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

<b>Background:</b> Certain respiratory pathogens are associated with reduced lung function and disease progression in people with CF (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, S549N, S549R, G551S, G1244E, S1251N, S1255P,</i> or <i>G1349D</i>). <b>Methods:</b> pwCF ≥6 y from IT, NL, and UK who were IVA naive or on IVA ≤18 mo at enrollment were eligible. Data were recorded 12 mo pre-IVA and up to 48 mo after enrollment. Microbiology cultures were taken via sputum, throat, or oropharyngeal swabs. <b>Results:</b> 65 of 73 (89%) completed the study; mean IVA exposure was 49.5 mo (range, 2-64 mo). Mean (SD) baseline age and ppFEV₁ were 26.9 (13.5) y and 64.83 (23.61), respectively. In the 12 mo 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, A fumigatus,</i> and <i>S maltophilia</i> was 55.1%, 30.4%, and 11.6%, respectively, in the 12 mo 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 mo 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 mo. Use of other chronic inhaled therapies was stable throughout the study. <b>Conclusions:</b> Lower prevalence of <i>P aeruginosa, A fumigatus,</i> and <i>S maltophilia</i> was observed with prolonged IVA treatment for up to 48 mo in real-world settings. Chronic medication use remained stable. <b>Sponsor:</b> Vertex