Patient-reported outcomes in patients with cystic fibrosis with a G551D mutation on ivacaftor treatment: results from a cross-sectional study.

BACKGROUND: Clinical studies demonstrate that ivacaftor (IVA) improves health-related quality of life (HRQoL) in patients aged ≥6 years with cystic fibrosis (CF). The real-world impact of IVA and standard of care (SOC) in groups of patients with G551D and F508del mutations, respectively, was assessed using a survey comprising disease-specific and generic HRQoL measures. METHODS: Patients with CF aged ≥12 years, or aged 6-11 years with caregiver support, with either (1) a G551D mutation and receiving IVA (G551D/IVA) for ≥3 months, or (2) homozygous for F508del and receiving SOC before lumacaftor/IVA availability (F508del/SOC), were eligible to participate in a cross-sectional survey. Demographic and clinical characteristics, and HRQoL measures were compared between patient groups, and multiple regression analyses were conducted. RESULTS: After differences in patient demographic and clinical characteristics were controlled for, significantly better scores were observed in the G551D/IVA group than in the F508del/SOC group on multiple domains of the validated Cystic Fibrosis Questionnaire-Revised and the EuroQol 5-dimensions 5-level questionnaire. CONCLUSIONS: G551D/IVA patients reported better HRQoL than F508del/SOC patients on generic and disease-specific measures in a real-world setting.

Impact of Treating Depression on Associated Comorbidities: A Systematic Literature Review.

Objective: To identify and summarize data that describe the impact of effectively treating major depressive disorder (MDD) on the severity or risk of serious comorbidities.Data Sources: MEDLINE, Embase, PsycINFO, Cochrane Database of Systematic Reviews, and several congresses were searched. Searches included terms related to MDD, randomized controlled trials (RCTs), and physical comorbidities and were restricted to English-language publications. Searches were conducted in November 2019 for the previous 2 years for conference proceedings; no date restriction was applied to the database searches.Study Selection: Included studies were RCTs or meta-analyses that assessed depression therapies. Studies were required to report a statistically significant improvement in depression scores as well as the concurrent impact on comorbidities. A total of 1,997 articles were initially identified for screening.Data Extraction: Two investigators extracted data and assessed study quality.Results: A total of 30 studies, including 24 RCTs (N = 6,333) and 6 meta/pooled analyses of RCTs, were included. Findings in several comorbidity categories were mixed; for example, in half (4 of 8) of the identified studies in people with cardiovascular disease and depression, individuals who received treatment leading to reduced depressive symptoms compared with a control arm also had a significantly decreased incidence of cardiovascular events or significantly improved cardiac disease symptom/severity scores compared with controls. Significant improvements in comorbid disease severity observed alongside improvements in depressive symptoms were also noted in studies of comorbid Parkinson's disease, multiple sclerosis, chronic pain and fibromyalgia, and chronic obstructive pulmonary disease.Conclusions: Effective treatment of MDD may lead to a reduction in the severity of certain serious comorbidities. These results highlight the importance of appropriate and timely treatment of MDD.

Impact of Major Depressive Disorder on Comorbidities: A Systematic Literature Review.

Objective: To summarize the breadth of data exploring the relationship between major depressive disorder (MDD) and both the incidence and the disease course of a range of comorbidities.Data Sources: The authors searched MEDLINE, Embase, PsycINFO, Cochrane Database of Systematic Reviews, and several prespecified congresses. Searches included terms related to MDD and several comorbidity categories, restricted to those published in the English language from 2005 onward.Study Selection: Eligibility criteria included observational studies within North America and Europe that examined the covariate-adjusted impact of MDD on the risk and/or severity of comorbidities. A total of 6,811 articles were initially identified for screening.Data Extraction: Two investigators extracted data and assessed study quality.Results: In total, 199 articles were included. Depression was significantly (P < .05) associated with an increased incidence of dementia and Alzheimer's disease as well as cognitive decline in individuals with existing disease; increased incidence and worsening of cardiovascular disease/events (although mixed results were found for stroke); worsening of metabolic syndrome; increased incidence of diabetes, particularly among men, and worsening of existing diabetes; increased incidence of obesity, particularly among women; increased incidence and worsening of certain autoimmune diseases; increased incidence and severity of HIV/AIDS; and increased incidence of drug abuse and severity of both alcohol and drug abuse.Conclusions: The presence of MDD was identified as a risk factor for both the development and the worsening of a range of comorbidities. These results highlight the importance of addressing depression early in its course and the need for integrating mental and general health care.

Measuring recovery in health-related quality of life during and after pulmonary exacerbations in patients with cystic fibrosis.

BACKGROUND: We explored the time-dependent impact of pulmonary exacerbations (PEx) on health-related quality of life (HRQoL) using Cystic Fibrosis Questionnaire-Revised (CFQ-R) data from 2 large cystic fibrosis (CF) trials. METHODS: This exploratory post-hoc analysis evaluated the impact of PEx on CFQ-R domains of functioning in 80 patients with CF (homozygous for F508del-CFTR), aged ≥14 years randomized to placebo in the TRAFFIC and TRANSPORT trials who experienced 1 PEx. RESULTS: Scores on the CFQ-R were significantly lower within 1 week of PEx start in 8 out of 12 domains (Respiratory Symptoms, Physical Functioning, Emotional Functioning, Health Perceptions, Role Functioning, Social Functioning, Eating, and Vitality). Patients whose PEx was treated with hospitalization or intravenous antibiotics had greater reductions in some domains of HRQoL compared with those treated with oral antibiotics. In the immediate weeks post-PEx, improvement was seen on Emotional Functioning, Respiratory Symptoms, and Health Perceptions, while further decline was seen for Eating, Physical Functioning, Role Functioning, Vitality, and Weight. For some measures (Physical Functioning, Vitality), full recovery to pre-PEx levels took several weeks. CONCLUSIONS: Pulmonary exacerbations have significant effects on multiple domains of HRQoL, and recovery across multiple domains post-PEx can take several weeks. These findings provide insight into the impact of PEx on patient HRQoL and recovery post-PEx. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT01807923 and NCT01807949.

Healthcare resource utilization associated with ivacaftor use in patients with cystic fibrosis.

OBJECTIVE: Ivacaftor was approved in 2012 to treat patients with cystic fibrosis (CF) with specific CFTR gene mutations. The objective of this analysis was to analyze the impact of ivacaftor on health resource utilization through analysis of claims data. METHODS: Patients diagnosed with CF aged ≥6 years prescribed ivacaftor between January 1, 2012 and July 31, 2014 with ≥12 months of continuous insurance coverage prior to and following the prescription were identified. All-cause and CF-specific healthcare resource utilization during the pre- and post-prescription periods and ivacaftor adherence levels were studied. RESULTS: The 79 identified patients had a mean age of 20.8 years, and 54% were female. The proportion of patients with inpatient admissions (all-cause and CF-related) was significantly higher in the pre index compared to post index period (p ≤ 0.05). Mean ivacaftor medication possession ratio was 0.8 (SD = 0.3), and 73% of patients had a medication possession ratio >0.80. LIMITATIONS: Only a small number of patients met the inclusion criteria. Additionally, claims data may contain errors or inconsistencies and cannot be used to determine if medications were taken as prescribed. CONCLUSIONS: Ivacaftor therapy was associated with significant reductions in hospitalizations along with high rates of adherence to treatment over 12 months.