S51 Characterisation of exacerbations of severe eosinophilic asthma on mepolizumab compared to placebo

Mepolizumab reduces exacerbations of severe eosinophilic asthma. However, even with mepolizumab treatment, exacerbations still occur in this population. We have previously shown that exacerbations on mepolizumab are associated with lower sputum eosinophil counts and lower decrements in symptoms measured by the visual analogue scale compared to placebo. To further characterise exacerbations on mepolizumab, we carried out a post-hoc comparison of exacerbations on treatment with mepolizumab or placebo in three previously reported placebo-controlled trials. We investigated whether exacerbations in each group differ with respect to change in lung function and symptoms in the period before and after starting oral corticosteroid (OCS) rescue treatment. Methods Diary card data was reviewed from the 3 studies; DREAM, a 52-week study of 3 doses of mepolizumab (75, 250 or 750 mg IV 4 weekly) versus placebo; MENSA, an 32-week study of 2 doses of mepolizumab (75 mg IV or 100 mg s/c 4 weekly) versus placebo; and MUSCA, a 24-week study of mepolizumab 100 mg s/c 4 weekly versus placebo. All studies recruited patients with severe eosinophilic asthma and a history of 2 or more exacerbations in the previous year. Mepolizumab dose groups were combined for analysis. Patients completed a daily diary card including a 6 point symptom score assessing asthma symptoms in the previous 24 hours and a best-of-three morning peak expiratory flow (PEF). Exacerbations requiring rescue OCS with at least 20 days of diary data in the period from 14 days prior to starting OCS (Day -14) to 14 days (Day 14) after starting OCS were included in the analysis. Results 1026 exacerbations were analysed. 476 occurred in 248 subjects on placebo and 550 occurred in 338 subjects on mepolizumab. Exacerbations on placebo were associated with a larger drop in PEF (-41.0 L/min [95% CI -47.3, -34.7]) compared to mepolizumab (-26.9 L/min [-32.7, -21.1]) over the 14 days prior to starting OCS. Exacerbations on placebo also tended to have a larger increase in daily symptom score compared to mepolizumab (0.81 points [0.68, 0.94] vs 0.65 points [0.54, 0.76] respectively). Conclusion Exacerbations that occur on mepolizumab are less severe in terms of worsening in PEF and symptom scores.