Department of Neurology, Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA.
Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia.
Ann Neurol. 2023 Jun;93(6):1053-1068. doi: 10.1002/ana.26626. Epub 2023 Apr 5.
CHAMPION-NMOSD (NCT04201262) is a phase 3, open-label, externally controlled interventional study evaluating the efficacy and safety of the terminal complement inhibitor ravulizumab in adult patients with anti-aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD). Ravulizumab binds the same complement component 5 epitope as the approved therapeutic eculizumab but has a longer half-life, enabling an extended dosing interval (8 vs 2 weeks).
The availability of eculizumab precluded the use of a concurrent placebo control in CHAMPION-NMOSD; consequently, the placebo group of the eculizumab phase 3 trial PREVENT (n = 47) was used as an external comparator. Patients received weight-based intravenous ravulizumab on day 1 and maintenance doses on day 15, then once every 8 weeks. The primary endpoint was time to first adjudicated on-trial relapse.
The primary endpoint was met; no patients taking ravulizumab (n = 58) had an adjudicated relapse (during 84.0 patient-years of treatment) versus 20 patients with adjudicated relapses in the placebo group of PREVENT (during 46.9 patient-years; relapse risk reduction = 98.6%, 95% confidence interval = 89.7%-100.0%, p < 0.0001). Median (range) study period follow-up time was 73.5 (11.0-117.7) weeks for ravulizumab. Most treatment-emergent adverse events were mild/moderate; no deaths were reported. Two patients taking ravulizumab experienced meningococcal infections. Both recovered with no sequelae; one continued ravulizumab treatment.
Ravulizumab significantly reduced relapse risk in patients with AQP4+ NMOSD, with a safety profile consistent with those of eculizumab and ravulizumab across all approved indications. ANN NEUROL 2023;93:1053-1068.
CHAMPION-NMOSD（NCT04201262）是一项 3 期、开放标签、外部对照的干预性研究，评估了末端补体抑制剂 ravulizumab 在抗水通道蛋白 4 抗体阳性（AQP4+）视神经脊髓炎谱系障碍（NMOSD）成年患者中的疗效和安全性。ravulizumab 与已批准的治疗药物 eculizumab 结合相同的补体成分 5 表位，但半衰期更长，可延长给药间隔（8 周 vs 2 周）。
CHAMPION-NMOSD 中由于 eculizumab 的可用性，无法使用安慰剂对照；因此，使用 eculizumab 3 期试验 PREVENT 的安慰剂组（n=47）作为外部对照。患者在第 1 天接受基于体重的静脉注射 ravulizumab，并在第 15 天接受维持剂量，然后每 8 周一次。主要终点是首次判定的试验内复发时间。
主要终点得到满足；没有服用 ravulizumab（n=58）的患者发生了判定复发（在 84.0 患者年的治疗期间），而 PREVENT 安慰剂组有 20 名患者发生了判定复发（在 46.9 患者年期间；复发风险降低 98.6%，95%置信区间 89.7%-100.0%，p<0.0001）。ravulizumab 的中位（范围）研究期间随访时间为 73.5（11.0-117.7）周。大多数治疗出现的不良事件为轻度/中度；没有死亡报告。两名服用 ravulizumab 的患者发生了脑膜炎球菌感染。两人均康复，无后遗症；其中 1 人继续接受 ravulizumab 治疗。
ravulizumab 显著降低了 AQP4+NMOSD 患者的复发风险，其安全性与所有已批准适应症的 eculizumab 和 ravulizumab 一致。ANN NEUROL 2023；93:1053-1068。
