单克隆抗体，靶向于CD52：alemtuzumab（商品名 Lemtrada 赛诺菲 Sanofi）获美国食品药品监督管理局(FDA)已批准为有复发性多发性硬化症(MS)患者的治疗。因为其安全性图形，Lemtrada的使用一般应保留对对MS适用的两种或更多药物治疗反应不足的患者。其疗效持续长达6年之久。
批准日期：2014年11月：公司：Genzyme
LEMTRADA（阿仑单抗[alemtuzumab]）注射用于静脉注射
美国初步批准：2001年
警告：
自动消毒，输注反应和恶心参见完整的装箱警告信息。 LEMTRADA导致严重的，有时致命的自身免疫性疾病，如免疫性血小板减少症和抗肾小球基底膜疾病。在最后一次给药48个月后，以周期性间隔监测完全血细胞计数，差异，血清肌酐水平和尿液尿量。
LEMTRADA导致严重的危及生命的输液反应。 LEMTRADA必须在适当的设备和人员的环境中进行管理，以管理过敏反应或严重的输液反应。每次输注后两个小时监测患者。让患者知道在2小时监测期后也可能发生严重的输注反应。
LEMTRADA可能导致恶性肿瘤的风险增加，包括甲状腺癌，黑素瘤和淋巴增生性疾病。执行基线和年度皮肤检查。
LEMTRADA仅通过限制性分发程序提供。
作用机制
阿仑单抗在多发性硬化中发挥其治疗作用的精确机制是未知的，但推测涉及结合CD52，存在于T和B淋巴细胞上的细胞表面抗原以及天然杀伤细胞，单核细胞和巨噬细胞。 细胞表面结合T淋巴细胞和B淋巴细胞后，alemtuzumab导致抗体依赖性细胞溶解和补体介导的裂解。
适用范围及用途
LEMTRADA是一种用于治疗复发型多发性硬化症（MS）患者的CD52定向细胞溶解单克隆抗体。由于其安全性，LEMTRADA的使用通常应保留给针对治疗MS的两种或多种药物反应不足的患者。
剂量和管理
通过静脉滴注4小时2次治疗LEMTRADA：第一疗程：连续5天为12mg /天。
第二疗程：第一疗程后12个月连续3天12毫克/日。
在每个治疗过程的前3天，用LEMTRADA输注前用皮质类固醇预处理。
从LEMTRADA给药的第一天开始，施用抗病毒药物进行疱疹预防，并在LEMTRADA给药完成后持续至少两个月，或直到CD4 +淋巴细胞计数超过200细胞/微升，以较晚者为准。
必须在给药前稀释。
剂量形式和强度
注射：在一次性小瓶中12mg/1.2mL（10mg/mL）。
禁忌症
人类免疫缺陷病毒感染。
警告和注意事项
甲状腺疾病：在开始治疗前，每3个月至最后一次输液后48个月获得甲状腺功能检查。
其他自身免疫性血细胞减少症：在最后一次输注后48个月内每月监测完整的血液计数。
考虑延迟LEMTRADA在活动性感染患者中的启动，直到感染得到完全控制。不要在LEMTRADA课程之后管理活的病毒疫苗。
不良反应
最常见的不良反应（发生率≥10％，干扰素β-1a）：皮疹，头痛，发热，鼻咽炎，恶心，尿路感染，疲劳，失眠，上呼吸道感染，疱疹病毒感染，荨麻疹，瘙痒，甲状腺疾病，真菌感染，关节炎
如何提供/存储和处理
如何提供
每个LEMTRADA纸箱（NDC：58468-0200-1）包含1个单次使用的小瓶，可提供12 mg/1.2mL（10mg/mL）。 瓶塞不用天然橡胶胶乳制成。
LEMTRADA是一种无菌，透明无色至无色至浅黄色的输液溶液，不含抗微生物防腐剂。
存储和处理
将LEMTRADA小瓶存放在2°C至8°C（36°F至46°F）。 不要冻结或摇晃。 存放在原装纸箱中以防止光线受损。
完说明书附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6236b0bc-82e9-4447-9a78-f57d94770269
Lemtrada (alemtuzumab)
IMPORTANT SAFETY INFORMATION
WARNING: AUTOIMMUNITY, INFUSION REACTIONS, AND MALIGNANCIES
∙LEMTRADA causes serious, sometimes fatal, autoimmune conditions such as immune thrombocytopenia and anti-glomerular basement membrane disease. Monitor complete blood counts with differential, serum creatinine levels, and urinalysis with urine cell counts at periodic intervals for 48 months after the last dose of LEMTRADA.
∙LEMTRADA causes serious and life-threatening infusion reactions. LEMTRADA must be administered in a setting with appropriate equipment and personnel to manage anaphylaxis or serious infusion reactions. Monitor patients for two hours after each infusion. Make patients aware that serious infusion reactions can also occur after the 2-hour monitoring period.
∙LEMTRADA may cause an increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders. Perform baseline and yearly skin exams.
∙Because of the risk of autoimmunity, infusion reactions, and malignancies, LEMTRADA is available only through restricted distribution under a Risk eva luation and Mitigation Strategy (REMS) Program. Call 1-855-676-6326 to enroll in the LEMTRADA REMS Program.
WARNINGS AND PRECAUTIONS
∙Autoimmunity: Treatment with LEMTRADA can result in the formation of autoantibodies and increase the risk of serious autoimmune mediated conditions, and may increase the risk of other autoimmune conditions because of the broad range of autoantibody formation. Obtain complete blood counts (CBC) with differential, serum creatinine levels, and urinalysis with cell counts before starting treatment and then at monthly intervals for 48 months after the last dose of LEMTRADA, or longer, if clinically indicated.
∙Infusion Reactions: LEMTRADA causes cytokine release syndrome resulting in infusion reactions. In clinical studies, 92% of LEMTRADA-treated patients experienced infusion reactions. Serious reactions occurred in 3% of these patients and included anaphylaxis in 2 patients (including anaphylactic shock), angioedema, bronchospasm, hypotension, chest pain, bradycardia, tachycardia (including atrial fibrillation), transient neurologic symptoms, hypertension, headache, pyrexia, and rash. In some patients, infusion reactions were reported more than 24 hours after LEMTRADA infusion. Premedicate patients with corticosteroids immediately prior to LEMTRADA infusion for the first 3 days of each treatment course. Consider pretreatment with antihistamines and/or antipyretics. Infusion reactions may occur despite pretreatment.
∙Malignancies: Monitor for symptoms of thyroid cancer. Because LEMTRADA is an immunomodulatory therapy, caution should be exercised in initiating LEMTRADA in patients with pre-existing or ongoing malignancies.
∙LEMTRADA REMS Program: Only prescribers, patients, pharmacies and healthcare facilities certified and enrolled in the REMS program can prescribe, receive, dispense or administer LEMTRADA. Healthcare facilities must have on-site access to equipment and personnel trained to manage infusion reactions (including anaphylaxis and cardiac and respiratory emergencies).
∙Immune thrombocytopenia (ITP) occurred in 2% of LEMTRADA-treated patients in clinical studies in MS. One LEMTRADA-treated patient developed ITP that went unrecognized prior to the implementation of monthly monitoring requirements, and died from an intracerebral hemorrhage. ITP has been diagnosed more than 3 years after the last LEMTRADA dose. If ITP is confirmed, promptly initiate medical intervention.
∙Glomerular nephropathies occurred in 0.3% of LEMTRADA-treated patients in MS clinical trials and have been diagnosed up to 40 months after the last dose of LEMTRADA. Anti-glomerular basement membrane (anti-GBM) disease can lead to renal failure requiring dialysis and transplantation and has in post-marketing cases of MS patients treated with alemtuzumab. Anti-GBM disease can be life threatening if untreated; early detection and treatment may decrease the risk of poor outcomes.
∙Autoimmune thyroid disorders occurred in 34% of LEMTRADA-treated patients in clinical studies. Newly diagnosed thyroid disorders occurred throughout the uncontrolled clinical study follow-up period, more than 7 years after the first LEMTRADA dose. Serious thyroid events occurred in 2% of patients, including cardiac and psychiatric events. In LEMTRADA-treated patients, 3% underwent thyroidectomy. In patients with an ongoing thyroid disorder, LEMTRADA should be administered only if the potential benefit justifies the potential risks. Obtain thyroid function tests prior to initiation of treatment and every 3 months until 48 months after the last infusion, or longer, if clinically indicated. Thyroid disease poses special risks in women who are pregnant.
∙Autoimmune cytopenias occurred in LEMTRADA-treated MS patients in clinical trials. One LEMTRADA-treated patient with autoimmune pancytopenia died from sepsis. Prompt medical intervention is indicated if a cytopenia is confirmed.
∙Infections occurred in 71% of LEMTRADA-treated patients compared to 53% of patients treated with interferon beta-1a. Serious infections occurred in 3% of patients treated with LEMTRADA and 1% of patients treated with interferon beta-1a and included: appendicitis, gastroenteritis, pneumonia, herpes zoster, and tooth infection. Consider delaying LEMTRADA administration in patients with active infection until the infection is fully controlled.
‒Do not administer live viral vaccines following a course of LEMTRADA, as patients may be at increased risk of infection.
‒Concomitant use of antineoplastic or immunosuppressive therapies could increase the risk of immunosuppression.
‒Herpes viral infection developed in 16% of LEMTRADA-treated patients compared to 3% of interferon beta-1a patients. Administer antiviral prophylaxis for herpetic viral infections starting on the first day of each treatment course and continue for a minimum of two months following treatment with LEMTRADA or until CD4+ lymphocyte count is ≥200 cells per microliter, whichever occurs later.
‒Cervical human papilloma virus (HPV) infection occurred in 2% of LEMTRADA-treated patients. Annual screening is recommended for female patients.
‒Active and latent tuberculosis cases occurred in 0.3% of LEMTRADA-treated patients, most often in endemic regions.
‒Fungal infections, especially oral and vaginal candidiasis, occurred in 12% of LEMTRADA-treated patients compared to 3% of interferon beta-1a patients.
‒Cases of listeria meningitis occurred within 1 month of LEMTRADA dosing. Advise patients to avoid or adequately heat foods that are potential sources for Listeria monocytogenes.
‒Before initiating LEMTRADA, consider screening patients at high risk of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection. Carriers of HBV and/or HCV who receive LEMTRADA may be at risk of irreversible liver damage relative to a potential virus reactivation.
∙Pneumonitis, including hypersensitivity pneumonitis and pneumonitis with fibrosis, occurred in 6 of 1217 (0.5%) LEMTRADA-treated patients in clinical studies. Advise patients to report symptoms of pneumonitis (e.g., shortness of breath, cough, wheezing, chest pain or tightness, and hemoptysis).
∙Drug Products with Same Active Ingredient: LEMTRADA contains the same active ingredient (alemtuzumab) found in CAMPATH®. If LEMTRADA is considered for use in a patient who has previously received CAMPATH, exercise increased vigilance for additive and long-lasting effects on the immune system.
Adverse Reactions
In clinical trials, the most common adverse reactions (incidence ≥10% and >interferon beta-1a) with LEMTRADA vs interferon beta-1a were: rash (53% vs 6%), headache (52% vs 23%), pyrexia (29% vs 9%), nasopharyngitis (25% vs 19%), nausea (21% vs 9%), urinary tract infection (19% vs 8%), fatigue (18% vs 13%), insomnia (16% vs 15%), upper respiratory tract infection (16% vs 13%), herpes viral infection (16% vs 3%), urticaria (16% vs 2%), pruritus (14% vs 2%), thyroid gland disorders (13% vs 3%), fungal infection (13% vs 4%), arthralgia (12% vs 9%), pain in extremity (12% vs 9%), back pain (12% vs 8%), diarrhea (12% vs 6%), sinusitis (11% vs 8%), oropharyngeal pain (11% vs 5%), paresthesia (10% vs 8%), dizziness (10% vs 5%), abdominal pain (10% vs 5%), flushing (10% vs 4%), and vomiting (10% vs 3%).
Use in Specific Populations
LEMTRADA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Autoantibodies may be transferred from the mother to the fetus during pregnancy. Placental transfer of anti-thyroid antibodies resulted in a case of neonatal Graves’ disease. Safety and effectiveness in pediatric patients less than 17 years of age have not been established. Use of LEMTRADA is not recommended in pediatric patients due to the risks of autoimmunity and infusion reactions, and because it may increase the risk of malignancies.