Furie Richard A, Mitrane Margaret, Zhao Enxu, Becker Patrice M
Hofstra Northwell School of Medicine, Northwell Health, Great Neck, New York, USA.
Manhattan BioPharm Consultants LLC, New York, New York, USA.
Lupus Sci Med. 2017 Dec 27;4(1):e000240. doi: 10.1136/lupus-2017-000240. eCollection 2017.
Post hoc analyses evaluated the effectiveness and safety of repository corticotropin injection (RCI) in patients with persistently active SLE over 52 weeks.
Patients were initially randomised to 40 U daily or 80 U every other day RCI (n=26) or placebo (n=12) for the 8-week double-blind period. Completers entered the open-label extension (OLE; n=33) receiving 16, 40 or 80 U RCI 1-3 times/week and were followed through week 52. Outcomes included proportion of responders based on a novel index (resolution of joint or skin activity using hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) without any worsening British Isles Lupus Assessment Group (BILAG) scores in other organ systems) or revised novel index (using SLE Responder Index (SRI) definition of BILAG worsening (1A or 2B)), proportion of responders by SRI and changes in total hSLEDAI and BILAG scores. Adverse events and laboratory values were assessed.
At week 52, 12.0% (3/25) RCI/RCI patients and 36.4% (4/11) placebo/RCI patients were responders using the novel index. The revised novel responder index demonstrated response rates of 48.0% (12/25) and 54.5% (6/11) in the RCI/RCI and placebo/RCI groups, respectively. Proportions of SRI responders were 40.0% (10/25) and 54.5% (6/11). In the RCI/RCI group, total hSLEDAI and BILAG scores declined from 10.0 and 15.7 at week 0 to 3.5 and 4.6 at week 52, respectively. Reductions in the placebo/RCI group on switching were observed (mean hSLEDAI: 9.1-3.3; BILAG: 13.5-2.6). Other disease activity endpoints also improved in both groups. No new safety signals were observed during the OLE.
RCI demonstrated durable effectiveness in patients with persistently active SLE despite moderate-dose corticosteroid therapy. Switching from placebo resulted in reduced disease activity during the OLE. These data provide the foundation for evaluation of RCI in a robustly powered study.
事后分析评估了长效促肾上腺皮质激素注射剂（RCI）在持续活动的系统性红斑狼疮（SLE）患者中超过52周的有效性和安全性。
在为期8周的双盲期，患者最初被随机分为每日注射40 U或隔日注射80 U的RCI组（n = 26）或安慰剂组（n = 12）。完成双盲期的患者进入开放标签扩展期（OLE；n = 33），接受每周1 - 3次16、40或80 U的RCI治疗，并随访至第52周。结局指标包括基于一种新指标（使用混合系统性红斑狼疮疾病活动指数（hSLEDAI）使关节或皮肤活动消退且其他器官系统的不列颠群岛狼疮评估组（BILAG）评分无任何恶化）或修订后的新指标（使用SLE缓解指数（SRI）对BILAG恶化（1A或2B）的定义）的缓解者比例、按SRI定义的缓解者比例以及总hSLEDAI和BILAG评分的变化。评估不良事件和实验室检查值。
在第52周时，使用新指标，RCI/RCI组中12.0%（3/25）的患者和安慰剂/RCI组中36.4%（4/11）的患者为缓解者。修订后的新缓解者指标显示，RCI/RCI组和安慰剂/RCI组的缓解率分别为48.0%（12/25）和54.5%（6/11）。SRI缓解者比例分别为40.0%（10/25）和54.5%（6/11）。在RCI/RCI组中，总hSLEDAI和BILAG评分分别从第0周的10.0和15.7降至第52周的3.5和4.6。在安慰剂/RCI组中，转换治疗后观察到评分下降（平均hSLEDAI：9.1 - 3.3；BILAG：13.5 - 2.6）。两组的其他疾病活动终点指标也有所改善。在OLE期间未观察到新的安全信号。
尽管接受了中等剂量的皮质类固醇治疗，RCI在持续活动的SLE患者中显示出持久的有效性。从安慰剂转换为RCI治疗在OLE期间使疾病活动度降低。这些数据为在一项有充分统计学效力的研究中评估RCI提供了基础。
