VEXAS综合征靶向疗法的疗效和安全性:FRENVEX回顾性研究。

IF 20.3 1区 医学 Q1 RHEUMATOLOGY
Jerome Hadjadj, Yann Nguyen, Dalila Mouloudj, Rim Bourguiba, Mael Heiblig, Hassina Aloui, Chloe McAvoy, Valentin Lacombe, Samuel Ardois, Corrado Campochiaro, Alexandre Maria, Cyrille Coustal, Thibault Comont, Estibaliz Lazaro, Francois Lifermann, Guillaume Le Guenno, Hervé Lobbes, Vincent Grobost, Roderau Outh, Julien Campagne, Anais Dor-Etienne, Alice Garnier, Yvan Jamilloux, Antoine Dossier, Maxime Samson, Sylvain Audia, Barbara Nicolas, Alexis Mathian, Baptiste de Maleprade, Benjamin De Sainte-Marie, Benoit Faucher, Jean-David Bouaziz, Jonathan Broner, Cyril Dumain, Carole Antoine, Benjamin Carpentier, Brice Castel, Celine Lartigau-Roussin, Etienne Crickx, Geoffroy Volle, Damien Fayard, Paul Decker, Thomas Moulinet, Anael Dumont, Alexandre Nguyen, Achille Aouba, Jean-Philippe Martellosio, Matthieu Levavasseur, Sebastien Puigrenier, Pascale Antoine, Jean-Thomas Giraud, Olivier Hermine, Carole Lacout, Nihal Martis, Jean-Denis Karam, Francois Chasset, Laurent Arnaud, Paola Marianetti, Christophe Deligny, Thibaud Chazal, Pascal Woaye-Hune, Murielle Roux-Sauvat, Aurore Meyer, Pierre Sujobert, Pierre Hirsch, Noemie Abisror, Pierre Fenaux, Olivier Kosmider, Vincent Jachiet, Olivier Fain, Benjamin Terrier, Arsène Mekinian, Sophie Georgin-Lavialle
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引用次数: 0

摘要

目的:空泡、E1酶、X连锁、自身炎症和体细胞(VEXAS)综合征是一种成人发病的自身炎症性疾病,与体细胞泛素样修饰激活酶1(UBA1)突变有关。我们旨在评估靶向疗法的疗效和安全性:多中心回顾性研究,包括至少接受过一种靶向疗法的经基因证实的VEXAS综合征患者。完全应答(CR)的定义是临床缓解、C反应蛋白(CRP)低于10毫克/升且泼尼松等效治疗剂量低于10毫克/天;部分应答(PR)的定义是临床缓解、CRP水平和糖皮质激素剂量降低50%:110名患者(中位年龄71(68-79)岁)接受了194种靶向治疗:78人(40%)接受了Janus激酶(JAK)抑制剂(JAKi)治疗,51人(26%)接受了白细胞介素(IL)-6抑制剂治疗,33人(17%)接受了IL-1抑制剂治疗,20人(10%)接受了肿瘤坏死因子(TNFα)阻断剂治疗,12人(6%)接受了其他靶向治疗。3 个月后,JAKi 的总体应答率(CR 和 PR)为 24%,IL-6 抑制剂为 32%,抗 IL-1 为 9%,TNFα 阻断剂或其他靶向疗法为 0%。6个月后,JAKi的总体应答率为30%,IL-6抑制剂为26%。与其他靶向疗法相比,JAKi在不中断治疗的情况下的存活时间明显更长。在中断治疗的患者中,JAKi的原发性失败、继发性失败、严重不良事件或死亡分别占43%、14%、19%和19%,IL-6抑制剂的原发性失败、继发性失败、严重不良事件或死亡分别占46%、11%、31%和9%:这项研究显示了JAKi和IL-6抑制剂的疗效,而其他疗法的疗效较低。这些结果需要在前瞻性试验中得到证实。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX.

Objectives: Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease associated with somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutations. We aimed to evaluate the efficacy and safety of targeted therapies.

Methods: Multicentre retrospective study including patients with genetically proven VEXAS syndrome who had received at least one targeted therapy. Complete response (CR) was defined by a clinical remission, C-reactive protein (CRP) ≤10 mg/L and a ≤10 mg/day of prednisone-equivalent therapy, and partial response (PR) was defined by a clinical remission and a 50% reduction in CRP levels and glucocorticoid dose.

Results: 110 patients (median age 71 (68-79) years) who received 194 targeted therapies were included: 78 (40%) received Janus kinase (JAK) inhibitors (JAKi), 51 (26%) interleukin (IL)-6 inhibitors, 33 (17%) IL-1 inhibitors, 20 (10%) tumour necrosis factor (TNFα) blockers and 12 (6%) other targeted therapies. At 3 months, the overall response (CR and PR) rate was 24% with JAKi, 32% with IL-6 inhibitors, 9% with anti-IL-1 and 0% with TNFα blockers or other targeted therapies. At 6 months, the overall response rate was 30% with JAKi and 26% with IL-6 inhibitors. Survival without treatment discontinuation was significantly longer with JAKi than with the other targeted therapies. Among patients who discontinued treatment, causes were primary failure, secondary failure, serious adverse event or death in 43%, 14%, 19% and 19%, respectively, with JAKi and 46%, 11%, 31% and 9%, respectively, with IL-6 inhibitors.

Conclusions: This study shows the benefit of JAKi and IL-6 inhibitors, whereas other therapies have lower efficacy. These results need to be confirmed in prospective trials.

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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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