Tafamidis for transthyretin familial amyloid polyneuropathy

作者：Teresa Coelho, Luı́s F. Maia, Ana Silva, Márcia Waddington‐Cruz, Violaine Planté‐Bordeneuve, Pierre Lozeron, Ole B. Suhr, Josep M. Campistol, Isabel Conceição, Hartmut Schmidt, Pedro Trigo, Jeffery W. Kelly, Richard Labaudinière, Jason Chan, Jeff Packman, Amy C. Wilson, Donna R. Grogan, Oscar C Imventarza, Pablo J Wainberg, Lucas M Berra, Henryk Maultasch, Jaime Gold, Juan Carlos Pare Bardera, Andree Zibert · 发表于：Neurology · 年份：2012 · DOI：10.1212/wnl.0b013e3182661eb1 · 被引用次数：806 · 研究领域：Amyloidosis: Diagnosis, Treatment, Outcomes、Alzheimer's disease research and treatments、Multiple Myeloma Research and Treatments

OBJECTIVES: To evaluate the efficacy and safety of 18 months of tafamidis treatment in patients with early-stage V30M transthyretin familial amyloid polyneuropathy (TTR-FAP). METHODS: In this randomized, double-blind trial, patients received tafamidis 20 mg QD or placebo. Coprimary endpoints were the Neuropathy Impairment Score-Lower Limbs (NIS-LL) responder analysis (<2-point worsening) and treatment-group difference in the mean change from baseline in Norfolk Quality of Life-Diabetic Neuropathy total score (TQOL) in the intent-to-treat (ITT) population (n = 125). These endpoints were also evaluated in the efficacy-evaluable (EE; n = 87) population. Secondary endpoints, including changes in neurologic function, nutritional status, and TTR stabilization, were analyzed in the ITT population. RESULTS: There was a higher-than-anticipated liver transplantation dropout rate. No differences were observed between the tafamidis and placebo groups for the coprimary endpoints, NIS-LL responder analysis (45.3% vs 29.5% responders; p = 0.068) and change in TQOL (2.0 vs 7.2; p = 0.116) in the ITT population. In the EE population, significantly more tafamidis patients than placebo patients were NIS-LL responders (60.0% vs 38.1%; p = 0.041), and tafamidis patients had better-preserved TQOL (0.1 vs 8.9; p = 0.045). Significant differences in most secondary endpoints favored tafamidis. TTR was stabilized in 98% of tafamidis and 0% of placebo patients (p < 0.0001). Adverse events were similar ...