Effects of elexacaftor/tezacaftor/ivacaftor therapy on mental health of patients with cystic fibrosis

Abstract

Introduction: The CFTR modulator drug elexacaftor/tezacaftor/ivacaftor (ETI) was shown to improve CFTR function and clinical symptoms in patients with cystic fibrosis (CF) with at least one F508del allele. Recently, some case reports suggested potential side effects of ETI on mental health with an increase in depressive symptoms and even suicide attempts in patients with CF. However, the general effects of this triple combination therapy on the mental health status of patients with CF remain largely unknown.Methods: We, therefore, performed a prospective, observational study in a real-life setting and investigated the relationship between initiation of ETI therapy and changes in mental health in adult patients with CF. We assessed Cystic Fibrosis Questionnaire-Revised (CFQ-R), Patient Health Questionnaire-9 (PHQ-9), Beck’s Depression Inventory – Fast Screen (BDI-FS) and Generalized Anxiety Disorder 7-item Scale (GAD-7) at baseline and 8–16 weeks after initiation of ETI.Results: In total, 70 adult patients with CF with at least one F508del allele and a median age of 27.9 years were recruited. After initiation of ETI, the CFQ-R respiratory domain score improved by 27.9 (IQR 5.6 to 47.2; p < 0.001). The PHQ-9 score of depressive symptoms decreased by 1.0 (IQR -3.0 to 0.3; p < 0.05) with an increase of 16.9% in the group with a minimal score after initiation of ETI and a decrease in the groups of mild (−11.3%) or moderate (−5.7%) scores compared to baseline. The BDI-FS score of depressive symptoms decreased from 1.0 (IQR 0.0–2.0) at baseline to 0.0 (IQR 0.0 to 2.0; p < 0.05) after initiation of ETI. The group with a minimal BDI-FS score increased by 8.0% after initiation of ETI, whereas the groups with mild (−4.9%), moderate (−1.6%) or severe (−1.6%) scores decreased compared to baseline. The GAD-7 score of anxiety symptoms did not change after initiation of ETI compared to baseline (0.0; IQR -2.0. to 0.0; p = 0.112).Conclusion: Initiation of ETI improves symptoms of depression in adult patients with CF with at least one F508del allele. However, symptoms of anxiety do not change after short-term therapy with ETI.

Elexacaftor/Tezacaftor/Ivacaftor Treatment and Depression-related Events

“…These studies, which involved 951 pwCF and reflected real-world experiences with up to 12 months of follow-up, did not indicate any systematic increases (i.e., worsening) in PHQ-9 scores on average, demonstrating either no change or a decrease (i.e., improvement) in assessed PHQ-9 (or PHQ-8) scores after ELX/TEZ/IVA initiation ( Table 3 ). Notably, one of those studies, a prospective observational cohort of 70 adults with CF treated with ELX/TEZ/IVA in Germany, reported a trend toward a decrease in patients describing suicidal ideation: Before therapy initiation, four patients (5.6%) reported suicidal ideation on the PHQ-9, and after therapy initiation, only one patient (1.4%) reported suicidal ideation ( 33 ). One additional study of 84 adults with CF reported no significant change in score on the Center for Epidemiologic Studies–Depression Scale after 6 months post ELX/TEZ/IVA initiation ( 32 ).…”

“…As part of this review, we identified 12 published articles and congress presentations that utilized the well-validated PHQ-9 (or PHQ-8) to evaluate depression symptoms both before and after ELX/TEZ/IVA initiation in more than 951 pwCF ( 33 , 35 – 45 ). These studies found that, on average, PHQ-9 (or PHQ-8) scores either decreased (indicating an improvement in depression symptoms) or showed no change after ELX/TEZ/IVA initiation.…”

Neuropsychiatric adverse effects from CFTR modulators deserve a serious research effort

“…The literature on ETI effects on depression and anxiety in PwCF evidences a general pattern reflecting increased quality of life for a majority, while a minority has new onset or worsened depression and/or anxiety. Piehler et al prospectively evaluated CF-related quality of life along with depression and anxiety in 70 adults with CF before and after initiation of ETI [ 12 ]. At the level of group statistics, this study showed that ETI improved CF-related quality of life, was associated with a very small but statistically significant improvement in median depression scores, and had no effect on median anxiety scores.…”

Questions and Answers? Depression Symptoms Associated with Elexacaftor/Tezacaftor/Ivacaftor Treatment for Cystic Fibrosis

“…Borawska-Kowalczyk and colleagues ( 10 ) reported that although there was no overall change in PHQ-9 score, 15% of pwCF had increased scores after ELX/TEZ/IVA initiation. Piehler and colleagues ( 11 ) demonstrated clearly that although overall the group showed reduction in depression symptoms as measured by PHQ-9, there was certainly a proportion of subjects who had worse PHQ-9 scores after commencing ELX/TEZ/IVA therapy; indeed PHQ-9 score increased by 17% in the group with minimal depression symptoms at baseline ( see Figure 1 ).…”

“…**Denotes P < 0.01 compared with baseline. Reprinted by permission from Reference 11 . ELX = elexacaftor; ETI = elexacaftor/tezacaftor/ivacaftor; IVA = ivacaftor; TEZ = tezacaftor.…”