What is the recommended treatment approach for a patient with Duchenne muscular dystrophy?

Treatment Approach for Duchenne Muscular Dystrophy

Glucocorticoid therapy with daily prednisone (0.75 mg/kg/day) or deflazacort (0.9 mg/kg/day) is the cornerstone of treatment for Duchenne muscular dystrophy and should be initiated during the plateau phase (typically age 4-8 years) to prolong ambulation, improve survival, and enhance quality of life. 1

Pharmacological Management: Glucocorticoids

When to Start

• Do not start glucocorticoids in children under 2 years who are still gaining motor skills 1
• Initiate therapy during the plateau phase when motor skills stop progressing but before clear decline begins, typically between ages 4-8 years 1
• Complete all recommended immunizations and establish varicella immunity before starting glucocorticoids 1
• Provide families with a steroid emergency card listing considerations for acute illness, fracture, infection, or surgery 1

First-Line Regimen Selection

• Prednisone 0.75 mg/kg/day is the first-line treatment unless pre-existing weight or behavioral issues favor deflazacort 1, 2
• Deflazacort 0.9 mg/kg/day should be considered as first-line when there are pre-existing weight or behavioral concerns 1
• Prednisone 10 mg/kg on weekends only is equally effective over 12 months compared to daily dosing, though long-term data are lacking 2

Expected Benefits

• Prolongs ambulation by 2-5 years 3
• Reduces risk of progressive scoliosis and need for spinal surgery 1, 2
• Stabilizes pulmonary function and delays need for noninvasive ventilation 1, 2
• Delays cardiomyopathy onset by 18 years of age 2
• Increases survival at 5-15 years of follow-up 2

Managing Side Effects

• If side effects are unmanageable, reduce dose by 25-33% and reassess in 1 month 1
• If obesity is concerning, switch from prednisone to deflazacort 1
• Do not abandon glucocorticoid therapy until at least one dose reduction and change to alternative regimen has been attempted 1
• Prednisone 0.75 mg/kg/day is associated with significant risk of weight gain, hirsutism, and cushingoid appearance 2
• Deflazacort may be associated with greater risk of cataracts than prednisone 2

Comparative Effectiveness

• Deflazacort and prednisone may be equivalent in improving motor function 2
• Prednisone may be associated with greater weight gain in the first years of treatment than deflazacort 2
• Deflazacort maintains ambulation longer and provides significant sparing of pulmonary function 4

Mutation-Specific Therapies

Exon Skipping Agents

• Eteplirsen (EXONDYS 51) is FDA-approved for patients with confirmed DMD gene mutations amenable to exon 51 skipping 5
• This indication is approved under accelerated approval based on increased dystrophin in skeletal muscle 5
• Dosing and administration should follow FDA labeling 5

Respiratory Management

Monitoring Schedule

• Regular pulmonary function monitoring is essential, including forced vital capacity (FVC) and peak cough flow (PCF) 1
• FVC should be expressed in liters and as % of predicted value for age and height 4
• PCF measurement should ideally be performed using an oronasal mask interface in sitting position 4

Triggers for Specialist Referral

• Any symptom or suspicion of sleep-disordered breathing should prompt referral to a specialist respiratory team, regardless of FVC values 4
• PCF < 270 L/min (in adults) or a decline in recorded value should prompt referral and consideration of airway clearance support 4
• FVC ≤50% of predicted value warrants specialist evaluation 4

Sleep-Disordered Breathing

• Symptoms include excessive daytime tiredness, disturbed sleep with frequent waking, witnessed apnea episodes, morning headaches, and poor appetite 4
• Initial evaluation should include clinical review, respiratory muscle strength assessment (FVC, sniff nasal inspiratory pressure, maximal inspiratory pressure), and sleep studies 4
• Nocturnal or full-time mechanical ventilation increases survival among patients with DMD who are hypercapneic 4

Perioperative Respiratory Care

• Preoperative evaluation by pulmonologist and cardiologist at least 2 months before surgery is mandatory 4, 1
• Assess for sleep hypoventilation preoperatively with sleep studies or nocturnal oximetry 4, 1
• If sleep studies are abnormal, patients can begin nocturnal noninvasive ventilation before surgery and extubate to noninvasive ventilation postoperatively 4
• Essential postoperative care includes aggressive airway clearance and respiratory support 4

Vaccination

• Inactivated influenza vaccine (subcutaneous) instead of live vaccine (nasal spray) must be used in patients on corticosteroids 4
• Pneumococcal polysaccharide conjugate vaccines (Prevenar13) should be given as per national guidance 4
• 23-valent pneumococcal polysaccharide vaccine should be given prior to initiation of corticosteroid therapy 4
• Live vaccines should be avoided in patients on corticosteroids 4

Cardiac Management

• ACE inhibitors or ARBs should be initiated by 10 years of age (barring contraindications) 1
• β-adrenergic blockade should be considered after ACE inhibitor/ARB initiation, especially with ventricular dysfunction or elevated heart rate 1

Orthopedic Management

• Surgical intervention for scoliosis should be considered when Cobb angle reaches 30-50 degrees 1
• No absolute pulmonary function contraindications for surgery exist; some patients with FVC as low as 20% of predicted have had good outcomes 1

Multidisciplinary Care Coordination

Monitoring Schedule

• Routine clinic appointments every 6 months 1
• Regular physical and occupational therapy assessments every 4 months 1
• Emotional adjustment screening at every clinic visit using standardized rating scales 1
• Comprehensive neuropsychological assessment at diagnosis 1

Patient and Family Education

• Education should begin as soon as possible after diagnosis and continue as a key component of ongoing care 4
• Families must understand the natural history of DMD, recognize early signs of pulmonary complications, and make informed choices about treatment options including noninvasive ventilation and ventilation via tracheostomy 4
• Provide anticipatory guidance on assessment and management of intercurrent respiratory illnesses 4

Therapies to Avoid

• Do not use supplements including coenzyme Q10, carnitine, amino acids, fish oil, vitamin E, or green tea extract—insufficient evidence exists for recommendation 1
• Oxandrolone (anabolic steroid) is not appropriate either with or without glucocorticoid therapy 1
• Botulinum toxin A has not been studied for safety in DMD and is inappropriate for contracture treatment/prevention 1

Common Pitfalls

• Starting glucocorticoids too early (before plateau phase in children under 4 years still gaining skills) exposes patients to unnecessary side effects without clear benefit 1
• Abandoning glucocorticoids prematurely due to side effects without attempting dose reduction or alternative regimens deprives patients of proven mortality and morbidity benefits 1
• Failing to provide steroid emergency card puts patients at risk during acute illness or surgical procedures 1
• Maintain a high index of suspicion for steroid-related complications at all times 1