P069 Effect of Orkambi therapy on the lung microbiota in people with cystic fibrosis (PwCF) over the first 12 months of therapy (ROCK Study)

Objectives: CFTR modulator therapy with Orkambi® (lumacaftor/ivacaftor) reduces the rate of decline of FEV1 in people with cystic fibrosis (PwCF) homozygous for the F508del mutation. However, the effect of Orkambi® on the composition and structure of the CF airway microbiota remains unclear. In this study, we determined the effect of therapy with Orkambi® on lung microbiota composition. Methods: PwCF (n = 37) from the Real-world Orkambi cohort Cork study (ROCK) in whom we previously have shown significant clinical improvements over 12 months [1Konstan et al.Lancet Respir Med. 2017; 5: 107-118Abstract Full Text Full Text PDF PubMed Scopus (220) Google Scholar, 2Arooj P et al.Thorax. 2022; 77: S26Google Scholar], provided a sputum sample at baseline (pretreatment) and at three-monthly intervals to a year post-treatment with Orkambi® (n = 196 samples). 16S MiSeq sequencing and clinical bacterial culture were performed in addition to qPCR for P. aeruginosa, S. aureus and H. influenzae. Results: There was no change in the levels of detection of bacteria during the study as determined by NGS, sputum culture and qPCR (Table 1). There was no significant difference in relative abundance of top 20 taxa (p > 0.05) or in community richness (p = 0.39) Shannon-Wiener diversity (p = 0.86), evenness (p = 0.66) or dominance (p = 0.78) between visits. Despite this there was a reduction in prescription oral (p < 0.0001) and IV antibiotics (p < 0.0001). For the main bacteria, good agreement was observed in detection between methods. However, significantly higher levels of Haemophilus spp. and Streptococcus spp. were detected by NGS compared to culture or qPCR, resulting from the lack of resolution to the level of species by NGS. Conclusion: Orkambi® treatment did not change the lung microbiota, despite a reduction in antibiotic usage. This indicates that Orkambi® treatment is having an effect on frequency of infective exacerbations for PwCF. Table 1(abstract: P069).NGS*Classification to level of genera only.CultureqPCRT0T3T6T9T12T0T3T6T9T12T0T3T6T9T12P. aeruginosa91.780.790.380.096.772.277.474.266.760.077.871.080.763.370.0S. aureus55.651.661.360.053.344.445.241.940.043.352.861.364.550.053.3H. influenzae38.941.954.843.353.32.83.23.26.73.311.13.29.76.720.0S. marcesens0.00.00.00.00.02.80.00.00.00.0N/AN/AN/AN/AN/AS. maltophilia13.916.119.413.320.05.612.99.76.710.0N/AN/AN/AN/AN/AB. multivorans2.83.23.20.03.32.83.23.23.33.3N/AN/AN/AN/AN/AP. mirabilis0.03.26.53.36.70.00.03.23.33.3N/AN/AN/AN/AN/AStreptococcus spp.100.096.8100.090.0100.00.03.23.23.30.0N/AN/AN/AN/AN/AA. fumigatusN/AN/AN/AN/AN/A8.319.416.16.716.7N/AN/AN/AN/AN/A* Classification to level of genera only. Open table in a new tab