Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial.

Abstract

BACKGROUND:

Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B).

METHODS:

We assessed the one-year-natural course of dysferlinopathy, and the safety and efficacy of deflazacort treatment in a double-blind, placebo-controlled cross-over trial. After one year of natural course without intervention, 25 patients with genetically defined dysferlinopathy were randomized to receive deflazacort and placebo for six months each (1 mg/kg/day in month one, 1 mg/kg every 2nd day during months two to six) in one of two treatment sequences.

RESULTS:

During one year of natural course, muscle strength declined about 2% as measured by CIDD (Clinical Investigation of Duchenne Dystrophy) score, and 76 Newton as measured by hand-held dynamometry. Deflazacort did not improve muscle strength. In contrast, there is a trend of worsening muscle strength under deflazacort treatment, which recovers after discontinuation of the study drug. During deflazacort treatment, patients showed a broad spectrum of steroid side effects.

CONCLUSION:

Deflazacort is not an effective therapy for dysferlinopathies, and off-label use is not warranted. This is an important finding, since steroid treatment should not be administered in patients with dysferlinopathy, who may be often misdiagnosed as polymyositis.

TRIAL REGISTRATION:

This clinical trial was registered at http://www.ClincalTrials.gov, identifier: NCT00527228, and was always freely accessible to the public.

• Authors: Maggie C Walter, Peter Reilich, Simone Thiele, Joachim Schessl, Herbert Schreiber, Karlheinz Reiners, Wolfram Kress, Clemens Müller-Reible, Matthias Vorgerd, Peter Urban, Bertold Schrank, Marcus Deschauer, Beate Schlotter-Weigel, Ralf Kohnen, Hanns Lochmüller
• Journal: Orphanet journal of rare diseases (Orphanet J Rare Dis) Vol. 8 Pg. 26 (Feb 14 2013) ISSN: 1750-1172 [Electronic] England
• PMID: 23406536 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Placebos
• Pregnenediones
• deflazacort

Topics

• Adolescent
• Adult
• Anti-Inflammatory Agents (therapeutic use)
• Cross-Over Studies
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Motor Activity
• Muscle Strength
• Muscular Dystrophies, Limb-Girdle (drug therapy, physiopathology)
• Placebos
• Pregnenediones (therapeutic use)
• Quality of Life
• Young Adult