ABSTRACT
Objectives: Elexacaftor/tezacaftor/ivacaftor (ETI) combination therapy - Kaftrio® was approved for use in the UK in August 2020 for those aged >12 years. Our study aimed to study the effects of ETI therapy on lung function and exercise performance. Methods: Two-centre retrospective analysis of clinical data obtained during patients’ annual review assessments. Patients had undergone spirometry and static lung volume measurements followed by an incremental maximal ramp cardiopulmonary exercise testing (CPET) performed on a cycle ergometer. Data were analysed using a paired sample t-test. Results: Lung function improvement did not reach statistical significance. Of note, four patients had a baseline (pre-ETI) FEV1 belowthe lower limit of normal (LLN <-1.64 Z scores), and one improved their FEV1 from 41% predicted to 87% with Kaftrio®. Five had a VO2peak% predicted below the LLN (< 85% predicted) prior to treatment and 8 post treatment. Therewas a significant fall in VO2peak % predicted, p = 0.03. However, this was not seen in the VO2peak relative to bodyweight, p = 0.07. There was also a significant fall in VO2 at anaerobic threshold (AT) as a % of predicted VO2peak, p = 0.01. Table 1. (Table Presented) (Table Presented) Conclusions: This real-world study suggests Kaftrio® does not improve exercise capacity in the majority of CF patients. It is hypothesised that the lack of improvement may be due to a reduced physical activity over the study period as a result of feeling better on Kaftrio® and also the SARSCoV2 pandemic. The decrease in VO2 at AT would support the hypothesis of physical deconditioning. The reasons for not seeing statistical differences in lung function are likely to represent the relatively high baseline FEV1 alongside small study numbers. In summary, whilst having the potential to be a performance-enhancing drug, performance gains on Kaftrio® can only occur if matched by training, and studies to investigate the training potential of Kaftrio® are required.