BACKGROUND Anifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1 investigated for the treatment of systemic lupus erythematosus (SLE), did not have a significant effect on the primary end point in a previous phase 3 trial. The current phase 3 trial used a secondary end point from that trial as the primary end point. METHODS We randomly assigned patients in a 1:1 ratio to receive intravenous anifrolumab (300 mg) or placebo every 4 weeks for 48 weeks. The primary end point of this trial was a response at week 52 defined with the use of the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA). A BICLA response requires reduction in any moderate-to-severe baseline disease activity and no worsening in any of nine organ systems in the BILAG index, no worsening on the Systemic Lupus Erythematosus Disease Activity Index, no increase of 0.3 points or more in the score on the Physician Global Assessment of disease activity (on a scale from 0 [no disease activity] to 3 [severe disease]), no discontinuation of the trial intervention, and no use of medications restricted by the protocol. Secondary end points included a BICLA response in patients with a high interferon gene signature at baseline; reductions in the glucocorticoid dose, in the severity of skin disease, and in counts of swollen and tender joints; and the annualized flare rate. RESULTS A total of 362 patients received the randomized intervention: 180 received anifrolumab and 182 received placebo. The percentage of patients who had a BICLA response was 47.8% in the anifrolumab group and 31.5% in the placebo group (difference, 16.3 percentage points; 95% confidence interval, 6.3 to 26.3; P = 0.001). Among patients with a high interferon gene signature, the percentage with a response was 48.0% in the anifrolumab group and 30.7% in the placebo group; among patients with a low interferon gene signature, the percentage was 46.7% and 35.5%, respectively. Secondary end points with respect to the glucocorticoid dose and the severity of skin disease, but not counts of swollen and tender joints and the annualized flare rate, also showed a significant benefit with anifrolumab. Herpes zoster and bronchitis occurred in 7.2% and 12.2% of the patients, respectively, who received anifrolumab. There was one death from pneumonia in the anifrolumab group. CONCLUSIONS Monthly administration of anifrolumab resulted in a higher percentage of patients with a response (as defined by a composite end point) at week 52 than did placebo, in contrast to the findings of a similar phase 3 trial involving patients with SLE that had a different primary end point. The frequency of herpes zoster was higher with anifrolumab than with placebo. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT02446899.).

中文翻译：

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Anifrolumab 在活动性系统性红斑狼疮中的试验。

背景 Anifrolumab 是一种针对 I 型干扰素受体亚基 1 的人单克隆抗体，用于治疗系统性红斑狼疮 (SLE)，在之前的 3 期试验中对主要终点没有显着影响。目前的 3 期试验使用该试验的次要终点作为主要终点。方法 我们以 1:1 的比例将患者随机分配接受静脉注射 anifrolumab（300 mg）或安慰剂，每 4 周一次，持续 48 周。该试验的主要终点是使用基于不列颠群岛狼疮评估组 (BILAG) 的综合狼疮评估 (BICLA) 定义的第 52 周的反应。BICLA 反应需要减少任何中度至重度基线疾病活动，并且 BILAG 指数中九个器官系统中的任何一个都没有恶化，系统性红斑狼疮疾病活动指数没有恶化，疾病活动的医师全球评估评分没有增加 0.3 分或更多（从 0 [无疾病活动] 到 3 [严重疾病]），没有停药试验干预，并且不使用方案限制的药物。次要终点包括基线时具有高干扰素基因特征的患者的 BICLA 反应；减少糖皮质激素的剂量、皮肤病的严重程度以及肿胀和触痛的关节数量；和年化的耀斑率。结果 共有 362 名患者接受了随机干预：180 名接受 anifrolumab，182 名接受安慰剂。有 BICLA 反应的患者百分比在 anifrolumab 组为 47.8%，在安慰剂组为 31.5%（差异为 16. 3个百分点；95% 置信区间，6.3 至 26.3；P = 0.001)。在具有高干扰素基因特征的患者中，有反应的百分比在 anifrolumab 组为 48.0%，在安慰剂组为 30.7%；在具有低干扰素基因特征的患者中，该百分比分别为 46.7% 和 35.5%。关于糖皮质激素剂量和皮肤病严重程度的次要终点，但不包括肿胀和触痛关节的计数以及年度复发率，也显示使用 anifrolumab 有显着益处。接受 anifrolumab 的患者分别有 7.2% 和 12.2% 发生带状疱疹和支气管炎。anifrolumab 组有 1 人死于肺炎。结主要终点。anifrolumab 带状疱疹的发生率高于安慰剂组。（由阿斯利康资助；ClinicalTrials.gov 编号为 NCT02446899。）。