Neurologic Stability During Tafamidis Treatment in Transthyretin Amyloidosis with a Mixed Phenotype: A Multicenter Real-World Study

Abstract

Real-world evidence on the effect of tafamidis in mixed-phenotype transthyretin (TTR) amyloidosis (ATTR amyloidosis) is limited. This study assessed changes in neurologic and other measures in patients with mixed-phenotype ATTR amyloidosis treated with tafamidis free acid 61 mg for ≥ 12 months in routine clinical practice. This observational, non-interventional, retrospective multicenter cohort study used anonymized data from four centers. Adults with variant or wild-type mixed-phenotype ATTR amyloidosis treated with tafamidis 61 mg for ≥ 12 months with pre- and post-treatment neurologic assessments were eligible. The primary objective was to assess changes in neurologic measures after ≥ 12 months of treatment; secondary and exploratory objectives were to assess changes in cardiac and frailty measures, modified body mass index (mBMI), and TTR concentration. Overall, 67 patients were included (median age 77.0 years; 79.1% male patients; 55.2% with variant ATTR amyloidosis). Median duration of treatment with tafamidis 61 mg was 35.0 months. Neuropathy Impairment Score (NIS) motor subscale, NIS reflex subscale, and Medical Research Council Scale for Muscle Strength scores showed a median change of 0 from baseline after ≥ 12 months of treatment. Cardiac measures demonstrated minimal change, although interventricular septal thickness (median change, 0.1 cm; p = 0.017) and left atrial diameter (median change, 0.3 cm; p = 0.018) increased modestly. Median change in mBMI was 6.7 g/L × kg/m 2 ( p = 0.925), and 90% of patients with data remained within the same Essential Frailty Toolset score range. TTR concentration increased significantly (median change, 3.0 mg/dL; p < 0.001). In this real-world study of patients with variant or wild-type mixed-phenotype ATTR amyloidosis, neurologic, cardiac, mBMI, and frailty measures were largely maintained after ≥ 12 months of treatment with tafamidis 61 mg. TTR concentration significantly increased. These findings provide real-world evidence of maintenance of neurologic function during treatment with tafamidis in mixed-phenotype ATTR amyloidosis. ClinicalTrials.gov, NCT06393465.