Anifrolumab可有效治療活動性系統性紅斑狼瘡
作者：
小柯機器人發布時間：2019/12/20 14:37:19
澳大利亞莫納什醫學中心Eric F. Morand小組在研究中取得進展。他們進行了Anifrolumab治療活動性系統性紅斑狼瘡的臨床研究。相關論文發表在2019年12月18日的《新英格蘭醫學雜誌》上。
Anifrolumab是一種抗I型幹擾素受體亞單位1的人源化單克隆抗體，用於治療系統性紅斑狼瘡（SLE），在此前的臨床3期試驗中對主要終點無明顯效果。因此，研究組將次要終點改為主要終點進行研究。
研究組招募了362例SLE患者，按1：1隨機分組，其中180例接受Anifrolumab治療，182例接受安慰劑治療，每4周靜脈注射一次，為期48周。綜合狼瘡評估（BICLA）緩解指中重度基線疾病活動減少，大不列顛群島狼瘡評估組（BILAG）指數中9個器官系統均無惡化，疾病活動整體評估得分增加不超過0.3分。
在第52周，Anifrolumab組的BICLA緩解率為47.8%，顯著高於安慰劑組（31.5%）。在具有高干擾素基因特徵的患者中，Anifrolumab組和安慰劑組的緩解率分別為48.0%和30.7%；而在具有低幹擾素基因特徵的患者中，兩組的應答率分別為46.7%和35.5%。Anifrolumab組中糖皮質激素使用劑量和皮膚疾病嚴重程度均優於安慰劑組，但帶狀皰疹和支氣管炎的發生率分別為7.2%和12.2%，且有1例患者死於肺炎。
總之，SLE患者每月進行一次Anifrolumab治療，緩解率顯著高於安慰劑組，但較易發生帶狀皰疹。
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