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¡¶The Lancet Regional Health - Europe¡·£ºPatient-reported, psychosocial and health economic outcomes in mild to moderate Friedreich's ataxia: baseline results of the PROFA study

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Friedreich's Ataxia (FA) is a rare autosomal recessive disorder characterized by progressive multisystemic degeneration, primarily affecting the nervous system, cardiac function, and sensory organs. The PROFA study, a European multicenter observational investigation, provides a comprehensive analysis of patient-reported outcomes, psychosocial health, and healthcare economics across different stages of disability in FA. This research aims to address critical gaps in understanding how FA impacts daily life, mental well-being, and societal costs, particularly as the disease progresses.

### Key Findings and Clinical Implications
1. **Multidimensional Burden Across Disability Stages**
The study identified a progressive decline in physical, cognitive, and psychosocial domains as FA disability stages increased from 1 to 5. Activities of daily living (measured by FARS-ADL) and health-related quality of life (PROM-Ataxia and EQ-5D-5L) showed significant deterioration with each stage. Communication disabilities (COMATAX) and informal care requirements also rose sharply, particularly in advanced stages. However, mental well-being (WEMWBS) remained relatively stable, suggesting resilience or adaptation mechanisms despite physical decline.

2. **Economic and Caregiver Burden**
Healthcare costs from a societal perspective surged to €32,679 annually in the most severely disabled patients, driven by informal care (58% of participants) and productivity losses. Formal care was utilized by 33.3% of patients, highlighting the dual reliance on professional and familial support. Informal caregivers provided an average of 12.2 hours per week, with demand escalating in later stages. These findings underscore the critical need for integrated care systems that address both medical and socioeconomic challenges.

3. **Impact of Omaveloxolone**
Approximately 32.7% of participants were receiving Omaveloxolone, a recently approved therapy targeting frataxin deficiency. While the study did not directly assess treatment effects, higher usage in patients with typical onset (younger, faster progression) suggests potential benefits in delaying functional decline. This aligns with prior observations that early-stage interventions may yield greater cumulative therapeutic effects.

### Methodological Innovations
The study employed a novel remote assessment protocol using a mobile health app (ATOM5) to collect patient-reported data at home. This approach minimized clinical visit burdens while ensuring consistent data collection across six European centers. Key outcomes included:
- **Physical Function**: SARA (ataxia severity) and FARS-ADL (daily living deficits) metrics showed strong correlation with disability stages.
- **Communication and Sensory Impairments**: The COMATAX tool revealed significant psychosocial strain from speech and hearing difficulties, particularly in advanced stages.
- **Psychological Health**: While the WEMWBS score declined with disability, it remained relatively stable, indicating potential resilience or undiagnosed support needs.

### Systemic and Caregiver Challenges
The study highlighted systemic gaps in FA care:
- **Informal Care Dominance**: Over 60% of patients relied on informal care, often provided by family members, with little opportunity for employment due to disease-related limitations.
- **Healthcare Utilization**: Formal care access was limited, with only 18.8% of participants using social care services. This disparity emphasizes underprovision of formal support systems.
- **Economic Impact**: Societal costs accounted for nearly 58% of total expenses, reflecting the disproportionate burden on caregivers and lost productivity.

### Future Directions and Research Priorities
1. **Longitudinal Tracking**: Ongoing data collection until 2028 will allow assessment of treatment efficacy (e.g., Omaveloxolone) and disease progression patterns.
2. **Expanded Outcome Measures**: Validation of newly developed tools (e.g., COMATAX) is essential for routine clinical use. Existing scales like PROM-Ataxia demonstrated moderate sensitivity to change but require further validation.
3. **Care System Optimization**: The study advocates for integrated care models addressing physical, communication, and mental health needs. Prioritizing caregiver support programs and formal care infrastructure could alleviate burdens.
4. **Therapeutic Evaluation**: Long-term follow-up will be critical to quantify the economic and quality-of-life benefits of disease-modifying therapies like Omaveloxolone.

### Conclusion
FA represents a profound multisystem disorder with cascading effects on individual well-being, family dynamics, and healthcare systems. The PROFA study advances our understanding by linking disability stages to measurable outcomes across physical, communication, and economic domains. Its findings advocate for a paradigm shift in FA care¡ªmoving beyond mobility support to holistic interventions that address communication barriers, mental health, and systemic economic impacts. As new therapies emerge, this framework will help evaluate their broader societal value and guide resource allocation.