Tafamidis for transthyretin familial amyloid polyneuropathy

• DOI: 10.1212/wnl.0b013e3182661eb1
• Publication Date: 2012-07-27T13:14:13Z
• Authors: Teresa Coelho; Luis F. Maia; Ana Martins da Silva; Marcia Waddington...; Violaine Planté-B...; Pierre Lozeron; Ole B. Suhr; Josep M. Campistol; Isabel Maria Conc...; Hartmut H.-J. Sch...; Pedro Trigo; Jeffery W. Kelly; Richard Labaudinière; Jason Chan; Jeff Packman; Amy Wilson; Donna R. Grogan; Oscar C Imventarza; Pablo J Wainberg; Lucas M Berra; Henryk Maultasch; Jaime Gold; Juan Carlos Pare ...; Andree Zibert
• Keywords: Clinical endpoint

To evaluate the efficacy and safety of 18 months tafamidis treatment in patients with early-stage V30M transthyretin familial amyloid polyneuropathy (TTR-FAP).In this randomized, double-blind trial, received 20 mg QD or placebo. Coprimary endpoints were Neuropathy Impairment Score-Lower Limbs (NIS-LL) responder analysis (<2-point worsening) treatment-group difference mean change from baseline Norfolk Quality Life-Diabetic total score (TQOL) intent-to-treat (ITT) population (n = 125). These also evaluated efficacy-evaluable (EE; n 87) population. Secondary endpoints, including changes neurologic function, nutritional status, TTR stabilization, analyzed ITT population.There was a higher-than-anticipated liver transplantation dropout rate. No differences observed between placebo groups for coprimary NIS-LL (45.3% vs 29.5% responders; p 0.068) TQOL (2.0 7.2; 0.116) In EE population, significantly more than responders (60.0% 38.1%; 0.041), had better-preserved (0.1 8.9; 0.045). Significant most secondary favored tafamidis. stabilized 98% 0% (p < 0.0001). Adverse events similar groups.Although not met associated no trend toward significant reduction worsening variables, supporting hypothesis that preventing dissociation can delay peripheral impairment.This study provides Class II evidence clinical progression TTR-FAP, as measured by QOL-DN score. outcomes demonstrated impairment tafamidis, which well tolerated over months.