TY - JOUR
T1 - Effect of Different Corticosteroid Dosing Regimens on Clinical Outcomes in Boys with Duchenne Muscular Dystrophy
T2 - A Randomized Clinical Trial
AU - Guglieri, Michela
AU - Bushby, Kate
AU - McDermott, Michael P.
AU - Hart, Kimberly A.
AU - Tawil, Rabi
AU - Martens, William B.
AU - Herr, Barbara E.
AU - McColl, Elaine
AU - Speed, Chris
AU - Wilkinson, Jennifer
AU - Kirschner, Janbernd
AU - King, Wendy M.
AU - Eagle, Michelle
AU - Brown, Mary W.
AU - Willis, Tracey
AU - Griggs, Robert C.
AU - Straub, Volker
AU - Van Ruiten, Henriette
AU - Childs, Anne Marie
AU - Ciafaloni, Emma
AU - Shieh, Perry B.
AU - Spinty, Stefan
AU - Maggi, Lorenzo
AU - Baranello, Giovanni
AU - Butterfield, Russell J.
AU - Horrocks, I. A.
AU - Roper, Helen
AU - Alhaswani, Zoya
AU - Flanigan, Kevin M.
AU - Kuntz, Nancy L.
AU - Manzur, Adnan
AU - Darras, Basil T.
AU - Kang, Peter B.
AU - Morrison, Leslie
AU - Krzesniak-Swinarska, Monika
AU - Mah, Jean K.
AU - Mongini, Tiziana E.
AU - Ricci, Federica
AU - Von Der Hagen, Maja
AU - Finkel, Richard S.
AU - O'Reardon, Kathleen
AU - Wicklund, Matthew
AU - Kumar, Ashutosh
AU - McDonald, Craig M.
AU - Han, Jay J.
AU - Joyce, Nanette
AU - Henricson, Erik K.
AU - Schara-Schmidt, Ulrike
AU - Gangfuss, Andrea
AU - Wilichowski, Ekkehard
AU - Barohn, Richard J.
AU - Statland, Jeffrey M.
AU - Campbell, Craig
AU - Vita, Giuseppe
AU - Vita, Gian Luca
AU - Howard, James F.
AU - Hughes, Imelda
AU - McMillan, Hugh J.
AU - Pegoraro, Elena
AU - Bello, Luca
AU - Burnette, W. Bryan
AU - Thangarajh, Mathula
AU - Chang, Taeun
N1 - Publisher Copyright:
© 2022 American Medical Association. All rights reserved.
PY - 2022/4/19
Y1 - 2022/4/19
N2 - 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.
AB - 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.
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U2 - 10.1001/jama.2022.4315
DO - 10.1001/jama.2022.4315
M3 - Article
C2 - 35381069
AN - SCOPUS:85128799842
SN - 0098-7484
VL - 327
SP - 1456
EP - 1468
JO - JAMA
JF - JAMA
IS - 15
ER -