强生单抗药物ustekinumab（商品名 Stelara）获FDA和欧盟批准批准上市，单独用药或与甲氨蝶呤（methotrexate）联合用药，用于18岁及以上活动性银屑病关节炎（active Psoriatic arthritis，PsA）及克罗恩病患者的治疗。 批准日期：2013年9月20日  公司：强生制药 STELARA®（优特克诺[ustekinumab]）注射剂 用于皮下或静脉内使用 美国初步批准：2009年 最近的主要变化 适应症和用法，克罗恩病：09/06 剂量与管理：09/06 剂量与管理：09/06 作用机制 Ustekinumab是与IL-12和IL-23细胞因子使用的p40蛋白亚基的特异性结合的人IgG1қ单克隆抗体。 IL-12和IL-23是参与炎性和免疫应答的天然存在的细胞因子，例如自然杀伤细胞激活和CD4+T细胞分化和激活。在体外模型中，ustekinumab显示通过破坏这些细胞因子与共享的细胞表面受体链IL-12Rβ1的相互作用来破坏IL-12和IL-23介导的信号传导和细胞因子级联。细胞因子IL-12和IL-23被认为是作为克罗恩病特征的慢性炎症的重要贡献者。在结肠炎的动物模型中，IL-12和IL-23的p40亚基的遗传缺失或抗体阻断是乌司他丁的靶标，被证明是保护性的。 适用范围及用途 STELARA®是一种人白细胞介素-12和-23拮抗剂，用于治疗成人患者： 中度至重度斑块性银屑病（Ps）谁是光疗或全身治疗的候选人。 活动性银屑病关节炎（PsA），单独或与甲氨蝶呤组合。 中度至严重的克罗恩病（CD）患者 失败或不容忍用免疫调节剂或皮质类固醇治疗，但从未破坏肿瘤坏死因子（TNF）阻滞剂或 失败或不容忍用一种或多种TNF阻断剂治疗。 剂量和管理 牛皮癣推荐成人皮下用量 体重范围（千克）剂量方案 初始和4周后皮下投予小于或等于100kg的45mg，随后每12周皮下投予45mg 最初和4周后皮下施用大于100kg的90mg，随后每12周皮下注射90mg 银屑病关节炎推荐成人皮下用量： 推荐剂量为45mg，最初皮下注射，4周后，随后每12周皮下注射45mg。 对于重度大于100 kg的中重度斑块性银屑病患者，推荐剂量为90mg，最初皮下注射，4周后，随后每12周皮下注射90 mg。 克罗恩病推荐的初始成人静脉注射剂量： 使用基于重量的给药的单次静脉输注： 重量范围（千克）推荐用量 最多55公斤260毫克（2vials） 大于55 kg至85 kg 390mg（3vials） 大于85公斤520毫克（4瓶） 克罗恩病推荐维持成人皮下用量： 在初次静脉内给药后8周皮下注射90mg剂量，然后每8周给药一次。 剂量形式和强度 小切口注射 注射：在单剂量预充式注射器中为45mg/0.5mL或90mg/mL 注射：在单剂量小瓶中为45mg/0.5mL 静脉注射 注射：在单剂量小瓶中130mg/26mL（5mg/mL）溶液 禁忌症 对乌斯卡单抗或任何赋形剂的临床显着超敏反应。 警告和注意事项 感染：发生严重感染。在任何临床上重要的活动性感染中，不要开始STELARA®。如果发生严重感染或临床重大感染，请考虑停止STELARA®直至感染消退。 特异性感染的理论风险：在IL-12/IL-23基因缺陷的患者中已经报道了分枝杆菌，沙门氏菌和卡介苗（BCG）疫苗的严重感染。这些感染的诊断试验应视为临床情况所决定。 结核病（TB）：在用STELARA®开始治疗之前评估患者的结核病。在服用STELARA®之前开始治疗潜伏性TB。 恶性肿瘤：STELARA®可能会增加恶性肿瘤的风险。STELARA®在具有或已知恶性肿瘤病史的患者中的安全性尚未得到评估。 超敏反应：可能会发生过敏反应或其他临床上显着的超敏反应。 可逆性后脑白质综合症（RPLS）：有一例报道。如果怀疑，立即治疗并停止STELARA®。 不良反应 最常见的不良反应是： 牛皮癣（≥3％）：鼻咽炎，上呼吸道感染，头痛，乏力。 克罗恩病，诱导（≥3％）：呕吐。 克罗恩病，维持（≥3％）：鼻咽炎，注射部位红斑，外阴阴道念珠菌病/真菌感染，支气管炎，瘙痒，尿路感染和鼻窦炎。 包装规格/存储和处理 STELARA®（ustekinumab）注射液是无菌，无防腐剂的无色至微黄色溶液。 STELARA®可用于含有45mg或90mg的单剂量预灌注注射器或含有45mg ustekinumab用于皮下使用的单剂量小瓶。每个预充式注射器配备有27号固定½英寸针头，针头安全护罩和包含干燥天然橡胶的针头盖。 STELARA®也可用于含有130mg ustekinumab的单剂量小瓶，用于静脉注射。 皮下使用NDC 45mg/0.5mL 单剂量预灌注注射器57894-060-03 90mg/mL 单剂量预灌注注射器57894-061-03 45mg/0.5mL 单剂量小瓶57894-060-02 静脉注射NDC 130mg/26mL（5mg/mL）单剂量小瓶57894-054-27 存储和稳定性 STELARA®小瓶和预充式注射器必须在2°C至8°C（36°F至46°F）下冷藏。将STELARA®小瓶直立存放。将产品保存在原始纸箱中以防止光直到使用时间。不要冻结不要动摇。 完整说明书附件： https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c77a9664-e3bb-4023-b400-127aa53bca2b STELARA® (ustekinumab) is indicated for the treatment of adult patients with active psoriatic arthritis. STELARA® can be used alone or in combination with methotrexate (MTX). STELARA® (ustekinumab) is indicated for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. STELARA® (ustekinumab) is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease who have: •failed or were intolerant to treatment with immunomodulators or corticosteroids, but never failed treatment with a tumor necrosis factor (TNF) blocker, or•failed or were intolerant to treatment with one or more TNF blockers. For plaque psoriasis and psoriatic arthritis: STELARA®, available as 45 and 90 mg, is a subcutaneous injection intended for use under the guidance and supervision of a physician with patients who will be closely monitored and have regular follow-up. Patients may self-inject with STELARA® after physician approval and proper training. Patients should be instructed to follow the directions provided in the Medication Guide. For Crohn’s disease: STELARA® for Intravenous Infusion is available as a 130 mg/26 mL (5 mg/mL) single-dose vial. It must be diluted, prepared, and infused by a healthcare professional for Crohn’s disease. STELARA®, available as 90 mg, is a subcutaneous injection intended for use under the guidance and supervision of a physician with patients who will be closely monitored and have regular follow-up. Patients may self-inject with STELARA® after physician approval and proper training. Patients should be instructed to follow the directions provided in the Medication Guide. IMPORTANT SAFETY INFORMATION Infections STELARA® (ustekinumab) may increase the risk of infections and reactivation of latent infections. Serious bacterial, fungal, and viral infections, some requiring hospitalization, were reported. In patients with psoriasis, serious infections included diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis and urinary tract infections. In patients with psoriatic arthritis, serious infections included cholecystitis. In patients with Crohn’s disease, serious or other clinically significant infections included anal abscess, gastroenteritis, ophthalmic herpes, pneumonia, and Listeria meningitis. Treatment with STELARA® should not be initiated in patients with a clinically important active infection until the infection resolves or is adequately treated. Consider the risks and benefits of treatment prior to initiating use of STELARA® in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur while on treatment with STELARA® and consider discontinuing STELARA® for serious or clinically significant infections until the infection resolves or is adequately treated. Theoretical Risk for Vulnerability to Particular Infections Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections from mycobacteria, Salmonella, and Bacillus Calmette-Guerin (BCG) vaccinations. Serious infections and fatal outcomes have been reported in such patients. It is not known whether patients with pharmacologic blockade of IL-12/IL-23 from treatment with STELARA® may be susceptible to these types of infections. Appropriate diagnostic testing should be considered, e.g., tissue culture, stool culture, as dictated by clinical circumstances. Pre-Treatment Evaluation of Tuberculosis (TB) Evaluate patients for TB prior to initiating treatment with STELARA®. Do not administer STELARA® to patients with active tuberculosis infection. Initiate treatment of latent TB before administering STELARA®. Closely monitor patients receiving STELARA® for signs and symptoms of active TB during and after treatment. Malignancies STELARA® is an immunosuppressant and may increase the risk of malignancy. Malignancies were reported among patients who received STELARA® in clinical studies. The safety of STELARA® has not been evaluated in patients who have a history of malignancy or who have a known malignancy. There have been reports of the rapid appearance of multiple cutaneous squamous cell carcinomas in patients receiving STELARA® who had risk factors for developing non-melanoma skin cancer (NMSC). All patients receiving STELARA®, especially those >60 years or those with a history of PUVA or prolonged immunosuppressant treatment, should be monitored for the appearance of NMSC. Hypersensitivity Reactions STELARA® is contraindicated in patients with clinically significant hypersensitivity to ustekinumab or excipients. Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with STELARA®. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue STELARA®. Reversible Posterior Leukoencephalopathy Syndrome (RPLS) One case of reversible posterior leukoencephalopathy syndrome (RPLS) was observed in clinical studies of psoriasis and psoriatic arthritis. No cases of RPLS were observed in clinical studies of Crohn’s disease. If RPLS is suspected, administer appropriate treatment and discontinue STELARA®. RPLS is a neurological disorder, which is not caused by an infection or demyelination. RPLS can present with headache, seizures, confusion, and visual disturbances. RPLS has been associated with fatal outcomes. Immunizations Prior to initiating therapy with STELARA®, patients should receive all age-appropriate immunizations recommended by current guidelines. Patients being treated with STELARA® should not receive live vaccines. BCG vaccines should not be given during treatment or within one year of initiating or discontinuing STELARA®. Exercise caution when administering live vaccines to household contacts of STELARA® patients, as shedding and subsequent transmission to STELARA® patients may occur. Non-live vaccinations received during a course of STELARA® may not elicit an immune response sufficient to prevent disease. Concomitant Therapies The safety of STELARA® in combination with other immunosuppressive agents or phototherapy was not evaluated in clinical studies of psoriasis. Ultraviolet-induced skin cancers developed earlier and more frequently in mice. In psoriasis studies, the relevance of findings in mouse models for malignancy risk in humans is unknown. In psoriatic arthritis studies, concomitant MTX use did not appear to influence the safety or efficacy of STELARA®. In Crohn’s disease studies, concomitant use of 6-mercaptopurine, azathioprine, methotrexate and corticosteroids did not appear to influence the overall safety or efficacy of STELARA®. Allergen Immunotherapy STELARA® may decrease the protective effect of allergen immunotherapy (decrease tolerance) which may increase the risk of an allergic reaction to a dose of allergen immunotherapy. Therefore, caution should be exercised in patients receiving or who have received allergen immunotherapy, particularly for anaphylaxis. Most Common Adverse Reactions The most common adverse reactions (≥3% and higher than that with placebo) in psoriasis clinical trials for STELARA® 45 mg, STELARA® 90 mg, or placebo were: nasopharyngitis (8%, 7%, 8%), upper respiratory tract infection (5%, 4%, 5%), headache (5%, 5%, 3%), and fatigue (3%, 3%, 2%), respectively. In psoriatic arthritis (PsA) studies, a higher incidence of arthralgia and nausea was observed in patients treated with STELARA® when compared with placebo (3% vs 1% for both). In Crohn’s disease induction studies, common adverse reactions (3% or more of patients treated with STELARA® and higher than placebo) reported through Week 8 for STELARA® 6 mg/kg intravenous single infusion or placebo included: vomiting (4% vs 3%). In the Crohn’s disease maintenance study, common adverse reactions (3% or more of patients treated with STELARA® and higher than placebo) reported through Week 44 were: nasopharyngitis (11% vs 8%), injection site erythema (5% vs 0%), vulvovaginal candidiasis/mycotic infection (5% vs 1%), bronchitis (5% vs 3%), pruritus (4% vs 2%), urinary tract infection (4% vs 2%) and sinusitis (3% vs 2%). 注：本品已获欧美等其他的国家批准上市，需要者请以在线咨询为准！ 美国上市包装的图片 欧洲上市包装的图片 强生单抗药Stelara获FDA和欧盟批准 2013年9月24日强生（JNJ）单抗药物Stelara（ustekinumab）获FDA批准，单独用药或与甲氨蝶呤（methotrexate）联合用药，用于18岁及以上活动性银屑病关节炎（active Psoriatic arthritis，PsA）患者的治疗。获批的治疗方法为：0周和4周注射45mg Stelara，随后每12周注射一次。 此外，Stelara也于9月23日获得了欧盟委员会（EC）的批准，单独用药或与甲氨蝶呤（methotrexate）联合用药，用于对非生物疾病修饰抗风湿药（DMARD）反应不足的活动性银屑病关节炎成人患者的治疗。 据估计，在欧洲有420万银屑病关节炎患者，在美国有超过200万的患者。 Stelara是首个也是唯一一个获批用于银屑病关节炎的抗IL-12/IL-23的药物 银屑病关节炎（PsA）是一种慢性炎症性疾病，其中关节痛是由机体免疫系统攻击自身健康组织所致。该病约影响30%的银屑病（psoriasis）患者。许多PsA患者使用抗肿瘤坏死因子（anti-TNF）药物治疗，如AbbVie的阿达木单抗（Humira）和强生的Remicade。 目前，银屑病关节炎中一个主要的未获满足的医疗需求是：有些患者对抗TNF（anti-TNF）制剂反应不足或由于各种原因不适用于抗TNF制剂且没有很好的治疗选择。临床上，在治疗这类患者时医生也一直在苦苦挣扎于采用何种疗法。现在，医生们有了一个除抗TNF制剂之外的选择，能够缓解这类患者的皮肤和关节症状。使患者有了一个以前从未有的新治疗选择。 Stelara是单抗药物优特克单抗(Ustekinumab)的商品名，是人白细胞介素IL-12和IL-23的拮抗剂，已获74个国家批准用于银屑病的治疗，该药能够通过与IL-12和IL-23所共有的p40亚单位相结合，阻止其与细胞表面的受体IL-12 β1相结合，来抑制这两种致炎性细胞因子（pro-inflammatory cytokine）。IL-12和IL-23是2种天然存在的蛋白质，被认为在免疫介导的炎症性疾病中发挥了关键作用，包括牛皮癣和牛皮癣关节炎。