Use a microsimulation model to assess the impact of earlier diagnosis and treatment on disease progression in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) in the US.

ATTRv-PN is an autosomal dominant disorder that leads to sensorimotor polyneuropathy and autonomic dysfunction. When untreated, ATTRv-PN can cause profound morbidity. Phenotypic heterogeneity results in delayed diagnosis and increased disease severity. Disease modifying therapies are available and most effective with early intervention. Improving time to diagnosis provides an opportunity to improve patient outcomes.

A microsimulation model incorporated incidence, diagnosis, treatment, familial amyloidotic polyneuropathy (FAP) stage progression, and mortality, to create a representative cohort of ATTRv-PN patients in the US. Disease progression was defined by annual Norfolk Quality of Life Diabetic Neuropathy (Norfolk QoL-DN) decline. Two scenarios were compared: 1) a current practice scenario, reflecting current time-to-diagnosis, diagnosis rates and treatment; and 2) an intervention scenario, assuming a halved time-to-diagnosis, and 100% of incident patients diagnosed and treated. Model outcomes included FAP stage distribution, progression between FAP stages, and Quality-Adjusted-Life-Years (QALYs) from 2025 to 2034.

The current practice scenario predicted that there would be 3,035 stage 1, 382 stage 2, and 536 stage 3 patients in 2034, in the US. The intervention scenario reduced the burden of advanced disease, with 41.2% and 37.7% fewer prevalent cases in FAP stages 2 and 3, respectively. Intervention was estimated to reduce progression to stages 2 and 3 by 37.8% and 31.5%, respectively, between 2025 and 2034. Slowed progression of PN symptoms in the intervention scenario was expected to result in 1,222 additional QALYs by 2034.

This model demonstrates early diagnosis and treatment with silencers are projected to slow ATTRv-PN progression and reduce prevalence of severe disease by over 40%. These findings underscore the importance of timely diagnosis and treatment in patients with ATTRv-PN.