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低剂量IL-2可望用于难治性狼疮治疗

Low-dose IL-2 shows promise for refractory lupus
作者:SHARON WORCESTER 来源:Frontline Medical News 2016-12-21 16:00点击次数:3598发表评论


A novel biologic treatment strategy involving subcutaneous low-dose interleukin-2 therapy for refractory systemic lupus erythematosus (SLE) showed promise in a single-center, combined phase I/IIa trial.


皮下注射低剂量IL-2作为难治性系统性红斑狼疮(SLE)生物治疗新策略,在一项单中心I/IIa期联合试验中显示出良好前景。


In 12 patients with active and refractory SLE – that is, patients with SLE disease activity index (SLEDAI) score of at least 6 who were on at least two different immunosuppressive therapies – low-dose IL-2 treatment led to an effective and cycle-dependent increase in the percentage of CD25hi cells among regulatory T cells (Treg). The increase was statistically significant (P less than .001), Jens Humrich, MD, and his colleagues reported in a late-breaking poster at the annual meeting of the American College of Rheumatology.


Jens Humrich博士及其同事在美国风湿病学会(ACR)年会上通过最新研究海报报告指出,在12例活动性难治性SLE患者(至少接受2种不同免疫抑制剂治疗,且SLE疾病活动性指数(SLEDAI)≥6)中,低剂量IL-2治疗可显著且周期依赖性增加调节性T细胞(Treg)中CD25hi细胞比率,该比率增加具有统计学显著意义(P<0.001)。


Further, a reduction in SLEDAI was seen in 10 patients (83.3%), and a clinical response occurred in 8 (66.7%), with complete resolution of clinical manifestations including rash, arthritis, myositis, and alopecia.


此外,10例患者(83.3%)SLEDAI下降,8例(66.7%)出现临床应答,皮症、关节炎、肌炎及脱发等临床症状得到完全消退。


However, a reduction in levels of anti-dsDNA antibodies was not observed, said Dr. Humrich of University Hospital Schleswig-Holstein in Lubeck, Germany.


然而,德国吕贝克石荷州大学医院的Humrich博士称,未观察到抗dsDNA抗体水平下降。


Treatment was safe; treatment-related adverse events were generally mild and transient, Dr. Humrich noted.


Humrich博士指出该治疗方案安全性良好,与治疗相关的不良事件通常属于轻度和一过性。


Study subjects received four treatment cycles each, with daily subcutaneous injections of recombinant human IL-2 (aldesleukin) at single doses of 0.75, 1.5, or 3.0 million IU on 5 consecutive days. Cycles were separated by a washout period of 9-16 days. Subjects were then followed for 9 weeks.


每例研究受试者接受4个周期的治疗,剂量分别为每日单剂量皮下注射重组人IL-2(aldesleukin)0.75、1.5或3.0百万单位,连续5日,周期间洗脱时间为9~16天,随访9周。


IL-2 is crucial for the growth and survival of Treg (and thus for the control of autoimmunity). Prior studies demonstrated the significance of acquired IL-2 deficiency and related Treg defects in the pathogenesis of SLE – and that compensation for IL-2 deficiency with low-dose IL-2 can correct these defects, he explained.


他解释称,IL-2对于Treg生存(因此也对自身免疫调节)至关重要。既往研究证实了获得性IL-2缺乏及其相关的Treg功能缺陷在SLE发病机理中的意义,因而通过低剂量IL-2补充IL-2缺乏可纠正这些缺陷。


In the current study, the primary aim was to show at least a twofold increase in the percentage of CD25hi cells among CD3+CD4+Foxp3+CD127lo Treg cells after the fourth treatment cycle vs. baseline, and secondary aims included clinical responses assessed by SLEDAI and changes in serologic and other immunologic parameters, he said.


他指出,该研究的主要目标是证明4个周期治疗后CD25hi/ CD3+CD4+Foxp3+CD127lo Treg比率至少比基线时增加2倍,次要目标包括通过SLEDAI评估临床应答、血清学以及其他免疫学指标改变等。


The findings suggest that low-dose IL-2 therapy can safely and selectively expand the Treg population and decrease disease activity in patients with active and refractory SLE.


结果表明,低剂量IL-2可安全且选择性增加活动性难治性SLE患者Treg细胞群,降低疾病活动性。


 “This study provides the basis for larger and placebo-controlled clinical studies aiming to prove the efficacy of this novel biologic treatment strategy,” the investigators concluded.


研究者总结指出:该研究为开展更大规模的安慰剂对照临床试验,证实这一生物治疗新策略的有效性奠定了基础。


Dr. Humrich reported having no disclosures.


Humrich博士报告无利益冲突披露。


独家授权,未经许可请勿转载!


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学科代码: 风湿病学     关键词:IL-2 难治性红斑狼疮 临床试验 ,新闻 爱思唯尔医学网, Elseviermed
来源: Frontline Medical News
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