Mepolizumab may help reduce exacerbations in eosinophilic COPD
The addition of the monoclonal antibody interleukin-5 inhibitor mepolizumab to maintenance therapy appears to reduce the rate of exacerbations in patients with eosinophilic phenotype chronic obstructive pulmonary disease (COPD), according to results of the phase III METREX* and METREO** trials presented at ERS 2017.
Patients aged ≥40 years with COPD and a history of moderate or severe exacerbations in the previous 12 months were, in addition to inhaled glucocorticoid-based triple maintenance therapy, randomized to receive mepolizumab (100 mg in the METREX [n=417] and 100 [n=223] or 300 mg [n=225] in the METREO trials) or placebo (n=419 and 226 in the METREX and METREO trials, respectively) subcutaneously every 4 weeks for 52 weeks.
Patients in the METREX trial were stratified according to blood eosinophilic count (eosinophilic: ≥150/mm3 at screening or ≥300/mm3 in the previous year; noneosinophilic: <150/mm3 at screening and no evidence of ≥300/mm3 in the past year), while METREO participants were restricted to patients with eosinophilic phenotype COPD.
Fewer exacerbations with mepolizumab
In the METREX trial, patients with eosinophilic phenotype COPD (n=462) assigned to mepolizumab had a lower mean annual rate of moderate (requiring treatment with systemic glucocorticoids, antibiotics, or both) or severe (requiring hospitalization or resulting in death) exacerbations compared with those on placebo (1.40 vs 1.71 per year, rate ratio, 0.82, 95 percent confidence interval, 0.68–0.98; p=0.04). [N Engl J Med 2017;doi:10.1056/NEJMoa1708208; ERS 2017, abstract OA 3194]
In the METREO trial, the mean annual rate of exacerbations was lowest in patients on mepolizumab 100 mg, followed by mepolizumab 300 mg, and placebo, though the findings were not significant (1.19, 1.27, and 1.49 per year, corresponding to rate ratios of 0.80; p=0.07 and 0.86; p=0.14 in the 100 mg and 300 mg groups vs placebo, respectively).
Median time to first exacerbation was longer among patients with eosinophilic phenotype COPD on mepolizumab compared with placebo only in the METREX trial (192 vs 141 days, hazard ratio, 0.75; p=0.04).
A meta-analysis of both trials found that the impact of mepolizumab on exacerbation rate was more evident in patients with higher eosinophil counts.
“[T]hese trials show the importance of blood eosinophils in COPD exacerbations,” said the researchers. “These findings suggest that eosinophilic airway inflammation contributes to COPD exacerbations and that the use of mepolizumab directed by blood eosinophil counts might represent a precision-medicine approach to the management of COPD in selected patients who continue to have exacerbations despite inhaled glucocorticoid-based triple maintenance therapy,” they said.
Comparable safety profile
Adverse event (AE) and serious AE incidence was comparable between patients on mepolizumab and placebo in both trials, with the most common AEs being exacerbation or worsening COPD, nasopharyngitis, headache, and pneumonia. Antidrug antibodies were present in 4 and <1 percent of patients on mepolizumab and placebo, respectively in METREX, while in METREO, antidrug antibodies were present in 6, 2, and 1 percent of patients on mepolizumab 100 mg, 300 mg, and placebo, respectively.
The researchers acknowledged that the small number of events posed a limitation as did a lack of information on exacerbation triggers.
“The results of the current trials indicate that a subgroup of patients with COPD may benefit from biologic therapies, but I think that blood eosinophil count is an imperfect biomarker and that other disease factors confound the eosinophil signal, even in carefully selected subgroups,” said Professor Christine McDonald from the Department of Respiratory and Sleep Medicine, Austin Health, Victoria, Australia, in a commentary. [N Engl J Med 2017;doi:10.1056/NEJMe1710326]
“[T]hese trials should promote further prospective studies aimed at clarifying the role of eosinophils in COPD … [and] encourage the development of new strategies for further stratifying patients, as an alternative to focusing solely on eosinophils,” said McDonald.