Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus: Results From Two Phase III Randomized, Double-Blind, Placebo-Controlled Trials.
Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus: Results From Two Phase III Randomized, Double-Blind, Placebo-Controlled Trials.
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DOI：
10.1002/art.39856
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发表时间：
2017-02
期刊：
影响因子：
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通讯作者：
EMBODY Investigator Group
中科院分区：
文献类型：
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作者：
Clowse ME;Wallace DJ;Furie RA;Petri MA;Pike MC;Leszczyński P;Neuwelt CM;Hobbs K;Keiserman M;Duca L;Kalunian KC;Galateanu C;Bongardt S;Stach C;Beaudot C;Kilgallen B;Gordon C;EMBODY Investigator Group
Epratuzumab是一种针对CD22的单抗，它在不大幅减少B细胞数量的情况下调节B细胞信号。本研究的目的是报道2个III期多中心随机、双盲、安慰剂对照试验的结果，即Embit 1和Emide 2试验，评估epratuzumab对中到重度活动期系统性红斑狼疮(SLE)患者的疗效和安全性。患者符合美国风湿病学会修订的系统性红斑狼疮分类标准≥4，抗核抗体和/或抗双链抗体阳性，系统性红斑狼疮疾病活动指数≥6(疾病活动增加)，≥1身体系统A级(严重疾病活动)或≥2身体系统B级(中度疾病活动)，并接受标准治疗，包括糖皮质激素强制治疗(5-60毫克/天)。BILAG-2004肾和中枢神经系统领域的A级评分被排除。患者以1：1：1的比例随机接受安慰剂、epratuzumab每周600 mg或epratuzumab每隔一周1200 mg，在每个12周给药周期的前4周进行输液，共4个周期。所有3个治疗组的患者也继续进行他们的标准治疗。主要终点是根据基于BILAG的综合狼疮评估(BICLA)定义的第48周的应答率，要求改善BILAG-2004评分，BILAG-2004评分、SLEDAI-2K评分或医生对疾病活动的全球评估没有恶化，同时没有不允许的药物变化。停止研究用药的患者被归类为无反应。在epratuzumab的体现1和体现2试验中，分别有793例和791例患者随机接受研究用药，分别有786例(99.1%)和788例(99.6%)，528例(66.6%)和533例(67.4%)完成研究。两组之间的主要终点在统计学上没有显著差异，48周的BICLA应答率在epratuzumab组和安慰剂组之间相似(应答率从33.5%到39.8%不等)。没有发现新的安全信号。在中度或重度活动期系统性红斑狼疮患者中，使用epratuzumab + 标准疗法的应答率没有比安慰剂 + 标准疗法组的改善。
Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double‐blind, placebo‐controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE). Patients met ≥4 of the American College of Rheumatology revised classification criteria for SLE, were positive for antinuclear antibodies and/or anti–double‐stranded DNA antibodies, had an SLE Disease Activity Index 2000 (SLEDAI‐2K) score of ≥6 (increased disease activity), had British Isles Lupus Assessment Group 2004 index (BILAG‐2004) scores of grade A (severe disease activity) in ≥1 body system or grade B (moderate disease activity) in ≥2 body systems (in the mucocutaneous, musculoskeletal, or cardiorespiratory domains), and were receiving standard therapy, including mandatory treatment with corticosteroids (5–60 mg/day). BILAG‐2004 grade A scores in the renal and central nervous system domains were excluded. Patients were randomized 1:1:1 to receive either placebo, epratuzumab 600 mg every week, or epratuzumab 1,200 mg every other week, with infusions delivered for the first 4 weeks of each 12‐week dosing cycle, for 4 cycles. Patients across all 3 treatment groups also continued with their standard therapy. The primary end point was the response rate at week 48 according to the BILAG‐based Combined Lupus Assessment (BICLA) definition, requiring improvement in the BILAG‐2004 score, no worsening in the BILAG‐2004 score, SLEDAI‐2K score, or physician's global assessment of disease activity, and no disallowed changes in concomitant medications. Patients who discontinued the study medication were classified as nonresponders. In the EMBODY 1 and EMBODY 2 trials of epratuzumab, 793 patients and 791 patients, respectively, were randomized, 786 (99.1%) and 788 (99.6%), respectively, received study medication, and 528 (66.6%) and 533 (67.4%), respectively, completed the study. There was no statistically significant difference in the primary end point between the groups, with the week 48 BICLA response rates being similar between the epratuzumab groups and the placebo group (response rates ranging from 33.5% to 39.8%). No new safety signals were identified. In patients with moderate or severely active SLE, treatment with epratuzumab + standard therapy did not result in improvements in response rates over that observed in the placebo + standard therapy group.