From Addenbrooke's Hospital, Cambridge, United Kingdom (D.R.W.J.); the University of Pennsylvania, Philadelphia (P.A.M.); and ChemoCentryx, Mountain View, CA (T.J.S., P.B.).
N Engl J Med. 2021 Feb 18;384(7):599-609. doi: 10.1056/NEJMoa2023386.
The C5a receptor inhibitor avacopan is being studied for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.
In this randomized, controlled trial, we assigned patients with ANCA-associated vasculitis in a 1:1 ratio to receive oral avacopan at a dose of 30 mg twice daily or oral prednisone on a tapering schedule. All the patients received either cyclophosphamide (followed by azathioprine) or rituximab. The first primary end point was remission, defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 (on a scale from 0 to 63, with higher scores indicating greater disease activity) at week 26 and no glucocorticoid use in the previous 4 weeks. The second primary end point was sustained remission, defined as remission at both weeks 26 and 52. Both end points were tested for noninferiority (by a margin of 20 percentage points) and for superiority.
A total of 331 patients underwent randomization; 166 were assigned to receive avacopan, and 165 were assigned to receive prednisone. The mean BVAS at baseline was 16 in both groups. Remission at week 26 (the first primary end point) was observed in 120 of 166 patients (72.3%) receiving avacopan and in 115 of 164 patients (70.1%) receiving prednisone (estimated common difference, 3.4 percentage points; 95% confidence interval [CI], -6.0 to 12.8; P<0.001 for noninferiority; P = 0.24 for superiority). Sustained remission at week 52 (the second primary end point) was observed in 109 of 166 patients (65.7%) receiving avacopan and in 90 of 164 patients (54.9%) receiving prednisone (estimated common difference, 12.5 percentage points; 95% CI, 2.6 to 22.3; P<0.001 for noninferiority; P = 0.007 for superiority). Serious adverse events (excluding worsening vasculitis) occurred in 37.3% of the patients receiving avacopan and in 39.0% of those receiving prednisone.
In this trial involving patients with ANCA-associated vasculitis, avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52. All the patients received cyclophosphamide or rituximab. The safety and clinical effects of avacopan beyond 52 weeks were not addressed in the trial. (Funded by ChemoCentryx; ADVOCATE ClinicalTrials.gov number, NCT02994927.).
C5a 受体抑制剂 avacopan 正在被研究用于治疗抗中性粒细胞胞浆抗体（ANCA）相关性血管炎。
在这项随机对照试验中，我们将 ANCA 相关性血管炎患者按 1:1 的比例随机分配，接受每日两次 30 毫克口服 avacopan 或口服泼尼松龙逐渐减量。所有患者均接受环磷酰胺（随后接受硫唑嘌呤）或利妥昔单抗治疗。主要终点为缓解，定义为第 26 周时 Birmingham Vasculitis Activity Score（BVAS）为 0（评分范围为 0 至 63，得分越高表示疾病活动度越高），且前 4 周内未使用糖皮质激素。次要终点为持续缓解，定义为第 26 周和第 52 周均缓解。两个终点均进行非劣效性（以 20 个百分点为界）和优效性检验。
共有 331 名患者接受随机分组；166 名患者被分配接受 avacopan 治疗，165 名患者被分配接受泼尼松龙治疗。两组患者的基线平均 BVAS 均为 16。第 26 周（主要终点之一）缓解的患者在接受 avacopan 治疗的 166 名患者中为 120 名（72.3%），在接受泼尼松龙治疗的 164 名患者中为 115 名（70.1%）（估计共同差异为 3.4 个百分点；95%置信区间[CI]为-6.0 至 12.8；P<0.001，非劣效性检验；P=0.24，优效性检验）。第 52 周（次要终点之一）持续缓解的患者在接受 avacopan 治疗的 166 名患者中为 109 名（65.7%），在接受泼尼松龙治疗的 164 名患者中为 90 名（54.9%）（估计共同差异为 12.5 个百分点；95%CI 为 2.6 至 22.3；P<0.001，非劣效性检验；P=0.007，优效性检验）。接受 avacopan 治疗的患者中有 37.3%发生严重不良事件（不包括血管炎恶化），接受泼尼松龙治疗的患者中有 39.0%发生严重不良事件。
在这项涉及抗中性粒细胞胞浆抗体相关性血管炎患者的试验中，avacopan 在第 26 周缓解方面不劣于泼尼松龙逐渐减量，但在第 52 周持续缓解方面优于泼尼松龙逐渐减量。所有患者均接受环磷酰胺或利妥昔单抗治疗。该试验未评估 avacopan 在第 52 周后治疗的安全性和临床效果。（由 ChemoCentryx 资助；ADVOCATE 临床试验.gov 编号，NCT02994927。）
