Toulouse University Hospital, Toulouse, France.
Am J Transplant. 2013 Jul;13(7):1724-33. doi: 10.1111/ajt.12303. Epub 2013 Jun 3.
Memory T cells play a central role in mediating allograft rejection and are a rational target for immunosuppressive therapy. Alefacept is a recombinant LFA3/IgG1 fusion protein that reduces the number of memory T cells in both psoriatic lesions and the peripheral circulation of psoriasis patients. This study evaluated the efficacy and safety of alefacept compared with placebo when combined with tacrolimus, mycophenolate mofetil and corticosteroids in de novo renal transplant recipients. Between December 2007 and March 2009 patients were randomized in a double-blind fashion to receive alefacept (n = 105) or placebo (n = 107) for 3 months and were then followed for a further 3 months. The primary efficacy endpoint was the incidence of biopsy-confirmed acute T cell mediated rejection (Banff grade ≥ 1) through Month 6. Memory T cell counts were significantly reduced in the alefacept group from Week 3 to study end compared with placebo. However, there was no significant difference between the alefacept and placebo groups for the primary efficacy endpoint (alefacept, 11.0% vs. placebo, 7.0%, p = 0.3). Patient and graft survival as well as renal function was similar between treatment groups. Safety and tolerability were generally similar between the treatment arms. Malignancy was higher in the alefacept treatment arm.
记忆 T 细胞在介导移植物排斥反应中起着核心作用，是免疫抑制治疗的合理靶点。阿莱夫塞普是一种重组 LFA3/IgG1 融合蛋白，可减少银屑病患者的皮损和外周循环中的记忆 T 细胞数量。本研究评估了阿莱夫塞普联合他克莫司、霉酚酸酯和皮质类固醇在初发肾移植受者中的疗效和安全性。2007 年 12 月至 2009 年 3 月，患者以双盲方式随机分为阿莱夫塞普（n = 105）或安慰剂（n = 107）组，分别接受 3 个月治疗，然后再随访 3 个月。主要疗效终点是 6 个月时通过活检证实的急性 T 细胞介导的排斥反应（Banff 分级≥1）的发生率。与安慰剂组相比，阿莱夫塞普组从第 3 周开始至研究结束时记忆 T 细胞计数显著降低。然而，阿莱夫塞普组和安慰剂组在主要疗效终点（阿莱夫塞普组 11.0%，安慰剂组 7.0%，p = 0.3）之间无显著差异。治疗组患者和移植物存活率以及肾功能相似。治疗组之间的安全性和耐受性通常相似。阿莱夫塞普治疗组的恶性肿瘤发生率较高。
