澳大利亚莫纳什医学中心Eric F. Morand小组在研究中取得进展。他们进行了Anifrolumab治疗活动性系统性红斑狼疮的临床研究。相关论文发表在2019年12月18日的《新英格兰医学杂志》上。

Anifrolumab是一种抗I型干扰素受体亚单位1的人源化单克隆抗体，用于治疗系统性红斑狼疮（SLE），在此前的临床3期试验中对主要终点无明显效果。因此，研究组将次要终点改为主要终点进行研究。

研究组招募了362例SLE患者，按1：1随机分组，其中180例接受Anifrolumab治疗，182例接受安慰剂治疗，每4周静脉注射一次，为期48周。综合狼疮评估（BICLA）缓解指中重度基线疾病活动减少，大不列颠群岛狼疮评估组（BILAG）指数中9个器官系统均无恶化，疾病活动整体评估得分增加不超过0.3分。

在第52周，Anifrolumab组的BICLA缓解率为47.8%，显著高于安慰剂组（31.5%）。在具有高干扰素基因特征的患者中，Anifrolumab组和安慰剂组的缓解率分别为48.0%和30.7%；而在具有低干扰素基因特征的患者中，两组的应答率分别为46.7%和35.5%。Anifrolumab组中糖皮质激素使用剂量和皮肤疾病严重程度均优于安慰剂组，但带状疱疹和支气管炎的发生率分别为7.2%和12.2%，且有1例患者死于肺炎。

总之，SLE患者每月进行一次Anifrolumab治疗，缓解率显著高于安慰剂组，但较易发生带状疱疹。

附：英文原文

Title: Trial of Anifrolumab in Active Systemic Lupus Erythematosus

Author: Eric F. Morand, M.B., B.S., Ph.D.,, Richard Furie, M.D.,, Yoshiya Tanaka, M.D., Ph.D.,, Ian N. Bruce, M.D.,, Anca D. Askanase, M.D., M.P.H.,, Christophe Richez, M.D., Ph.D.,, Sang-Cheol Bae, M.D., Ph.D., M.P.H.,, Philip Z. Brohawn, M.B.A.,, Lilia Pineda, M.D.,, Anna Berglind, Ph.D.,, and Raj Tummala, M.D.

Issue&Volume: 2019-12-18

Abstract: 

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.

DOI: 10.1056/NEJMoa1912196

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1912196