英文药名: Orencia (Abatacept)

中文药名: 阿巴西普注射剂

品牌药生产厂家: Bristol Meyers Squibb

药品介绍

商品名：Orentia
通用名：阿巴西普abatacept
开发与上市厂商：本品由百时美施贵宝公司(Bristol-MyersSquibb)开发，2005年3月在美国首次上市，同年在加拿大上市。

适应症：
本品适用于经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成年患者。本品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。

药理：
本品为选择性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，且大里存在于RA患者的关节滑膜中。T-细胞完全瀚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。本品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。
临床研究显示，本品剂最达到约IOmglkg时，血浆中可溶性IL-2受体(slL一2R)，IL一6、类风湿因子(RF)、C反应蛋白(CRP).间质金属蛋白酶-3(MMP-3y及丁NF一a的水平均出现下降。但上述生物反应标记物水平的变化与本品治疗RA的作用关联尚待明确。

临床评价
5项随机双盲安慰剂对照的临床研究对本品疗效和安全性进行了评价.入选息者为18岁及以上经美国风湿病学会(ACR)标准确诊的活动性RA患者。研究中患者静脉输注本品或安慰剂』起始时及第2和4周各给药1次此后每R周1次。
一项针对122例经至少一种非生物制品类DMARD药物治疗或依那西普(etanercept)治疗无效的活动性RA一项针对122例经至少一种非生物制品类DMARD药物治疗或依那西普tetanercepty治疗无效的活动性RA患者的研究中患者随机接受本品(0.5、2或9Omg/kg)或安慰剂治疗为期8周。另3项研究评价了本品的疗效和安全性.第2和3项纳入患者为对甲氨蝶呤治疗应答不足并继续接受维持剂量甲氨蝶吟治疗者第4项研究纳入患者为对TNF阻断剂应答不足并随机停用TNF阻断剂的患者，而其他DMARD药物则可继续使用.这3项研究均为期12个月口第5项研究纳入的患者为虽接受现有OMARD药物治疗但仍须其他疗法介入的活动性RA患者.其首要目的也是评价本品的安全性.该项研究为期B个月.

不良反应
本品最严重不良反应为严重感染和恶性肿瘤。最常见的不良反应(治疗组发生率》10%)为头痛、上呼吸道感染‘鼻咽炎和恶心。
需要临床干预(中断或停用本品)的最常见不良反应为感染.其中需要中断治疗的最常见感染为上呼吸道感染(1.0%).支气管炎{0.7%]和带状疙疹(0.7%).需要停药的最常见感染为肺炎(0.2%》、局部感染(0.2%)和支气管炎(0.1%)。

注意事项
本品不宜用于对其活性成分及其他成分过敏者安慰剂对照临床研究显示接受本品十下NF阻断剂联合治疗的患者感染发生率高于仅接受下N「阻断剂者，前者的感染和严重感染发生率分别为63%和4.4%,后者则分别为43%和0.8%。但临床研究并未证明两者联用对疗效提高有重要作用.所以目前不推荐本品与TNF阻断剂联用。当患者由下NF阻断剂疗法转用本品治疗时.应监测患者的感染体征。

用法用量
本品需在有条件下的医疗机构静脉输注给药。本品剂量达54mg/kg时.未见表观毒性作用。对于过量用药者.建议监测其不良反应体征和症状.并给予适当的对症疗法。本品用药剂量详见表，应以30分钟静脉输注方式给药.

制剂
本品为一次性使用玻璃小瓶装低压冻干粉制剂.每瓶含本品250mg.美国规定使用时.本品须溶解于14mL美国药典(USP)标准的无菌注射用水中.并且只能使用随瓶配备的无硅酮一次性使用注射器及，8-21号计量注射针。

关于类风湿性关节炎

类风湿性关节炎是慢性系统性自身免疫性疾病。其特点为骨连接（或滑膜）炎症，导致骨连接病变，伴随慢性疼痛、僵硬、肿胀。类风湿关节炎会由于骨关节变形而引起活动障碍和功能减退。此病在女性中更为常见，占全部患者的75％。

The FDA has approved a subcutaneous (SC) formulation of Bristol-Myers Squibb’s Orencia (abatacept) for the treatment of moderately to severely active rheumatoid arthritis (RA) in adults, either as monotherapy or in combination with disease-modifying antirheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists. 1

The intravenous (IV) formulation of Orencia was approved in 2005 for the same indication as the SC formulation, along with an additional indication as monotherapy or in conjunction with methotrexate for moderately to severely active polyarticular juvenile idiopathic arthritis in patients 6 years and older. 1,2 Both indications carry the limitation that Orencia should not be administered with TNF antagonists. 1 In the United States, it is estimated that RA affects 1.3 million adults and 300,000 children. 3 Approximately 75% of patients diagnosed with the condition are women. 2

PHARAMACOLOGY AND PHARMACOKINETICS

Orencia is a selective T cell costimulation modulator. Neither age nor gender affected the pharmacokinetics of Orencia. No formal studies have evaluated the impact of either renal or hepatic impairment on the pharmacokinetics of Orencia. 1

DOSING AND ADMINISTRATION 

Orencia IV should be dosed by patient weight as follows:

•Less than 60 kg: 500 mg
• 60 to 100 kg: 750 mg
• More than 100 kg: 1000 mg

After the initial dose, subsequent IV doses should be given at 2 and 4 weeks, and then every 4 weeks thereafter. The solution should be administered as a 30-minute infusion and should be prepared with a silicone-free disposable syringe. Only sterile water should be used for reconstitution of the powder and the final product must be administered with a filter. Orencia SC should be given after 1 IV loading dose of Orencia per the weightbased guidelines. The first 125-mg SC dose should be given within a day of the IV dose, followed by weekly SC doses of 125 mg. Patients unable to receive the IV infusion can initiate SC treatment without the IV loading dose.

Patients aged 6 to 17 years with juvenile idiopathic arthritis should receive a 10-mg/kg/dose as an IV infusion. Patients weighing 75 kg or more should be dosed by the adult dosing guidelines, with a maximum dose of 1000 mg. After the initial dose, subsequent IV doses should be given at 2 and 4 weeks, and then every 4 weeks thereafter. Each infusion should be given over 30 minutes. Unused solution should be discarded immediately. 1

CLINICAL TRIALS

Orencia SC was evaluated in a randomized, double-blind, double-dummy, multinational trial to determine the noninferiority of Orencia SC plus methotrexate (MTX) to Orencia IV plus MTX. The trial consisted of 1457 patients with moderate-to-severe RA; most study participants had not responded adequately to MTX alone. The SC arm received a single IV loading dose of Orencia, followed by Orencia 125 mg SC weekly plus MTX. The IV arm received MTX plus Orencia IV per the weight-based dosing guidelines on day 1, 15, 29, and every 4 weeks thereafter. At the end of the 6-month study, each arm experienced comparable response rates. 2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

There are no contraindications to treatment with Orencia.

Orencia should not be given to patients concomitantly using a TNF antagonist, as this combination may increase the risk of serious infections. Hypersensitivity, anaphylaxis, and anaphylactoid reactions may occur during treatment with Orencia. Patients who have a history of recurrent infections or underlying conditions predisposing them to infections may experience more infections while using Orencia. Orencia should be discontinued if a serious infection occurs. Patients should be screened for latent tuberculosis (TB) infections prior to initiating treatment with Orencia; patients who test positive should be treated for TB before beginning Orencia.

Live vaccines should not be given during treatment with Orencia or within 3 months of discontinuation of Orencia. Pediatric patients should be brought up-to-date on all vaccinations prior to treatment with Orencia. Orencia may blunt the effectiveness of some immunizations. Patients with chronic obstructive pulmonary disease may develop more frequent respiratory adverse effects. Orencia is Pregnancy Category C and should not be used while breast-feeding.

The most common adverse effects (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. 1

References
1. Orencia complete prescribing information. http://packageinserts.bms.com/pi/pi_orencia.pdf. Accessed December 2011.
 
2. U.S. Food and Drug Administration approves subcutaneous formulation of ORENCIA (abatacept), a proven non-anti-TNF biologic for adults with moderate to severe rheumatoid arthritis. www.bms.com/news/press_releases/pages/default.aspx. Accessed December 2011.
 
3. The Arthritis Foundation. www.arthritis.org/who-gets-rheumatoid-arthritis.php. Accessed December 2011.