ORENCIA® (abatacept) Important Safety Information Indication and Usage ORENCIA® (abatacept) is a prescription medicine that reduces signs and symptoms in adults with moderate to severe rheumatoid arthritis (RA), including those who have not been helped enough by other medicines for RA. ORENCIA may prevent further damage to your bones and joints, and may help your ability to perform daily activities. ORENCIA also reduces signs and symptoms in children and adolescents 6 years of age and older with moderate to severe polyarticular juvenile idiopathic arthritis (JIA). ORENCIA can also make your immune system less able to fight infections, so you may be more likely to get infections or any infection you have may get worse. It is important to tell your doctor if you think you have any infections. Important Safety Information About ORENCIA® (abatacept) Before you receive treatment with ORENCIA, a lyophilized powder for intravenous infusion, you should tell your doctor about all your medical conditions, including if you:   Have any kind of infection even if it is small (such as an open cut or sore) or an infection that is in your whole body (such as the flu).     Have an infection that will not go away or a history of infections that keep coming back.     Have had tuberculosis (TB), a positive skin test for TB, or if you recently have been in close contact with someone who has had TB. If you get any of the symptoms of TB (a dry cough that doesn't go away, weight loss, fever, night sweats), call your doctor right away. Before you start ORENCIA, your doctor may examine you for TB or perform a skin test.   Have or have had viral hepatitis. Before you use ORENCIA, your doctor may examine you for hepatitis.   Have a history of chronic obstructive pulmonary (lung) disease (COPD).   Are scheduled to have surgery.   Are allergic to any of the following ingredients in ORENCIA: abatacept, maltose, monobasic sodium phosphate, or sodium chloride for administration.   Recently received a vaccination or are scheduled for any vaccination. You should not take live vaccines if you are receiving ORENCIA.   Have diabetes and use a blood glucose monitor to check your sugar levels. The infusion of ORENCIA contains maltose, a sugar that can give falsely high blood glucose readings with some monitors on the day you receive your infusion. Your doctor may tell you to use a different way to monitor your blood sugar levels.   Are pregnant, planning to become pregnant, or are thinking about becoming pregnant. It is not known if ORENCIA can harm your unborn baby.   Are breast-feeding. You will need to decide to either breast-feed or receive treatment with ORENCIA, but not both.   Take any other kinds of medicine, including prescription and nonprescription medicines, vitamins, and herbal supplements.   Are taking other biologic medicines to treat RA or JIA such as: Enbrel® (etanercept), Humira® (adalimumab), Remicade® (infliximab), Kineret® (anakinra) or Rituxan® (rituximab). You may have a higher chance of getting a serious infection if you take ORENCIA with other biologic medicines.  Possible Side Effects of ORENCIA® (abatacept) ORENCIA can cause serious side effects including:   Serious infections. Patients receiving ORENCIA have a higher chance of getting infections including pneumonia, and other infections caused by viruses, bacteria, or fungi. Call your doctor immediately if you feel sick or get any of the following signs of infection: fever, feel very tired, cough, feel flu-like, or warm, red or painful skin.    Allergic reactions. Allergic reactions can happen on the day of treatment or the day after receiving ORENCIA. Tell your doctor or get emergency medical help right away if you have hives, swollen face, eyelids, lips, tongue, throat or trouble breathing.    Cancer (malignancies). Certain kinds of cancer have been reported in patients receiving ORENCIA. It is not known if ORENCIA increases your chance of getting certain kinds of cancer.    Vaccinations. You should not receive ORENCIA with certain types of vaccines. ORENCIA may cause some vaccinations to be less effective.    Respiratory problems in patients with COPD. You may get certain respiratory problems more often if you receive ORENCIA and have COPD, including: worsened COPD, pneumonia, cough, or trouble breathing.  The more common side effects with ORENCIA in both adults and children are headache, upper respiratory tract infection, sore throat, and nausea. Other side effects in children may include diarrhea, cough, fever, and abdominal pain. 风湿关节炎治疗药 新药名称： 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。 3.适应证： 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。 4.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。 5.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. 6.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%)。 7.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。 8.用法与用量 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. 9.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254mg.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。