IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial.
IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial.
复制标题
DOI：
10.1136/ard.2008.092932
复制
发表时间：
2008-11
影响因子：
27.4
通讯作者：
Kremer J
中科院分区：
文献类型：
--
作者：
Emery P;Keystone E;Tony HP;Cantagrel A;van Vollenhoven R;Sanchez A;Alecock E;Lee J;Kremer J
III期RADIATE研究检查了tocilizumab（一种抗IL-6受体单克隆抗体）在肿瘤坏死因子（TNF）拮抗剂治疗难治性类风湿性关节炎（RA）患者中的疗效和安全性。499例对一种或多种TNF拮抗剂反应不充分的患者被随机分配接受8 mg/kg或4 mg/kg托珠单抗或安慰剂（对照）静脉注射，每4周一次，稳定的甲氨蝶呤持续24周。评估了ACR 20缓解、次要疗效和安全性终点。8 mg/kg、4 mg/kg和对照组分别有50.0%、30.4%和10.1%的患者在24周时达到ACR 20（托珠单抗组与对照组相比均小于p<0.001）。在第4周，与对照组相比，8 mg/kg托珠单抗组更多患者达到ACR 20（小于p = 0.001）。 无论最近抗TNF治疗失败或治疗失败的次数如何，患者都有反应。第24周时的DAS 28缓解率（DAS 28 <2.6）明显与剂量相关，8 mg/kg、4 mg/kg和对照组分别为30.1%、7.6%和1.6%（与对照组相比，8 mg/kg组小于p=0.001，4 mg/kg组小于p=0.053）。 大多数不良事件为轻度或中度，总发生率分别为84.0%、87.1%和80.6%。托珠单抗组中发生率较高的最常见不良事件为感染、胃肠道症状、皮疹和头痛。对照组严重不良事件的发生率（11.3%）高于8 mg/kg组（6.3%）和4 mg/kg组（7.4%）。托珠单抗联合甲氨蝶呤可有效地快速和持续改善TNF拮抗剂治疗效果不佳的RA患者的体征和症状，且安全性特征可控。NCT00106522。
The phase III RADIATE study examined the efficacy and safety of tocilizumab, an anti-IL-6 receptor monoclonal antibody in patients with rheumatoid arthritis (RA) refractory to tumour necrosis factor (TNF) antagonist therapy. 499 patients with inadequate response to one or more TNF antagonists were randomly assigned to receive 8 mg/kg or 4 mg/kg tocilizumab or placebo (control) intravenously every 4 weeks with stable methotrexate for 24 weeks. ACR20 responses, secondary efficacy and safety endpoints were assessed. ACR20 was achieved at 24 weeks by 50.0%, 30.4% and 10.1% of patients in the 8 mg/kg, 4 mg/kg and control groups, respectively (less than p<0.001 both tocilizumab groups versus control). At week 4 more patients achieved ACR20 in 8 mg/kg tocilizumab versus controls (less than p = 0.001). Patients responded regardless of most recently failed anti-TNF or the number of failed treatments. DAS28 remission (DAS28 <2.6) rates at week 24 were clearly dose related, being achieved by 30.1%, 7.6% and 1.6% of 8 mg/kg, 4 mg/kg and control groups (less than p = 0.001 for 8 mg/kg and p = 0.053 for 4 mg/kg versus control). Most adverse events were mild or moderate with overall incidences of 84.0%, 87.1% and 80.6%, respectively. The most common adverse events with higher incidence in tocilizumab groups were infections, gastrointestinal symptoms, rash and headache. The incidence of serious adverse events was higher in controls (11.3%) than in the 8 mg/kg (6.3%) and 4 mg/kg (7.4%) groups. Tocilizumab plus methotrexate is effective in achieving rapid and sustained improvements in signs and symptoms of RA in patients with inadequate response to TNF antagonists and has a manageable safety profile. NCT00106522.
登录
查看更多内容
类风湿关节炎与骨关节炎的心血管风险：急性期反应相关的胰岛素敏感性降低和高密度脂蛋白胆固醇以及类风湿关节炎中代谢综合征特征的聚类。
DOI：
10.1186/ar428
发表时间：
2002
期刊：
ARTHRITIS RESEARCH
影响因子：
--
作者：
Dessein, PH;Stanwix, AE;Joffe, BI
通讯作者：
Joffe, BI
影响因子：
27.4
作者：
Nishimoto, N;Kishimoto, T;Yoshizaki, K
通讯作者：
Yoshizaki, K
影响因子：
--
作者：
Hyrich, Kimme L.;Lunt, Mark;Silman, Alan J.
通讯作者：
Silman, Alan J.
影响因子：
--
作者：
Cohen, Stanley B.;Emery, Paul;Totoritis, Mark C.
通讯作者：
Totoritis, Mark C.
影响因子：
5.5
作者：
Bombardieri, S.;Ruiz, A. A.;Burmester, G. R.
通讯作者：
Burmester, G. R.