Late-breaking abstract: Oral corticosteroid-sparing effect of mepolizumab in severe eosinophilic asthma: The SIRIUS study

Abstract

Background: There is an unmet treatment need in a sub-population of severe asthma patients who, despite the use of maximal inhaled therapy, require regular treatment with oral corticosteroids (OCS). Objective: To study the steroid-sparing effect of mepolizumab in severe eosinophilic asthma. Methods: We conducted a randomized, double-blind placebo controlled trial of mepolizumab (n=69) administered as monthly injections of 100mg subcutaneously for 6 months vs placebo (n=66) in patients with severe, OCS dependent asthma, whose treatment was optimized prior to randomization. Results: Patients on mepolizumab 100mg SC achieved greater reductions in OCS dose compared to placebo (p=0.008); 54% (37/69) of mepolizumab patients achieved iÝ50% reduction in OCS dose compared to 33% (22/66) of placebo patients. The median reduction from baseline OCS dose was 50% with mepolizumab compared to 0% with placebo (p=0.007). Despite the lower OCS dose patients on mepolizumab had a 32% reduction in the rate of exacerbations (1.44 vs 2.12/year; p=0.042), and fewer exacerbations resulting in hospital admission (0 v s 7). The mean reductions in ACQ and SGRQ with mepolizumab compared to placebo were 0.52, (p=0.004) and 5.8 (p=0.019). The safety profile of mepolizumab was similar to placebo. Conclusions: Mepolizumab had a significant oral steroid-sparing effect and reduced the frequency of exacerbations. Mepolizumab also resulted in significant improvements in asthma control and quality of life, despite a reduced OCS dose. Treatment with mepolizumab in this population with significant impairment and high risk for side effects from OCS provides an important therapeutic alternative. Funding: GSK MEA115575-NCT01691508.