一项评估沙利鲁单抗治疗巨细胞动脉炎患者的疗效和安全性的 3 期随机、双盲、安慰剂对照研究。
A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritis.
机构信息
Medical Centre for Rheumatology Berlin-Buch, Immanuel Krankenhaus Berlin, Lindenberger Weg 19, Berlin, 13125, Germany.
Southend University Hospital, Mid and South Essex NHS Foundation Trust, Essex, UK.
出版信息
Arthritis Res Ther. 2023 Oct 16;25(1):199. doi: 10.1186/s13075-023-03177-6.
BACKGROUND
Giant cell arteritis (GCA) is primarily treated with glucocorticoids (GCs), which have substantial toxicity. Tocilizumab, an interleukin-6-receptor inhibitor (IL-6Ri), showed beneficial effects in GCA, leading to its approval. This study investigated the efficacy and safety of sarilumab (another IL-6Ri) in GCA.
METHODS
This Phase 3, double-blind study comprised a 52-week treatment period and a 24-week follow-up phase. Eligible GCA patients were randomized to receive sarilumab 200 mg (SAR200 + 26W) or 150 mg (SAR150 + 26W) with a 26-week GC taper, or placebo with a 52-week (PBO + 52W) or 26-week (PBO + 26W) GC taper. The primary efficacy endpoint was sustained remission (SR) at week 52. Additional endpoints were SR at week 24, cumulative GC dose, and safety. The study was discontinued prematurely due to protracted recruitment timelines, because of the impact of COVID-19. Therefore, only descriptive statistics were summarized.
RESULTS
Of the planned 360 subjects, only 83 were randomized and 36 were included in the week 52 analysis. At week 52, 46% (n = 6/13) of patients in SAR200 + 26W, 43% (n = 3/7) in SAR150 + 26W, 30% (n = 3/10) in PBO + 52W, and 0 (n = 0/6) in PBO + 26W taper groups achieved SR. Sensitivity analyses, excluding acute-phase reactants from the SR definition, showed similar results for SAR groups, but 60% (n = 6/10) in PBO + 52W and 17% (n = 1/6) in PBO + 26W taper groups achieved SR at week 52. Similar findings were noted at week 24. The proportions of patients who adhered to GC taper from week 12 through week 52 in each group were as follows: 46% (n = 6/13, SAR200 + 26W), 43% (n = 3/7, SAR150 + 26W), 60% (n = 6/10, PBO + 52W), and 33% (n = 2/6, PBO + 26W). The median actual cumulative GC dose received in the SAR200 + 26W group was lower than other groups. Most patients (80-100%) experienced treatment-emergent adverse events, with similar incidences reported across groups.
CONCLUSIONS
Owing to the small sample size due to the early termination, it is difficult to draw clear conclusions from this study. There were no unexpected safety findings.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03600805. Registered on July 26, 2018.
背景
巨细胞动脉炎（GCA）主要采用糖皮质激素（GCs）治疗，但GCs 毒性较大。白细胞介素-6 受体抑制剂（IL-6Ri）托珠单抗在 GCA 中的疗效良好，已获得批准。本研究旨在评估沙利鲁单抗（另一种 IL-6Ri）在 GCA 中的疗效和安全性。
方法
这是一项 III 期、双盲研究，包括 52 周的治疗期和 24 周的随访期。符合条件的 GCA 患者被随机分为沙利鲁单抗 200mg（SAR200+26W）或 150mg（SAR150+26W）联合 26 周 GC 减量、或安慰剂联合 52 周（PBO+52W）或 26 周（PBO+26W）GC 减量组。主要疗效终点为第 52 周时持续缓解（SR）。其他终点包括第 24 周时的 SR、累积 GC 剂量和安全性。由于 COVID-19 的影响，招募时间延长，研究提前终止，因此仅汇总了描述性统计数据。
结果
原计划纳入 360 例患者，仅有 83 例患者被随机分组，36 例患者纳入第 52 周分析。第 52 周时，SAR200+26W 组有 46%（n=6/13）、SAR150+26W 组有 43%（n=3/7）、PBO+52W 组有 30%（n=3/10）、PBO+26W 组有 0%（n=0/6）患者达到 SR。敏感性分析排除 SR 定义中的急性期反应物后，SAR 组也得到了类似的结果，但 PBO+52W 组有 60%（n=6/10）、PBO+26W 组有 17%（n=1/6）患者在第 52 周时达到 SR。第 24 周也观察到类似的结果。在每个治疗组中，从第 12 周至第 52 周期间坚持 GC 减量的患者比例如下：SAR200+26W 组为 46%（n=6/13）、SAR150+26W 组为 43%（n=3/7）、PBO+52W 组为 60%（n=6/10）、PBO+26W 组为 33%（n=2/6）。SAR200+26W 组患者实际接受的累积 GC 剂量中位数低于其他组。大多数患者（80-100%）发生了治疗出现的不良事件，各组报告的发生率相似。
结论
由于早期终止导致样本量较小，难以从本研究中得出明确的结论。未发现意外的安全性发现。
试验注册
ClinicalTrials.gov NCT03600805。注册于 2018 年 7 月 26 日。
Zotero 插件