小柯机器人

英国纽卡斯尔大学Michela Guglieri团队研究了不同皮质类固醇给药方案对杜氏肌营养不良男孩临床结局的影响。2022年4月5日，该研究成果发表在《美国医学会杂志》上。

皮质类固醇可改善杜氏肌营养不良症男孩的力量和功能。然而，关于最佳方案和剂量仍存在不确定性。

为了比较3种最常用的皮质类固醇方案治疗杜氏肌营养不良症的疗效和不良反应，研究组进行了一项双盲、平行组、随机临床试验，共招募了196名4-7岁的杜氏肌营养不良症男孩，他们之前没有接受过皮质类固醇治疗；2013年1月30日至2016年9月17日，这些患者在5个国家的32个诊所进行了登记。研究组对这些男孩进行了为期3年的评估，最后一次随访为2019年10月16日。

将参与者随机分组，其中65名接受每日强的松治疗，65名接受每日地夫可特治疗，66名接受间歇强的松治疗（连续用药10天，然后停用10天）。总体主要结局包括3个终点：从地面起身的速度（上升/秒）、用力肺活量（升）和参与者或家长对治疗的总体满意度（通过药物治疗满意度问卷[TSQM；得分范围，0到100]进行测评），每个终点在基线检查后的所有研究随访中取平均值。两两组比较采用的bonferroni校正显著性水平为0.017。

196名随机分配男孩的平均年龄为5.8岁，其中164名（84%）完成了试验。每日强的松组和每日地夫可特组的主要疗效均显著优于间歇性强的松组，但每日治疗方案之间无显著差异。组间差异主要归因于从地面起身的速度，每日强的松组比间歇性强的松组快0.06上升/秒，每日地夫可特组比间歇性强的松组快0.06上升/秒，每日强的松组比每日地夫可特组慢0.004上升/秒。

用力肺活量和TSQM总体满意度子量表得分的两两组间比较无统计学意义。最常见的不良事件包括异常行为（每日强的松组22例[34%]、每日地夫可特组25例[38%]、间歇性强的松组24例[36%]）、上呼吸道感染（分别为24例[37%]、19例[29%]和24例[36%]）和呕吐（19例[29%]、17例[26%]和15例[23%]）。

研究结果表明，对于杜氏肌营养不良症患者，每日强的松或每日地夫可特治疗，与使用10天停药10天的间歇性强的松治疗相比，在3年的综合结局中，包括运动功能、肺功能和治疗满意度的测量结果显著改善；两种每日皮质类固醇方案之间没有显著差异。

附：英文原文

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

Author: 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, FOR-DMD Investigators of the Muscle Study Group, Volker Straub, Henriette van Ruiten, Anne-Marie Childs, Emma Ciafaloni, Perry 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

Issue&Volume: 2022-04-05

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.

DOI: 10.1001/jama.2022.4315

Source: https://jamanetwork.com/journals/jama/fullarticle/2790925

JAMA-Journal of The American Medical Association：《美国医学会杂志》，创刊于1883年。隶属于美国医学协会，最新IF：157.335
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