Anti-IL-4/IL-13 for the treatment of asthma: the story so far

ABSTRACT

Introduction: Severe asthma is a global health concern with high morbidity and mortality. Understanding of its complex pathophysiology continues to increase, providing specific immune targets for therapeutic intervention.

Areas covered: In this review, we focus on the role of IL-4 and IL-13 in severe asthma and on the biologic therapies developed to target them, particularly dupilumab, a monoclonal antibody against the IL-4 receptor α subunit and IL-4/IL-13 receptor complex. A literature search was undertaken for all studies of monoclonal antibodies against IL-4 and IL-13.

Expert Opinion: Dupilumab decreases the rate of severe asthma exacerbations and improves symptoms, lung function, and quality of life. Importantly, these effects are also observed during reduction of maintenance oral corticosteroid doses. Those with the highest T2 biomarkers derive the greatest benefit and the presence of atopic dermatitis or chronic rhinosinusitis with or without nasal polyposis may recommend dupilumab as the preferred biologic treatment for a patient.

KEYWORDS:

• T2 asthma
• biologics
• dupilumab
• IL-4
• IL-13

Article Highlights

• Type 2 inflammation is present in approximately 50% of severe asthmatics.

• The IL-4/IL-13 pathway is very important in asthmatics with type 2 inflammation.

• Dupilumab is a monoclonal antibody directed against the IL-4 receptor and IL-4/IL-13 receptor complex and has efficacy in decreasing exacerbation rates and symptoms, and improving lung function and quality of life in moderate to severe asthma.

• Dupilumab efficacy is not affected by reducing oral corticosteroid dose in corticosteroid-dependant asthmatics.

• Dupilumab has efficacy against type-2 inflammation-mediated comorbidities including chronic rhinosinusitis and nasal polyposis.

This box summarizes key points contained in the article.

Declaration of interest

A Moran has received speaker fees from AstraZeneca and sponsorship from AstraZeneca and Chiesi to attend international scientific meetings. In the last 5 years, ID Pavord has received speaker’s honoraria for speaking at sponsored meetings from Astra Zeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron and GSK and payments for organizing educational events from AZ, GSK, Sanofi/Regeneron and Teva. He has received honoraria for attending advisory panels with Genentech, Sanofi/Regeneron, Astra Zeneca, Boehringer Ingelheim, GSK, Novartis, Teva, Merck, Circassia, Chiesi and Knopp and payments to support FDA approval meetings from GSK. He has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, Astra Zeneca, Teva and Chiesi. He has received a grant from Chiesi to support a phase 2 clinical trial in Oxford. He is co-patent holder of the rights to the Leicester Cough Questionnaire and has received payments for its use in clinical trials from Merck, Bayer and Insmed. In 2014-5 he was an expert witness for a patent dispute involving Astra Zeneca and Teva. 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.