(015) Depression and Anxiety in Patients with Cystic Fibrosis after Six Months on Elexacaftor-Tezacaftor-Ivacaftor

Abstract:

Background: Cystic fibrosis (CF) is a life-limiting disease with chronic, debilitating pulmonary, endocrine, gastrointestinal, and other symptoms. Patients with CF have higher rates of anxiety and depression than the general population (Quittner 2014). Elexacaftor-tezacaftor-ivacaftor (ETI) has resulted in significant improvement of physical CF symptoms by targeting defects in in the CF transmembrane regulator proteins transcribed by the deltaF508 mutation (Middleton 2019). This data is part of a 5 year study monitoring medical and psychiatric symptoms, especially anxiety and depression, in patients taking ETI.



Methods: This is a single center, Nationwide Children’s Hospital IRB approved, longitudinal observational study evaluating the effects of ETI treatment on mood and anxiety. Eligible participants were recruited during routine CF clinic visits. Subjects are administered standardized validated measures for anxiety and depression at baseline, 1, 3, 6, 9, 12, 18, 24, 36, 48, and 60 months. Measures include the PHQ-9, GAD-7, adult and pediatric PROMIS Depression and Anxiety Scales.



Results: 184 subjects (93 males, 91 females), completed all anxiety and depression measures at the 6 month mark. Thirty-two of 184 received pediatric measures. Linear mixed-effects model was used to evaluate changes of primary outcomes, PHQ-9, GAD-7, and PROMIS over the study visits. All statistical analyses are performed in R version 4.0 (R Core Team, Vienna, Austria). Normal range score rates at baseline then 6 months were: PHQ-9, 67%/78%; GAD-7, 71%/79%; adult PROMIS Depression, 87%/91%; pediatric PROMIS Depression, 91%/85%; adult PROMIS Anxiety, 83%/87%; pediatric PROMIS Anxiety, 91%/95%. Overall trends were toward stability to slight improvement on all measures, with only 5 respondents reporting shifts from “normal” to “severe” symptoms. No study participants required emergency or inpatient psychiatric care during this 6 month period.



Discussion: A significant majority of 184 patients with CF demonstrated normal scores on measures of depression and anxiety during their first 6 months on ETI. These results indicate trends toward improvement in mental health upon initiation of ETI in this sample. While this does not reflect each individual case, it indicates that patients with CF collectively may have decreased anxiety and depression during this time period. While improvements in anxiety and depression as CF symptoms improve with ETI treatment make intuitive sense, the first 6 months of this study occurred during the COVID-19 pandemic. Hence, anxiety and depression may also have been affected by social isolation, changes in routine, and fear of contracting COVID-19.



Conclusion/Implications:. Continued follow-up is required to evaluate the relationships of CF medical symptoms, depression, anxiety, and ETI treatment over time.



References:



Middleton PG, et al. (2019). Elexacaftor-Tezacaftor-Ivacaftor for cystic fibrosis with a single Phe508del allele. NEJM, 381(19):1809-19.



Quittner AL, et al. (2014). Prevalence of depression and anxiety in patients with cystic fibrosis and parent caregivers. Thorax, 69:1090-97.