Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children
Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children
复制标题
DOI：
10.1001/jama.2021.0694
复制
发表时间：
2021-02-01
影响因子：
120.7
通讯作者：
Angoulvant, Francois
中科院分区：
文献类型：
--
作者：
Ouldali, Naim;Toubiana, Julie;Angoulvant, Francois
儿童多系统炎症综合征（MIS-C）是与严重急性呼吸综合征冠状病毒2感染相关的最严重的儿科疾病，可能危及生命，但最佳治疗策略尚不清楚。目的比较静脉注射免疫球蛋白（IVIG）联合甲基强的松龙与单独使用IVIG作为misc的初始治疗。设计、环境和参与者：来自国家监测系统的回顾性队列研究，采用倾向评分匹配分析。所有疑似misc病例均报告给法国国家公共卫生局。包括符合世界卫生组织定义的确诊misc病例。该研究于2020年4月1日开始，随访于2021年1月6日结束。IVIG和甲基强的松龙与单独IVIG的暴露。主要结局和测量主要结局是在初始治疗后2天持续发热或在7天内发烧复发，这定义了治疗失败。次要结局包括二线治疗、血流动力学支持、一线治疗后急性左心室功能障碍和儿科重症监护病房的住院时间。主要分析涉及倾向得分匹配最小卡尺为0.1。结果181例疑似MIS-C患儿中，111例符合世界卫生组织定义（女性58例，占52%；中位年龄8.6岁[四分位数间距4.7 ~ 12.1]）。五名儿童没有接受这两种治疗。总体而言，IVIG和甲基强的松龙组34名儿童中有3名（9%）和单独IVIG组72名儿童中有37名（51%）对治疗无反应。IVIG联合甲基强的松龙治疗与单独IVIG治疗失败的风险较低（绝对风险差为-0.28 [95% CI, -0.48至-0.08]；优势比[OR]为0.25 [95% CI， 0.09至0.70];P = 0.008）。IVIG和甲基泼尼松龙治疗与单独IVIG治疗相比，使用二线治疗的风险也显著降低（绝对风险差，-0.22 [95% CI, -0.40至-0.04]；OR, 0.19 [95% CI， 0.06至0.61];P = 0.004），血流动力学支持（绝对风险差，-0.17 [95% CI, -0.34至-0.004]；OR, 0.21 [95% CI， 0.06至0.76]），初始治疗后发生急性左心室功能障碍(绝对风险差，-0.18 [95% CI, -0.35至-0.01]；OR, 0.20 [95% CI， 0.06至0.66])和儿科重症监护病房的住院时间（中位数，4天vs 6天；天数差异，-2.4天[95% CI， -4.0至-0.7]）。结论和相关性在misc患儿中，与单独使用IVIG相比，IVIG联合甲基强的松龙治疗与更有利的发热过程相关。研究解释受到观察设计的限制。
IMPORTANCE Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown.OBJECTIVE To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C.DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021.EXPOSURES IVIG and methylprednisolone vs IVIG alone.MAIN OUTCOMES AND MEASURES The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1.RESULTS Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]).CONCLUSIONS AND RELEVANCE Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.