Diagnosis and treatment of ADHD in pediatric patients during the first year of elexacaftor/tezacaftor/ivacaftor.

BACKGROUND: With elexacaftor/tezacaftor/ivacaftor (ETI), children with cystic fibrosis (CwCF) are living healthier lives with a focus on typical developmental issues such as attention deficit/hyperactivity disorder (ADHD). This paper characterizes CwCF with ADHD within the first year of ETI treatment. METHODS: This retrospective, observational analysis examines a subgroup of CwCF participating in a longitudinal study obtaining prospective data regarding the impact of ETI on mental health. All participants started on ETI were offered enrollment, with rolling enrollment as younger children became eligible. Clinical data regarding CF symptoms, mental health diagnoses, medications, changes in mental health symptoms and BMI were collected via chart review. RESULTS: Before ETI, ADHD diagnoses were identified in 21 children; an additional 3 were diagnosed within the first year. Eleven children were treated with ADHD medication at ETI initiation; nine children did not use ADHD medication during the study period. In the 1-year follow-up, four children started ADHD medication. Of the 11 who started ETI on ADHD medication, five increased doses, three changed medications and/or decreased dose, and one discontinued medication. Two children experienced no changes to their treatment. CONCLUSION: Most CwCF on ADHD medication underwent changes in dosing and/or medication after ETI initiation. Several children were diagnosed with ADHD after starting ETI. The role of ETI in these recent diagnoses and treatment plans is unclear. Given the prevalence of pediatric ADHD diagnoses and the medication changes that were needed by this population, additional research is warranted to clarify the relationship between ETI and ADHD in CwCF.

Clinical change 2 years from start of elexacaftor-tezacaftor-ivacaftor in severe cystic fibrosis.

RATIONALE: Limited published research is available on the impact of elexacaftor/tezacaftor/ivacaftor (ETI) beyond the initial few months postdrug initiation, especially for those who initiated therapy via individual investigational new drug application. The experiences of patients with cystic fibrosis (CF) experiencing severe lung disease were reviewed for significant improvements in clinical symptoms and quality of life. OBJECTIVES: To examine clinical outcomes 2 years post-ETI in patients with CF and advanced lung disease. METHODS: This single center institutional review board-approved, retrospective chart review assessed clinical markers (percent predicted forced expiratory volume in 1 s, weight, sweat chloride), quality of life and computed tomography scans in patients with advanced lung disease who met criteria for compassionate use/expanded access program due to high risk of death or transplant need within 2 years. RESULTS: Eighteen identified patients (ages 15-49 years) initiated drug between July and September 2019. Clinical markers indicated that therapy was well tolerated, not discontinued by any participant, and lab values did not indicate medical concern or discontinuation. Monitoring results indicated the safety of modulator therapy as there were no adverse clinical occurrences and all patients presented universal stabilization. There were no deaths and no transplants by the end of the study. CONCLUSIONS: This study focused on patients with CF eligible for modulator therapy and were initiated due to advanced lung disease. Initiation of modulator therapy was deemed safe and resulted in objective positive changes in nutrition, cough, FEV1 , subjective reports of clinical status, level of activity, and a reduction in burden of treatment.

Clinical management of pediatric patients with cystic fibrosis and autism spectrum disorder.

BACKGROUND: Cystic Fibrosis (CF) and autism spectrum disorder (ASD) are life-long conditions with intense treatment burdens for patients and families. Patients with a concurrent diagnosis (CF-ASD) experience unique obstacles to CF care. This study describes the experiences of our multidisciplinary CF team in caring for patients with CF-ASD and provides insight into provider and parental perspectives on clinical management. METHODS: This is a three-part qualitative study involving (1) retrospective chart review of patients with CF-ASD, (2) surveys with multidisciplinary care team members, and (3) semistructured interviews with caregivers of patients with CF-ASD. Challenges in clinical management of this specific cohort were compiled using data from chart review and care team surveys. Strategies to address these concerns were identified and rated by individual families based on relevance and practicality. RESULTS: Within our CF center, 12 patients have an official diagnosis of ASD. Median age of patients with CF-ASD was 8.5 years (range 3-20 years), 67% were male, and 83% were on highly effective modulator therapy. Clinical barriers included sensory processing issues, environmental overstimulation, intolerance to procedures and to disrupted routines. Potentially impactful strategies include patient-specific coping plans, guided behavioral interventions, parental advocacy, and improved communication between the family and multidisciplinary team. CONCLUSION: Children with CF-ASD face extraordinary challenges beyond the experience of neurotypical children with CF. Increased awareness of this complex dual diagnosis will help providers be sensitive to the unique needs of these patients, help build consistent and trustworthy relationships with their families and deliver effective clinical care despite limitations.