Division of Immunology, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts.
Arthritis Rheumatol. 2023 Aug;75(8):1466-1476. doi: 10.1002/art.42495. Epub 2023 May 16.
Evidence regarding effectiveness of interleukin-1 receptor antagonism in multisystem inflammatory syndrome in children (MIS-C) is lacking. We characterized variation in initial treatment with anakinra and evaluated cardiovascular outcomes associated with adding anakinra to standard initial therapy.
We conducted a retrospective cohort study of MIS-C cases in a US surveillance registry from November 2020 to December 2021. Day 0 was the first calendar day of immunomodulatory treatment. Factors associated with initial anakinra use (days 0-1) were identified. We compared cases in patients ages 2-20 years receiving intravenous immunoglobulin (IVIG) and glucocorticoids versus anakinra plus IVIG and/or glucocorticoids on days 0-1, using inverse probability weighting to balance disease severity. Primary outcomes were vasopressor requirement on day 3 and impaired left ventricular ejection fraction on days 3-4. The secondary outcome was 50% reduction in C-reactive protein on day 3.
Among 1,516 MIS-C cases at 44 sites, 193 (13%) patients received anakinra alone or with other immunomodulators as initial treatment (range 0-74% by site). Site accounted for 59% of residual variance in anakinra use. After balancing disease severity, initial treatment with anakinra plus IVIG and/or glucocorticoids (n = 121) versus IVIG plus glucocorticoids (n = 389) was not associated with significant differences in vasopressor requirement (25.6% versus 20.1%, respectively; risk ratio [RR] 1.27 [95% confidence interval (95% CI) 0.88-1.84]), ventricular dysfunction (33.7% versus 25.7%, respectively; RR 1.31 [95% CI 0.98-1.75]), or C-reactive protein reduction.
We identified substantial variation in initial anakinra use in a real-world population of children with MIS-C, but no average short-term improvement in cardiovascular outcomes associated with early addition of anakinra to IVIG and/or glucocorticoids compared to IVIG and glucocorticoids alone.
缺乏白细胞介素-1 受体拮抗剂在儿童多系统炎症综合征（MIS-C）中有效性的证据。我们描述了初始使用阿那白滞素治疗的变化，并评估了在标准初始治疗中添加阿那白滞素与心血管结局的关系。
我们对 2020 年 11 月至 2021 年 12 月期间美国监测登记处的 MIS-C 病例进行了回顾性队列研究。第 0 天是免疫调节治疗的第一天。确定了初始使用阿那白滞素（第 0-1 天）的相关因素。我们比较了年龄在 2-20 岁的患者在第 0-1 天接受静脉注射免疫球蛋白（IVIG）和糖皮质激素与阿那白滞素加 IVIG 和/或糖皮质激素的病例，使用逆概率加权来平衡疾病严重程度。主要结局是第 3 天需要使用血管加压药和第 3-4 天左心室射血分数受损。次要结局是第 3 天 C 反应蛋白减少 50%。
在 44 个地点的 1516 例 MIS-C 病例中，有 193 例（13%）患者单独或联合其他免疫调节剂作为初始治疗（按地点计算，范围为 0-74%）。地点占阿那白滞素使用的 59%残余方差。在平衡疾病严重程度后，阿那白滞素加 IVIG 和/或糖皮质激素（n=121）与 IVIG 和糖皮质激素（n=389）的初始治疗在需要使用血管加压药方面无显著差异（分别为 25.6%和 20.1%；风险比[RR]1.27[95%置信区间（95%CI）0.88-1.84]），心室功能障碍（分别为 33.7%和 25.7%；RR 1.31[95%CI 0.98-1.75]）或 C 反应蛋白降低。
我们在儿童 MIS-C 的真实世界人群中发现了初始使用阿那白滞素的大量差异，但与单独使用 IVIG 和糖皮质激素相比，早期添加阿那白滞素至 IVIG 和/或糖皮质激素并未带来平均短期心血管结局的改善。
