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百时美施贵宝IIIb期新数据支持Orencia/MTX用于RA的一线治疗

来源:生物谷 2014-06-12 07:12

2014年6月12讯 /生物谷BIOON/ --百时美施贵宝(BMS)6月10日公布了类风湿关节炎(RA)药物Orencia(阿巴西普,abatacept)一项IIIb期临床试验AVERT的新数据。数据表明,与甲氨蝶呤(MTX)治疗组相比,Orencia+MTX治疗组在研究的第12个有显著更高比例的患者实现DAS28 CRP<2.6(定义为疾病缓解)(60.9% vs 45.2%)。此外,Boolean、CDAI、SDAI缓解分析数据以及更严厉的缓解评价措施,均证明Orencia+MTX组合疗法具有较高的缓解率。AVERT研究的数据,进一步支持了将Orencia+MTX组合疗法用于RA的一线生物治疗。

该项研究的数据将提交至本周举行的欧洲抗风湿联盟(EULAR)2014年年会。

AVERT是一项IIIb期阳性对照研究,在351例出现RA症状不到2年、抗CPP抗体阳性、DAS28 CRP>3.2、对氨甲喋呤和RA生物制剂初治的RA患者中开展。研究中,患者随机分配至3个组,接受12个月(每月1次)的治疗:1)Orencia 125mg皮下注射+甲氨蝶呤(MTX)组合疗法;2)Orencia 125mg皮下注射单药疗法;3)MTX单药疗法。

经12个月治疗后,取得DAS28 CRP<3.2(表明低疾病活动)的患者将继续进入12个月的停药期,停药期中所有药物均撤回。研究的共同主要终点是,研究的第12个月及研究的12个月和18个月中组合疗法治疗组相对于MTX单药治疗组实现DAS28 CRP<2.6(定义为疾病缓解)的患者比例。

关于Orencia(abatatacept,阿巴西普):

Orencia由百时美施贵宝开发,于2005年首次在美国上市。该药皮下注射制剂(SC)和静脉注射制剂(IV)均适用于经1种或多种缓解病情抗风湿药(OMARQ),如甲氨蝶呤、肿瘤坏死因子TNF)阻断剂洽疗但应答不足的中、重度活动性类风湿关节炎(RA)患者,可延缓疾病带来的结构性损伤进程.改善患者躯体功能减轻息者体征和症状。

Orencia为选择性T细胞共刺激调节剂,通过与抗原递呈细胞上的CDBO和CD86结合.抑制T细胞的激活。激活的T-细胞与类风湿性关节炎(RA)发病机制相关,且大量存在于RA患者的关节滑膜中。T-细胞完全激活至少需要得到来自抗原递呈细胞的2种信号传导,其中下细胞上的CD28与抗原递呈细胞上CD80或CD86的相互作用就是共刺激信号传导的关键步骤。

Orencia通过与抗原递星细胞上CD80和CD8结合进而阻断两者与下细胞上的CD28的相互作用.从而抑制T-细胞的激活。(生物谷Bioon.com)

英文原文:AVERT Trial Demonstrates High Rates of DAS-defined Remission with Orencia? (abatacept) in Combination with Methotrexate (MTX) in Adult Patients with Early Rheumatoid Arthritis (RA)

First line therapy with Orencia plus MTX resulted in 60.9% of patients with early RA achieving DAS-defined remission at month 12 of treatment

Additional analysis of Boolean, CDAI, and SDAI remission, more clinically stringent measures of remission, also showed high remission rates for Orencia plus MTX

AVERT provides further evidence supporting use of Orencia plus MTX as first line biologic therapy for RA

Tuesday, June 10, 2014 6:40 pm EDT

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) announced today its first release of new data from a Phase IIIb RA trial showing that the T-cell co-stimulation modulator, Orencia ? (abatacept), in combination with methotrexate (MTX) achieved significantly higher rates of DAS-defined (DAS28 CRP <2.6) remission at 12 months than treatment with standard of care agent MTX (60.9% vs. 45.2%, respectively), in biologic and MTX-na?ve patients with early active RA. The data are being presented this week at the 2014 annual meeting of the European League Against Rheumatism (EULAR).

In this trial, known as AVERT (Assessing Very Early Rheumatoid arthritis Treatment), a co-primary endpoint assessed maintenance of remission following the withdrawal of all RA drug therapy including Orencia, MTX and steroids. A small but statistically significantly higher number of patients treated with Orencia plus MTX, versus MTX alone, for 12 months maintained remission 6 months after all RA treatment was withdrawn.

Orencia was well tolerated in the study patients. In particular, serious adverse events, serious infection events and discontinuation due to serious adverse events were comparable to patients treated with MTX.

“Remission of both clinical symptoms and radiographic joint damage is an important and achievable goal in the management of rheumatoid arthritis, particularly in the early disease phase,” said Paul Emery, M.D., Arthritis Research UK Professor of Rheumatology and Head of the Academic Division of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, United Kingdom. “Data from the AVERT trial show that patients taking a combination of Orencia plus methotrexate achieved higher rates of remission than treating them with methotrexate alone. Interestingly, this benefit was maintained in some patients even after all RA treatment had been withdrawn.”

“These data demonstrating higher remission rates and a similar safety profile for Orencia plus methotrexate versus methotrexate alone, in conjunction with insights from the withdrawal phase of the study, support the use of Orencia as a first line biologic therapy for patients with RA,” said Michael Giordano, senior vice president, head of development, Oncology and Immunology, Bristol-Myers Squibb.

Data from the AVERT Trial

AVERT is a Phase IIIb, active-controlled study including 351 adult patients with symptoms of RA for less than two years, positive for anti-CCP antibodies, DAS28 CRP >3.2 and na?ve to treatment with methotrexate and biologic therapies for RA. The patients were randomly assigned to 12 months of weekly treatment in one of three groups: Orencia 125 mg subcutaneous plus MTX; Orencia 125 mg subcutaneous alone; or MTX alone. Participants who had a DAS28 CRP <3.2 (indicating low disease activity) after the 12-month treatment phase were able to continue in a withdrawal period up to 12 months, where all RA treatment including Orencia, MTX and steroids were withdrawn. The co-primary endpoints compared the proportion of patients with DAS28 CRP <2.6 (defined as disease remission in the trial) at month 12 and both months 12 and 18 for combination therapy versus MTX alone.

At 12 months, significantly more patients on Orencia combination therapy achieved DAS28-defined remission (60.9%, Orencia plus MTX; 45.2%, MTX alone). Similar results at 12 months were seen with more stringent measures of efficacy including Boolean remission (37.0%, Orencia plus MTX; 22.4%, MTX alone), CDAI remission (42%, Orencia plus MTX; 27.6% MTX alone), and SDAI remission (42%, Orencia plus MTX; 25% MTX alone).

Greater benefits on MRI endpoints were also observed with combination therapy vs. MTX alone, including improvements in synovitis and osteitis, and less progression of joint erosions. At 12 months the adjusted mean change from baseline in total synovitis score was -2.35 for Orencia plus MTX vs. -0.68 for MTX alone; the adjusted mean change from baseline in total osteitis score was -2.58 for Orencia plus MTX vs. -0.68 for MTX alone; and the adjusted mean change from baseline in total erosion score was 0.19 for Orencia plus MTX vs. 1.52 for MTX alone.

A monotherapy arm of the AVERT trial resulted in a similar number of patients treated with Orencia in the absence of MTX achieving DAS-defined remission as compared to MTX-treated patients at 12 months (42.5% versus 45.2%, respectively). While the rates were similar at 12 months, Orencia monotherapy resulted in trends towards higher DAS-defined remission rates than MTX monotherapy at most earlier time points.

After 12 months, following rapid treatment withdrawal of all RA therapy including Orencia, MTX and steroids in patients achieving DAS <3.2, 79.4% of patients went back on therapy because of worsening RA symptoms. However, a small and statistically significantly higher number of patients treated with Orencia combination therapy were able to maintain drug-free remission versus MTX alone up to Month 18 (14.8% versus 7.8%, respectively), 6 months after drug withdrawal. Drug-free remission rates were 12.4% for Orencia monotherapy.

Orencia, as monotherapy or in combination with MTX, in early RA patients had a comparable safety profile to MTX. Over 12 months of treatment, 6.7%, 12.1%, and 7.8% of patients on Orencia plus MTX, Orencia alone, and MTX alone, respectively, experienced a serious adverse event and 1.7%, 4.3% and 2.6% led to discontinuation. Serious infections were observed in 0.8% of patients in the combination arm and 3.4% in the Orencia monotherapy arm. None of the patients in the MTX alone arm experienced a serious infection.

About Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic, chronic, autoimmune disease characterized by inflammation in the lining of joints (or synovium), causing joint damage with chronic pain, stiffness, swelling and fatigue. RA causes limited range of motion and decreased joint function. The condition is more common in women than in men, who account for 75% of patients diagnosed with RA.

About ORENCIA? (abatacept)

ORENCIA SC and IV is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. ORENCIA may be used as monotherapy or concomitantly with disease-modifying antirheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists.

ORENCIA IV is indicated for reducing signs and symptoms in pediatric patients 6 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis. ORENCIA IV may be used as monotherapy or concomitantly with methotrexate (MTX). ORENCIA SC has not been studied in pediatric patients.

ORENCIA should not be administered concomitantly with TNF antagonists.

ORENCIA is not recommended for use concomitantly with other biologic rheumatoid arthritis (RA) therapy, such as anakinra.

ORENCIA is intended for use under the guidance of a physician or healthcare practitioner.

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