背景:ATregs功能不足是自身免疫和炎性疾病病理生理学的核心,低剂量白细胞介素-2(IL-2LD)可以特异性激活Tregs。
目的:评估IL-2LD的治疗潜力,并选择进一步临床发展的疾病,我们表演了一个开放标签,阶段2a,疾病发现,“篮子试验”涉及13种不同自身免疫性疾病之一的患者。
方法:81例患者接受IL-2LD(100万IU/天)治疗5天,然后是每两周注射一次.前48名患者接受稀释的Proleukin®,而随后的33人收到了现成的ILT-101®。主要终点是第8天与基线相比的Tregs变化。关键次要终点包括使用临床总体印象(CGI)量表进行临床疗效评估,疾病特异性评分,和EuroQL-5D-5L。
结果:我们的研究揭示了Tregs的普遍和显著的扩展和激活,没有伴随的Teffs激活,在所有13种自身免疫性疾病中。Proleukin®和即用型ILT-101®对Tregs均表现出相同的效果。CGI得分反映活动,严重程度,在总体患者群体中,疗效显著降低.在六个疾病队列中,至少有六名患者的五个疾病特异性临床评分得到了改善,即强直性脊柱炎,系统性红斑狼疮,Behçet病,干燥综合征,和系统性硬化症。荨麻疹是唯一与治疗相关的严重不良事件。
结论:IL-2LD耐受性良好,在13种自身免疫性疾病中表现出特异性Treg激活和临床改善。
结论:通过IL-2LD刺激Tregs是一种有希望的治疗策略,IL-2LD对于整合到组合治疗方法中具有相当大的希望。
A Tregs insufficiency is central to autoimmune and inflammatory diseases pathophysiology and low dose interleukin-2 (IL-2LD) can specifically activate Tregs.
To assess IL-2LD therapeutic potential and select diseases for further clinical development, we performed an open-label, phase 2a, disease-finding, \"basket trial\" involving patients with one of 13 different autoimmune diseases.
81 patients treated with IL-2LD (1 million IU/day) for 5 days, followed by fortnightly injections. The first 48 patients received diluted Proleukin®, while the subsequent 33 received ready-to-use ILT-101®. The primary endpoint was the change in Tregs at day-8 compared to baseline. Key secondary endpoints included clinical efficacy assessments using the Clinical Global Impression (CGI) scale, disease-specific scores, and EuroQL-5D-5L.
Our study unveiled a universal and significant expansion and activation of Tregs, without concomitant Teffs activation, across all 13 autoimmune diseases. Both Proleukin® and ready-to-use ILT-101® demonstrated identical effects on Tregs. CGI scores reflecting activity, severity, and efficacy were significantly reduced in the overall patient population. Disease-specific clinical scores improved in five of the six disease cohorts with at least six patients, namely ankylosing spondylitis, systemic lupus erythematosus, Behçet\'s disease, Sjögren\'s syndrome, and systemic sclerosis. Urticaria was the only severe adverse event related to treatment.
IL-2LD was well-tolerated, exhibiting specific Treg activation and clinical improvements across the 13 autoimmune diseases.
Tregs stimulation by IL-2LD is a promising therapeutic strategy and IL-2LD holds considerable promise for integration into combinatorial therapeutic approaches.