Blood eosinophil count, exacerbation rate, and time to exacerbation were all bettered among patients who sustained therapy versus those who discontinued.
Wendy C. Moore, MD
Continued mepolizumab (NUCALA) was associated with decreased blood eosinophil count and exacerbations, as well as a longer time to exacerbations, compared to patients with asthma who discontinued therapy, according to new study findings.
In new GlaxoSmithKline-funded COMET trial data planned for presentation at the American Thoracic Society (ATS) 2020 International Conference this year, a team of investigators reported sustained clinical benefits in patients with severe eosinophilic asthma who received continuous mepolizumab for ≥3 years without treatment gaps of ≥12 weeks.
The long-term efficacy and safety findings from the follow-up assessment of COLUMBA and COSMEX trial patients extends clinical understanding of the benefit of the interleukin-5 (IL-5) biologic.
Investigators, led by Wendy C. Moore, MD, of the Wake Forest School of Medicine, sought to examine outcomes of continued versus stopped mepolizumab after long-term treatment. COMET was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study including eligible patients who completed the COLUMBA or COSMEX trial.
Patients had received continuous mepolizumab treatment for ≥3 years and remained on asthma controller medication or therapy.
Moore and colleagues randomized patients 1:1 to subcutaneous mepolizumab 100 mg every 4 weeks for 52 weeks, or stopped mepolizumab for a switch to placebo. Patients were able to switch back to open-label mepolizumab following an exacerbation.
Investigators assessed for a primary endpoint of time to first clinically significant exacerbation—defined as an even requiring systemic corticosteroids, emergency department (ED) visit, or hospitalization.
Secondary endpoints included time to decreased asthma control as per Asthma Control Questionnaire-5 score increase by ≥0.5 points from baseline; time to first exacerbation requiring ED visit/hospitalization’ and blood eosinophil count ratio to baseline.
Cox proportional hazards models and mixed model repeated models adjusted for coviarates were used to assess intent-to-treat population endpoints.
The observed population included 295 patients (144 mepolizumab; 151 placebo). Prior mean mepolizumab exposure in patients was 46.6 months.
Exacerbations were reported in just 46% of patients who continued therapy, versus 59% of patients switched to placebo. Time to first exacerbation was significantly longer in patients on mepolizumab than placebo (hazard ratio [HR], 0.62; 95% CI, 0.45-0.86; P = .004).
Time to decrease in asthma control was also significantly longer in treated patients versus placebo (HR, 0.66; 95% CI, 0.49-0.88; P = .005). No treatment difference in the time to first exacerbation requiring ED visit per hospitalization following few events in both groups were observed (HR, 1.33; 95% CI, 0.50-3.51; P = .57).
Patients who continued mepolizumab maintained an eosinophil count at 40-60 cells/µL, while placebo patient counts increased to 270 cells/µL by week 12—a difference maintained until week 52 (HR, 0.16; 95% CI, 0.13-0.20; P <.001).
In assessing for safety, Moore and colleagues reported a similar incidence of exposure-adjusted averse events between treatment arms (2740 vs 3098 per 1000 patient-years). The safety profile, overall, was consistent with previous trials.
“These results support continued mepolizumab treatment having sustained clinical benefits in most patients with severe eosinophilic asthma,” investigators concluded.
The study, “Outcomes Following Continuation or Stopping Long-Term Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma: The Randomized Comet Trial,” was published online by ATS.