Mixed results for biologic in eosinophilic COPD


20 Sep 2017

A subgroup of patients with COPD may benefit from biologic therapies, results of two Phase III trials suggest, but the jury is out on exactly which patients will benefit the most.

The METREX trial, presented at ERS and published in the NEJM found 100 mg subcutaneous mepolizumab (Nucala) every four weeks for 52 weeks when added to triple therapy significantly reduced the rate of exacerbations from 1.71 to 1.40 per year  in people with eosinophilic phenotype disease.

Time to the first exacerbation was also longer with mepolizumab than placebo (192 v 141 days).

However a second trial (METREO) failed to reproduce the findings, with 100 mg or 300 mg of the monoclonal antibody reducing the rate of exacerbations but not by a statistically significant amount.

Professor Christine McDonald, director of respiratory and sleep medicine at Austin Health, told the limbic the inconsistent findings may be related to underpowering of one study, the relatively low numbers of exacerbations overall, or other patient characteristics.

“There was a 18% reduction in moderate to severe exacerbations in METREX which was significant, and a 20% reduction in METREO which was not significant.”

“It is encouraging because of the positivity of METREX and also the signal in METREO even though it is non-significant.”

Professor McDonald said a number of retrospective studies had suggested blood eosinophil counts were a useful biomarker to target maximally treated patients who may benefit from agents such as the IL-5 inhibitor.

“More prospective studies are needed and these two studies provide important prospective data looking specifically at targeting the IL-5 pathway.”

“However, I don’t think these studies give us the fine grain detail of who exactly will benefit. Within the groups there were current and former smokers as well as non-smokers. Patients with current asthma were excluded but not smokers with past asthma, although non-smokers with past asthma were. Atopy was not specifically examined.”

“There may be other phenotypic factors which are important in determining response to treatment in COPD in conjunction with the degree of blood eosinophilia.”

Professor McDonald said in a NEJM editorial that IL-5 inhibitors have been found beneficial in patients with refractory eosinophilic asthma.

“The results of the current trials indicate that a sub-group of patients with COPD may benefit from biologic therapies, but I think that blood eosinophil count is an imperfect marker and that other disease factors confound the eosinophil signal, even in carefully selected subgroups.”

Already a member?

Login to keep reading.

Email me a login link