CHANNELOPATHIES AND RELATED DISORDERS: EP.228 Efficacy and safety of mexiletine in non-dystrophic myotonias: a randomized, double-blind, placebo-controlled, cross-over study

Abstract

Mexiletine – a non-selective voltage-gated sodium channel blocker – is one of the most effective treatments available for patients with non-dystrophic myotonias but has been prescribed off-label for more than 30 years. We investigated the efficacy and safety of MEXiletine in non-dystrophic MYOtonias in a randomized clinical trial (MYOMEX). The MYOMEX study was a multicenter, double-blind, placebo-controlled, cross over study aimed at patients with genetically defined myotonia congenita (MC) and paramyotonia congenita (PC). The primary endpoint was the self-reported score of stiffness severity on a 100-mm visual analogic scale (VAS). Mexiletine was started at 200 mg/day and titrated by increments of 200 mg every three days to reach a maximum dose of 600 mg/day in one week for a total treatment duration of 18 days for each cross-over period. The modified intent-to-treat population included 25 patients (13 with MC and 12 with PC; mean age, 43.0 years; male, 68.0%). The median stiffness VAS score for patients receiving mexiletine was 71.0 at baseline and decreased to 16.0 at the end of the treatment period while the score did not change for placebo (81.0 at baseline vs. 78.0 at end of treatment). A mixed effects linear model analysis on ranked absolute changes showed a significant effect of treatment (p<0.001). The overall quality of life score of the Individualized Neuromuscular Quality of Life questionnaire (INQoL) was significantly improved (p<0.001) and significant treatment effect was observed on all INQoL domains. No clinically significant adverse events or ECG conduction abnormalities were reported in this study. The MYOMEX study provides evidence that mexiletine significantly reduces myotonia in non-dystrophic myotonias independent of the type of channelopathy and is well tolerated.