Heart drug could ease rare muscle disorder

By Eleanor McDermid, Senior medwireNews Reporter

The anti-arrhythmic drug mexiletine may improve symptoms in patients with nondystrophic myotonias, shows a small randomized trial published in JAMA.

Patients in the double-blind crossover study reported less stiffness during mexiletine treatment than during placebo treatment, and also had improvements on secondary endpoints, report Richard Barohn (University of Kansas Medical Center, Kansas City, USA) and colleagues.

Mexiletine, a sodium channel blocker, has been prescribed off-label to treat nondystrophic myotonias, but these findings represent the first formal trial of the medication.

The trial was conducted within the Rare Disease Clinical Research Network; involvement of seven neuromuscular centers from four countries yielded 59 patients with nondystrophic myotonia, aged an average of 43 years. About a third of the patients were taking antimyotonic medications at baseline, with 22% taking off-label mexiletine. Patients stopped these treatments and adhered to a washout period before starting the study drugs.

During the first 4-week treatment period, patients taking mexiletine (200 mg, three times daily) rated their muscle stiffness at an average of 2.53 on a scale from 1 (minimal) to 9 (worst ever). The rating by patients taking matching placebo was a significant 1.68 points higher, at 4.21.

"Overall, most effect sizes were more than 0.5, which in the literature corresponds with moderate responsiveness, and more than 0.8, which corresponds with large responsiveness, for many outcomes," say Barohn et al.

There followed a 1-week washout period, after which patients switched to the alternative treatment. During this period, the average muscle stiffness ratings were 1.60 for mexiletine and 5.27 for placebo, corresponding to a significant 3.68-point difference.

The researchers note that the effect of mexiletine in the second treatment period was markedly greater than in the first period. They say this could be due to unintentional unblinding, caused by a noticeable beneficial effect of mexiletine or by the presence or absence of side effects. Either of these scenarios could cause patients to under- or overestimate their scores.

"The fairest interpretation we can propose is that the treatment effect lies somewhere between the estimates from period 1 (-1.68) and period 2 (-3.68)," say Barohn and team.

The most frequent side effects were gastrointestinal discomfort, experienced by nine patients when taking mexiletine and one when taking placebo. One patient experienced mild transient cardiac effects in the mexiletine phase, as did one in the placebo phase.

Mexiletine was also associated with significant improvements in Individualized Neuromuscular Quality of Life summary quality of life scores (14.0 vs 16.7 points). On clinical examination, patients had less handgrip myotonia when using mexiletine, at 0.164 seconds compared with 0.494 seconds when taking placebo.

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