Oral Glucocorticoid Sparing Effect of Mepolizumab in Eosinophilic Asthma | Journal Scan

Study Questions:

What is the effect of mepolizumab adjunctive therapy in reducing the use of maintenance oral glucocorticoids while maintaining asthma control in patients with severe eosinophilic asthma?


In SIRIUS (Mepolizumab Steroid-Sparing Study in Subjects With Severe Refractory Asthma), a randomized, double-blind trial involving 135 patients with severe eosinophilic asthma, the investigators compared the glucocorticoid-sparing effect of mepolizumab (at a dose of 100 mg) with that of placebo administered subcutaneously every 4 weeks for 20 weeks. The primary outcome was the degree of reduction in the glucocorticoid dose (90 to 100% reduction, 75 to <90% reduction, 50 to <75% reduction, >0 to <50% reduction, or no decrease in oral glucocorticoid dose, a lack of asthma control during weeks 20-24, or withdrawal from treatment). Other outcomes included the rate of asthma exacerbations, asthma control, and safety. The authors used a negative binomial generalized linear model with a log-link function with adjustment for covariates to analyze the rate of clinically significant exacerbations.


The likelihood of a reduction in the glucocorticoid-dose stratum was 2.39 times greater in the mepolizumab group than in the placebo group (95% confidence interval, 1.25-4.56; p = 0.008). The median percentage reduction from baseline in the glucocorticoid dose was 50% in the mepolizumab group, as compared with no reduction in the placebo group (p = 0.007). Despite receiving a reduced glucocorticoid dose, patients in the mepolizumab group, as compared with those in the placebo group, had a relative reduction of 32% in the annualized rate of exacerbations (1.44 vs. 2.12, p = 0.04) and a reduction of 0.52 points with respect to asthma symptoms (p = 0.004), as measured on the Asthma Control Questionnaire 5 (in which the minimal clinically important difference is 0.5 points). The safety profile of mepolizumab was similar to that of placebo.


The authors concluded that in patients requiring daily oral glucocorticoid therapy to maintain asthma control, mepolizumab had a significant glucocorticoid-sparing effect, reduced exacerbations, and improved control of asthma symptoms.


This study reports that among patients with severe eosinophilic asthma in whom doses of oral glucocorticoids had been reduced as much as possible before starting study treatment, those who received subcutaneous mepolizumab had significantly greater reductions in the maintenance oral glucocorticoid dose than did those receiving placebo. Mepolizumab also had a significantly beneficial effect on exacerbations, asthma control, and quality of life, even though patients had a clinically relevant reduction in the dose of oral glucocorticoids. It seems reasonable to consider anti–interleukin-5 therapy for patients with severe asthma who are receiving high doses of systemic glucocorticoids, and who continue to have an elevated eosinophil count in sputum or blood.

Clinical Topics: Novel Agents

Keywords: Antibodies, Monoclonal, Humanized, Asthma, Eosinophils, Glucocorticoids, Interleukin-5, Pulmonary Eosinophilia, Quality of Life, Questionnaires

< Back to Listings