S61 Respiratory microbiology outcomes from an observational study of ivacaftor in people with cystic fibrosis and non-G551D gating mutations (VOCAL)

<h3>Introduction and Objectives</h3> Certain respiratory pathogens are associated with reduced lung function and disease progression in people with cystic fibrosis (pwCF). We report respiratory microbiology results from a Phase 4 observational study (NCT02445053) assessing real-world effectiveness of ivacaftor (IVA) in pwCF with non-<i>G551D</i> gating mutations (<i>G178R</i>, <i>S549N</i>, <i>S549R</i>, <i>G551S</i>, <i>G1244E</i>, <i>S1251N</i>, <i>S1255P</i> or <i>G1349D</i>). <h3>Methods</h3> PwCF aged ≥6 years in Italy, the Netherlands and the UK who were IVA-naïve or on IVA for ≤18 months at enrolment were eligible. Data were recorded for 12 months pre-IVA and up to 48 months after enrolment. Microbiology cultures were taken via sputum, throat or oropharyngeal swabs. <h3>Results</h3> 65 of 73 (89%) completed the study; mean IVA exposure was 49.5 months (range, 2–64). Mean (standard deviation) baseline age and percent predicted forced expiratory volume in 1 second were 26.9 (13.5) years and 64.83 (23.61), respectively. In the 12 months pre-IVA, 279 cultures were obtained from 69 pwCF and 182 cultures in 64 pwCF at year 4 following IVA treatment. Prevalence of <i>P. aeruginosa</i>, <i>A. fumigatus</i> and <i>S. maltophilia</i> was 55.1%, 30.4% and 11.6%, respectively, in the 12 months pre-IVA and was reduced to 52.9%, 18.6% and 7.1% in year 1 and 41.5%, 16.9% and 4.6% in year 2 on IVA. Sustained or further reductions were observed through 48 months of treatment. Prevalence of other pathogens was variable or too low to evaluate. 70% of pwCF were on chronic oral and/or inhaled antibiotics pre-IVA vs 68% at 48 months. Use of other chronic inhaled therapies was stable throughout the study. <h3>Conclusions</h3> Lower prevalence of <i>P. aeruginosa</i>, <i>A. fumigatus</i> and <i>S. maltophilia</i> was observed with prolonged IVA treatment for up to 48 months in real-world settings. Chronic medication use remained stable. Please refer to page A189 for declarations of interest related to this abstract.