Prednisone in Duchenne Dystrophy (Griggs)
(1991)Objective
To define the time course and dose response of prednisone treatment in boys with Duchenne muscular dystrophy
Study Summary
• Prednisone produced rapid muscle strength improvement detectable as early as 10 days after starting therapy
• Higher dose (0.75 mg/kg/day) was superior to lower dose at 3 months but had more side effects
• Higher dose (0.75 mg/kg/day) was superior to lower dose at 3 months but had more side effects
Intervention
Prednisone 0.75 mg/kg/day vs prednisone 0.3 mg/kg/day vs placebo
Inclusion Criteria
Boys aged 5-15 years with Duchenne dystrophy
Study Design
Arms: Prednisone 0.75 mg/kg/day, Prednisone 0.3 mg/kg/day, Placebo
Patients per Arm: 34 (0.75 mg/kg), 33 (0.3 mg/kg), 32 (placebo)
Outcome
• Both prednisone doses significantly improved muscle strength vs placebo as early as 10 days
• At 3 months, 0.75 mg/kg/day was significantly superior to 0.3 mg/kg/day
• 0.75 mg/kg/day group had weight gain, cushingoid appearance, and hirsutism at 6 months
• At 3 months, 0.75 mg/kg/day was significantly superior to 0.3 mg/kg/day
• 0.75 mg/kg/day group had weight gain, cushingoid appearance, and hirsutism at 6 months
Bottom Line
Prednisone at 0.75 mg/kg/day produced rapid and significant improvement detectable at 10 days, and was superior to 0.3 mg/kg/day at 3 months, establishing the dose-response relationship for corticosteroid therapy in DMD.
Major Points
- Prednisone 0.75 mg/kg/day significantly improved muscle strength in DMD at 6 months: +0.43 SD vs -0.85 SD (placebo) and -0.49 SD (0.3 mg/kg); P=0.003.
- Functional improvement: time to rise from floor, climb 4 stairs, walk 9 meters — all improved with high-dose prednisone.
- 103 boys (ages 5-15) with DMD. 6-month, double-blind, 3-arm (prednisone 0.75mg, 0.3mg, placebo).
- 0.75 mg/kg/day was clearly superior; 0.3 mg/kg showed intermediate benefit.
- Weight gain (2.7 kg) and cushingoid features common with 0.75 mg/kg — main limiting side effects.
- Published NEJM 1989 (Griggs et al.). NIH funded.
- Landmark trial establishing corticosteroids as standard of care for DMD — still used 35+ years later.
- Most boys with DMD now receive deflazacort (CINRG study) or prednisone based on this evidence.
- Mechanism: anti-inflammatory + membrane stabilization. Delays loss of ambulation by ~2-3 years.
- Led to routine corticosteroid use in DMD, the first effective pharmacotherapy for any muscular dystrophy.
Study Design
- Study Type
- Phase 3 randomized controlled trial
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 99
- Follow-up
- 6 months
- Countries
- USA
Primary Outcome
Definition: Average muscle strength score
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| No significant improvement | Significant improvement in both groups vs placebo from 10 days | - |
Limitations & Criticisms
- Short follow-up of 6 months
- No long-term data on maintaining benefit
- Limited side effect detail in abstract
Citation
Arch Neurol. 1991 Apr;48(4):383-8