Department of Infectious Disease, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 Wenhuaxi Road, Jinan, 250012, Shandong Province, P. R. China.
Jinan Center for Disease Control and Prevention, Jinan, 250021, Shandong, China.
BMC Med. 2024 May 20;22(1):204. doi: 10.1186/s12916-024-03421-z.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease, and its morbidity and mortality are increasing. At present, there is no specific therapy available. An exacerbated IFN-I response and cytokine storm are related to the mortality of patients with SFTS. Ruxolitinib is a Janus kinase (JAK) 1/2 inhibitor that can block proinflammatory cytokines and inhibit the type I IFN pathway. We aimed to explore the use of ruxolitinib plus standard of care for severe SFTS.
We conducted a prospective, single-arm study of severe SFTS. We recruited participants aged 18 years or older who were admitted to the hospital with laboratory-confirmed severe SFTS and whose clinical score exceeded 8 points within 6 days of symptom onset. Participants received oral ruxolitinib (10 mg twice a day) for up to 10 days. The primary endpoint was 28-day overall survival. The secondary endpoints included the proportion of participants who needed intensive care unit (ICU) admission, total cost, changes in neurologic symptoms and clinical laboratory parameters, and adverse events (AEs) within 28 days. A historical control group (HC group, n = 26) who met the upper criteria for inclusion and hospitalized from April 1, 2021, to September 16, 2022, was selected and 1:1 matched for baseline characteristics by propensity score matching.
Between Sep 16, 2022, and Sep 16, 2023, 26 participants were recruited into the ruxolitinib treatment group (RUX group). The 28-day overall mortality was 7.7% in the RUX group and 46.2% in the HC group (P = 0.0017). There was a significantly lower proportion of ICU admissions (15.4% vs 65.4%, p < 0.001) and total hospitalization cost in the RUX group. Substantial improvements in neurologic symptoms, platelet counts, hyperferritinemia, and an absolute decrease in the serum SFTS viral load were observed in all surviving participants. Treatment-related adverse events were developed in 6 patients (23.2%) and worsened in 8 patients (30.8%), and no treatment-related serious adverse events were reported.
Our findings indicate that ruxolitinib has the potential to increase the likelihood of survival as well as reduce the proportion of ICU hospitalization and being tolerated in severe SFTS. Further trials are needed.
ChiCTR2200063759, September 16, 2022.
严重发热伴血小板减少综合征（SFTS）是一种新兴的蜱传传染病，其发病率和死亡率正在上升。目前，尚无特效疗法。IFN-I 反应和细胞因子风暴的加剧与 SFTS 患者的死亡率有关。鲁索利替尼是一种 Janus 激酶（JAK）1/2 抑制剂，可阻断促炎细胞因子并抑制 I 型 IFN 途径。我们旨在探讨鲁索利替尼联合标准治疗严重 SFTS 的效果。
我们进行了一项前瞻性、单臂研究，纳入了因实验室确诊的严重 SFTS 而入院且发病后 6 天内临床评分超过 8 分的年龄在 18 岁及以上的患者。参与者接受口服鲁索利替尼（每日两次，每次 10 毫克）治疗，最多 10 天。主要终点为 28 天总生存率。次要终点包括需要入住重症监护病房（ICU）的参与者比例、总费用、神经症状和临床实验室参数的变化以及 28 天内的不良事件（AE）。选择了 2021 年 4 月 1 日至 2022 年 9 月 16 日符合纳入标准上限的历史对照组（HC 组，n=26），并通过倾向评分匹配进行了 1:1 基线特征匹配。
在 2022 年 9 月 16 日至 2023 年 9 月 16 日期间，共有 26 名患者被纳入鲁索利替尼治疗组（RUX 组）。RUX 组的 28 天总死亡率为 7.7%，HC 组为 46.2%（P=0.0017）。RUX 组 ICU 入住率（15.4%比 65.4%，p<0.001）和总住院费用显著降低。所有存活患者的神经症状、血小板计数、高铁蛋白血症均有显著改善，血清 SFTS 病毒载量绝对值下降。6 名患者（23.2%）发生治疗相关不良事件，8 名患者（30.8%）不良事件恶化，但未报告与治疗相关的严重不良事件。
我们的研究结果表明，鲁索利替尼可能增加严重 SFTS 患者的生存率，并降低 ICU 住院率和患者的耐受性。需要进一步的临床试验。
ChiCTR2200063759，2022 年 9 月 16 日。
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