Rebif（interferon beta-1a）已被FDA批准用于治疗复发性多发性硬化症。Rebif已被证明可以减少临床恶化的频率，并延缓MS患者身体残疾的累积。该产品的推荐剂量为每周三次44微克，通过皮下注射给药。Rebif提供一次性预装注射器。
批准日期：2013年1月1日 公司：EMD Serono, Inc
REBIF（干扰素β-1a[interferon beta-1a]），用于皮下注射
最初的美国批准：1996年
最近的重大变化
警告和注意事项，血栓性微血管病：10/2015
作用机制
REBIF（干扰素β-1a）在患有多发性硬化症的患者中发挥其治疗作用的机制尚不清楚。
适应症和用法
REBIF是一种干扰素β，用于治疗患有多发性硬化症的患者，以减少临床恶化的频率并延缓身体残疾的累积。
剂量和给药
仅用于皮下注射
推荐剂量为22mcg或44mcg，每周皮下注射三次。
滴定：通常，起始剂量应为每周规定剂量时间的20％，并且在4周时间内增加至每周皮下注射22mcg或44mcg的目标推荐剂量。
治疗日镇痛和/或退热药可能有助于改善flulikesymptoms。
剂量形式和强度
注射：在单剂量预填充注射器中，在0.2mL中为8.8mcg，在0.5mL中为22mcg或44mcg。
注射：在单剂量自动注射器中，在0.2mL中为8.8mcg，在0.5mL中为22mcg或44mcg。
禁忌症
对天然或重组干扰素β，人白蛋白或制剂的任何其他组分过敏的历史。
警告和注意事项
抑郁症和自杀症：建议患者立即报告抑郁症和/或自杀意念的症状;如果出现抑郁症，请考虑停止REBIF。
肝损伤：监测肝功能检查;监测患者肝脏损伤的体征和症状;如果发生肝损伤，可考虑停用REBIF。
过敏反应和其他过敏反应：如果过敏反应发生，则停用REBIF。
注射部位反应包括坏死：在完全愈合之前，不要将REBIF施用于受影响的区域;如果发生多处病变，则停止REBIFuntil皮肤病变的愈合。
外周血量减少：监测全血细胞计数。
血栓性微血管病变：已报道血栓性微血管病变病例。如果出现与TMA一致的临床症状和实验室检查，则停止REBIF。
癫痫发作：监测癫痫发作给患者，特别是那些已经存在癫痫症的患者。
不良反应
对照临床试验中最常见的不良反应是注射液紊乱，流感样症状，腹痛，抑郁，抬高
肝酶和血液学异常。
要报告疑似不良反应，请致电1-800-283-8088分机与EMD Serono联系。 5563或FDA，1-800-FDA-1088或www.fda.gov/medwatch
用于特定人群
怀孕：根据动物数据，可能会造成胎儿伤害。
包装提供/存储和处理
REBIF作为无菌溶液提供，不含防腐剂，可在以下包装中找到：
预填充注射器：
REBIF（干扰素β-1a）滴定装，NDC 44087-8822-1-六REBIF 8.8mcg预填充注射器和6个REBIF 22mcg预填充注射器
REBIF（干扰素β-1a）22mcg预充式注射器
- 1个REBIF 22mcg预充式注射器，NDC 44087-0022-1
-12个REBIF 22mcg预充式注射器，NDC 44087-0022-3
REBIF（干扰素β-1a）44mcg预充式注射器
- 1个REBIF 44mcg预装注射器，NDC 44087-0044-1
- 12个REBIF 44 mcg预装注射器，NDC 44087-0044-3
REBIF Rebidose自动注射器：
REBIF Rebidose（干扰素β-1a）滴定包，NDC 44087-0188-1
- 6个REBIF Rebidose 8.8mcg自动注射器，带有石灰绿色注射器按钮和6个
REBIF Rebidose 22mcg，黄色注射器按钮。
REBIF Rebidose（干扰素β-1a）22mcg自动注射器
- 12个REBIF Rebidose 22mcg自动注射器，带黄色注射器按钮，NDC：44087-3322-1
REBIF Rebidose（干扰素β-1a）44mcg自动注射器
-12个REBIF Rebidose 44mcg自动注射器，带有青绿色注射器按钮，NDC：44087-3344-1
REBIF应冷藏在36°F至46°F（2°C至8°C）之间。不要冻结。如果需要，REBIF可以储存在36°F至77°F（2°C至25°C）之间长达30天，远离热源和光线，但冷藏是首选。
请勿在包装上印刷的失效日期之后使用。REBIF不含防腐剂。
每个预装注射器和REBIF Rebidose自动注射器用于单剂量。应该丢弃未使用的部分。
完整说明书附件：https://www.emdserono.com/content/dam/web/corporate/non-images/country-specifics/us/pi/rebif-pi.pdf
REBIF (interferon beta-1a), for subcutaneous injection
Initial U.S. Approval: 1996

General Information
Rebif (interferon beta-1a) has been approved by the FDA for the treatment of relapsing forms of multiple sclerosis. Rebif has been shown to decrease the frequency of clinical exacerbations and delay the accumulation of physical disability in patients with MS. The recommended dose of the product is 44 mcg three times per week to be administered by subcutaneous injection. Rebif is supplied in single-use, pre-filled syringes.
Rebif previously was approved in Europe in 1998 and currently is registered for use in over 70 countries.
Clinical Results
The approval of Rebif was based on the results of two large multi-center studies eva luating the safety and efficacy of the drug in patients with relapsing-remitting multiple sclerosis (RRMS). The first study was a randomized, double-blind, placebo controlled study of 560 subjects with multiple sclerosis for at least one year. Subjects received either placebo, Rebif 22 mcg or Rebif 44 mcg administered three times a week for a duration of two years. Results indicated that both the 22 mcg and 44 mcg doses of Rebif significantly reduced the number of exacerbations per subject as compared to placebo. There was no statistically significant difference between percent reduction of exacerbations in subjects receiving 22 mcg (29% reduction) and 44 mcg (32% reduction). A secondary endpoint was the progression of disability, defined as an increase in the Kurtzke Expanded Disability Status Scale (EDSS) of at least 1 point sustained for at least 3 months. Results showed that the time to onset of progression in disability sustained for three months was significantly longer in subjects treated with either dose or Rebif than in subjects received placebo only.
The second study was a randomized, open-label, eva luator-blinded, active comparator study comparing the effects of Rebif 44 mcg to those of Avonex 30 mcg in 677 subjects with RRMS who had not been treated with interferon before. Subjects received either Rebif 44 mcg (three times weekly, subcutaneously) or Avonex 30 mcg (once weekly, intramuscularly) and underwent repeated clinical and MRI assessments during the course of treatment. Results showed that during the first 24 weeks of treatment, 75% of subjects receiving Rebif did not experience a relapse, compared to 63% of subjects receiving Avonex who did not experience a relapse during the same period. This difference was statistically significant. In addition, researchers assessed the combined unique active lesions as measured by MRI. At 24 weeks, Rebif-treated subjects had an average of 0.8 active lesions per scan, while Avonex-treated patients averaged 1.2 leasions per scan. This represents a reduction of approximately one-third of lesion activity in the subjects receiving Rebif.
Side Effects
In clinical trials, the most commonly reported adverse reactions to Rebif were:
Injection site disorders
Flu-like symptoms
Abdominal pain
Depression
Elevation of liver enzymes
Blood cell abnormalities
Depression and suicidal indeation have been reported to occur more frequently in patients being treated with interferon compounds, including Rebif.
Mechanism of Action
Interferons are a family of naturally occurring proteins that are produced by eukaryotic cells in response to viral infection and other biological inducers. Interferons possess immunomodulatory, antiviral and antiproliferative biological activities. They exert their biological effects by binding to specific receptors on the surface of cells… Type 1 interferons have considerably overlapping but also distinct biological activities. Interferon beta is produced naturally by various cell types including fibroblasts and macrophages. Binding of interferon beta to its receptors initiates a complex cascade of intracellular events that leads to the expression of numerous interferon-induced gene products and markers, including 2’,5’-oligoadenylate synthetase, beta 2-microglubin and neopterin, which may mediate some of the biological activities. The specific interfereon-induced proteins and mechanisms by which interferon beta-1a exterts its effects in multiple sclerosis have not been fully defined.  
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200952600351028.pdf