The impact of twice-weekly low dose prednisone on the side-effect profile and muscle pathophysiology in DMD: preliminary findings


Clinical Trials

Poster Number: M186


Tanja Taivassalo, PhD, University of Florida, Sean Forbes, PhD, University of Florida, Donovan Lott, PT, PhD, University of Florida, Cathy Powers, University of Florida, Angelina Bernier, MD, University of Florida, Carla Zingariello, DO, University of Florida, John T. Sladky, MD, University of Florida, Glenn Walter, PhD, University of FL Department of Physiology and Aging, Rebecca J. Willcocks, PhD, University of Florida, Krista Vandenborne, PT, PhD, University of Florida, Michael J. Daniels, PhD, University of Florida, H. Lee Sweeney, PhD, University of Florida

BACKGROUND: A steroid treatment regimen that minimizes side effects and maximizes clinical benefits for Duchenne muscular dystrophy (DMD) is needed. Recent pre-clinical work assessed intermittent (once-weekly) low-dose steroids and reported benefits (decreased sarcolemmal injury) comparable to daily-dosing, but with less steroid-induced atrophy and greater impact on muscle performance (Quattrocelli, 2017). OBJECTIVE: To translate these preclinical findings, we determined the 12-month impact of low-dose, intermittent prednisone (0.75 mg/kg, twice-weekly) on the steroid-associated side-effect profile, muscle pathophysiology and function in DMD. We hypothesized that compared to standard daily-dosing, twice-weekly prednisone will produce a lesser impact on growth velocity, body mass index (BMI), DEXA-bone mineral density (BMD), and cortisol; but similar impact on efficacy as determined by function, serum creatine kinase (CK), magnetic resonance spectroscopy inflammation (MRS-T2) and fat fraction (MRS-FF) within the vastus lateralis muscle. The efficacy of daily-dosing on muscle pathophysiology was previously established as reduction in MRS-T2 by 3-4 ms and slowing of FF increase to 10% in 12-months (Arpan, 2014). METHODS: In this ongoing open-label exploratory study, steroid-naïve DMD boys (4-8 years) underwent a 12-month, twice-weekly prednisone regimen with assessments at baseline, 6 and 12 months. RESULTS: Six boys (5.3+1.4 years) completed the study without adverse effects or behavioral disturbances. Growth velocity was maintained (+5.9+1.1 cm, p<0.01) with no rapid rise in BMI (17.4+2.4 to 17.8+2.9) or change in DEXA lumbar z-score (-1.6+0.3 to -1.3+0.5) after 12-months and cortisol levels remained normal (>7 mcg/dL). Muscle MRS-T2 decreased by 3.1+1.6 ms (p<0.05) after 6 months, with no significant increase in MRS-FF after 12-months (8.1+8.0 to 8.2+7.8%). Serum CK (20,747+4648 to 13,130+5129 U/L, p=0.07) and 10-meter walk/run time (5.2+0.5 to 4.1+0.6, p=0.056) improved slightly. CONCLUSIONS: Preliminary findings suggest twice-weekly, low-dose prednisone in DMD does not result in side-effects associated with daily-dosing, and is effective in reducing muscle inflammation (MRS-T2) and slowing disease progression (MRS-FF). Ongoing comparison to natural history data will determine whether efficacy is similar to daily-dosing.