Monitoring safety and effectiveness of Tafamidis in transthyretin amyloidosis in Italy: a 3-year longitudinal multicenter study in a non-endemic area

Abstract

Background Tafamidis is a transthyretin (TTR) stabilizer able to prevent mutated TTR tetramer dissociation into amyloidogenic monomers. There have been a few encouraging studies on safety and long-term efficacy of Tafamidis in early-onset Val30Met TTR-familial amyloid polyneuropathy (TTR-FAP) patients. However, less is known about its efficacy in later stages of the disease and in non-Val30Met mutations. Methods Multi-center observational study on symptomatic TTR-FAP patients prescribed to receive tafamidis. We followed up patients according to a standardized protocol including general medical, cardiological and neurological assessments at baseline and every 6 months up to 3 years. Results 61 (42 males) patients were recruited. Only 28% of enrolled subjects had the common Val30Met mutation, mean age of onset was remarkably late (59 years) and 18% was in an advanced disease stage at study entry. Tafamidis proved safe and well-tolerated. One third of patients did not show significant progression along 36 months, independently from mutation type and disease stage. Neurological function worsened particularly in the first 6 months but slowed significantly thereafter. Fifteen percent of patients showed cardiac disease progression and 30% new onset of cardiomyopathy. A higher mBMI at baseline was associated with better preservation on neurological function. Conclusions Neuropathy and cardiomyopathy progressed in a significant proportion of patients despite treatment. However, the worsening of neurological function slowed after the first 6 months and also subjects with more advanced neuropathy, as well as patients with non-Val30Met mutation, benefited from Tafamidis treatment. Body weight preservation is an important favorable prognostic factor.