OBJECTIVE To evaluate the efficacy and safety of ustekinumab through 1 year in a phase II trial in patients with systemic lupus erythematosus (SLE). METHODS Eligible patients were diagnosed as having clinically active SLE (based on Systemic Lupus International Collaborating Clinics criteria), despite standard background therapy. Active disease was defined by an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 as well as having ≥1 British Isles Lupus Assessment Group (BILAG) A organ domain score and/or ≥2 BILAG B organ domain scores present at screening. Patients (n = 102) were randomized (3:2) to receive either ustekinumab (~6 mg/kg of single intravenous infusion at week 0, then 90-mg subcutaneous injections every 8 weeks beginning at week 8) or a matching placebo added to standard therapy. At week 24, the placebo group crossed over to receive a subcutaneous 90-mg dose of ustekinumab every 8 weeks, and the original ustekinumab group continued to receive therapy through week 40. Maintenance of efficacy was assessed using the SLEDAI-2K, the SLE Responder Index 4 (SRI-4), physician global assessment, and mucocutaneous and joint disease measures in a modified intent-to-treat population. RESULTS SRI-4 response rates were significantly greater in the ustekinumab group (62%) versus the placebo group (33%) in the week 24 primary end point analysis (P = 0.006) and were maintained at week 48 (63.3%) in the ustekinumab group. In the ustekinumab group, response rates across other disease measures were also maintained through week 48. Among patients in the placebo group who crossed over to ustekinumab treatment (n = 33), increased response rates across efficacy measures were noted. Among all ustekinumab-treated patients, 81.7% had ≥1 adverse event (AE), and 15.1% had ≥1 serious AE through week 56. No deaths, malignancies, opportunistic infections, or tuberculosis cases were observed. CONCLUSION Ustekinumab provided sustained clinical benefit in patients with SLE through 1 year, with a safety profile consistent with other indications.

中文翻译：

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在患有活动性系统性红斑狼疮的患者进行的II期多中心，前瞻性，随机，双盲，安慰剂对照的交叉试验II期中，维持Ustekinumab的疗效和安全性至一年。

目的在一项II期临床试验中评估ustekinumab对系统性红斑狼疮（SLE）患者的疗效和安全性。方法尽管进行了标准的背景治疗，但符合条件的患者仍被诊断为具有临床活动性SLE（基于系统性狼疮国际合作诊所标准）。活动性疾病的定义是，SLE疾病活动指数2000（SLEDAI-2K）得分≥6，并且具有不小于1的不列颠群岛狼疮评估组（BILAG）的器官域评分和/或≥2的BILAG B器官域评分出现在筛选。患者（n = 102）被随机分配（3：2）接受ustekinumab（从第0周开始约6 mg / kg的单次静脉输注，然后从第8周开始每8周皮下注射90 mg）到标准疗法。在第24周，安慰剂组每8周进行一次皮下注射90毫克剂量的ustekinumab，最初的ustekinumab组继续接受治疗直至第40周。使用SLEDAI-2K，SLE应答指数4（SRI）评估疗效-4），医师总体评估以及经改良的意向性治疗人群的皮肤粘膜和关节疾病措施。结果在第24周的主要终点分析中，ustekinumab组的SRI-4应答率（62％）显着高于安慰剂组（33％）（P = 0.006），并在第48周保持在（48％）（63.3％）。 ustekinumab组。在ustekinumab组中，贯穿第48周，其他疾病措施的缓解率也保持不变。在安慰剂组中，转用ustekinumab治疗的患者（n = 33），注意到所有功效指标的反应率都有所提高。在所有接受ustekinumab治疗的患者中，到第56周，有≥1不良事件（AE），有15.1％的≥1严重AE。未观察到死亡，恶性肿瘤，机会性感染或结核病病例。结论Ustekinumab可为SLE患者提供持续1年的临床益处，其安全性与其他适应症一致。