After careful consideration, the American Thoracic Society canceled its annual meeting that was to take place in Philadelphia, Pennsylvania from May 15-20, because of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Although the live events will not proceed as planned, our readers can still find coverage of research that was scheduled to be presented at the meeting. A virtual event is being planned for later this year.


Patients with severe eosinophilic asthma who are treated with mepolizumab and subsequently stop treatment have increased blood eosinophil counts, increased disease exacerbations, shorter duration to first exacerbation, and reduced asthma control compared with patients who continue therapy, according to the results of the COMET (ClinicalTrials.gov Identifier: NCT02555371) trial intended to be presented at the American Thoracic Society (ATS) International Conference. (Select research is slated to be presented in a virtual format later this year.)

Patients with severe eosinophilic asthma were enrolled in the double-blind, multicenter COMET trial after completing the COLUMBA (ClinicalTrials.gov Identifier: NCT01691859) or COSMEX (ClinicalTrials.gov Identifier: NCT02135692) trials. Trial participants had received continuous mepolizumab for ≥3 years (prior mean exposure, 46.6 months) and received asthma controller therapy. Patients were randomly assigned to either continuous subcutaneous mepolizumab 100 mg every 4 weeks for 52 weeks (n=144) or placebo following mepolizumab cessation (n=151). If an exacerbation occurred, patients could switch back to open-label mepolizumab.

The primary end point of the trial was the time to first clinically significant exacerbation that required systemic corticosteroids, a visit to the emergency department (ED), or hospitalization. Secondary end points included time to decrease in asthma control, time to first exacerbation that required ED visit/hospitalization, and blood eosinophil count ratio.

Approximately 46% (n=66) of patients who continued mepolizumab treatment experienced an exacerbation, whereas 59% (n=89) of patients who stopped therapy had an exacerbation. Continuation of mepolizumab was associated with a significantly longer time to first clinically significant exacerbation compared with mepolizumab cessation (hazard ratio [HR], 0.62; 95% CI, 0.45-0.86; P =.004). Patients who continued therapy also had a longer time to asthma control reduction (HR, 0.66; 95% CI, 0.49-0.88; P =.005).

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By week 12, patients who continued on mepolizumab maintained their eosinophil counts at 40 to 60 cells/μL compared with an increase to 270 cells/μL in patients who stopped mepolizumab (mepolizumab vs placebo ratio, 0.19; 95% CI, 0.15-0.24; P <.001). This significant difference in eosinophil counts was maintained until week 52 (ratio, 0.16; 95% CI, 0.13-0.20; P <.001). No difference was observed between mepolizumab and placebo in terms of the incidence of exposure-adjusted adverse events (2740 vs 3098 adverse events/1000 patient-years exposure, respectively).

The researchers suggested their findings “support continued mepolizumab treatment having sustained clinical benefits in most patients with severe eosinophilic asthma.”

Disclosure: This clinical trial was supported by GlaxoSmithKline. Please see the original reference for a full list of authors’ disclosures.

Reference

Moore WC, Kornmann O, Humbert M, et al. Outcomes following continuation or stopping long-term mepolizumab treatment in patients with severe eosinophilic asthma: the randomized Comet trial. Am J Respir Crit Care Med. 2020;201:A4211.