Biological therapies for eosinophilic asthma

ABSTRACT

Introduction: Severe uncontrolled asthma is by definition refractory to traditional therapies or can be controlled only with therapies that have intolerable side effects. Monoclonal antibodies that target interleukin (IL)-5/IL-5Rα, IgE, and IL-4Rα have shown favorable results in clinical trials, including reductions in asthma exacerbations and other important clinical outcomes. These biological agents offer treatment alternatives to patients with uncontrolled severe eosinophilic asthma.

Areas covered: This article reviews how the shifting emphasis toward identifying distinct asthma phenotypes has led to the approval of biological therapies that preferentially benefit patients with severe eosinophilic asthma. The clinical trials that led to the approval of these biologic treatments are discussed in detail.

Expert opinion: Biologic therapies targeting the IL-5, IgE, IL-4/IL-13 signaling pathways have been successful in clinical trials in subjects with severe eosinophilic asthma. Some of these agents have also been successful regardless of peripheral blood eosinophil counts. These treatments have shown a relatively favorable safety profile in clinical trials, although long-term safety data for some of these agents are limited. Due to the high costs associated with these medications, they should be reserved for select patients where they yield a therapeutic and pharmacoeconomic advantage.

KEYWORDS:

• Asthma
• eosinophil
• monoclonal antibody
• mepolizumab
• reslizumab
• omalizumab
• dupilumab
• benralizumab
• IL-5
• IgE
• IL-4
• IL-13

Article highlights

• Approximately 5–10% of asthmatics have severe asthma that is refractory to treatment, accounting for approximately 50% of asthma-related health-care costs.

• Over the past two decades, emphasis has been placed on identifying asthma phenotypes and endotypes to create individualized therapy for subjects with severe asthma refractory to treatment.

• Clinical trials show efficacy and favorable safety profile for monoclonal antibodies targeting IL-5, IgE, IL-4/IL-13 signaling pathways for individuals with severe eosinophilic asthma.

• Long-term safety data are limited for many of these agents.

• High costs associated with these agents warrant careful selection.

This box summarizes key points contained in the article.

Declaration of interest

T. B. Casale has received grants and consulting fees to his university employer from Teva, Sanofi-Genzyme, Novartis, Astra Zeneca, Genentech. 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.

Additional information

Funding

This paper was not funded.