Evidence from a phase 3 trial indicates that patients with severe eosinophilic asthma who stopped mepolizumab after 3 years or more of use had worsened outcomes compared with patients who continued on the drug, according to recent research originally released as an abstract for the American Thoracic Society (ATS) Conference 2020.
“As the first-in-class anti-IL5 biologic approved by the FDA in 2015, the efficacy and safety of Nucala (mepolizumab) as a treatment for severe eosinophilic asthma are well established, however the impact of stopping treatment after long-term use was previously unclear,” Wendy C. Moore, MD, of Wake Forest School of Medicine in Winston-Salem, North Carolina, said in an interview with MD /alert.
Moore and colleagues enrolled 295 patients in the randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase 3 COMET study, where patients from the COLUMBA and COSMEX trials were randomized to continue receiving 100 mg of subcutaneous mepolizumab (144 patients) or placebo (151 patients) every 4 weeks for up to 52 weeks. Patients were required to have been on mepolizumab for at least 3 years without a treatment gap lasting 12 weeks or longer in addition to still taking their asthma controller medication or therapy. If a patient experienced an exacerbation during the trial, they had the option to switch to mepolizumab in an open-label fashion.
The researchers examined clinically significant exacerbations as a primary endpoint, which was defined as an exacerbation aided by systemic corticosteroids, a visit to the emergency department, or hospitalization. Secondary outcomes included the amount of time before a patient experienced a decrease in asthma control, an initial exacerbation that led to a hospitalization or emergency department visit, and the patient’s blood eosinophil count ratio from baseline.
At 52 weeks, 66 of 144 patients (46%) in the mepolizumab group and 89 of 151 patients (59%) in the placebo group had an exacerbation. In the group who continued mepolizumab, Dr. Moore and colleagues saw an improved time to first clinically significant exacerbation (HR, 0.62; 95% CI, 0.45-0.86; P = .004) and a longer time to decreased asthma control (HR, 0.66; 95% CI, 0.49-0.88; P = .005, but there was no difference between groups regarding time to an exacerbation leading to a visit to the emergency department or hospitalization (HR, 1.33; 95% CI, 0.50-3.51; P = .570).
At 12 weeks, eosinophil count in the mepolizumab group was between 40-60 cells/µL and those who stopped treatment had their counts raised to 270 cells/µL (ratio, 0.19; 95% CI, 0.15-0.24; P < .001), which persisted until 52 weeks (ratio, 0.16; 95% CI, 0.13-0.20; P < .001). The researchers noted similar rates of adverse events in the mepolizumab and placebo groups (2740 vs 3098 adverse events per 1,000 patient-years exposure), and a consistent safety profile for mepolizumab.
“COMET adds to the body of data that supports Nucala as an effective long-term maintenance treatment for people living with severe eosinophilic asthma,” Moore said. “We are pleased that the study results support continued Nucala treatment having sustained clinical benefits in most people with severe eosinophilic asthma.”