The FINANCIAL — GlaxoSmithKline plc (GSK) on October 27 announced results from the ‘LABA’ (long acting beta2-agonist) safety study, AUSTRI (SAS115359). The study compared Advair Diskus, a combination of the LABA, salmeterol, and the inhaled corticosteroid (ICS), fluticasone propionate (FP), to FP monotherapy and showed that Advair (FSC) had a safety profile comparable to FP when used to treat adolescent and adult patients with asthma, assessed by the composite endpoint of serious asthma-related events (deaths, intubations or hospitalisations).
Results from the 26-week AUSTRI study, which randomised 11,751 patients across 33 countries into the study, showed FSC twice-daily (100/50mcg, 250/50mcg or 500/50mcg) demonstrated non-inferiority compared to corresponding doses of FP twice-daily (100mcg, 250mcg or 500mcg), on the risk of serious asthma-related events, Hazard Ratio (HR) 1.029, (95% CI 0.638, 1.662) p=0.003. No asthma-related deaths were seen in either arm of the study. There were a total of 67 patients with serious asthma-related events across the study with 34 patients with events on FSC treatment and 33 patients with events on FP treatment. There were two asthma-related intubations in the trial, both in the FP arm; the remaining events were asthma-related hospitalisations, according to GlaxoSmithKline.
AUSTRI was undertaken as a post-marketing requirement of GSK for the US Food and Drug Administration (FDA). Three other manufacturers of LABA-containing products, which are also indicated for the treatment of asthma, undertook identical studies designed to evaluate whether the addition of a LABA to an ICS increased the risk of an event in the composite endpoint of serious asthma-related events (deaths, intubations or hospitalisations) in adolescents and adults. AUSTRI is the first of the large-scale safety studies to report results. These findings will be shared with the FDA to discuss next steps.
In addition to the AUSTRI study, GSK is also conducting a second LABA safety study, VESTRI, in children aged 4 – 11 years of age. This study will complete last patient last visit this week and is on track to report at the end of Q1 2016.
AUSTRI Study (SAS115359)
A global, multicentre, randomised stratified, double-blind, parallel-group active comparator, 26 week study in adolescents (12 – 17 years of age) and adults (18 years of age and older) whose asthma warrants treatment with controller asthma therapy. Patients were required to have a history of asthma for at least one year prior to randomisation and experienced a severe asthma exacerbation requiring treatment with oral corticosteroids (or their equivalent) or an asthma-related hospitalisation in the year prior to treatment, but not in the 30 days prior to randomisation.
Patients were randomised to either FSC or FP. The FP (ICS) treatment dose (100mcg, 250mcg or 500mcg) was determined by the previous use of controller medications and an assessment of the patient’s asthma control. Upon entry into the study, patients took part in a screening period of up to two weeks, a randomisation visit (visit 2) followed by a treatment period of 26 weeks where patients attended 3 on-treatment clinic visits. Months where there was not a visit, patients were contacted by telephone. Serious adverse events were collected within six months after the first use of study drug or seven days after the last date of study drug treatment, whichever date was greater. Patients were permitted to use albuterol/salbutamol rescue medication throughout the study.
The primary analysis was to determine whether the addition of LABA to ICS therapy (FSC) is non-inferior to ICS therapy alone (FP) on risk of a composite of serious asthma events (asthma-related hospitalisation, intubation and death). To demonstrate non-inferiority, a predefined margin of 2 was required, meaning the upper limit of the 95% confidence interval needed to be less than two to rule out a doubling in the risk of incidence on FSC compared with FP. All serious asthma related events were adjudicated by an independent committee.