Paul M O'Byrne1. 1. Department of Medicine, McMaster University, Hamilton, Ontario, Canada. obyrnep@mcmaster.ca
Abstract
BACKGROUND: Patients with severe refractory asthma represent a small subset of the asthmatic population (between 5% and 10% of all patients) but are the greatest burden to the health care system. New treatment approaches developed to manage some of the phenotypes of severe refractory asthma have included humanized monoclonal antibodies (hMabs). OBJECTIVE: To review the evidence and ascertain whether hMabs provide clinical benefit to patients with severe refractory asthma. METHODS: Studies that examined the efficacy of hMabs against immunoglobulin (Ig) E, tumour necrosis factor-alpha, interleukin (IL)-5, and IL-4⁄IL-13 in patients with severe refractory asthma were reviewed and summarized. RESULTS: Treatment with anti-IgE improved asthma control and reduced severe exacerbations in patients with severe asthma and elevated serum IgE levels. Treatments with hMabs that block tumour necrosis factor-alpha are unlikely to be useful in asthma treatment. In contrast, hMabs that block IL-5 have consistently shown benefit in reducing severe exacerbations in patients with severe refractory asthma with persistent eosinophilia. Finally, hMabs that block IL-13 may provide benefit in patients with elevated blood periostin levels. DISCUSSION: hMabs that block IgE are approved for the treatment of allergic asthma. It is likely that blocking IL-5 will also provide benefit in patients with severe asthma with persistent eosinophilia. These studies have emphasized the importance of careful phenotyping of patients with severe refractory asthma before embarking on treatment with hMabs.
BACKGROUND:Patients with severe refractory asthma represent a small subset of the asthmatic population (between 5% and 10% of all patients) but are the greatest burden to the health care system. New treatment approaches developed to manage some of the phenotypes of severe refractory asthma have included humanized monoclonal antibodies (hMabs). OBJECTIVE: To review the evidence and ascertain whether hMabs provide clinical benefit to patients with severe refractory asthma. METHODS: Studies that examined the efficacy of hMabs against immunoglobulin (Ig) E, tumour necrosis factor-alpha, interleukin (IL)-5, and IL-4⁄IL-13 in patients with severe refractory asthma were reviewed and summarized. RESULTS: Treatment with anti-IgE improved asthma control and reduced severe exacerbations in patients with severe asthma and elevated serum IgE levels. Treatments with hMabs that block tumour necrosis factor-alpha are unlikely to be useful in asthma treatment. In contrast, hMabs that block IL-5 have consistently shown benefit in reducing severe exacerbations in patients with severe refractory asthma with persistent eosinophilia. Finally, hMabs that block IL-13 may provide benefit in patients with elevated blood periostin levels. DISCUSSION: hMabs that block IgE are approved for the treatment of allergic asthma. It is likely that blocking IL-5 will also provide benefit in patients with severe asthma with persistent eosinophilia. These studies have emphasized the importance of careful phenotyping of patients with severe refractory asthma before embarking on treatment with hMabs.
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