Pharmacotherapy of severe asthma

Severe asthma is a complex and heterogeneous phenotype where management can be challenging. While many patients with severe asthma respond to high-dose inhaled corticosteroids in combination with a long-acting beta-agonist, there remains a significant subset of patients that require oral corticosteroids to control symptoms. Alternative therapies are needed to help reduce the need for continuous oral corticosteroids; however, there are currently very few effective options. Several new alternatives to oral corticosteroids have been evaluated in severe asthma as add-on to conventional therapy. These include macrolide antibiotics, omalizumab, tumor necrosis factor-alpha inhibitors, cytokine receptor antagonists, and bronchial thermoplasty. The challenge with these entities is determining the appropriate phenotype of severe asthma where effectiveness is demonstrated, given the significant heterogeneity of the disease. Therefore, there is a crucial need to better understand the mechanisms and pathophysiology of severe asthma so more effective immunomodulators and biologic therapies can emerge.