Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study.
Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study.
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DOI：
10.1136/ard.2008.105197
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发表时间：
2010-01
影响因子：
27.4
通讯作者：
Genovese MC
中科院分区：
文献类型：
--
作者：
Jones G;Sebba A;Gu J;Lowenstein MB;Calvo A;Gomez-Reino JJ;Siri DA;Tomsic M;Alecock E;Woodworth T;Genovese MC
抗白细胞介素（IL）6受体抗体托珠单抗可抑制IL 6的信号传导，IL 6是类风湿性关节炎（RA）发病机制中的关键细胞因子。通过AMBITION研究评价托珠单抗单药治疗与甲氨蝶呤相比在既往甲氨蝶呤/生物制剂治疗未失败的活动性RA患者中的疗效和安全性。这项为期24周的双盲、双模拟、平行组研究将673例患者随机分配至托珠单抗8 mg/kg每4周一次，或甲氨蝶呤，从7.5 mg/周开始，在8周内滴定至20 mg/周，或安慰剂8周，随后接受托珠单抗8 mg/kg。主要终点是在第24周达到美国流变学学会（ACR）20应答的患者比例。意向治疗分析表明，托珠单抗优于甲氨蝶呤治疗，在第24周时具有更高的ACR 20应答率（69.9 vs 52.5%; p<0.001）和28关节疾病活动评分（DAS 28）<2.6的比率（33.6 vs 12.1%）。从第12周开始，托珠单抗组的平均高敏C反应蛋白在正常范围内，而甲氨蝶呤组的水平仍升高。托珠单抗组严重不良事件的发生率为3.8%，甲氨蝶呤组为2.8%（p = 0.50），严重感染的发生率分别为1.4%和0.7%。 可逆性3级中性粒细胞减少（3.1% vs 0.4%）和总胆固醇升高> 240 mg/dl（13.2% vs 0.4%）的发生率较高，丙氨酸氨基转移酶升高>3×-<5×正常上限的发生率较低（1.0% vs 2.5%）。托珠单抗单药治疗优于甲氨蝶呤单药治疗，在既往接受甲氨蝶呤或生物制剂治疗未失败的患者中，可快速改善RA体征和症状，并具有有利的获益-风险。NCT00109408
The anti-interleukin (IL) 6 receptor antibody tocilizumab inhibits signalling of IL6, a key cytokine in rheumatoid arthritis (RA) pathogenesis. To evaluate through the AMBITION study the efficacy and safety of tocilizumab monotherapy versus methotrexate in patients with active RA for whom previous treatment with methotrexate/biological agents had not failed. This 24-week, double-blind, double-dummy, parallel-group study, randomised 673 patients to either tocilizumab 8 mg/kg every 4 weeks, or methotrexate, starting at 7.5 mg/week and titrated to 20 mg/week within 8 weeks, or placebo for 8 weeks followed by tocilizumab 8 mg/kg. The primary end point was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 24. The intention-to-treat analysis demonstrated that tocilizumab was better than methotrexate treatment with a higher ACR20 response (69.9 vs 52.5%; p<0.001), and 28-joint Disease Activity Score (DAS28) <2.6 rate (33.6 vs 12.1%) at week 24. Mean high-sensitivity C-reactive protein was within the normal range from week 12 with tocilizumab, whereas levels remained elevated with methotrexate. The incidence of serious adverse events with tocilizumab was 3.8% versus 2.8% with methotrexate (p = 0.50), and of serious infections, 1.4% versus 0.7%, respectively. There was a higher incidence of reversible grade 3 neutropenia (3.1% vs 0.4%) and increased total cholesterol ⩾240 mg/dl (13.2% vs 0.4%), and a lower incidence of alanine aminotransferase elevations >3×–<5× upper limit of normal (1.0% vs 2.5%), respectively. Tocilizumab monotherapy is better than methotrexate monotherapy, with rapid improvement in RA signs and symptoms, and a favourable benefit–risk, in patients for whom treatment with methotrexate or biological agents has not previously failed. NCT00109408
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影响因子：
--
作者：
Keystone, EC;Kavanaugh, AF;Chartash, EK
通讯作者：
Chartash, EK
影响因子：
5.5
作者：
Bernatsky, S.;Hudson, M.;Suissa, S.
通讯作者：
Suissa, S.
DOI：
10.1196/annals.1351.039
发表时间：
2006-01-01
期刊：
BASIC AND CLINICAL ASPECTS OF NEUROENDOCRINE IMMUNOLOGY IN RHEUMATIC DISEASES
影响因子：
--
作者：
Seriolo, Bruno;Paolino, Sabrina;Cutolo, Maurizio
通讯作者：
Cutolo, Maurizio
影响因子：
4.9
作者：
Kishimoto T
通讯作者：
Kishimoto T
影响因子：
168.9
作者：
Klareskog, L;van der Heijde, D;Sanda, M
通讯作者：
Sanda, M