诺华公司(NVS)宣布，美国食品与药品管理局(FDA)已批准了其研制的Extavia(重组干扰素β-1b)用于治疗多发性硬化症。Extavia还被批准用于经历这种疾病的首次发作，并且拥有与多发性硬化症相符合的症状的患者。早在今年5月，Extavia获得了欧盟的上市批准。

Extavia是干扰素β-1b的一种形式，诺华表示，该药自上世纪90年代初以来一直是多发性硬化症的标准治疗药。该公司表示，美国大约有40万人患有多发性硬化症，其中大约80%是复发好转型。

在多发性硬化病人中常见认知功能障碍、抑郁症和社交功能改变,90%的病人感到疲乏。帕蒂等进行的多发性硬化症的认知损害(COGIMUS)研究,是在意大利开展的一项前瞻性、探索性的队列试验。

研究始于2004年1月,目的是在RRMS病人(EDSS≤4.0)中进行干扰素β-1a(22μg或44μg,,皮下注射,每周3次)的疗效研究。病人轻度失能,研究共计3年。

次要终点包括认知功能与临床检测的关联、EDSS评分变化、继发进展型多发性硬化(SPMS)的进展和复发率。研究者在有、无认知障碍和(或)抑郁症状的病人中评价了基线MRI检测的差异,也评价了认知功能障碍对病人社交功能及疲乏的影响。

研究表明,在MRI上,T1和T2病变和脑容量值似乎与认知功能障碍和抑郁有关,缓解病情药(DMD)如干扰素β-1a能减缓病情进展,也可能对病人的认知行为和情绪有益。

肌肉注射干扰素β-1a的效果研究：

该研究是在未经治疗的复发缓解型MS病人(RRMS)中,评价病人生活质量(QoL)情况,并对肌肉注射干扰素β-1a的影响进行研究。这是在德国进行的前瞻性、多中心观察研究,1157例病人每周接受1次干扰素β-1a(30μg)治疗。在基线和12个月期间进行5次随访。主要终点是用欧洲QoL问卷进行的QoL评估。结果显示,即使在MS早期,病人的QoL已经受到影响。接受注射干扰素β-1a治疗的病人,其MS病情得到缓解,QoL改善。

皮下注射干扰素β-1a的疗效研究：

该研究旨在评价RRMS病人接受干扰素β-1a治疗后,在磁共振成像(MRI)上所显示的短期疗效。该研究是在成年RRMS病人中进行的Ⅲb多中心研究,病人的扩展功能障碍分级(EDSS)评分≤5.5,疾病持续时间>12个月,随机分组前6个月出现≥1个临床事件和≥1个脑部钆增强MRI病变。病人以2∶1的比例分组,随机接受干扰素β-1a(皮下注射,44μg,每周3次)治疗或安慰剂治疗,研究共计16周(双盲期)。主要终点是16周时有独特活性的复合(CUA)脑病变。结果显示,干扰素β-1a对RRMS病人作用快速而有效。

相关热点聚焦
■ 中和抗体检测有用

   保利切利等在RRMS病人中进行了中和抗体对β干扰素影响的上市后评价研究。研究纳入556例RRMS病人,对病人随访5年,评价病人在中和抗体阳性和中和抗体阴性情况下,对β干扰素临床应答的差异。

   研究证实,中和抗体阳性可导致疾病活动,使β干扰素的疗效降低。研究也显示中和抗体对病人远期失能有不良影响。这意味着在做治疗决策时,检测中和抗体水平可能有用。

■ 治疗失败的界定

    对治疗应答进行定义的目的是鉴别出早期治疗无应答者,治疗无应答者的比例随治疗应答的定义不同而异,基于MS复发制定的治疗标准敏感性差,阳性预测价值也不佳。

    治疗无应答者在基线时,疾病的临床活性较高,基线EDSS值可预测远期失能。

    目前关于MRI预测治疗应答的前瞻性资料有限,而早期EDSS值增加可能是一个不良应答的临床标识。

■ 治疗失败的处理

    对DMD治疗失败的病人可采用如下处理方法:在干扰素治疗药物间转换;在一种干扰素治疗上加用其他药物进行联合治疗;从单用干扰素治疗转换成那他珠单抗或米托蒽醌的增强治疗。用β干扰素治疗病人应该检查疾病活动度,因为可能存在中和抗体阳性。

  药物联用(干扰素β-1a与克拉屈滨联用的SENTINEL研究)导致的毒性应引起人们重视。

Manufacturer: Novartis Pharmaceuticals Corp

Pharmacological Class: Immunomodulator

Active Ingredient(s): Interferon beta-1b 0.3mg/vial; pwd for SC inj after reconstitution; contains albumin (human), mannitol.

Indication(s): To reduce frequency of clinical exacerbations in relapsing multiple sclerosis (MS).

IntPharmacology: erferon beta-1b is a Type I interferon that has various immunomodulatory effects. Its mechanism of action in treating

patients with MS is unknown.

Clinical Trials:

Study 1 was a two-year, parallel design study in which patients with relapsing-remitting MS were randomized to treatment with either interferon beta-1b, dosed at 0.05mg or 0.25mg every other day, or placebo. The primary outcome measures were the frequency of exacerbations per patient and the proportion of exacerbation-free patients. The annual exacerbation rate for the patients in the interferon beta-1b 0.25mg treatment group was 0.9, compared to 1.31 for placebo. The proportion of exacerbation-free patients was 25% for the interferon beta-1b 0.25mg group, compared to 16% for placebo.

Studies 2 and 3 were conducted to assess the effect of this drug in patients with secondary progressive MS. Both studies enrolled patients who had evidence of disability progression, and Study 2 also included patients with two relapses within the previous two years. Patients in Study 2 were randomized to either interferon beta-1b 0.25mg or placebo; patients in Study 3 were given interferon beta-1b 0.25mg, interferon beta-1b 0.16mg/m2, or placebo, every other day for 3 years. The primary outcome measure was progression of disability, defined as a 1 point increase in the Kurtzke expanded disability status scale (EDSS), or a 0.5 point increase in the score for patients with baseline EDSS ≥6. In Study 2, time to progression in EDSS was longer in the interferon beta-1b treatment group. In Study 3, the rates of progression did not differ significantly between treatment groups. Multiple analyses failed to identify a patient subset where treatment with interferon beta-1b was associated with delayed progression of disability. Both Studies 2 and 3 showed a statistically significant decrease in the incidence of relapses associated with interferon beta-1b treatment.

Legal Classification:

Rx

Adults:

≥18 years: initially 0.0625mg SC every other day; increase by 25% every 2 weeks to target dose of 0.25mg SC every other day.

Children:

<18 years: not recommended.

Precaution(s):

Depression. Suicidal ideation. Monitor CBC, differential, platelets, chemistries, liver function (at 1, 3, and 6 months then periodically). Thyroid disorders. Elderly. Pregnancy (Cat. C; may be abortifacient). Nursing mothers: not recommended.

Adverse Reaction(s):

Lymphopenia, neutropenia, leukoprnia, lymphadenopathy, headache, insomnia, incoordination, hypertension, dyspnea, abdominal pain, increased liver enzymes, rash, skin disorder, hypertonia, myalgia, urinary urgency, metrorrhagia, impotence, asthenia, flu-like symptoms, pain, peripheral edema, chest pain, malaise, injection site reactions/necrosis (suspend therapy if multiple lesions occur); anaphylaxis.

How Supplied:

Single-use vials—15 (w. prefilled diluent syringe, supplies)

Last Updated:

10/29/2009