细胞因子导向疗法治疗VEXAS综合征的疾病轨迹和糖皮质激素暴露。

IF 20.3 1区 医学 Q1 RHEUMATOLOGY
Benjamin A Turturice, Alice Fike, Bhavisha A Patel, Emma M Groarke, Fernanda Gutierrez-Rodriguez, Karyssa Stonick, Hannah Berrett, Shanni Liu, Ivana Darden, Kaitlin A Quinn, Neal S Young, Peter C Grayson
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引用次数: 0

摘要

目的:确定细胞因子导向治疗对液泡、e1酶、x -连锁、自身炎症、躯体(VEXAS)患者糖皮质激素使用和临床结果的长期影响。方法:前瞻性随访VEXAS患者的输血依赖、造血干细胞移植或死亡事件。回顾性评估实验室结果、糖皮质激素暴露和临床措施与白介素-6定向治疗(抗il6r)或Janus激酶抑制剂(JAKi)治疗开始的关系。根据UBA1变异和变异等位基因分数≥10%的典型克隆造血(CHVAF≥10%)对患者进行分层。结果:71例VEXAS患者(81.7%有抗il6r或JAKi暴露),无事件生存率因基因型和伴有CHVAF≥10%:p.M41V (HR[95%可信区间(CI)]: 5.7[1.5-20.4])或伴有CHVAF≥10%的p.M41L/T(风险比[HR]: 5.7[1.6-20.8])与p.M41L相比存在差异。没有观察到事件发生率与暴露于抗il6r或JAKi之间的关联。p.M41V基因型有贫血、c反应蛋白(CRP)水平升高和单核细胞减少症的最高风险。在4.8年(四分位间距[IQR] 3.0, 8.1)的中位随访中,无论变异或疾病持续时间如何,患者的平均糖皮质激素剂量为0.15 mg/天强的松。在前瞻性访问中,仅2.7%的访问中观察到≤10 mg/天强的松的临床缓解。抗il6r或JAKi治疗没有临床意义的降低(结论:单独的细胞因子导向治疗不会改变血液病进展的风险,也不会显著减少VEXAS患者的糖皮质激素暴露。这些数据为今后的介入研究提供了基准。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Disease Trajectories and Glucocorticoid Exposure in VEXAS Syndrome Treated with Cytokine-Directed Therapies.

Objectives: To establish the long-term impact of cytokine-directed therapies on glucocorticoid use and clinical outcomes in Vacuoles, E1-enzyme, X-linked, Autoinflammatory, Somatic (VEXAS).

Methods: Patients with VEXAS were prospectively followed for events of transfusion dependence, haematopoietic stem cell transplantation or death. Laboratory results, glucocorticoid exposure and clinical measures were retrospectively assessed in relationship to treatment initiation with interleukin-6-directed therapies (anti-IL6R) or Janus kinase inhibitors (JAKi). Patients were stratified by UBA1 variants and presence of typical clonal haematopoiesis with variant allele fraction ≥ 10% (CHVAF10%).

Results: In 71 VEXAS patients (81.7% with anti-IL6R or JAKi exposure), event-free survival differed by genotype and presence of concomitant CHVAF10%: p.M41V (HR [95% confidence interval (CI)]: 5.7 [1.5-20.4]) or p.M41L/T with CHVAF10% (hazard ratio [HR]: 5.7 [1.6-20.8]) compared to p.M41L. No association between event rates and exposure to anti-IL6R or JAKi was observed. The p.M41V genotype had the highest risk of anaemia, elevated C-reactive protein (CRP) levels, and monocytopenia. Over a median follow-up of 4.8 (interquartile range [IQR] 3.0, 8.1) years, the patients' mean glucocorticoid dose was >15 mg/day prednisone regardless of variant or disease duration. At prospective visits, clinical remission on ≤10 mg/day prednisone was observed in only 2.7% of visits. Treatment with anti-IL6R or JAKi showed no clinically meaningful reduction (<5 mg/day difference) in steroid exposure at 1 year post-treatment. No attenuation in the progression of anaemia was observed in response to anti-IL6R and JAKi.

Conclusions: Cytokine-directed therapies alone do not alter the risk of haematologic disease progression or significantly reduce glucocorticoid exposure in VEXAS. These data provide benchmarks for future interventional studies.

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来源期刊
Annals of the Rheumatic Diseases
Annals of the Rheumatic Diseases 医学-风湿病学
CiteScore
35.00
自引率
9.90%
发文量
3728
审稿时长
1.4 months
期刊介绍: Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal covering all aspects of rheumatology, which includes the full spectrum of musculoskeletal conditions, arthritic disease, and connective tissue disorders. ARD publishes basic, clinical, and translational scientific research, including the most important recommendations for the management of various conditions.
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