Longitudinal Effects of Elexacaftor/Tezacaftor/Ivacaftor: Multidimensional Assessment of Neuropsychological Side Effects and Physical and Mental Health Outcomes in Adolescents and Adults.

BACKGROUND: Italy initiated elexacaftor/tezacaftor/ivacaftor (ETI) for people with cystic fibrosis (pwCF) in July 2021. It has led to dramatic improvements in lung function, BMI, sweat chloride, and respiratory symptoms. However, few data are available on side effects or effects on a broad range of outcomes. RESEARCH QUESTION: How does ETI affect mental health, cognitive processing, neuropsychological side effects, GI symptoms, and health-related quality of life over time? STUDY DESIGN AND METHODS: This was a prospective, "real-world" longitudinal study. Participants were recruited consecutively and evaluated at initiation (T0) and after 1 month, 3 months, and 6 months of starting treatment. Assessments included depression (nine-item Patient Health Questionnaire), anxiety (seven-item Generalized Anxiety Disorder), cognition (Symbol Digit Modalities Test), GI Symptom Tracker, and health-related quality of life (Cystic Fibrosis Questionnaire-Revised). Based on literature, an ad hoc questionnaire was developed to assess side effects: insomnia, headache, memory problems, "brain fog," and concentration problems. Following descriptive analyses, longitudinal data were analyzed by using mixed models for repeated measures, controlling for age and sex when appropriate. RESULTS: Ninety-two consecutive pwCF (female/male, 46/46; mean age, 25.4 years) participated. FEV1 increased initially and then remained stable. BMI also increased significantly from T0 to 6 months (P < .01). Depression improved from T0 to 1 month (P < .001); however, no changes in anxiety were found. Cognitive processing improved from T0 to subsequent assessments. Positive changes were reported on the GI Symptom Tracker for stools and adherence challenges, although no changes were found for abdominal pain and digestion. Side effects occurred in 10% to 29%, with no reduction over time; insomnia increased significantly across time. Female participants reported more side effects than male participants (ie, insomnia, headache, concentration problems, brain fog). INTERPRETATION: This prospective study evaluated the effects of ETI using multiple measures. Significant improvements were found in many domains; however, side effects were reported by a substantial proportion of pwCF, with no improvements over time. Female participants reported more side effects than male participants. pwCF should be followed up systematically to assess the frequency of side effects after starting this new modulator.

Telemonitoring in Cystic Fibrosis: A 4-year Assessment and Simulation for the Next 6 Years.

BACKGROUND: Innovative technologies and informatics offer a wide range of services to health districts, doctors, nurses, and patients, and is changing the traditional concept of health care. In the last few years, the availability of portable devices, their easiness to transport and use, and the capability to collect and transmit various clinical data have resulted in the fast development of telemedicine. However, despite its potential impact in improving patient conditions, and its cost effectiveness reported in literature, telemedicine is not in daily practice. OBJECTIVE: The aim of this study is to provide evidence of the positive impact of telemonitoring proving the sustainability of an application by sending spirometry outcomes from patients' homes to the hospital doctors via the Internet, and from doctors to patients by an additional phone call solution. METHODS: We examined collected data related to clinical improvement of patients with cystic fibrosis (CF). The patients were followed-up at home using telemonitoring for a period of 10 years, with the aims to prove the sustainability of the methodology (transmissions of spirometry from the patients' home to the doctors and feedback from the doctors to the patients by phone call from the hospital). We stored and analyzed all spirometry transmissions received, and tested the possible presence to decrease the costs between the standard clinical trial (only ambulatory visits) and standard clinical trial with telemonitoring for the follow-up of patients with CF (telemedicine). This was done through an economic analysis of the costs for patients followed at home by telemonitoring. We assessed four years of observation and a simulation of total long-term costs between 2010 and 2020. RESULTS: We discovered a potential saving of €40,397.00 per patient for 10 years, actualized at €36,802.97 for the follow-up of all patients enrolled. CONCLUSIONS: The results from the study suggest that telemedicine can improve the health of patients with CF. It is a relatively cheap and potentially sustainable solution, compared to standard clinical trials. However, to establish and prove the long-term effectiveness and cost-effectiveness, more controlled psychological and behavioral studies are needed.