首个B细胞消耗剂Uplizna（inebilizumab-cdon，前称MEDI-551）获美国FDA批准，用于治疗神经脊髓炎谱系障碍(NMOSD)！
近日，美国食品和药物管理局（FDA）已批准其抗CD19单抗药物Uplizna（inebilizumab-cdon，前称MEDI-551），在初始剂量后作为一年2次的维持方案，用于治疗抗水通道蛋白-4（AQP4）抗体阳性的视神经脊髓炎频谱障碍（NMOSD）成人患者。
NMOSD是一种罕见的、破坏性的、补体介导的中枢神经系统自身免疫性疾病，其特征是复发，每次复发都会导致残疾的逐步累积，包括失明和麻痹，有时甚至过早死亡。在NMOSD患者中，大约80%的患者体内存在水通道蛋白-4（AQP4）的自身抗体，这些AQP4-IgG自身抗体被认为是由浆母细胞和浆细胞产生，主要与中枢神经系统中的星形胶质细胞结合。AQP4-IgG抗体与中枢神经系统的结合被认为会引发攻击，从而损害视神经、脊髓和大脑。失明、瘫痪、感觉丧失、膀胱和肠道功能障碍、神经痛和呼吸衰竭都可能是该病的表现。每次NMOSD攻击都会导致进一步的伤害和残疾。
批准日期：2020年06月12日 公司：Viela Bio，Inc
UPLIZNA（inebilizumab-cdon）注射液，静脉使用
美国初次批准：2020年
作用机理
inebilizumab-cdon在NMOSD中发挥治疗作用的确切机制尚不清楚，但推测涉及与CD19结合，CD19是存在于带前成熟B淋巴细胞上的细胞表面抗原。在细胞表面与B淋巴细胞结合后，inebilizumab-cdon导致抗体依赖性细胞溶解。
适应症和用途
UPLIZNA是CD19定向的溶细胞抗体，可用于治疗成抗水通道蛋白（AQP4）抗体阳性的成年患者视神经脊髓炎光谱症（NMOSD）。
剂量和给药
•在第一剂之前，需要进行乙肝病毒，定量血清免疫球蛋白和结核病筛查。
•每次输注之前：
o确定是否存在活动感染。
o与皮质类固醇，抗组胺药和解热药一起用药。
•在给药前，UPLIZNA必须在250mL的0.9％氯化钠注射液中稀释。
•UPLIZNA以滴定至完成的静脉输注方式给药，约90分钟。推荐剂量为：
o初始剂量：300mg静脉输液，两周后再进行第二次300mg静脉输液
o后续剂量（从第一次输注开始6个月开始）：每6个月单次300mg静脉输注。
•在输液期间以及输液完成后至少一小时内密切监视患者。
剂量形式和强度
•注射：在单剂量小瓶中加入100mg/10mL（10mg/mL）溶液。
禁忌症
•先前输注UPLIZNA会危及生命。
•活动性乙型肝炎感染。
•活动性或未经治疗的潜伏性结核病。
警告和注意事项
•输液反应：在输液前进行药物治疗。
输液反应的管理建议取决于反应的类型和严重性。如果有生命危险，请永久停用UPLIZNA或发生禁用输液反应。
•感染：对于活动性感染患者，请延迟UPLIZNA给药，直至感染消失。不建议在治疗期间和停药后直至B细胞补充前，用减毒活疫苗进行疫苗接种。
•免疫球蛋白水平：在开始使用UPLIZNAuntil B细胞补充治疗之前，期间和之后监测免疫球蛋白的水平。如果患者发生严重的机会性感染或如果免疫球蛋白水平表明免疫功能受损，则考虑再发感染，请考虑停用UPLIZNA。
•胎儿风险：根据动物数据可能会造成胎儿伤害。劝告女性对胎儿有潜在危险的生殖潜力，并在治疗期间和停止UPLIZNA后6个月内使用有效的避孕方法。
不良反应
最常见的不良反应（至少10％的接受UPLIZNA治疗且大于安慰剂的患者）为尿路感染和关节痛。
要报告可疑的不良反应，请联系Viela Bio，Inc.。请致电1-855-558-4352或FDA请致电1-800-FDA-1088或www.fda.gov/medwatch。
包装供应/存储和处理方式
供应方式
UPLIZNA（inebilizumab-cdon）注射剂为透明至微乳白色，无色至微
黄色溶液，提供为：
•一箱包含三个100mg/10mL单剂量小瓶–NDC 72677-551-01。
储存和处理
•用原装纸箱存放在2°C至8°C（36°F至46°F）的冰箱中，以防止光照。
•不要冻结。
•请勿摇晃。
•垂直存放小瓶。
完整说明资料附件： https://vielabio.com/wp-content/uploads/UPLIZNA-B761142-PI-Final.pdf FDA APPROVAL OF UPLIZNA™ (INEBILIZUMAB-CDON) FOR THE TREATMENT OF NEUROMYELITIS OPTICA SPECTRUM DISORDER (NMOSD)
U.S. Food and Drug Administration (FDA) has approved UPLIZNATM (inebilizumab-cdon) for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-AQP4 antibody positive as a twice-a-year maintenance regimen following initial doses. Approximately 80%1 of all patients with NMOSD test positive for anti-AQP4 antibodies.
IMPORTANT SAFETY INFORMATION
UPLIZNATM is contraindicated in patients with:
A history of life-threatening infusion reaction to UPLIZNATM
Active hepatitis B infection
Active or untreated latent tuberculosis
WARNINGS AND PRECAUTIONS
Infusion Reactions: UPLIZNATM can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions. Administer pre-medication with a corticosteroid, an antihistamine, and an anti-pyretic.
Infections: The most common infections reported by UPLIZNATM-treated patients in the randomized and open-label periods included urinary tract infection(20%), nasopharyngitis (13%), upper respiratory tract infection(8%), and influenza(7%). Delay UPLIZNATM administration in patients with an active infection until the infection is resolved.
Increased immunosuppressive effects are possible if combining UPLIZNATM with another immunosuppressive therapy.
The risk of hepatitis B virus(HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNATM. Do not administer to patients with active hepatitis.
Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNATM clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNATM and perform an appropriate diagnostic eva luation.
Patients should be eva luated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNATM.
Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion.
Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNATM treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNATM until B-cell repletion especially in patients with opportunistic or recurrent infections.
Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNATM.
Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNATM and greater than placebo) were urinary tract infection and arthralgia.
