在56年来第一个批准的新狼疮药物 在Benlysta之前，FDA在1955年批准治疗狼疮药物，羟基氯喹[hydroxychloroquine](商品名氯奎宁) [Plaquenil]和皮质激素。1948年批准阿司匹林治疗狼疮。 FDA药物评价和研究中心药物评价II部主任Curtis Rosebraugh, M.D., M.P.H. 说“Benlysta，当与使用已有治疗，对寻求帮助处理与这种疾病相关症状的医疗保健人员和患者可能是重要新治疗方法” 批准日期： 2011年3月9日；公司：Human Genome Sciences, Inc.和GlaxoSmithKline 一般描述 BENLYSTA(belimumab)是一种对可溶性人B淋巴细胞刺激剂蛋白(BLyS，也被称为BAFF和TNFSF13B)特异性的人IgG1λ单克隆抗体。Belimumab分子量接近147 kDa。Belimumab是通过重组DNA技术在一种哺乳动物细胞表达系统中生产的。 BENLYSTA是以一种消毒，白色至灰白色，无防腐剂，为静脉输注的冻干粉供应。在用注射用无菌水，USP，配制[见剂量和给药方法(2.3)]。各单次使用小瓶输送在0.16 mg/mL枸橼酸，0.4 mg/mL聚山梨醇80，2.7 mg/mL枸橼酸钠，和80 mg/mL蔗糖，pH 6.5的80 mg/mL belimumab。 作用机制 BENLYSTA是一种BLyS-特异性抑制剂阻断可溶性BLyS，一种B-细胞生存因子，与其在B细胞受体上的结合。BENLYSTA不直接与B细胞结合，但结合BLyS，BENLYSTA抑制B细胞的生存，包括自身反应性B细胞，和减少B细胞分化至产生免疫球蛋白的浆细胞。 适应证和用途 BENLYSTA是一种B-淋巴细胞刺激剂(BLyS)-特异性抑制剂适用于治疗正在接受标准治疗的有活动性，自身抗体-阳性，全身性红斑狼疮成年患者(1, 14)。 使用限制： 尚未在有严重活动性狼疮肾炎或严重活动性中枢神经系统狼患者疮中评价BENLYSTA的疗效(1)。尚未研究BENLYSTA与其它生物制品或静脉环磷酰胺联用(1)。不建议在这些情况中使用BENLYSTA。 剂量和给药方法 （1）推荐给药方案是对头3剂间隔2-周10 mg/kg和其后间隔4-周。配制，稀释和只作为静脉输注在1小时期间给药。(2.1) （2）为预防输注反应和超敏性反应考虑预防给药(2.2) 剂型和规格 单次使用belimumab冻干粉小瓶： （1）每小瓶120 mg (3) （2）每小瓶400 mg (3) 禁忌证 既往对belimumab过敏反应。(4) 警告和注意事项 （1）死亡率：临床试验的对照阶段期间用BENLYSTA比用安慰剂报道更多死亡。(5.1) （2）严重感染：在接受免疫抑制剂，包括BENLYSTA患者中曾报道严重和有时致命性感染。有慢性感染患者中慎用。BENLYSTA治疗期间如患者发生新感染考虑中断BENLYSTA治疗。(5.2) （3）超敏性反应，包括过敏反应：曾报道严重反应。应由准备处理过敏反应保健提供者给予BENLYSTA。给予BENLYSTA期间和后适当时间监视患者。(2.2, 5.4) （4）抑郁：在BENLYSTA研究中曾报道抑郁和自杀倾向。应指导患者如经受新或恶化的抑郁，自杀想法或其它情绪变化联系他们的保健提供者。(5.6) （5）免疫接种：不应同时给予活疫苗与BENLYSTA。(5.7) 不良反应 在临床试验中常见不良反应(≥5%)是：恶心，腹泻，发热，鼻咽炎，支气管炎，失眠，肢体疼痛，抑郁，偏头痛，和咽炎。(6.1) 在特殊人群中使用 妊娠：可得到注册。(8.1) 如何供应/贮藏和处置 BENLYSTA是一种无菌，无防腐剂冻干粉，为配制，稀释，和静脉输注，在单次使用玻璃小瓶内供应，小瓶有一个不含乳胶橡胶瓶塞和翻转密封。每5-mL小瓶含120 mg belimumab。每个20-mL小瓶含400 mg belimumab 。 BENLYSTA按以下供应：120 mg belimumab在5-mL单次使用小瓶    NDC 49401-101-01 400 mg belimumab在 20-mL单次使用小瓶    NDC 49401-102-01 BENLYSTA小瓶贮藏在冰箱温度2°至8°C间(36°至46°F)。小瓶用前贮存在原盒内应避光保护。不要冻结。 避免暴露于热。不要使用超过有效期的药物。 Benlysta: first targeted lupus treatment Benlysta (belimumab) is licensed as add-on therapy in patients with autoantibody-positive systemic lupus erythematosus (SLE) who have high disease activity despite standard treatment PHARMACOLOGY Belimumab is a monoclonal antibody specific for the soluble human B lymphocyte stimulator protein, BLyS. It inhibits the differentiation of B cells into antibody-producing plasma cells. CLINICAL STUDIES Two pivotal randomised trials showed that the addition of belimumab to standard care improves control of disease activity in SLE. BLISS-76 and BLISS-52 enrolled seropositive SLE patients (n=819 and n=865, respectively). In addition to standard treatment, patients received belimumab 10mg/kg or 1mg/kg or placebo by intravenous infusion on days 0, 14 and 28, and every 28 days thereafter. In both studies, response rates at week 52 (as determined by the SLE Responder Index) were significantly higher in patients treated with the 10mg/kg dose of belimumab than in patients who received placebo. In a pooled analysis of the two studies, the combined response rate was 51% for belimumab 10mg/kg compared with 39% for placebo (p<0.0001). Belimumab was well tolerated in both studies, with rates of adverse events similar to placebo. ------------------------------------------------- Medication name Generic name: Belimumab-Injection Brand name(s): Benlysta Uses This medication is used to treat a certain type of lupus, systemic lupus erythematosus, in patients who are receiving other lupus medicines. It works by binding to a protein (found in high levels in patients with active lupus) in the blood and limiting the activity of the protein. It helps decrease the symptoms of lupus. Belimumab is a type of medication called a monoclonal antibody. How to use Read the Medication Guide provided by your pharmacist before you start using belimumab and each time you get a treatment. Discuss the risks and benefits of belimumab treatment. If you have any questions, ask your doctor or pharmacist.This medication is given by injection into a vein by a health care professional. It should be injected slowly over 1 hour. The first 3 doses are given every 2 weeks. After the third dose, it is usually given every 4 weeks, or as directed by your doctor. The dosage is based on your weight.Your doctor may prescribe other medications for you to take before the start of your treatment to help prevent serious side effects.This medication may cause very serious reactions during or after treatment. These reactions occur more often during the first and second treatments. Your doctor will monitor you closely. If you have a reaction, your treatment will be temporarily stopped. Tell your doctor or nurse immediately if any of these effects occur: headache, slow heartbeat, muscle pain, dizziness/fainting, nausea, or rash/itching.Use this medication regularly to get the most benefit from it. It may help to mark your calendar with a reminder.Tell your doctor if your condition does not improve or if it worsens. Precautions Before using belimumab, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: infections (current infections, infections that return), mental/mood problems (such as depression, thoughts of suicide), cancer.Belimumab can make you more likely to get infections or may worsen any current infections. Therefore, wash your hands well to prevent the spread of infection. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if you have been exposed to an infection or for more details.Do not have immunizations/vaccinations without the consent of your doctor. Tell your doctor if you have had any recent immunizations. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits, and reliable forms of birth control with your doctor. The manufacturer recommends the use of reliable forms of birth control during treatment and for at least 4 months after your last treatment. It is unknown if this drug passes into breast milk. Consult your doctor before breast-feeding. Drug interactions Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.A product that may interact with this drug is: natalizumab. Side effects See also How to Use section.Nausea, diarrhea, or trouble sleeping may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects. Tell your doctor right away if you have any serious side effects, including: mental/mood changes (such as new/worsening depression, thoughts of suicide), signs of cancer (such as fever, night sweats, unusual tiredness, unexplained weight loss, swollen glands, unusual lumps/growths).This medication can lower your body's ability to fight an infection. You may be more likely to get serious infections such as pneumonia, urinary tract infection, and skin infections. It may also be harder to fight an infection you already have. Tell your doctor right away if you develop signs of a serious infection while using this drug, such as: fever, chills, sore throat, cough, pain or burning with urination, urinating often, bloody diarrhea, coughing up mucus.Get medical help right away if you have any serious side effects, including: heart problems (such as chest/jaw/left arm pain, shortness of breath, unusual sweating, dizziness).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345. Missed dose For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor or pharmacist immediately to establish a new dosing schedule. Overdose If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Notes Laboratory and/or medical tests may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details. Medical alert Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (US) or 1-800-668-1507 (Canada). Storage Not applicable. This medication is given in a clinic and will not be stored at home. Photos by medication strengthClick the "Photos" link to see sample photographs for a specific medication strength. Common strengths Benlysta 120 mg IV Solution Benlysta 400 mg IV Solution