New Treatment for Duchenne Muscular Dystrophy

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The Food and Drug Administration (FDA) has approved deflazacort (Emflaza) for use in the treatment of Duchenne muscular dystrophy. Deflazacort is the first corticosteroid approved by the FDA for this indication.
Duchenne muscular dystrophy, the most common type of muscular dystrophy, is a genetic disorder characterized by progressive muscle deterioration and weakness starting in childhood. It is caused by the absence of dystrophin, a protein found primarily in skeletal and cardiac muscle cells. Dystrophin protects these cells from the injury that can result from the muscles’ continual contraction and relaxation. In addition to losing the ability to walk, patients with Duchenne muscular dystrophy can develop life-threatening cardiac and respiratory conditions as the disease progresses. The disorder primarily affects boys, although it can occur rarely in girls.
Deflazacort produces antiinflammatory and immunosuppressive effects, but exactly how it exerts its therapeutic effect in Duchenne muscular dystrophy is unknown. The drug does not “cure” the disorder, instead it slows down the disease process, offering limited improvement. Deflazacort was shown to improve muscle strength in a multicenter, randomized, double-blind, placebo- and active-controlled study of 196 male patients, ages five to 15 years, with documented mutation of the dystrophin gene and onset of muscle weakness before age five. The increase in muscle strength was observed after 12 weeks of deflazacort use and was maintained throughout the 52-week trial. In a second randomized, double-blind, placebo-controlled trial of 29 male patients ages six to 12 years with a Duchenne muscular dystrophy diagnosis who received deflazacort or placebo for 104 weeks, the results were not statistically different between the groups; however, this may be related to the limited number of subjects in the placebo arm at two years (participants were discontinued once the disease progressed and they were unable to walk). After six and 12 months of treatment, however, there was a trend toward improved muscle strength and the time until loss of ambulation appeared to be longer with deflazacort compared with placebo, although, according to the FDA, “assessments at these intervals were not statistically controlled for multiple comparisons.” Long-term effects on cardiac muscle were not studied.
Common adverse effects of deflazacort are similar to those of all other corticosteroids and include facial fullness (Cushingoid appearance), weight gain, increased appetite, increased risk of minor infections (upper respiratory tract infections, cough, nasopharyngitis), hirsutism, and central obesity. Another common adverse effect is the frequent voiding of small amounts of urine during the day. Less frequent adverse effects, also found with long-term corticosteroid use, include problems with endocrine function (hypothalamic–pituitary–adrenal axis suppression, Cushing's syndrome, and hyperglycemia), immunosuppression and increased susceptibility to serious infections (new infections or the exacerbation, dissemination, or reactivation of latent infections that may be severe and possibly fatal—the label warns of exacerbation of systemic fungal or threadworm infections and reactivation of hepatitis B virus or amebiasis infections), hypertension, changes in sodium and potassium levels, risk of gastrointestinal perforation, serious skin rashes, behavioral and mood changes (euphoria, insomnia, mood swings, personality changes, severe depression, and psychosis), decreased bone density, and ophthalmic changes (cataracts, infections, and glaucoma).
Interactions are possible with drugs that, like deflazacort, are metabolized by the cytochrome P-450 (CYP) 3A4 isoenzyme system. Nurses and NPs who work with patients with Duchenne muscular dystrophy should complete a careful drug history and assess for medications that may interact with deflazacort. If patients are receiving moderate or strong CYP3A4 inhibitors, it is recommended they be given one-third of the recommended deflazacort dose to avoid an increase in total drug exposure. Drugs that are moderate or strong CYP3A4 inducers should be avoided because they will likely reduce deflazacort's efficacy.

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