The cooperative international neuromuscular research group Duchenne natural history study: glucocorticoid treatment preserves clinically meaningful functional milestones and reduces rate of disease progression as measured by manual muscle testing and other commonly used clinical trial outcome measures

Muscle Nerve. 2013 Jul;48(1):55-67. doi: 10.1002/mus.23808. Epub 2013 May 6.

Abstract

introduction: Glucocorticoid (GC) therapy in Duchenne muscular dystrophy (DMD) has altered disease progression, necessitating contemporary natural history studies.

Methods: The Cooperative Neuromuscular Research Group (CINRG) DMD Natural History Study (DMD-NHS) enrolled 340 DMD males, ages 2-28 years. A comprehensive battery of measures was obtained.

Results: A novel composite functional "milestone" scale scale showed clinically meaningful mobility and upper limb abilities were significantly preserved in GC-treated adolescents/young adults. Manual muscle test (MMT)-based calculations of global strength showed that those patients <10 years of age treated with steroids declined by 0.4 ± 0.39 MMT unit/year, compared with -0.4 ± 0.39 MMT unit/year in historical steroid-naive subjects. Pulmonary function tests (PFTs) were relatively preserved in steroid-treated adolescents. The linearity and magnitude of decline in measures were affected by maturational changes and functional status.

Conclusions: In DMD, long-term use of GCs showed reduced strength loss and preserved functional capabilities and PFTs compared with previous natural history studies performed prior to the widespread use of GC therapy.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Biomedical Research / methods
  • Biomedical Research / standards
  • Child
  • Child, Preschool
  • Clinical Trials as Topic / methods
  • Clinical Trials as Topic / standards
  • Cohort Studies
  • Cross-Sectional Studies
  • Diagnostic Techniques, Neurological* / standards
  • Disease Progression*
  • Glucocorticoids / therapeutic use*
  • Humans
  • International Cooperation*
  • Longitudinal Studies
  • Male
  • Muscle Strength / physiology
  • Muscular Dystrophy, Duchenne / diagnosis
  • Muscular Dystrophy, Duchenne / drug therapy*
  • Muscular Dystrophy, Duchenne / epidemiology
  • Outcome Assessment, Health Care / methods*
  • Outcome Assessment, Health Care / standards
  • Prospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Glucocorticoids