Exacerbations Increased After Discontinuing Long-term Use of Mepolizumab for Severe Eosinophilic Asthma

A heightened risk of exacerbations and a decline in asthma control may occur in patients with asthma who discontinue use of mepolizumab after long-term use compared with those who maintain the therapy. 

Researchers conducted a global, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to compare discontinuing vs continuation of long-term mepolizumab treatment—a targeted, humanized, anti-interleukin (IL)-5 monoclonal antibody in patients with severe eosinophilic asthma. 

Patients who previously completed 1 of 2 open-label trials and received continuous mepolizumab treatment for 3 years or longer were randomly assigned 1:1 to discontinue (switch to placebo) or continue subcutaneous mepolizumab, 100 mg every 4 weeks for 52 weeks.

The sign of a first clinically significant exacerbation post-randomization was the primary endpoint. Secondary end-points were designated as time to the first exacerbation necessitating hospitalization or emergency department visit and time to a decline in asthma control, defined as an increase from baseline (start of double-blind treatment) in Asthma Control Questionnaire-5 score of 0.5 units or greater and ratio to baseline in blood eosinophil count at weeks 12, 24, 36, and 52.

Results revealed that patients discontinuing (n = 151) vs continuing (n = 144) mepolizumab had considerably quicker times to first clinically significant exacerbation (HR, 1.61; 95% CI, 1.17-2.22, p = .004) and reduction in asthma control (HR, 1.52; 95% CI, 1.13-2.02, p = .005). Patients discontinuing mepolizumab also had greater blood eosinophil counts at week 52 than those who continued treatment (270 vs 40 cells/µL).

Differences in efficacy outcomes between groups were also observed when evaluated from week 12 (16 weeks after last mepolizumab dose). Adverse events in patients continuing mepolizumab were consistent with previous studies and the incidence of exacerbations necessitating hospitalization/emergency department visit were rare.

Regarding patients who discontinued mepolizumab, the safety profile was consistent with other eosinophilic asthma populations.

The authors concluded that by 12 weeks, patients who discontinued long-term (≥ 3) mepolizumab treatment experienced their first clinically noteworthy exacerbation in a shorter time and experienced rising blood eosinophil counts back to pretreatment levels. These patients also experienced decreases in asthma control, quality of life, and lung function compared with those who continued mepolizumab. Moreover, the findings revealed that continued use of mepolizumab is correlated with sustained clinical benefits in patients with severe eosinophilic asthma, and results provide additional evidence that blood eosinophils are an appropriate biomarker for treatment response to mepolizumab.

—Yvette C. Terrie, BSPharm, RPh

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. 2022;59(1):2100396. doi:10.1183/13993003.00396-2021