美国FDA于2010年1月 8日批准Genentech和Roche公司新单抗Actemra (tocilizumab)注射剂治疗中度至严重活动性类风湿性关节炎。公司副总裁认为“批准标识RA治疗向前重要一步，为此非常严重疾病患者提供一种新选择”。

ACTEMRA (tocilizumab)是一种免疫球蛋白IgG1(γ1，κ)子类重组人源化抗-人白介素6(IL-6)受体单抗，有典型的H2L2多肽结构。每条轻链和重链分别由214和448氨基酸组成。四条多肽链通过分子内和分子间二硫键连接，ACTEMRA的相对分子质量约148 kDa。
适应证：ACTEMRA?(tocilizumab)是白介素-6(IL-6)受体抑制剂用于类风湿性关节炎治疗：适用于一种或更多TNF 拮抗剂治疗反应不佳的中度至严重-活动性类风湿性关节炎成年患者。
剂量和用法：类风湿性关节炎。ACTEMRA可单独使用或与氨甲喋呤或其它DMARD联用。
1.  成年推荐剂量每4周：患者对一种或更多TNF拮抗剂反应不佳：当与DMARD联用或单药治疗时，推荐起始量是4 mg/kg接着基于临床反应增至8 mg/kg。嗜中性绝对计数(ANC)低于2000/mm3, 血小板计数低于100,000/mm3，或ALT或AST高于正常上限(ULN)1.5倍患者建议不要开始用ACTEMRA。
2.  建议每次输注ACTEMRA剂量不要超过800 mg。
3.  给药 为静脉输注用无菌术稀释至100 mL 0.9%氯化钠。在1小时期间单次静脉滴注。不要推注。
4.  调整剂量 建议对某些剂量-相关实验室变化处理包括肝酶升高、白细胞减少、和血小板减少。
剂型和规格：ACTEMRA的单次使用小瓶(20 mg/mL)：80 mg/4 mL；200 mg/10 mL和400 mg/20 mL。
禁忌证：无
注意事项：
1.  严重感染 –活动性感染，包括局部感染期间不要给予ACTEMRA。如发生严重感染， 中断ACTEMRA直至感染被控制。
2.  胃肠道(GI)穿孔 – 患者可能处在增加风险，慎用。
3.  建议进行实验室监查 – 由于嗜中性、血小板、脂质、和肝功能检验治疗相关变化潜在后果。
4.  曾发生过敏或严重超敏反应。
5.  用ACTEMRA不应给予活疫苗。
不良反应：最常见不良反应(发生率5%)：上呼吸道感染、鼻咽炎、头痛、高血压、ALT升高。
严重感染风险:
1.  接受ACTEMRA患者中曾发生严重感染导致住院或死亡包括结核(TB)、细菌性、侵袭性真菌、病毒,和其它机会性感染。
2.  如发生严重感染，中断ACTEMRA直至感染被控制。
3.  进行潜伏TB检验；如阳性，在开始用ACTEMRA前先开始治疗TB。
活动性TB治疗期间监查所有患者，即使初始潜伏TB检验阴性。

Indication(s):

Moderately-to severely-active rheumatoid arthritis in patients who have had an inadequate response to ≥1 TNF blocker. May be used with methotrexate or DMARDs.

Pharmacology:

Interleukin-6 (IL-6) is produced by monocytes and lymphocytes in the bloodstream and by synovial and endothelial cells in the joints, leading to systemic and local production of IL-6 in patients affected by inflammatory processes such as rheumatoid arthritis. Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors, and has been shown to inhibit IL-6-mediated signaling through these receptors.

Clinical Trials:

The efficacy and safety of tocilizumab was assessed in five randomized, double-blind studies in patients >18 years with active rheumatoid arthritis. Tocilizumab was given every 4 weeks as monotherapy (Study I), in combination with methotrexate (MTX) (Studies II and III) or other DMARDs (Study IV) in patients with an inadequate response to those drugs, or in combination with MTX in patients with an inadequate response to TNF antagonists (Study V). The primary endpoint was the proportion of patients who achieved an ACR20 response at week 24. In all studies, patients treated with tocilizumab 8mg/kg had statistically significant ACR20, ACR50, and ACR70 response rates versus MTX- or placebo-treated patients at week 24. Patients with inadequate response to DMARDs or TNF antagonist therapy treated with tocilizumab 4mg/kg had lower response rates compared to patients treated with tocilizumab 8mg/kg.

Legal Classification:

Rx

Adults:

Give once every 4 weeks as a 60-minute IV infusion. Initially 4mg/kg, may increase to 8mg/kg based on clinical response. Do not start if ANC<2000/mm³, platelets <100000/mm³, or ALT/AST >1.5xULN. Reduce dose to 4mg/kg if elevated liver enzymes, neutropenia, or thrombocytopenia occur (see literature).

Children:

Not recommended.

Precaution(s):

ANC <500mm³, platelets <50000mm³, or ALT/AST >5xULN: not recommended. Monitor neutrophils, platelets, liver function tests every 4–8 weeks. Active hepatic disease or impairment: not recommended. HBV or HCV infection. Increased risk of serious or fatal infections (eg, TB, bacterial sepsis, invasive fungal). Active infections: do not give therapy. Chronic or history of recurring or opportunistic infections. Conditions that predispose to infection. Travel to, or residence in, areas with endemic TB or mycoses. Test for and treat latent TB prior to starting therapy. Monitor closely if new infection develops; discontinue if serious or opportunistic infection or sepsis develop. Monitor lipids 4–8 weeks after initiation, then every 6 months. Immunosuppression. CNS demyelinating disorders. Malignancies. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interaction(s):

Increased risk for infection with concomitant immunosuppressants (eg, TNF antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies, selective co-stimulation modulators). Avoid live vaccines. Caution with CYP3A4 substrate drugs (eg, oral contraceptives, lovastatin, atorvastatin). Monitor warfarin, cyclosporine, theophylline, other drugs that are CYP450 substrates with narrow therapeutic indices.

Adverse Reaction(s):

Upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT; infusion reactions, neutropenia, thrombocytopenia, gastrointestinal perforations, increased lipids.

How Supplied:

Single-use vials (80mg/4mL,
200mg/10mL, 400mg/20mL)—1, 4

Last Updated:

2/12/2010