Furie Richard, Steffgen Jürgen, Fagan Nora, Romero-Diaz Juanita, Avihingsanon Yingyos, Boumpas Dimitrios T, Noppakun Kajohnsak, Wu Jing, Revollo Ivette, Jayne David R
Division of Rheumatology, Northwell Health and Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA.
TA Inflammation Medicine, Boehringer Ingelheim International GmbH, Biberach, Germany.
Lupus. 2025 Apr;34(5):460-473. doi: 10.1177/09612033251326990. Epub 2025 Mar 19.
ObjectiveTo evaluate the long-term efficacy and safety of different doses of BI 655064 versus placebo added to standard of care during maintenance treatment for lupus nephritis (LN).Methods1293.13 was an exploratory, phase II maintenance trial. Patients were eligible for entry if they had completed 1 year of randomised treatment with BI 655064 (120, 180 or 240 mg) or placebo in the 1293.10 trial, responded to treatment at Year 1 (complete renal response [CRR], partial renal response or urinary protein/creatinine ratio ≤1) and consented to continue treatment. The primary endpoint was the proportion of patients with CRR without renal flares at Year 2. Secondary endpoints included change from baseline in Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores and safety/tolerability.Results69/121 patients (57.0%) from the 1293.10 trial entered 1293.13. The adjusted proportion of patients with CRR decreased in all groups between Year 1 (BI 655064: 53.4%-72.7%; placebo: 71.4%) and Year 2 (BI 655064: 48.2%-59.5%; placebo: 57.5%). At Year 2, mean decreases in total SELENA-SLEDAI scores were greatest with BI 655064 240 mg (-10.6 points), followed by 120 mg (-8.9 points), 180 mg (-7.2 points) and placebo (-5.3 points). SELENA-SLEDAI non-renal scores decreased at Year 1 (BI 655064: -3.0 to -3.4; placebo: -1.8); this pattern remained with BI 655064 during Year 2 (-2.4 to -4.1), whereas placebo returned to near-baseline scores (-0.4). Over 2 years of treatment, almost all patients (97.1%) experienced ≥1 adverse event (AE). Compared with the other groups, higher rates of serious AEs (42.9% vs 23.1%-33.3%)-mainly driven by serious infections (23.8% vs 7.7%-14.3%)-and severe AEs (47.6% vs 13.3%-28.6%) were reported with BI 655064 240 mg.ConclusionsThis exploratory, phase II maintenance trial failed to demonstrate the benefits of BI 655064 on renal outcomes in the treatment of LN. However, some benefits in total and non-renal SELENA-SLEDAI scores were observed.
目的
评估在狼疮性肾炎（LN）维持治疗期间，不同剂量的BI 655064与添加至标准治疗方案中的安慰剂相比的长期疗效和安全性。
方法
1293.13是一项探索性II期维持试验。如果患者在1293.10试验中完成了1年的BI 655064（120、180或240mg）或安慰剂随机治疗，在第1年对治疗有反应（完全肾脏反应[CRR]、部分肾脏反应或尿蛋白/肌酐比值≤1）且同意继续治疗，则符合入组条件。主要终点是第2年无肾脏复发的CRR患者比例。次要终点包括狼疮性肾炎国家评估 - 系统性红斑狼疮疾病活动指数（SELENA - SLEDAI）评分相对于基线的变化以及安全性/耐受性。
结果
1293.10试验中的69/121名患者（57.0%）进入了1293.13试验。在第1年（BI 655064：53.4% - 72.7%；安慰剂：71.4%）和第2年（BI 655064：48.2% - 59.5%；安慰剂：57.5%）之间，所有组中CRR患者的校正比例均下降。在第2年，BI 655064 240mg组的SELENA - SLEDAI总分平均下降幅度最大（-10.6分），其次是120mg组（-8.9分）、180mg组（-7.2分）和安慰剂组（-5.3分）。SELENA - SLEDAI非肾脏评分在第1年下降（BI 655064：-3.0至-3.4；安慰剂：-1.8）；第2年BI 655064组仍保持这种下降趋势（-2.4至-4.1），而安慰剂组恢复到接近基线的评分（-0.4）。在2年的治疗期间，几乎所有患者（97.1%）都经历了≥1次不良事件（AE）。与其他组相比，BI 655064 240mg组报告的严重AE发生率更高（42.9%对23.1% - 33.3%），主要由严重感染导致（23.8%对7.7% - 14.3%），严重AE发生率也更高（47.6%对13.3% - 28.6%）。
结论
这项探索性II期维持试验未能证明BI 655064在治疗LN时对肾脏结局有益处。然而，在SELENA - SLEDAI总分和非肾脏评分方面观察到了一些益处。
