Qualitative evaluation of the symptoms and quality of life impacts of long-chain fatty acid oxidation disorders.

BACKGROUND: Long-chain fatty acid oxidation disorders (LC-FAOD) are a group of rare autosomal-recessive genetic disorders characterized by metabolic deficiencies in which the body is unable to convert long-chain fatty acids into energy. To date, however, there is limited understanding of the patient experience of LC-FAOD. METHODS: The symptoms, observable signs, and quality of life (QoL) impacts associated with LC-FAOD were explored via a focus group (n = 8) and semi-structured interviews (n = 6) with patients and caregivers of patients with LC-FAOD, and interviews (n = 4) with expert clinicians. Data were analyzed via thematic analysis and summarized in a conceptual model. RESULTS: Participants reported a wide range of signs and symptoms associated with LC-FAOD, broadly categorized as musculoskeletal, endocrine/nutritional/metabolic, neurological, gastrointestinal/digestive, sensory, cardiovascular, respiratory, urological, and constitutional. LC-FAOD were reported to have a significant impact on various aspects of patients' lives including physical functioning, participation in daily activities, emotional/psychological wellbeing, and social functioning. Lifestyle modifications (such as diet and exercise restrictions) were necessary because of the condition. Symptoms were typically episodic in presentation often arising or exacerbated during catabolic conditions such as prolonged exercise, fasting, physiological stress, and illness/infection. Symptoms were also commonly reported to lead to emergency room visits, hospitalization, and clinical complications. CONCLUSION: LC-FAOD have a considerable impact on patients' lives. There is a high degree of concordance in the signs, symptoms, and impacts of LC-FAOD reported by patients, caregivers, and clinicians; however, there were many symptoms and impacts that were only reported by patients and caregivers, thus demonstrating that insights from patient/caregiver experience data are integral for informing medical product development and facilitating patient-centered care.

Results from a 78-week, single-arm, open-label phase 2 study to evaluate UX007 in pediatric and adult patients with severe long-chain fatty acid oxidation disorders (LC-FAOD).

Long-chain fatty acid oxidation disorders (LC-FAOD) are rare disorders characterized by acute crises of energy metabolism and severe energy deficiency that may present with cardiomyopathy, hypoglycemia, and/or rhabdomyolysis, which can lead to frequent hospitalizations and early death. An open-label Phase 2 study evaluated the efficacy of UX007, an investigational odd-carbon medium-chain triglyceride, in 29 subjects with severe LC-FAOD. UX007 was administered over 78 weeks at a target dose of 25-35% total daily caloric intake (mean 27.5%). The frequency and duration of major clinical events (hospitalizations, emergency room visits, and emergency home interventions due to rhabdomyolysis, hypoglycemia, and cardiomyopathy) occurring during 78 weeks of UX007 treatment was compared with the frequency and duration of events captured retrospectively from medical records for 78 weeks before UX007 initiation. The mean annualized event rates decreased from 1.69 to 0.88 events/year following UX007 initiation (p = 0.021; 48.1% reduction). The mean annualized duration rate decreased from 5.96 to 2.96 days/year (p = 0.028; 50.3% reduction). Hospitalizations due to rhabdomyolysis, the most common event, decreased from 1.03 to 0.63 events/year (p = 0.104; 38.7% reduction). Initiation of UX007 eliminated hypoglycemia events leading to hospitalization (from 11 pre-UX007 hospitalizations, 0.30 events/year vs. 0; p = 0.067) and intensive care unit (ICU) care (from 2 pre-UX007 ICU admissions, 0.05 events/year vs. 0; p = 0.161) and reduced cardiomyopathy events (3 events vs. 1 event; 0.07 to 0.02 events/year; 69.7% decrease). The majority of treatment-related adverse events (AEs) were mild to moderate gastrointestinal symptoms, including diarrhea, vomiting, and abdominal or gastrointestinal pain, which can be managed with smaller, frequent doses mixed with food.

Development and preliminary evidence of the psychometric properties of the GNE myopathy functional activity scale.

AIM: GNE myopathy, a rare, severe, progressive myopathy, presents with lower extremity distal muscle weakness. The GNE myopathy functional activity scale (GNEM-FAS) evaluates the impact of GNE myopathy on functioning in adults. This paper presents the psychometric validation of the GNEM-FAS. PATIENTS & METHODS: Validation of the GNEM-FAS was performed using data from a randomized, double-blind, placebo-controlled Phase-II study (n = 46). RESULTS: Domain score distributions were acceptable. Moderate inter-item correlations (typical range, 0.40-0.70), strong item convergent and discriminant validity and high internal consistency reliability (α = 0.88-0.92) supported the instrument structure. Test-retest reliability was strong (ICC range: 0.87-0.95). Scale scores distinguished among subjects with differing disease severity (p < 0.05). CONCLUSION: This study provides preliminary evidence of the GNEM-FAS as a valid, reliable assessment.