背景: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,发病率和死亡率都在增加。目前,没有特定的治疗方法.加剧的IFN-I应答和细胞因子风暴与SFTS患者的死亡率相关。Ruxolitinib是一种Janus激酶(JAK)1/2抑制剂,可以阻断促炎细胞因子并抑制I型IFN途径。我们旨在探索鲁索利替尼加标准治疗严重SFTS的应用。
方法:我们进行了前瞻性,重度SFTS的单臂研究。我们招募了18岁或以上的参与者,他们因实验室证实的严重SFTS入院,并且在症状发作后6天内临床评分超过8分。参与者接受口服鲁索利替尼(10mg,每天两次)长达10天。主要终点是28天总生存期。次要终点包括需要重症监护病房(ICU)入院的参与者比例,总成本,神经系统症状和临床实验室参数的变化,和28天内的不良事件(AE)。历史对照组(HC组,n=26),从2021年4月1日至2022年9月16日,符合入选标准并住院,并通过倾向评分匹配与基线特征进行1:1匹配。
结果:在2022年9月16日至2023年9月16日之间,招募了26名参与者进入鲁索替尼治疗组(RUX组)。RUX组28天总死亡率为7.7%,HC组为46.2%(P=0.0017)。ICU入院的比例明显较低(15.4%vs65.4%,p<0.001)和RUX组的总住院费用。神经系统症状的实质性改善,血小板计数,高铁蛋白血症,并且在所有存活的参与者中观察到血清SFTS病毒载量绝对降低。6例患者(23.2%)出现治疗相关不良事件,8例患者(30.8%)出现恶化,未报告与治疗相关的严重不良事件.
结论:我们的研究结果表明,鲁索替尼有可能增加生存的可能性,并降低ICU住院的比例,并在严重SFTS中被耐受。需要进一步的试验。
背景:ChiCTR2200063759,2022年9月16日。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: ChiCTR2200063759, September 16, 2022.