Efficacy and Safety of Obinutuzumab in Active Systemic Lupus Erythematosus.

Its efficacy and safety in patients with active systemic lupus erythematosus (SLE) are yet to be determined.

其在活动性系统性红斑狼疮（SLE）患者中的疗效和安全性尚未确定。

Methods

We conducted a phase 3, multicenter, double-blind, placebo-controlledtrial involving adults with active SLE but without proliferative or membranous lupus nephritis who were receiving standard therapy.

我们开展了一项III期、多中心、双盲、安慰剂对照试验，对象为正在接受标准治疗的活动性系统性红斑狼疮(SLE)成人患者，但不包括增殖性或膜性狼疮性肾炎患者。

Patients were randomly assigned in a 1:1 ratio to receive obinutuzumab (1000 mg) or placebo on day 1 and weeks 2, 24, and 26.

患者按1:1的比例随机分配，分别在第1天以及第2周、第24周和第26周接受obinutuzumab（1000毫克）或安慰剂。

In the prespecified analysis, the primary end point at week 52 was a response on the SLE Responder Index 4 (SRI-4), defined by a reduction from baseline of at least 4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, no worsening of disease as assessed by the British Isles Lupus Assessment Group (BILAG) 2004 index and Physician's Global Assessment, and no intercurrent events (i.e., major concomitant-therapy violation, receipt of rescue medication, or early discontinuation of trial participation due to death, lack of efficacy, or adverse events).

在预先设定的分析中，主要终点是在第52周时系统性红斑狼疮反应指数4（SRI-4）的反应，该指数定义为从基线开始系统性红斑狼疮疾病活动指数2000（SLEDAI-2K）评分至少减少4分，通过英国群岛狼疮评估小组（BILAG）2004指数和医师总体评估没有疾病恶化，并且没有并发事件（即重大合并治疗违规，接受救援药物，或因死亡、缺乏疗效或不良事件而提前中断试验参与）。

Results

Of 303 patients who underwent randomization, 151 were assigned to receive obinutuzumab and 152 to receive placebo.

在随机化的303名患者中，有151名被分配接受奥布珠单抗治疗，另外152名被分配接受安慰剂。

At week 52, an SRI-4 response was observed in 76.7% of the patients in the obinutuzumab group and in 53.5% of those in the placebo group (adjusted difference, 23.1 percentage points; 95% confidence interval[CI], 12.5 to 33.6; P<0.001).

在第52周时，观察到76.7%的患者在奥布珠单抗组和53.5%的患者在安慰剂组中出现了SRI-4反应（调整后的差异为23.1个百分点；95%置信区间[CI]，12.5至33.6；P<0.001）。

In an additional analysis whereby nonfatal intercurrent events did not affect response status, the respective percentages were 85.4% and 68.5% (adjusted difference, 16.8 percentage points; 95% CI, 7.1 to 26.4).

在一项额外的分析中，非致命的并发事件不影响反应状态，相应的百分比分别为85.4%和68.5%（调整后的差异为16.8个百分点；95%置信区间[CI]，7.1至26.4）。

Obinutuzumab was superior to placebo with respect to all key secondary end points: BILAG-based Composite Lupus Assessment response, sustained reduction in glucocorticoid dose, sustained SRI-4 response, SRI-6 response, and time to first BILAG-defined flare.

奥布替珠单抗在所有关键次要终点方面均优于安慰剂：基于BILAG的复合红斑狼疮评估反应、糖皮质激素剂量的持续减少、持续的SRI-4反应、SRI-6反应以及首次BILAG定义的发作时间。

Adverse events were reported in 88.7% of the patients in the obinutuzumab group and in 81.5% of those in the placebo group, and serious adverse events in 15.9% and 11.9%, respectively.

在奥布替珠单抗组中有88.7%的患者报告了不良事件，在安慰剂组中有81.5%的患者报告了不良事件，严重不良事件分别为15.9%和11.9%。

One patient in the obinutuzumab group and 3 in the placebo group died during the double-blindperiod.

在双盲期间，奥布珠单抗组有1名患者死亡，而安慰剂组有3名患者死亡。

Conclusions

Among adults with active SLE, treatment with obinutuzumab was superior to placebo with respect to the primary and all key secondary end points.

在活动性系统性红斑狼疮成人患者中，奥布珠单抗治疗在主要和所有关键次要终点方面均优于安慰剂。

(Funded by F.

(由F.资助

Hoffmann-La Roche; ALLEGORY ClinicalTrials.gov number, NCT04963296.).

罗氏资助; ALLEGORY临床试验注册号, NCT04963296。)