Stopping long-term mepolizumab may lead to exacerbations, loss of asthma control

In patients with severe eosinophilic asthma, cessation of mepolizumab may lead to increased exacerbations and reductions in asthma control, according to results of the COMET* trial.

Study participants were 295 adults (mean age 56 years, 59 percent female) with severe eosinophilic asthma who had received mepolizumab continuously** for ≥3 years and had completed and remained on asthma control treatment throughout the open-label COLUMBA or COSMEX trials***. Patients who were current smokers and had <80 percent adherence to asthma control medications in the abovementioned trials were excluded. After screening and open-label phases, the patients were randomized 1:1 to either continue mepolizumab or stop mepolizumab and switch to placebo.

Patients had asthma for a mean duration of 24 years and a mean 0.7 exacerbations in the previous year. Prior to randomization in COMET, they had received mepolizumab for a median 44 months (1,145 patient-years). Thirteen percent of patients were on oral corticosteroids at baseline (median 5 mg/day).

The risk of a first clinically significant exacerbation – requiring corticosteroids, emergency department (ED) visit, or hospitalization – was significantly increased in patients who stopped compared with those who continued mepolizumab (59 percent vs 46 percent with ≥1 exacerbation; hazard ratio [HR], 1.61, 95 percent confidence interval [CI], 1.17–2.22; p=0.004). [ATS 2020, session B93]

The incidence of exacerbation requiring ED visit or hospitalization (5 percent [stopped mepolizumab] vs 7 percent [continued mepolizumab]) or hospitalization (4 percent vs 1 percent) was rare in both groups. “It is possible that physicians may have switched patients to open-label mepolizumab (from either double-blind placebo or mepolizumab) before a more severe exacerbation occurred,” suggested study author Professor Wendy Moore from the Wake Forest School of Medicine, Winston-Salem, North Carolina, US.

Time to reduced asthma control (≥0.5-point increase in ACQ-5^# from baseline) was shorter among patients who stopped vs continued mepolizumab, with a higher risk of reduced control in the former (HR, 1.52, 95 percent CI, 1.13–2.02; p=0.005).

Blood eosinophil counts increased among those who stopped mepolizumab, increasing to 270 cells/μL by week 12 and continuing until week 52 (stopped:continued ratio: 6.19; p<0.001), while among those who continued mepolizumab, blood eosinophil count was maintained at 40–60 cells/μL.

“Differences in efficacy outcomes were seen from week 12 (16 weeks after the last dose),” noted Moore.

“The safety profile of mepolizumab was consistent with previous trials,” she continued. Adverse events (AEs) occurred in 64 and 78 percent of patients who stopped and continued mepolizumab, respectively. AEs related to study treatment were rare, occurring in <1 and 3 percent, respectively. Serious AEs occurred in 7 and 6 percent, respectively. The most common AE of special interest in both groups was infection (44 and 58 percent, respectively).

Prior to this study, there was no data on the impact of stopping treatment after 1 year of therapy with mepolizumab, said Moore.

“[In COMET,] patients with severe eosinophilic asthma who stopped long-term (≥3 years) mepolizumab treatment [experienced] an increase in exacerbations and shorter time to first exacerbation, a reduction in asthma control, and an increase in blood eosinophil counts back to pre-treatment levels [vs those who continued],” she said.

“These results support continued mepolizumab treatment having sustained clinical benefits in patients with severe eosinophilic asthma,” she concluded.