Mepolizumab discontinuation increases asthma exacerbations, blood eosinophil count

Continued mepolizumab treatment yielded sustained clinical benefit in most patients with severe eosinophilic asthma, according to data scheduled for presentation at the American Thoracic Society International Conference.

Wendy Moore

The randomized, double-blind, placebo-controlled, parallel-group, multicenter COMET study assessed patient outcomes following continued or discontinued mepolizumab (Nucala, GlaxoSmithKline) after long-term treatment. Eligible patients completed the COLUMBA or COSMEX trials, were treated with mepolizumab for 3 years or more and remained on asthma controller medication/therapy. Patients were randomly assigned to subcutaneous mepolizumab 100 mg every 4 weeks for 52 weeks or to discontinue mepolizumab and switch to placebo.

“The therapeutic effects of mepolizumab are sustained with long-term therapy and discontinuation of this therapy may lead to loss of asthma control and risk of exacerbations,” Wendy C. Moore, MD, professor of pulmonary, critical care, allergy and immunologic medicine at Wake Forest School of Medicine, told Healio.

The primary endpoint of the COMET study was time to first clinically significant asthma exacerbation. Secondary endpoints included time to decrease in asthma control, time to first asthma exacerbation requiring ED visits and/or hospitalization, and blood eosinophil count.

In total, 144 patients were randomly assigned to continued mepolizumab and 151 to placebo. Of those, 46% on the mepolizumab group experienced asthma exacerbations compared with 59% of the placebo group. Patients who continued mepolizumab had a significantly longer time to first clinically significant asthma exacerbation (HR = 0.62; 95% CI, 0.45-0.86) and time to decrease in asthma control (HR = 0.66; 95% CI, 0.49-0.88) compared with those who discontinued treatment. There were no differences in time to first asthma exacerbation requiring ED visits and/or hospitalization with continued or discontinued treatment (HR = 1.33; 95% CI, 0.5-3.51).

Patients continuing mepolizumab treatment maintained eosinophil count at 40 cells/L to 60 cells/L while eosinophil counts in patients who discontinued mepolizumab increased to 270 cells/L by week 12 (mepolizumab vs. placebo ratio = 0.19; 95% CI, 0.15-0.24; P < .001). The difference in eosinophil count between the two groups was maintained until week 52 (ratio = 0.16; 95% CI, 0.13-0.2; P < .001).

The incidence of exposure-adjusted adverse events were similar for both groups and the safety profile was consistent with previous mepolizumab trials, according to the researchers.

“Patients who stopped mepolizumab had an increase in blood eosinophil count, an increase in exacerbations, a shorter time to first exacerbation and a reduction in asthma control vs. those who continued mepolizumab,” Moore and colleagues wrote in the abstract. “These results support continued mepolizumab treatment having sustained clinical benefits in most patients with severe eosinophilic asthma.”