Mental Health Changes in Adolescents and Adults With Cystic Fibrosis After Initiation of Elexacaftor/Tezacaftor/Ivacaftor Therapy: Insights From the Longitudinal Resilience Impacted by Positive Stressful Events (RISE) Study

Abstract

Background: Starting elexacaftor/tezacaftor/ivacaftor (ETI) is considered a positive life event for people with cystic fibrosis (pwCF). Nevertheless, some individuals report a decline in mental health after commencing ETI. Research Question: How do various mental health indicators of pwCF ≥ 12 years of age change after starting ETI, and can potentially more vulnerable subgroups, in terms of their mental health, be identified? Study Design and Methods: This was a prospective 60-week longitudinal cohort study with questionnaire-based measurements of mental health 12 weeks before (t0) and 12, 24, and 48 weeks after starting ETI (t1, t2, and t3, respectively). Subgroups were defined by age, sex, lung function at baseline, earlier use of any other modulator, and use of psychotropic medications. Data were analyzed using a covariance pattern model with a general variance covariance matrix. Results: In total, 174 (98.31%), 146 (82.49%), 141 (79.66%), and 142 (80.23%) participants completed or partially completed the questionnaires at t0, t1, t2, and t3, respectively. The data showed an overall statistically significant and clinically relevant improvement in psychosocial health (P < .001; change in [Δ] estimated marginal means [EMM] t0-t3, 7.68), no change in anxiety symptoms (P = .46; ΔEMM t0-t3 = −0.42), a statistically significant but not clinically relevant improvement in depressive symptoms (P < .001; ΔEMM t0-t3 = −1.25), and a statistically significant and clinically relevant improvement in respiratory-related quality of life (P < .001; ΔEMM t0-t3 = 19.55) after the initiation of ETI. Female patients, those with lower lung function, and those using psychotropic medications at baseline seem to be more susceptible to lower mental health scores after starting ETI on several indicators, compared with their counterparts. Interpretation: In this study, pwCF experienced an improvement in all mental health indicators, except in anxiety symptoms. Clinical physicians should be aware that female patients, people with lower lung function, and those using psychotropic medications might be more prone to less favorable mental health improvement.