LATE-BREAKING ABSTRACT: Safety of salmeterol/fluticasone propionate (FSC) compared to fluticasone propionate (FP) in 4-17 yr olds with asthma

Background: Studies have shown an excess of serious asthma events in subjects taking long-acting β 2 -agonist (LABAs). In children the excess was in hospitalizations but studies were not designed to detect if risk is mitigated with concomitant use of inhaled corticosteroids. VESTRI (completed March, 2016) in 4-11yr, and the12-17yr subset of AUSTRI (NEJM, 2016) an adult trial, assessed the risk of FSC in asthmatics 4-17yr. Objective: To study whether FSC is non-inferior to FP for a composite endpoint of serious asthma events (hospitalization, intubation or death). A secondary objective is whether FSC is superior to FP to reduce severe exacerbations requiring oral corticosteroids. Methods: Randomized, double-blind, parallel, 26-wk studies in subjects on daily asthma therapy with an exacerbation in the prior year. The safety endpoint was time to first serious asthma event. For VESTRI, non-inferiority criteria was a FSC/FP hazard ratio (HR) less than 2.675 (upper bound of the 95% CI). The adolescent subset with 1230 subjects was not powered to address the safety endpoint. Results: In VESTRI of 6208 subjects randomized, 27 FSC and 21 FP had a serious asthma event [FSC/FP HR=1.285 (95% CI 0.73-2.27)], achieving non-inferiority (p Conclusion: No evidence of increased protocol-defined serious asthma events with FSC compared to FP in children 4-17yr was seen. Funding: GSK (115358, 115359).