ABSTRACT
Background: With the introduction of new cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (elexacaftor/tezacaftor/ ivacaftor), peoplewith CF experiencing severe lung disease can experience significant improvements in clinical symptoms. Method(s): This single-center institutional review board-approved retrospective chart review identified patients with advanced lung disease who met criteria for a compassionate use or expanded access program because of high risk of death or transplant need within 2 years. Clinical data collection for all patients began at baseline, 2 to 4 weeks after therapy initiation, and continued every 3 months for 2 years. Datawere collected on demographic characteristics, clinic progress notes, clinical labs, forced expiratory volume in 1 minute (FEV1),weight, body mass index, respiratory colonization, and hospitalizations after drug initiation. Patients also completed sinus and chest computed tomography (CT) to track clinical changes. Result(s): Eighteen people with CF (aged 15-49, 56% male) from a large midwestern CF center who initiated drug therapy between July and September 2019 in an inpatient hospital or clinic setting were identified. Clinical markers (Table 1) indicated that modulator therapy was well tolerated and not discontinued by any participant;safety lab values did not indicate medical concern or discontinuation. There were 90 admissions for the group in the 2 years before therapy and 17 admissions during the 2 years after, although seven of the posttherapy admissions were for nonrespiratory indications. Monitoring results indicated the safety of modulator therapy because there were no adverse clinical occurrences or laboratory events, and all patients presented with universal stabilization. There have been no deaths and no transplants. Unlike lumacaftor/ivacaftor, therewere no problems with chest tightness or any difficulty with troublesome increases in expectoration burden or choking during initiation of therapy. Most had significant reduction in or loss of spontaneous cough and sputum production. The impact on microbial colonization is unclear, because even in this severe group, inability to produce sputum on command led to considerable missing data in follow-up, leaving colonization status at follow-up unclear. Conclusion(s): This study focused on people with CF who qualified for modulator therapy based on advanced lung disease. Initiation of modulator therapy was deemed safe and resulted in objective positive changes in nutrition;cough;FEV1);and subjective reports of clinical status, level of activity, and reduction in burden of treatment. No evidence was found of difficulty managing the increased expectoration during initial therapy. Limitations were noted in missing data during the COVID-19 pandemic, small sample size, and delayed follow-up for drug monitoring.(Table Presented) Clinical indicators before and after modulator therapy *Completed post-drug initiation (earlier than 12 months), **24 months before and after therapy initiationCopyright © 2022, European Cystic Fibrosis Society. All rights reserved
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. Method(s): 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. Result(s): 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(s): 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. Copyright © 2022