Presentation (CTI)

OBJECTIVES: Neurofibromatosis type 1 (NF1) is a rare genetic disorder characterized by multisystem involvement, tumor development, and risk of malignant transformation. Despite therapeutic advances, the overall burden of NF1, particularly from a health economics and outcomes research (HEOR) perspective, remains incompletely characterized. This study aimed to synthesize evidence on epidemiology, clinical and economic burden, disease progression, and treatment landscape in NF1 to inform health technology assessment (HTA) and value-based decision-making.
METHODS: A targeted literature review was conducted using PubMed and Embase to identify peer-reviewed studies published between 2016 and 2026 reporting on NF1 epidemiology, disease burden, malignancy risk, healthcare utilization, and treatment outcomes. Studies were selected based on predefined criteria focusing on human populations and relevance to clinical and HEOR domains. Evidence was qualitatively synthesized across key domains, including clinical burden, healthcare resource use, treatment patterns, and outcomes relevant to economic evaluation.
RESULTS: NF1 is an autosomal dominant disorder with an incidence of approximately 1 in 2,500-3,000 births and a prevalence of 1 in 3,000-7,000 individuals, characterized by significant clinical heterogeneity. Common manifestations include café au lait macules, freckling, neurofibromas, and Lisch nodules, with involvement of the skin and nervous system. NF1 is associated with increased morbidity, including a 2.7- to 4-fold higher malignancy risk and reduced life expectancy. Plexiform neurofibromas are linked to functional impairment, chronic pain, and risk of malignant transformation. From a HEOR perspective, NF1 imposes substantial burden due to lifelong monitoring, multidisciplinary care, surgical interventions, and complications, alongside significant quality-of-life impairment. Although targeted therapies such as MEK inhibitors have shown clinical benefit, uncertainties remain regarding long-term outcomes, cost-effectiveness, and access.
CONCLUSIONS: NF1 represents a high-burden rare disease with substantial unmet need and evolving treatment options. Robust HEOR evidence is critical to inform HTA, reimbursement decisions, and long-term value assessment of emerging therapies.