dohme, and Boehringer Ingelheim; has served as a speaker for CV Therapeutics, Novartis,Merck Sharp & Dohme, and Roche; has served as a consultant for CV Therapeutics, Duska Therapeutics, Neuro-Search A/S, Boehringer Ingelheim, and Forest Laboratories; and has received payment for developing educational presentations from Merck Sharp & Dohme, Pfizer, and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.