O4.3 Biologic therapies

Recent post hoc analyses of data from a number of studies involving patients with COPD have highlighted the blood eosinophil count as a potentially important biomarker of response to glucocorticoid treatment, but it is not known whether targeting interleukin-5 to reduce eosinophil activity can also affect clinical outcomes in COPD. A phase 2a trial of benralizumab,  a humanized monoclonal antibody to interleukin-5 receptor alpha, did not demonstrate benefit in terms of exacerbations  or quality of life in a group of patients with COPD who had at least one exacerbation in the preceding year and a sputum count of ≥ 3% in the preceding year, however the investigators felt that a prespecified  subgroup analysis of patients with higher blood eosinophil counts supported further investigation  of the effects of this drug in patients with COPD and eosinophilia (Brightling 2014).  Pavord and colleagues have compared the interleukin-5 inhibitor mepolizumab with placebo in patients with COPD in two 12-month randomised, controlled, parallel-group trials (METREX and METREO) (Pavord 2017). In METREX, the annual rate of moderate or severe exacerbations was significantly lower in the mepolizumab group than in the placebo group (1.4 vs. 1.71 per year; rate ratio, 0.82; 95% CI, 0.68 to 0.98; P = 0.04). The time to first exacerbation was also significantly longer in the mepolizumab group than in the placebo group, but there were no significant differences in outcomes when patients were not stratified according to eosinophilic phenotype. In contrast, no significant differences in exacerbation rates were detected in METREO. There was no significant between-group difference in the rate of exacerbations that led to an emergency department visit or hospitalisation or in measures of patients’ symptoms in either trial.

The results of the current trials indicate that an eosinophilic subgroup of patients with COPD may benefit from biologic therapies, although it is noted that, although patients with current asthma were excluded, those with a past history of asthma or atopy were not. Further prospective studies are awaited.