An update on the currently available and emerging synthetic pharmacotherapy for uncontrolled asthma

ABSTRACT

Introduction

The treatment of uncontrolled asthma has improved because of triple therapy that includes a long-acting muscarinic antagonist (LAMA) and biological drugs, but several patients are resistant to corticosteroids and/or cannot achieve adequate asthma control using such therapies.

Areas covered

Herein, the authors review the current and emerging synthetic pharmacotherapy for uncontrolled asthma to overcome obstacles and limitations of biological therapies. The authors also provide their expert perspectives and opinion on the treatment of uncontrolled asthma

Expert opinion

LAMAs should be added to inhaled corticosteroid/long-acting β₂-agonist combinations much earlier than currently recommended by the Global Initiative for Asthma strategy because they can influence the course of small airways disease, reducing lung hyperinflation and improving asthma control. Biological therapies are a major advance in the treatment of severe asthma, but their use is still very limited for several reasons. An alternative to overcome the use of biological therapies is to synthesize compounds that target inflammation-signaling pathways. Several pathways have been identified as potential targets to design either therapeutic or prophylactic drugs against asthma. Some new compounds have already been tested in humans, but results have often been disappointing probably because existing phenotypic and endotypic variants may unpredictably limit the therapeutic value of blocking a specific pathway in most asthmatics, although there may be a substantial benefit for a subgroup of patients.

KEYWORDS:

• Uncontrolled asthma
• pharmacotherapy
• synthetic drugs
• bronchodilators
• anti-inflammatory agents

Article highlights

• The recommendations for the treatment of uncontrolled asthma have undergone a drastic change in the last decade.

• ICSs, LABAs and LAMAs are the mainstay of synthetic drug treatment of asthma, but in 4%-10% of patients, asthma remains uncontrolled.

• The current approach in these patients is to use targeted biological therapies, although such therapies do not always adequately control the disease.

• An alternative to overcome the use of biological therapies is to synthesise compounds that target inflammation-signalling pathways.

• Several new agents are under clinical development, but it is difficult to predict which ones will be approved for use in asthma because many attempts are proving to be partially, or even totally, ineffective.

Declaration of Interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This manuscript was not funded.