Columbia University Medical Center, New York, New York, USA.
Mallinckrodt Pharmaceuticals, Bedminster, New Jersey, USA.
Lupus Sci Med. 2020 Apr 21;7(1):e000383. doi: 10.1136/lupus-2020-000383. eCollection 2020.
SLE is a chronic inflammatory autoimmune disease characterised by the excessive production of autoantibodies, immune complexes and proinflammatory cytokines. Repository corticotropin injection (RCI) is a naturally sourced complex mixture of adrenocorticotropic hormone analogues and other pituitary peptides. RCI is approved by the US Food and Drug Administration for use during an exacerbation or as maintenance therapy in select cases of SLE. This paper discusses the design and baseline characteristics of a multicentre, double-blind, randomised, placebo-controlled, 24-week clinical trial evaluating the effect of RCI in reducing disease activity for patients with persistently active SLE despite moderate-dose corticosteroid use.
Efficacy will be evaluated using the SLE Responder Index-4 (SRI-4), SLE Disease Activity Index-2000 (SLEDAI-2K), British Isles Lupus Assessment Group-2004 (BILAG-2004) and Physician's Global Assessment (PGA). The primary efficacy endpoint will be the proportion of SRI-4 responders at week 16. Secondary and exploratory endpoints will include changes in disease activity scores over time, prednisone dose and biomarkers of inflammation and bone turnover. The safety and tolerability profile of RCI will also be evaluated through adverse event profiles, physical examination, clinical laboratory tests and serum cortisol levels.
Target enrolment for this global study is 270 patients, and as of 15 November 2019, the modified intent-to-treat population included 169 patients. The study cohort had 91.7% women, had a mean age of 39.7 years, mean SLEDAI-2K total score of 9.9, mean BILAG-2004 total score of 18.1, mean PGA of 59.7 and mean prednisone or equivalent daily dose of 11.1 mg. A total of 79.3% and 64.5% of patients were receiving concomitant antimalarial or immunosuppressive therapy, respectively.
Data from this study will provide valuable insights into the therapeutic role of RCI in refractory SLE, as well as important information regarding its safety profile.
SLE 是一种慢性炎症性自身免疫性疾病，其特征是过度产生自身抗体、免疫复合物和促炎细胞因子。促肾上腺皮质激素释放因子（RCI）是一种天然来源的促肾上腺皮质激素类似物和其他垂体肽的复杂混合物。RCI 已获得美国食品和药物管理局批准，可用于治疗某些选择病例的 SLE 发作或维持治疗。本文讨论了一项多中心、双盲、随机、安慰剂对照、24 周临床试验的设计和基线特征，该试验评估了 RCI 对持续接受中等剂量皮质类固醇治疗但仍处于活动期的 SLE 患者降低疾病活动度的效果。
使用 SLE 应答指数-4（SRI-4）、SLE 疾病活动指数-2000（SLEDAI-2K）、不列颠群岛狼疮评估组-2004（BILAG-2004）和医生总体评估（PGA）评估疗效。主要疗效终点为第 16 周时 SRI-4 应答者的比例。次要和探索性终点包括随时间变化的疾病活动评分、泼尼松剂量以及炎症和骨转换的生物标志物的变化。还将通过不良事件概况、体格检查、临床实验室检查和血清皮质醇水平评估 RCI 的安全性和耐受性。
该全球研究的目标入组人数为 270 人，截至 2019 年 11 月 15 日，修改后的意向治疗人群包括 169 名患者。研究队列中 91.7%为女性，平均年龄为 39.7 岁，平均 SLEDAI-2K 总分为 9.9，平均 BILAG-2004 总分为 18.1，平均 PGA 为 59.7，平均泼尼松或等效日剂量为 11.1mg。分别有 79.3%和 64.5%的患者正在接受联合抗疟药或免疫抑制剂治疗。
这项研究的数据将为 RCI 在难治性 SLE 中的治疗作用提供有价值的见解，并为其安全性概况提供重要信息。
