Background: Limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9), a rare progressive neuromuscular disorder caused by FKRP variants, leads to defective α-dystroglycan glycosylation. LGMD2I/R9 is characterized by progressive muscle weakness, loss of ambulation, cardiomyopathy, and respiratory decline. Long-term data on LGMD2I/R9 are limited; its impact on life expectancy is poorly defined. We developed a health outcomes model to assess the relationship between LGMD2I/R9 complications and mortality and estimate life expectancy and medical costs.
Methods: A Markov state-transition model estimated life expectancy in life-years (LYs), quality-adjusted LYs (QALYs), and healthcare costs in patients (pts) with LGMD2I/R9. Model inputs were derived from a targeted literature review evaluating risks of key clinical complications (ambulation, respiratory decline, cardiomyopathy). Mortality risk was informed by published data describing associations among cardiomyopathy, noninvasive ventilation, and mortality. Each model cycle represented 1 year. Results were stratified by FKRP genotype to capture differences in disease progression. Deterministic 1-way sensitivity and scenario analyses evaluated model robustness.
Results: In the base case analysis, modeled LYs for pts with LGMD2I/R9 were estimated at 64.3–72.6 years, depending on genotype, corresponding to an estimated 6- to 14-year reduction vs the US general population average of 78.4 years. QALYs were 32.1–34.5, reflecting reduced health-related quality of life following loss of ambulation. Cardiomyopathy and respiratory insufficiency (requiring noninvasive ventilation) were identified as primary drivers of mortality across pt subgroups. Lifetime medical costs were substantial, with an estimated $2.81–$3.25 million per pt; pts with heterozygous/other FKRP variants incurred the highest costs due to earlier loss of ambulation. In sensitivity analyses, LYs were most influenced by cardiomyopathy-related mortality and QALYs by ambulatory utilities. Scenario analyses using EQ-VAS vs EQ-5D utilities produced slightly higher QALYs.
Conclusions: LGMD2I/R9 is associated with reduced LYs and QALYs, driven primarily by cardiomyopathy and loss of ambulation, respectively, with outcomes and lifetime burden varying by genotype. Results align with patterns in other muscular dystrophies, supporting model assumptions and highlighting the relative disease burden of LGMD2I/R9.