Effect of Different Corticosteroid Dosing Regimens on Clinical Outcomes in Boys with Duchenne Muscular Dystrophy: A Randomized Clinical Trial

Michela Guglieri, Kate Bushby, Michael P. McDermott, Kimberly A. Hart, Rabi Tawil, William B. Martens, Barbara E. Herr, Elaine McColl, Chris Speed, Jennifer Wilkinson, Janbernd Kirschner, Wendy M. King, Michelle Eagle, Mary W. Brown, Tracey Willis, Robert C. Griggs, Volker Straub, Henriette Van Ruiten, Anne Marie Childs, Emma CiafaloniPerry B. Shieh, Stefan Spinty, Lorenzo Maggi, Giovanni Baranello, Russell J. Butterfield, I. A. Horrocks, Helen Roper, Zoya Alhaswani, Kevin M. Flanigan, Nancy L. Kuntz, Adnan Manzur, Basil T. Darras, Peter B. Kang, Leslie Morrison, Monika Krzesniak-Swinarska, Jean K. Mah, Tiziana E. Mongini, Federica Ricci, Maja Von Der Hagen, Richard S. Finkel, Kathleen O'Reardon, Matthew Wicklund, Ashutosh Kumar, Craig M. McDonald, Jay J. Han, Nanette Joyce, Erik K. Henricson, Ulrike Schara-Schmidt, Andrea Gangfuss, Ekkehard Wilichowski, Richard J. Barohn, Jeffrey M. Statland, Craig Campbell, Giuseppe Vita, Gian Luca Vita, James F. Howard, Imelda Hughes, Hugh J. McMillan, Elena Pegoraro, Luca Bello, W. Bryan Burnette, Mathula Thangarajh, Taeun Chang

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Importance: Corticosteroids improve strength and function in boys with Duchenne muscular dystrophy. However, there is uncertainty regarding the optimum regimen and dosage. Objective: To compare efficacy and adverse effects of the 3 most frequently prescribed corticosteroid regimens in boys with Duchenne muscular dystrophy. Design, Setting, and Participants: Double-blind, parallel-group randomized clinical trial including 196 boys aged 4 to 7 years with Duchenne muscular dystrophy who had not previously been treated with corticosteroids; enrollment occurred between January 30, 2013, and September 17, 2016, at 32 clinic sites in 5 countries. The boys were assessed for 3 years (last participant visit on October 16, 2019). Interventions: Participants were randomized to daily prednisone (0.75 mg/kg) (n = 65), daily deflazacort (0.90 mg/kg) (n = 65), or intermittent prednisone (0.75 mg/kg for 10 days on and then 10 days off) (n = 66). Main Outcomes and Measures: The global primary outcome comprised 3 end points: rise from the floor velocity (in rise/seconds), forced vital capacity (in liters), and participant or parent global satisfaction with treatment measured by the Treatment Satisfaction Questionnaire for Medication (TSQM; score range, 0 to 100), each averaged across all study visits after baseline. Pairwise group comparisons used a Bonferroni-adjusted significance level of.017. Results: Among the 196 boys randomized (mean age, 5.8 years [SD, 1.0 years]), 164 (84%) completed the trial. Both daily prednisone and daily deflazacort were more effective than intermittent prednisone for the primary outcome (P <.001 for daily prednisone vs intermittent prednisone using a global test; P =.017 for daily deflazacort vs intermittent prednisone using a global test) and the daily regimens did not differ significantly (P =.38 for daily prednisone vs daily deflazacort using a global test). The between-group differences were principally attributable to rise from the floor velocity (0.06 rise/s [98.3% CI, 0.03 to 0.08 rise/s] for daily prednisone vs intermittent prednisone [P =.003]; 0.06 rise/s [98.3% CI, 0.03 to 0.09 rise/s] for daily deflazacort vs intermittent prednisone [P =.017]; and -0.004 rise/s [98.3% CI, -0.03 to 0.02 rise/s] for daily prednisone vs daily deflazacort [P =.75]). The pairwise comparisons for forced vital capacity and TSQM global satisfaction subscale score were not statistically significant. The most common adverse events were abnormal behavior (22 [34%] in the daily prednisone group, 25 [38%] in the daily deflazacort group, and 24 [36%] in the intermittent prednisone group), upper respiratory tract infection (24 [37%], 19 [29%], and 24 [36%], respectively), and vomiting (19 [29%], 17 [26%], and 15 [23%]). Conclusions and Relevance: Among patients with Duchenne muscular dystrophy, treatment with daily prednisone or daily deflazacort, compared with intermittent prednisone alternating 10 days on and 10 days off, resulted in significant improvement over 3 years in a composite outcome comprising measures of motor function, pulmonary function, and satisfaction with treatment; there was no significant difference between the 2 daily corticosteroid regimens. The findings support the use of a daily corticosteroid regimen over the intermittent prednisone regimen tested in this study as initial treatment for boys with Duchenne muscular dystrophy. Trial Registration: ClinicalTrials.gov Identifier: NCT01603407.

Original languageEnglish (US)
Pages (from-to)1456-1468
Number of pages13
JournalJAMA
Volume327
Issue number15
DOIs
StatePublished - Apr 19 2022
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine

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