University of Oklahoma Health Sciences Center, Oklahoma City.
Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California, Los Angeles.
Arthritis Rheumatol. 2018 Feb;70(2):266-276. doi: 10.1002/art.40360.
To evaluate the efficacy and safety of atacicept, an antagonist of B lymphocyte stimulator/APRIL-mediated B cell activation, in patients with systemic lupus erythematosus (SLE).
ADDRESS II is a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm, phase IIb study evaluating the safety and efficacy of atacicept in patients with SLE (ClinicalTrials.gov identifier NCT01972568). Patients with active, autoantibody-positive SLE receiving standard therapy were randomized (1:1:1) to receive atacicept (75 mg or 150 mg) or placebo for 24 weeks. The primary end point was the SLE responder index 4 (SRI-4) at week 24.
The intent-to-treat (ITT) population included 306 patients. There was a trend toward an improved SRI-4 response rate with atacicept 75 mg (57.8%; adjusted odds ratio [OR] 1.78, P = 0.045) and 150 mg (53.8%; adjusted OR 1.56, P = 0.121) at week 24 as compared with placebo (44.0%) (primary analysis; using the screening visit as baseline). In a prespecified sensitivity analysis using study day 1 as baseline, a significantly larger proportion of patients receiving atacicept 75 mg and 150 mg achieved an SRI-4 response at week 24 compared with placebo. In predefined subpopulations with high levels of disease activity (HDA) at baseline, serologically active disease, or both, statistically significant improvements in the SRI-4 and SRI-6 response rates were seen with atacicept versus placebo. A severe risk of disease flare was reduced with atacicept therapy in both the ITT and the HDA populations. The risks of serious adverse events and serious or severe infection were not increased with atacicept as compared with placebo.
Atacicept treatment showed evidence of efficacy in SLE, particularly in HDA and serologically active patients. Reductions in disease activity and severe flare were observed with atacicept treatment, with an acceptable safety profile.
评估 B 淋巴细胞刺激因子/ APRIL 介导的 B 细胞激活拮抗剂 atacicept 在系统性红斑狼疮（SLE）患者中的疗效和安全性。
ADDRESS II 是一项为期 24 周、多中心、随机、双盲、安慰剂对照、平行臂、IIb 期研究，评估 atacicept 在 SLE 患者中的安全性和疗效（ClinicalTrials.gov 标识符 NCT01972568）。接受标准治疗的活动性、自身抗体阳性的 SLE 患者随机（1:1:1）接受 atacicept（75mg 或 150mg）或安慰剂治疗 24 周。主要终点是第 24 周的 SLE 应答指数 4（SRI-4）。
意向治疗（ITT）人群包括 306 例患者。与安慰剂组（44.0%）相比，atacicept 75mg（57.8%；调整后的优势比[OR] 1.78，P = 0.045）和 150mg（53.8%；调整后的 OR 1.56，P = 0.121）组在第 24 周的 SRI-4 应答率呈改善趋势（主要分析；以筛查访视为基线）。在以研究日 1 为基线的预设敏感性分析中，接受 atacicept 75mg 和 150mg 治疗的患者在第 24 周达到 SRI-4 应答的比例显著高于安慰剂组。在基线疾病活动水平较高（HDA）、血清学活动疾病或两者并存的预设亚组中，与安慰剂相比，atacicept 治疗在 SRI-4 和 SRI-6 应答率方面均有显著改善。在 ITT 和 HDA 人群中，atacicept 治疗可降低严重疾病发作的风险。与安慰剂相比，atacicept 治疗并未增加严重不良事件和严重或严重感染的风险。
atacicept 治疗在 SLE 中显示出疗效证据，特别是在 HDA 和血清学活跃患者中。与安慰剂相比，观察到 atacicept 治疗可降低疾病活动度和严重发作，具有可接受的安全性。
