Drug evaluation: mepolizumab in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality globally, marked by persistent respiratory symptoms and exacerbations. It is now acknowledged to be a heterogeneous disease with respect to clinical expression and key driving mechanisms. Standard therapies, including bronchodilators and corticosteroids, often fail to adequately control symptoms and exacerbations in patients and there is an important unmet need for new treatments. There has been encouraging progress with biological treatments for patients with COPD and type-2 airway inflammation, a phenotype found in approximately 40% of COPD cases. The first of these, Mepolizumab, is a monoclonal antibody targeting interleukin-5 (IL-5), and thereby reducing blood and tissue eosinophil numbers. Here we review the initial clinical trial data with mepolizumab in type-2 high COPD. We suggest that the modest efficacy seen in patients with severe disease may not be reflective of the impact of treatment in patients with active type-2 inflammation and less associated lung and extra-pulmonary damage. We suggest that the way forward is to assess whether clinically important modification of disease course occurs with treatment in patients with high disease activity and low associated damage.