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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Michela Guglieri - , Newcastle upon Tyne Hospitals NHS Foundation Trust (Author)
  • Kate Bushby - , Newcastle upon Tyne Hospitals NHS Foundation Trust (Author)
  • Michael P. McDermott - , University of Rochester (Author)
  • Kimberly A. Hart - , University of Rochester (Author)
  • Rabi Tawil - , University of Rochester (Author)
  • William B. Martens - , University of Rochester (Author)
  • Barbara E. Herr - , University of Rochester (Author)
  • Elaine McColl - , Newcastle University (Author)
  • Chris Speed - , Newcastle University, Newcastle upon Tyne Hospitals NHS Foundation Trust (Author)
  • Jennifer Wilkinson - , Newcastle University (Author)
  • Janbernd Kirschner - , University of Freiburg, University of Bonn (Author)
  • Wendy M. King - , Ohio State University (Author)
  • Michelle Eagle - , Newcastle upon Tyne Hospitals NHS Foundation Trust (Author)
  • Mary W. Brown - , University of Rochester (Author)
  • Tracey Willis - , The Robert Jones and Agnes Hunt Orthopaedic and District Hospital NHS Trust (Author)
  • Robert C. Griggs - , University of Rochester (Author)
  • Volker Straub - , Newcastle upon Tyne Hospitals NHS Foundation Trust (Author)
  • Henriette Van Ruiten - , Newcastle upon Tyne Hospitals NHS Foundation Trust (Author)
  • Anne Marie Childs - , Leeds Teaching Hospitals NHS Trust (Author)
  • Emma Ciafaloni - , University of Rochester (Author)
  • Perry B. Shieh - , University of California at Los Angeles (Author)
  • Stefan Spinty - , Alder Hey Children's NHS Foundation Trust (Author)
  • Lorenzo Maggi - , IRCCS Fondazione Istituto Neurologico Carlo Besta - Milano (Author)
  • Giovanni Baranello - , IRCCS Fondazione Istituto Neurologico Carlo Besta - Milano, University College London (Author)
  • Russell J. Butterfield - , University of Utah (Author)
  • I. A. Horrocks - , The Shrewsbury and Telford Hospital NHS Trust (Author)
  • Helen Roper - , University Hospitals Birmingham NHS Foundation Trust (Author)
  • Zoya Alhaswani - , University Hospitals Birmingham NHS Foundation Trust (Author)
  • Kevin M. Flanigan - , Nationwide Children’s Hospital (Author)
  • Nancy L. Kuntz - , Children's Memorial Hospital (Author)
  • Adnan Manzur - , Great Ormond Street Hospital for Children NHS Trust (Author)
  • Basil T. Darras - , Harvard University (Author)
  • Peter B. Kang - , Harvard University, University of Minnesota System (Author)
  • Leslie Morrison - , University of New Mexico (Author)
  • Monika Krzesniak-Swinarska - , University of New Mexico (Author)
  • Jean K. Mah - , University of Calgary (Author)
  • Tiziana E. Mongini - , University of Turin (Author)
  • Federica Ricci - , University of Turin (Author)
  • Maja Von Der Hagen - , Department of Paediatrics, Division of Neuropediatrics (Author)
  • Richard S. Finkel - , Nemours Children's Health, St. Jude Children Research Hospital (Author)
  • Kathleen O'Reardon - , Nemours Children's Health (Author)
  • Matthew Wicklund - , Pennsylvania State University, University of Colorado Denver (Author)
  • Ashutosh Kumar - , Pennsylvania State University (Author)
  • Craig M. McDonald - , University of California at Davis (Author)
  • Jay J. Han - , University of California at Davis (Author)
  • Nanette Joyce - , University of California at Davis (Author)
  • Erik K. Henricson - , University of California at Davis (Author)
  • Ulrike Schara-Schmidt - , University of Duisburg-Essen (Author)
  • Andrea Gangfuss - , University of Duisburg-Essen (Author)
  • Ekkehard Wilichowski - , University of Göttingen (Author)
  • Richard J. Barohn - , University of Missouri (Author)
  • Jeffrey M. Statland - , University of Kansas (Author)
  • Craig Campbell - , Western University (Author)
  • Gian Luca Vita - , University of Messina (Author)
  • Gian Luca Vita - , IRCCS Centro Neurolesi Bonino Pulejo - Messina (Author)
  • James F. Howard - , University of North Carolina at Chapel Hill (Author)
  • Imelda Hughes - , Manchester University NHS Foundation Trust (Author)
  • Hugh J. McMillan - , University of Ottawa (Author)
  • Elena Pegoraro - , University of Padua (Author)
  • Luca Bello - , University of Padua (Author)
  • W. Bryan Burnette - , Vanderbilt University (Author)
  • Mathula Thangarajh - , Virginia Commonwealth University (Author)
  • Taeun Chang - , George Washington University (GWU) (Author)

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.

Details

Original languageEnglish
Pages (from-to)1456-1468
Number of pages13
JournalJAMA
Volume327
Issue number15
Publication statusPublished - 19 Apr 2022
Peer-reviewedYes

External IDs

PubMed 35381069

Keywords

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