英文药名：Lemtrada(alemtuzumab)

中文药名：阿仑单抗注射液

生产厂家：Genzyme
药品介绍
2014年11月18日，美国食品药品监督管理局(FDA)已批准LemtradaTM(阿仑单抗)为有复发性多发性硬化症(MS)患者的治疗。
Lemtrada给药方案为两个一年疗程，采用独特的剂量。第一疗程是通过静脉输注连续五天给药，第二个疗程使在12个月后连续输注3天。
批准日期：2014年11月：公司：Genzyme
作用机制
阿仑单抗在多发性硬化症发挥其治疗作用的精确机制不知道但是被假设涉及与CD52结合，T和B淋巴细胞上，和天然杀伤细胞，单核细胞，和巨噬细胞上存在的一种细胞表面抗原。结合至T和B淋巴细胞细胞表面后，阿仑单抗导致抗体依赖性细胞溶解和补体介导溶解。
适应证和用途
LEMTRADA是一个指向CD52细胞溶解单抗适用为有多发性硬化症(MS)复发型患者的治疗。因为其安全性图形，LEMTRADA的使用一般应保留为已对适用治疗MS两种或更多药物的反应不足患者。
剂量和给药方法
⑴对2个治疗疗程历时4个小时通过静脉输注给予LEMTRADA。
⒈ 第一个疗程：在连续5天12 mg/day。
⒉ 第二个疗程：在第一疗程后12个月12 mg/day在连续3天。
⑵ 在每个治疗疗程的头3天，输注LEMTRADA前用皮质类固醇预先给药。
⑶ 为预防带状疱疹在LEMTRADA给药的第一天开始给予抗病毒药和在LEMTRADA给药完成后连续最小两个月或直至CD4+淋巴细胞计数每微升高于200细胞，任何一个发生以后。
⑷ 给药前必须稀释。
剂型和规格
注射液：12mg/1.2mL(10mg/mL)在一次性使用小瓶。
禁忌证
有人类免疫缺血性病毒感染。
警告和注意事项
⑴甲状腺疾病：开始治疗前和每3个月获得甲状腺功能检验直至末次输注后48个月。
⑵其他自身免疫血细胞减少：每月监视完全学细胞计数直至末次输注后48个月。
⑶有活动性感染患者考虑延迟开始LEMTRADA直至感染完全控制。LEMTRADA疗程后不要给予活病毒疫苗。
不良反应
最常见不良反应(发生率和>干扰素β-1a)：皮疹，头痛，发热，鼻咽炎，恶心，泌尿道感染，疲乏，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，肢体痛，背痛，腹泻，窦炎，口咽痛，感觉异常，眩晕，腹痛，潮红，和呕吐。
特殊人群中使用
妊娠：根据动物数据，可能致胎儿危害。

Brand Name
Lemtrada
Common Name
alemtuzumab
Alemtuzumab relaunched as Lemtrada for multiple sclerosis
The selective immunosuppressant alemtuzumab, previously used to treat certain blood cancers, is now available for patients with relapsing-remitting multiple sclerosis (MS) that has been confirmed as active by clinical or imaging features.
Alemtuzumab (Lemtrada) binds to the CD52 surface antigen found at high levels on T and B lymphocytes, and at lower levels on natural killer cells, monocytes and macrophages. This causes both antibody-dependent and complement-mediated cell lysis. The resultant depletion and repopulation of lymphocytes is thought to reduce the risk of MS relapse and ultimately delay disease progression.
Unlike existing MS treatments that require administration daily or several times a week, Lemtrada is given as a short course of intravenous infusions (12mg once daily for five days) followed 12 months later with a second short course (12mg once daily for three days).
Lemtrada must be administered where adequate facilities are available for the management of infusion-related, potentially anaphylactic reactions. Patients should receive pretreatment with corticosteroids, plus antihistamines and/or antipyretics if necessary.
Clinical studies
Investigators assessed alemtuzumab for relapsing-remitting MS in three randomised, rater-blinded clinical trials: a 3-year phase II study in patients with early MS (CAMMS223, n=334); and two 24-month phase III studies in patients who had not received prior therapy (CARE-MS I, n=581) or had relapsed following first-line treatment (CARE-MS II, n=840).
In all studies, patients were randomised to receive subcutaneous interferon beta-1a (44 microgram three times a week) or annual cycles of intravenous alemtuzumab (12mg once daily for 5 days, followed 12 months later by a second 3-day course). The CAMMS223 and the CARE-MS II study also investigated alemtuzumab at a higher 24mg daily dose given in the same regimen as the 12mg dose. In the CARE-MS II study, however, dosing at this level was discontinued to aid recruitment, although data were included in the safety analysis.
The primary efficacy endpoints in all three studies were the percentage of patients with sustained (≥6 months) accumulation of disability (SAD) and the annualised relapse rate (ARR).
In the CAMMS223 study, alemtuzumab therapy was suspended before the planned study end date after 3 patients developed immune thrombocytopenic purpura, one of whom died. Analysis showed that alemtuzumab reduced the risk of 6-month SAD by 71% compared with interferon (HR 0.29, 95% CI 0.16-0.54, p<0.001). ARR was reduced by 74% in the alemtuzumab group compared with the interferon group (HR 0.26, 95% CI 0-16-0.41, p<0.001). There were no significant differences in outcomes between the alemtuzumab groups.
In the CARE-MS I study, in which patients were randomised to alemtuzumab or interferon beta in a 2:1 ratio, 22% (82) of patients who received alemtuzumab relapsed compared with 40% (75) of those given interferon, corresponding to a 54.9% reduction with alemtuzumab (rate ratio 0.45, 95% CI 0.32-0.63, p<0.0001). However, there was no significant difference in SAD between the two treatment arms.
In the CARE-MS II study, in which patients were randomised to alemtuzumab or interferon in 4:1 ratio, 35% (147) of patients in the alemtuzumab group experienced relapses compared with 51% (104) of those in the interferon group, corresponding to a 49.4% reduction with alemtuzumab (rate ratio 0.51, 95% CI 0.39-0.65, p<0.0001). SAD occurred in 13% (54) of patients treated with alemtuzumab versus 20% (40) of those who received interferon (HR 0.58, 95% CI 0.38-0.87, p=0.008).
Safety profile
The most common adverse events associated with alemtuzumab are rash, headache, pyrexia and respiratory tract infections. Severe autoimmune conditions, including thyroid disorders, nephropathy and immune thrombocytopenic purpura, have been reported in some patients. Individuals who are prescribed alemtuzumab should be warned of the risks before starting treatment and be given a patient alert card and patient guide; they must also be advised of the need to consent to follow-up for at least 48 months after the final dose.
NICE approved
In its most recent set of recommendations, the National Institute for Health and Care Excellence (NICE) has approved alemtuzumab for use on the NHS within its licensed indication.
About Lemtrada™ (alemtuzumab)
The Lemtrada clinical development program included two pivotal randomized Phase III studies comparing treatment with Lemtrada to Rebif® (high-dose subcutaneous interferon beta-1a) in patients with RRMS who had active disease and were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II), as well as an ongoing extension study. In CARE-MS I, Lemtrada was significantly more effective than Rebif at reducing annualized relapse rates; the difference observed in slowing disability progression did not reach statistical significance. In CARE-MS II, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates, and accumulation of disability was significantly slowed in patients given Lemtrada vs. interferon beta-1a.
The most common side effects of Lemtrada are infusion associated reactions, infections (upper respiratory tract and urinary tract), lymphopenia and leukopenia. Serious autoimmune conditions can occur in patients receiving Lemtrada. A comprehensive risk management program will support early detection and management of these autoimmune events. 2/3
Alemtuzumab is a monoclonal antibody that selectively targets CD52, a protein abundant on T and B cells. Treatment with alemtuzumab results in the depletion of circulating T and B cells thought to be responsible for the damaging inflammatory process in MS. Alemtuzumab has minimal impact on other immune cells. The acute anti-inflammatory effect of alemtuzumab is immediately followed by the onset of a distinctive pattern of T and B cell repopulation that continues over time, rebalancing the immune system in a way that potentially reduces MS disease activity.