Discontinued Mepolizumab Treatment Increases Asthma Exacerbations

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A new study scheduled for presentation at the American Thoracic Society 2020 Virtual International Conference this August found continued mepolizumab treatment sustained clinical benefits in most patients with severe eosinophilic asthma.

“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 versus those who continued mepolizumab,” said researchers in the abstract. “These results support continued mepolizumab treatment having sustained clinical benefits in most patients with severe eosinophilic asthma.”

The randomized, double-blind, placebo-controlled, parallel-group, multicenter COMET study examined patient outcomes after continuing or discontinuing mepolizumab after long-term treatment.

Eligible patients completed the COLUMBA or COSMEX trials, received continuous mepolizumab treatment for ≥3 years (no treatment gaps ≥12 weeks), and remained on asthma controller medication. Patients were randomized to continue subcutaneous mepolizumab 100 mg every 4 weeks for 52 weeks or to stop mepolizumab and switch to placebo.

Primary endpoint was the time to first clinically significant exacerbation (ie, requiring systemic corticosteroids, emergency department [ED] visit or hospitalization); secondary endpoints included time to decrease in asthma control, time to first exacerbation requiring ED visit/hospitalization, and blood eosinophil count ratio to baseline.

Overall, 144 patients received mepolizumab and 151 received placebo (prior mean mepolizumab exposure 46.6 months). Of those, 46% of patients who continued mepolizumab vs 59% of patients who stopped mepolizumab and switched to placebo experienced an asthma exacerbation.

Patients continuing vs discontinuing mepolizumab had a significantly longer time to first clinically significant exacerbation (hazard ratio [HR]: 0.62 [95% confidence interval (CI): 0.45-0.86]; P=0.004) and longertime to decrease in asthma control (HR: 0.66 [95% CI: 0.49-0.88]; P=0.005). There was also no treatment difference in the time to first exacerbation requiring ED visit/hospitalization (HR: 1.33 [95% CI: 0.50-3.51]; P=0.570) between groups.

Also, patients who continued mepolizumab treatment maintained their eosinophil count at 40-60 cells/µL, while counts increased to 270 cells/µL by week 12 in patients who stopped the treatment (mepolizumab vs placebo ratio: 0.19 [95% CI: 0.15-0.24]; P<.001). This difference was seen until week 52 (HR: 0.16 [95% CI: 0.13-0.2]; P<.001).

Researchers also found the incidence of exposure-adjusted adverse events (AE) while receiving randomized treatment was similar for both groups and the safety profile was consistent with previous trials.