Effect of Discontinuing Long-Term Mepolizumab on Asthma Exacerbation

Patients with severe eosinophilic asthma who stopped long-term mepolizumab therapy had more exacerbations and less disease control compared with patients who continued treatment, according to findings of the COMET study that were recently published in the European Respiratory Journal.

The COMET study (ClinicalTrials.gov Identifier: NCT02555371) explored the clinical effect of discontinuing mepolizumab treatment following long-term use. COMET, a randomized, double-blind, placebo-controlled, parallel-group, multicenter study, enrolled individuals who had completed the COLUMBA study (ClinicalTrials.gov Identifier: NCT01691859) or the COSMEX study (ClinicalTrials.gov Identifier: NCT02135692) and who had all received continuous treatment with mepolizumab for at least 3 years. Participants were randomly assigned in a 1:1 ratio into groups that either continued mepolizumab 100 mg every 4 weeks for an additional 52 weeks or stopped this therapy (ie, switched to placebo).

The primary study endpoint was the time to the first clinically significant exacerbation. The 151 participants who stopped mepolizumab had significantly shorter times to an initial clinically significant asthma exacerbation compared with the 144 participants who continued mepolizumab (hazard ratio [HR], 1,61; 95% CI, 1.17 to 2.22; P =.004).

Reductions in asthma control were also observed in those who stopped mepolizumab therapy vs those who continued (HR, 1.52; 95% CI, 1.13 to 2.02; P =.005). From week 12, worsening asthma control, based on increased scores on the Asthma Control Questionnaire-5 (ACQ-5), was observed in those stopping mepolizumab therapy vs those continuing (79.0% vs 63.1%, respectively); however, the 95% CI values overlapped. At week 52, differences in ACQ-5 scores were seen (hazard ratio [HR], 0.23; 95% CI, -0.02 to 0.48; P=.067) but were not statistically significant. Higher blood eosinophil counts were reported at week 52 in the stopping vs the continuing group (270 vs 40 cells/µL, respectively; HR, 6.19; 95% CI, 4.89-7.83; P<.001).

Participants who stopped mepolizumab therapy also demonstrated reductions in quality of life and lung function. Adverse events reported with mepolizumab were similar to those in prior studies. In participants who discontinued mepolizumab treatment, the safety profile was consistent with that observed in other populations of patients with eosinophilic asthma.

The investigators concluded that the findings from this study support the sustained clinical benefits of mepolizumab in patients with severe eosinophilic asthma, reinforcing that blood eosinophils are a suitable biomarker for mepolizumab treatment response.

Disclosure: This study was funded by GlaxoSmithKline. Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Moore WC, Kornmann O, Humbert M, et al. Stopping versus continuing long-term mepolizumab treatment in severe eosinophilic asthma (COMET study). Eur Respir J. Published online July 15, 2021. doi: 10.1183/13993003.00396-2021