美国FDA已经批准一种用于中到重度银屑病的成人用生物制剂—Stelara (ustekinumab)斑块状银屑病是一种免疫系统疾病，可导致皮肤细胞过量生成。
美国大约600万人患有斑块状银屑病，该病以增厚的发炎斑块，通常覆盖有银色鳞屑的红色皮肤为特征。“这一批准为斑块状银屑病患者提供了治疗选择，这种病可以导致病人从疼痛到瘙痒等严重的身体不适，从而导致对自己形象充满自信的患者丧失自信”FDA药品评价与研究中心III期药物评估办公室负责人Julie Beitz说。Stelara是一种单克隆抗体，可模仿人体自身生成的抗体，该抗体是免疫系统一个组成部分。这种生物制剂通过抑制超量产生的皮肤细胞以及致炎的两种蛋白活性来治疗银屑病。三个包含2266名患者的临床试验评估该生物制剂是安全并且有效的。

由于Stelara能减小机体抵抗感染的能力，该产品具有增加感染的危险性。一些使用该药物的患者报道严重感染，并且他们中的许多需要住院。这些由病毒，真菌，或细菌引起的感染遍布全身。也有增加癌症发展的可能。FDA需要危险评估，并且需要缓解的策略或关于Stelara的REMS，即包括以治疗医生为目标的联络计划和对患者的药物指导。

Stelara由强生的全资子公司Centocor Ortho Biotech公司生产。

处方资料的重点

STELARA (ustekinumab)
注射剂，为皮下使用
美国2009年初次批准

剂量和给药方法，对给药的一般考虑
剂量和给药方法, 为STELARA给药指导装配针头安全保护预装注射器

适应证和用途

STELARA是一种人白介素-12和-23拮抗剂适用于治疗成年患者(18岁或以上)有中度至严重斑块性银屑病是光疗和全身治疗的备选者。

剂量和给药方法

STELARA 是通过皮下注射给药。
对患者体重 <100 kg (220 lbs)，推荐剂量是最初45 mg和4周后，接着每12周45 mg。
对患者体重 >100 kg (220 lbs), 推荐剂量最初是90 mg和4周后，接着每12周90 mg。

剂型和规格

45 mg/0.5 mL在单次使用预装注射器中
90 mg/1 mL在单次使用预装注射器中
45 mg/0.5 mL在单次使用小瓶中
90 mg/1 mL在单次使用小瓶中

禁忌证

无  

警告和注意事项

感染：曾发生严重感染。任何临床上重要活动性感染是不要开始用STELARA。如发生严重感染停止STELARA直至感染解决。

特殊感染的理论风险：遗传上缺乏IL-12/IL-23患者曾报道来自分枝杆菌、沙门氏菌和卡介苗(BCG)免疫接种严重感染。临床情况指示应考虑诊断检验。

结核(TB)评价：开始用STELARA?治疗前评价患者TB。给STELARA?前开始潜伏TB治疗。

恶性病：STELARA可能增加恶性病风险。尚未评价有恶性病史或已知恶性病患者用STELARA。

可逆性后脑白质脑病综合征(RPLS)：报道1例。如怀疑立即治疗和停用STELARA。

不良反应

最常见不良反应(发生率>3%和大于安慰剂)：鼻咽炎、上呼吸道感染、头痛、和疲劳。

为报告怀疑不良反应，请联系Centocor Ortho Biotech公司或FDA

药物相互作用

活疫苗：用STELARA不应给予活疫苗。

同时治疗：尚未评价STELARA与免疫抑制剂或光疗联用的安全性。

Stelara
Janssen-Cilag has launched Stelara for the treatment of moderate to severe plaque psoriasis where other therapies are ineffective, not tolerated or contraindicated.

PHARMACOLOGY

Ustekinumab is a human monoclonal antibody that binds with high affinity and specificity to the shared p40 protein subunit of human interleukins 12 and 23, thereby preventing interaction with IL12Rβ1 receptor proteins expressed on the surface of immune cells.1 Abnormal regulation of IL-12 and IL-23 has been associated with immune-mediated diseases such as psoriasis. It is believed that by preventing IL-12 and IL-23 contributions to immune cell activation, ustekinumab interrupts signalling and cytokine cascades that are relevant to psoriasis pathology.1

CLINICAL STUDIES

The safety and efficacy of ustekinumab in patients with moderate to severe plaque psoriasis was assessed in two double-blind placebo-controlled trials (PHOENIX 1 and 2).2,3

In PHOENIX 1 (n=766) patients were randomised to receive ustekinumab 45mg or 90mg at weeks 0 and 4, then every 12 weeks, or placebo at weeks 0 and 4 with crossover to ustekinumab (45mg or 90mg) at weeks 12 and 16, then every 12 weeks. At week 40, patients in the ustekinumab groups with at least 75 per cent improvement from baseline in psoriasis area and severity index score (PASI 75) at weeks 28 and 40 were re-randomised to continue maintenance treatment with ustekinumab or placebo.

In PHOENIX 2 (n=1230), patients were randomised to ustekinumab or placebo as in PHOENIX 1. At week 28, partial responders (≥PASI 50, < PASI 75 response) were re-randomised to ustekinumab every 12 weeks or to intensified dosing every eight weeks.*

In both trials significantly more patients receiving ustekinumab achieved a PASI 75 response at week 12 than did those receiving placebo. Onset of efficacy was rapid with significantly more patients in the ustekinumab groups achieving PASI 50 by week 2 and PASI 75 by week 4, compared with placebo.

In PHOENIX 1, maintenance of PASI 75 response was significantly better in patients re-randomised at week 40 to receive maintenance therapy than in those receiving placebo through at least one year.

In PHOENIX 2, dosing intensification in the ustekinumab 90mg group resulted in a higher PASI 75 response rate at week 52 than did continuing at 12-weekly dosing, an improvement not seen in the ustekinumab 45mg group.

Treatment was well tolerated in both trials and clinical improvements were paralleled by improvements in patient-reported outcomes, as measured by dermatology life quality index.

Ustekinumab was compared with etanercept in another trial involving 903 patients with moderate to severe plaque psoriasis where ciclosporin, methotrexate or PUVA were ineffective, not tolerated or contraindicated. Patients treated with two doses of 45mg or 90mg ustekinumab at weeks 0 and 4 demonstrated significantly superior response compared with those treated with etanercept 50mg twice weekly through week 12 (PASI 75 response at week 12 achieved by 68 per cent and 74 per cent of patients vs 57 per cent in the etanercept group).

*  recommends a 12-week dosing interval.

斑块状银屑病新型治疗药STELARA将在欧洲上市

近日，欧盟委员会批准治疗斑块型银屑病的新型生物制剂STELARA（TM） （ustekinumab）在欧洲27个国家上市销售。该药治疗成人中-重度斑块型银屑病，主要用于那些对其他全身性治疗药物（包括ciclosporin，methotrexate和PUVA等）应答不充分，有禁忌症候或耐受不好的患者。在欧洲国家，有2-3%的人深受银屑病困扰。
这次ustekinumab获准的依据是在两项大型关键III期临床实验中获取的数据，该实验属多中心随机双盲安慰剂对照实验，共招募了2000名受试患者，主要检测药物治疗中-重度斑块型银屑病的安全性和疗效。结果发现，2/3的受试者达到了主要临床终点，用药12周以后，在病变面积和病情严重指数的改善至少达到75%。
上述临床实验结果表明，患者使用ustekinumab治疗之后，能有效缓解病情，提高生活质量。而且该药每年只需注射4次，它为患者带来了全新的治疗选择。
在用药过程中，最常见的副作用为关节痛、咳嗽、头痛、注射部位出现红斑、鼻咽炎和上呼吸道感染，这些不良反应多数都比较轻微，未影响治疗。该药导致的严重副作用主要为重度感染、恶性肿瘤和心血管疾病等，但出现这些不良反应的几率极小，与预计的情况相符。