依洛尤单抗的疗效和安全性与 I 型干扰素基因特征和 SLE 患者的临床亚组有关：两项 III 期临床试验汇总数据的事后分析。
Anifrolumab efficacy and safety by type I interferon gene signature and clinical subgroups in patients with SLE: post hoc analysis of pooled data from two phase III trials.
机构信息
Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds, Leeds, UK.
NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
出版信息
Ann Rheum Dis. 2022 Jul;81(7):951-961. doi: 10.1136/annrheumdis-2021-221425. Epub 2022 Mar 25.
OBJECTIVES
To characterise the efficacy and safety of anifrolumab in patients with systemic lupus erythematosus (SLE) according to interferon gene signature (IFNGS), demographic and clinical subgroups.
METHODS
We performed post hoc analyses of pooled data from the 52-week phase III TULIP-1/TULIP-2 placebo-controlled trials of intravenous anifrolumab in moderate-to-severe SLE. Outcomes were assessed in predefined subgroups: IFNGS (high/low), age, sex, body mass index, race, geographic region, age of onset, glucocorticoid use, disease activity and serological markers.
RESULTS
In pooled data, patients received anifrolumab 300 mg (360/726) or placebo (366/726); 82.6% were IFNGS-high. IFNGS-high patients had greater baseline disease activity and were more likely to have abnormal serological markers versus IFNGS-low patients. In the total population, a greater proportion of patients treated with anifrolumab versus placebo achieved British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at week 52 (difference 16.6%; nominal p<0.001). BICLA response treatment differences with anifrolumab versus placebo were comparable to the total population across most predefined subgroups, including subgroups for baseline glucocorticoid dosage (<10/≥10 mg/day prednisone/equivalent) and for clinical disease activity (SLE Disease Activity Index 2000 score <10/≥10). Subgroups with larger treatment differences included IFNGS-high patients (18.2%), patients with abnormal baseline serological markers (23.1%) and Asian patients (29.2%). The safety profile of anifrolumab was similar across subgroups.
CONCLUSIONS
Overall, this study supports the consistent efficacy and safety of anifrolumab across a range of patients with moderate-to-severe SLE. In a few subgroups, small sample sizes limited conclusions from being drawn regarding the treatment benefit with anifrolumab.
TRIAL REGISTRATION NUMBER
NCT02446912, NCT02446899.
目的
根据干扰素基因特征（IFNGS）、人口统计学和临床亚组，描述阿尼鲁单抗治疗系统性红斑狼疮（SLE）患者的疗效和安全性。
方法
我们对静脉注射阿尼鲁单抗治疗中重度 SLE 的两项 52 周 III 期 TULIP-1/TULIP-2 安慰剂对照试验的汇总数据进行了事后分析。在预先设定的亚组中评估了结局：IFNGS（高/低）、年龄、性别、体重指数、种族、地理位置、发病年龄、糖皮质激素使用、疾病活动度和血清学标志物。
结果
在汇总数据中，患者接受阿尼鲁单抗 300mg（360/726）或安慰剂（366/726）治疗；82.6%的患者 IFNGS 高。IFNGS 高患者基线疾病活动度更高，且更可能存在异常血清学标志物，与 IFNGS 低患者相比。在总体人群中，与安慰剂相比，接受阿尼鲁单抗治疗的患者在第 52 周时达到英国狼疮评估组综合狼疮评估（BICLA）应答的比例更高（差异 16.6%；名义 p<0.001）。在大多数预先设定的亚组中，阿尼鲁单抗与安慰剂相比的 BICLA 应答治疗差异与总体人群相当，包括基线糖皮质激素剂量亚组（<10/≥10mg/天泼尼松/等效）和临床疾病活动度亚组（SLE 疾病活动度指数 2000 评分<10/≥10）。治疗差异较大的亚组包括 IFNGS 高患者（18.2%）、基线血清学标志物异常患者（23.1%）和亚洲患者（29.2%）。亚组间阿尼鲁单抗的安全性特征相似。
结论
总体而言，这项研究支持阿尼鲁单抗在一系列中重度 SLE 患者中具有一致的疗效和安全性。在一些亚组中，由于样本量较小，无法得出关于阿尼鲁单抗治疗获益的结论。
临床试验注册
NCT02446912，NCT02446899。
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