Abstract
Asthma is a common chronic inflammatory condition of the airways affecting over 300 million people world-wide. In 5%-10% of cases, it is severe, with disproportionate healthcare resource utilization including costs associated with frequent exacerbations and the long-term health effects of systemic steroids. Characterization of inflammatory pathways in severe asthma has led to the development of targeted biological and small molecule therapies which aim to achieve disease control while minimizing corticosteroid-associated morbidity. Herein, we review currently licensed agents and those in development, and speculate how drug therapy for severe asthma might evolve and impact on clinical outcomes in the near future.
Highlights
Asthma is a common airways disease, affecting over 300 million people worldwide [1], characterised by fluctuating symptoms of wheeze, dyspnoea, chest tightness and cough, accompanied by variable airflow obstruction [2].Current guidelines recommend that pharmacological therapy for uncontrolled disease is escalated in a step wise manner, without phenotypic differentiation, until a patient is classed to have severe asthma [2, 3]
Severe asthma is defined in those for whom ‘guidelines suggested medication for Global Initiative for Asthma (GINA) steps 4-5 asthma (high dose inhaled corticosteroids (ICS) and long-acting beta-2-agonists (LABA) or leukotriene receptor antagonist (LTRA)/theophylline) or regular oral corticosteroids are required for ≥50% of the previous year to prevent it becoming uncontrolled or which remains uncontrolled despite this therapy’
In this article we present an overview of the pathophysiology of severe asthma, use evidence from key clinical trials to discuss corresponding treatment options, and their impact upon different severe asthma phenotypes and specific clinical outcomes
Summary
Asthma is a common airways disease, affecting over 300 million people worldwide [1], characterised by fluctuating symptoms of wheeze, dyspnoea, chest tightness and cough, accompanied by variable airflow obstruction [2]. Following an initial study demonstrating good effect in patients with nasal polyposis [61], 2 parallel phase 3 trials were reported [62] which randomised 953 subjects on high dose asthma treatment with a history of exacerbations to 4weekly reslizumab infusions versus placebo, with the primary outcome exacerbation rate over 52 weeks. 3 serious adverse events were deemed related to the trial agent; one case of pneumonia and stroke in the same patient receiving low dose treatment, and one case of Guillain-Barre syndrome in the medium dose group These results confirm the significant role of epithelial cytokines in asthma pathogenesis and suggest that targeting upstream cytokine pathways may improve control across inflammatory profiles, representing a promising option for those with T2 disease and possibly beyond T2-mediated inflammation
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