The Effects of Stopping vs Continuing Mepolizumab for Severe Eosinophilic Asthma

In patients with severe eosinophilic asthma, continuing long-term treatment with mepolizumab has been shown to sustain clinically important improvements in health outcomes. However, patients who discontinued therapy experienced a higher risk for worsening asthma and reduced disease control, according to a study published in the journal ERJ Open Research.

For the current study, researchers analyzed results of the randomized, double-blind, placebo-controlled COMET study (ClinicalTrials.gov Identifier: NCT02555371) to determine the effects on clinically important health outcomes when stopping vs continuing long-term mepolizumab therapy in patients with severe eosinophilic asthma. In the COMET study, all patients were randomly assigned 1:1 to continue treatment with mepolizumab 100 mg subcutaneously every 4 weeks (n=144) or to discontinue mepolizumab (n=151), along with standard-of-care asthma therapy. At any time following an exacerbation, patients could switch to open-label mepolizumab. The health outcome endpoints evaluated included time to first asthma worsening (ie, composite endpoint of rescue use, symptoms, awakening at night, and morning peak expiratory flow [PEF]); patient-assessed and clinician-assessed global rating of asthma severity and overall perception of response to therapy; and unscheduled health care resource utilization.

To be eligible for enrollment in COMET, patients with severe eosinophilic asthma were required to have been treated with 3 years or more of continuous mepolizumab, with no break greater than 12 weeks between any 2 doses of mepolizumab.

Results of the study showed that patients who discontinued mepolizumab compared with participants who continued mepolizumab demonstrated a statistically significant increased risk for and a shorter time to first asthma worsening (hazard ratio [HR], 1.71; 95% CI, 1.17 to 2.52; P =.006), which included decreased asthma control (ie, increased risk for first worsening in  rescue use [HR, 1.36; 95% CI, 1.00 to 1.84; P =.047] and morning PEF [HR, 1.77; 95% CI, 1.21 to 2.59; P =.003]). Among patients who discontinued mepolizumab compared with those who continued treatment, a significantly higher likelihood of any unscheduled health care resource utilization was also reported (HR, 1.81; 95% CI, 1.31 to 2.49; P <.001). Further, both patients and clinicians reported greater asthma severity and a less favorable perceived response to treatment among those who stopped mepolizumab compared with those who continued treatment.

Patients who continued treatment with mepolizumab experienced milder asthma and a more favorable response to therapy.

“The data presented here, in conjunction with the primary COMET results, suggest that for patients with severe eosinophilic asthma, continued mepolizumab treatment sustains clinically important improvements in health outcomes perceived by both patients and clinicians, beyond 3 years, and that morning PEF could be a potential early predictive marker of loss of therapeutic response,” the study authors wrote.

Disclosure: 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  

Liu MC, Bel EH, Kornmann O, et al. Health outcomes after stopping long-term mepolizumab in severe eosinophilic asthma: COMET. ERJ Open Res. Published online January 10, 2022. doi:10.1183/23120541.00419-2021