van Vollenhoven R F, Kinnman N, Vincent E, Wax S, Bathon J
Karolinska Institute, Stockholm, Sweden.
Arthritis Rheum. 2011 Jul;63(7):1782-92. doi: 10.1002/art.30372.
To assess the efficacy, safety, and biologic activity of atacicept in tumor necrosis factor antagonist-naive patients with rheumatoid arthritis (RA) in whom the response to methotrexate treatment was inadequate.
In this phase II study, patients with active RA (n = 311) were randomized 1:1:1:1 to receive placebo, atacicept 150 mg weekly with or without a 4-week loading period (twice-weekly dosing), or open-label adalimumab 40 mg every other week, for 25 weeks. The primary end point was 20% improvement in disease severity according to the American College of Rheumatology criteria, assessed using the C-reactive protein level (ACR20-CRP), at week 26. Secondary end points included additional assessments of efficacy, biologic activity, and safety.
The proportion of patients meeting the primary end point (ACR20-CRP response) did not differ significantly in the atacicept groups and the placebo group (46% in the placebo group, 45% in the atacicept loading group, and 58% in the atacicept nonloading group). In contrast, an ACR20-CRP response was observed in 71% of patients in the adalimumab group (P < 0.001 versus placebo). ACR50-CRP response rates were significantly higher in all active-treatment groups compared with placebo, but ACR70-CRP response rates were superior only in the adalimumab group. Atacicept treatment reduced the levels of serum IgG, IgA, and IgM rheumatoid factor and the levels of circulating mature B cells and plasma cells. The effects of treatment were similar with and without loading. Immunoglobulin levels returned toward baseline values during the treatment-free followup period (week 38). The most frequent adverse events associated with atacicept represented common illnesses. No serious infections occurred among patients treated with atacicept.
The primary end point (ACR20-CRP response) was not met despite significant biologic effects of atacicept that were consistent with its proposed mechanism of action. Modest effects of atacicept were seen for some secondary efficacy end points. Treatment with atacicept raised no new safety concerns.
评估阿他西普对甲氨蝶呤治疗反应不足的初治类风湿关节炎（RA）患者的疗效、安全性及生物学活性。
在这项II期研究中，311例活动期RA患者按1:1:1:1随机分组，分别接受安慰剂、每周150 mg阿他西普（有或无4周负荷期，即每周给药两次），或开放标签的每两周40 mg阿达木单抗治疗，为期25周。主要终点为第26周时根据美国风湿病学会标准，使用C反应蛋白水平评估的疾病严重程度改善20%（ACR20-CRP）。次要终点包括对疗效、生物学活性和安全性的额外评估。
阿他西普组和安慰剂组达到主要终点（ACR20-CRP反应）的患者比例无显著差异（安慰剂组为46%，阿他西普负荷组为45%，阿他西普非负荷组为58%）。相比之下，阿达木单抗组71%的患者出现ACR20-CRP反应（与安慰剂组相比，P < 0.001）。与安慰剂组相比，所有活性治疗组的ACR50-CRP反应率均显著更高，但ACR70-CRP反应率仅在阿达木单抗组更高。阿他西普治疗降低了血清IgG、IgA和IgM类风湿因子水平以及循环成熟B细胞和浆细胞水平。有无负荷期的治疗效果相似。在无治疗随访期（第38周）免疫球蛋白水平恢复至基线值。与阿他西普相关的最常见不良事件为常见疾病。接受阿他西普治疗的患者未发生严重感染。
尽管阿他西普具有与其作用机制相符的显著生物学效应，但未达到主要终点（ACR20-CRP反应）。阿他西普对一些次要疗效终点有一定作用。阿他西普治疗未引发新的安全问题。
