Ruxolitinib plus standard of care in severe hospitalized adults with severe fever with thrombocytopenia syndrome (SFTS): an exploratory, single-arm trial

• Published in: BMC medicine 2024-05, Vol.22 (1), p.204-9, Article 204
• Main Authors: Wen, Sai, Xu, Nannan, Zhao, Lianhui, Yang, Lulu, Yang, Hui, Chang, Caiyun, Wang, Shanshan, Qu, Chunmei, Song, Li, Zou, Wenlu, He, Yishan, Wang, Gang
• Format: Article
• Language: English
• Subjects: Adult; Adverse events; Aged; Care and treatment; Clinical trials; Consent; COVID-19; Creatinine; Cytokine storm; Cytokines; Development and progression; Diagnosis; Drug dosages; Female; Fever; Health services; Hospital patients; Hospitalization; Humans; Hyperthermia; Infectious diseases; Inflammation; Inhibitor drugs; Interferon; Janus kinase; Kinases; Laboratories; Leukopenia; Male; Middle Aged; Morbidity; Mortality; Multiple organ dysfunction syndrome; Nitriles - therapeutic use; Patients; Prospective Studies; Pyrazoles - therapeutic use; Pyrimidines - therapeutic use; Ruxolitinib; Severe fever with thrombocytopenia syndrome; Severe Fever with Thrombocytopenia Syndrome - drug therapy; Signs and symptoms; Standard of Care; Survival; Thrombocytopenia; Tick-borne diseases; Treatment Outcome; Variables; Viral infections
• ISSN: 1741-7015; 1741-7015
• 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