(254) Patient perception of the impact of elexacaftor/tezacaftor/ivacaftor and the COVID-19 pandemic on physical and mental health

Background: The combination cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (Trikafta) was FDA approved in late 2019. Initiation of elexacaftor/tezacaftor/ivacaftor has been efficacious in increasing lung function and reducing CF exacerbations leading to decreased hospitalizations and use of home IV antibiotics [1]. Anecdotally some patients have attributed elexacaftor/tezacaftor/ivacaftor to a decline in mental health despite the clinical improvements observed with modulator therapy. The aim of this pilot study was to determine if the initiation of elexacaftor/tezacaftor/ivacaftor was associated with a decline in mental health.

Methods: All patients in our adult CF clinic were administered a survey to assess both physical and mental health. Because the initiation of elexacaftor/tezacaftor/ivacaftor was near the start of the COVID-19 pandemic in March 2020, mental health changes attributed to COVID-19 were used as an internal control. The survey consisted of 8 questions. Questions 1-3 were regarding how the COVID-19 pandemic had affected their physical health (Q1), anxiety (Q2), and depression (Q3). Responses were on a ranked scale of 1-5 with 1 being significantly improved and 5 being significantly worsened. Question 4 was a yes or no question asking if they were on elexacaftor/tezacaftor/ivacaftor. Questions 5-7 were regarding how elexacaftor/tezacaftor/ivacaftor had affected physical health (Q5), anxiety (Q6), and depression (Q7). The same scoring scale for Q1-3 was used. Question 8 was a free text box asking patients if they would like to share anything else about their mental or physical health in the past 2 years.

Results: The survey was administered to 82 patients, with 78 (95%) taking elexacaftor/tezacaftor/ivacaftor. Regarding the effects of COVID-19 pandemic on their physical health, 3 (4%), 69 (83%), 10 (12%) of responders felt that it had improved, no effect, and declined, respectively. Regarding the effect of elexacaftor/tezacaftor/ivacaftor on physical health, 71 (91%), 5 (4%), 3 (4%) of responders felt that it had improved, no effect, and declined, respectively. Regarding the effects of COVID-19 pandemic on their mental health, 1 (1%), 48 (59%), 34 (41%) of responders felt that it had improved, no effect, and declined, respectively. Regarding the effects of elexacaftor/tezacaftor/ivacaftor on their mental health, 18 (25%), 48 (59%), 6 (8.5%) of responders felt that it had improved, no effect, and declined, respectively. Elexacaftor/tezacaftor/ivacaftor was initiated 56 ± 16 days (mean ± standard error of the mean) before the beginning of the COVID-19 pandemic (March 20, 2020).

Conclusions: In this pilot study, patients associated a decline in mental health with COVID-19 more frequently than the initiation of elexacaftor/tezacaftor/ivacaftor. The COVID-19 pandemic introduces a large confounding variable in evaluating mental health associated with elexacaftor/tezacaftor/ivacaftor. Due to the close proximity of initiation of elexacaftor/tezacaftor/ivacaftor the start of the pandemic, it is impossible to determine if mental health decline was associated with one over the other. Further investigation and monitoring are necessary to investigate the impact of elexacaftor/tezacaftor/ivacaftor on mental health.

Acknowledgements:

References: [1] Middleton PG, Mall MA, Drevinek P, et al. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019;381(19):1809-1819. https://doi.org/10.1056/NEJMoa1908639