Hamidou Mohamed, Néel Antoine, Poupon Joel, Amoura Zahir, Ebbo Mikael, Sibilia Jean, Viallard Jean-Francois, Gaborit Benjamin, Volteau Christelle, Hardouin Jean Benoit, Hachulla Eric, Rieger François
Department of Internal Medicine, CHU Nantes, Nantes Université, Nantes, France.
Department of Biological Toxicology, AP-HP, Lariboisière Hospital, University Paris VII, Paris, France.
Arthritis Res Ther. 2021 Mar 3;23(1):70. doi: 10.1186/s13075-021-02454-6.
Lupus animal model has shown that arsenic trioxide (ATO), a treatment of acute promyelocytic leukaemia, could be effective in SLE. This is the first clinical study to determine the safety and efficacy of a short course of intravenous ATO in patients with active SLE.
This phase IIa, open-label, dose-escalating study enrolled 11 adult SLE patients with a non-organ threatening disease, clinically active despite conventional therapy. Patients received 10 IV infusions of ATO within 24 days. The first group received 0.10 mg/kg per injection, with dose-escalating to 0.15 mg/kg in a second group, and to 0.20 mg/kg in a third group. The primary endpoint was the occurrence of adverse events (AEs) and secondary endpoints were the number of SLE Responder Index 4 (SRI-4) responders at week 24 and reduction of corticosteroid dosage. In an exploratory analysis, we collected long-term data for safety and attainment of lupus low disease activity state (LLDAS).
Four serious AEs occurred (grade 3 neutropenia, osteitis, neuropathy), 2 of which were attributable to ATO (neutropenia in the 2 patients treated with mycophenolate). Two patients suffered a severe flare during the last 4 weeks of the trial. At W24, five patients among 10 were SRI-4 responders. Overall, mean corticosteroid dosage decreased from 11.25 mg/day at baseline to 6 mg/day at W24 (P < 0.01). In the long term, 6 patients attained LLDAS at W52, which continued at last follow-up (median LLDAS duration 3 years, range 2-4).
A short course of ATO has an acceptable safety profile in SLE patients and encouraging efficacy.
ClinicalTrials.gov, NCT01738360 registered 30 November 2012.
狼疮动物模型显示，用于治疗急性早幼粒细胞白血病的三氧化二砷（ATO）可能对系统性红斑狼疮（SLE）有效。这是第一项确定短期静脉注射ATO对活动性SLE患者安全性和有效性的临床研究。
这项IIa期、开放标签、剂量递增研究纳入了11例患有非器官威胁性疾病的成年SLE患者，尽管接受了传统治疗，但临床仍处于活动期。患者在24天内接受10次静脉注射ATO。第一组每次注射剂量为0.10mg/kg，第二组剂量递增至0.15mg/kg，第三组递增至0.20mg/kg。主要终点是不良事件（AE）的发生情况，次要终点是第24周时SLE反应指数4（SRI-4）反应者的数量以及皮质类固醇剂量的减少。在探索性分析中，我们收集了安全性和狼疮低疾病活动状态（LLDAS）达成情况的长期数据。
发生了4例严重不良事件（3级中性粒细胞减少、骨炎、神经病变），其中2例归因于ATO（2例接受霉酚酸酯治疗的患者出现中性粒细胞减少）。2例患者在试验的最后4周内出现严重病情复发。在第24周时，10例患者中有5例为SRI-4反应者。总体而言，皮质类固醇的平均剂量从基线时的11.25mg/天降至第24周时的6mg/天（P<0.01）。从长期来看，6例患者在第52周时达到LLDAS，并在最后一次随访时持续保持（LLDAS持续时间中位数为3年，范围为2至4年）。
短期使用ATO对SLE患者具有可接受的安全性和令人鼓舞的疗效。
ClinicalTrials.gov，NCT01738360，于2012年11月30日注册。
