Abstract
Background: Previous studies showed that intravenous (IV) mepolizumab (anti-IL5 mAb) inhibits eosinophilic airway inflammation and significantly reduces exacerbations in severe eosinophilic asthma; whether similar efficacy is seen with subcutaneous (SC) administration is unknown.
Objective: To compare the effect of mepolizumab administered SC or IV with placebo (Pbo) on the frequency of exacerbations in severe eosinophilic asthma, along with additional efficacy and safety parameters.
Methods: A 32 week randomized, double-blind, double-dummy study with mepolizumab 100mg SC or 75mg IV or Pbo given every 4 weeks in 576 patients with severe asthma treated with optimal therapy, a history of exacerbations and evidence of eosinophilic inflammation. Primary outcome: rate of exacerbations. Other outcomes included pre-bronchodilator FEV1, SGRQ and ACQ-5.
Results: Mepolizumab 100mg SC produced a 53% reduction (p<0.001), and 75mg IV a 47% reduction (p<0.001) in exacerbations versus Pbo. Hospitalization or ED visits were reduced by 61% in the SC group (p=0.015) and by 32% in the IV group (p=0.299). Improvements were observed in FEV1: difference from Pbo at week 32, SC (98mL, p=0.028) and IV (100mL, p=0.025). Compared to Pbo, SGRQ reduced by 7.0 and 6.4 and ACQ-5 by 0.44 and 0.42 after treatment with mepolizumab SC and IV, respectively (all p<0.001). Safety profile of mepolizumab was similar to Pbo.
Conclusions: Mepolizumab, whether administered SC or IV, significantly reduced the frequency of exacerbations and improved lung function, quality of life and asthma control. The results support the use of mepolizumab as an add-on therapy in severe eosinophilic asthma.
Funding: GSK (MEA115588; NCT01691521).
- © 2014 ERS