日美国食品与药物管理局（FDA）发布公告，批准tocilizumab（Actemra）单独给药或与甲氨蝶呤（methotrexate）联用，用于治疗2岁及以上儿童的活动性全身型幼年特发性关节炎（SJIA）。

SJIA，或称Still病，是儿童中一种罕见的、有可能威胁生命的疾病，可导致全身严重炎症。SJIA与其他幼年特发性关节炎（JIA）类型有别。据估计，每1000名儿童中有2名患有JIA，而SJIA占到所以JIA患者的约10%。

Actemra是一种白介素6受体阻滞剂，于2010年1月8日经FDA批准用于治疗对其他药物反应不佳的成人中度至严重活动性类风湿性关节炎。

“Actemra的这种新适应证为有这种罕见疾病的孩子提供了第一个经批准的治疗方法。”FDA药物评估和研究中心肺、过敏和风湿病产品部主任Badrul Chowdhury博士说。

一个国际多中心对照试验证明了Actemra的安全性和有效性。试验中，112例患者接受Actemra或安慰剂每两周1次的注射。研究参与者为患有SJIA、年龄在2岁至17岁之间、对非甾体类抗炎药和类固醇反应不佳或不能耐受的患者。接受Actemra的患者中，85%有治疗反应，而接受安慰剂的患者为24%。从长期来看，试验随访期间，接受Actemra的SJIA患者中，有3例发生巨噬细胞活化综合征（MAS）。MAS是儿童全身性炎症性疾病有致命可能的并发症，被认为是由某些免疫细胞过度激活和增殖造成的。

本品有提示严重感染的黑框警告。接受Actemra治疗的患者如发生严重感染，应停止使用Actemra，直至感染控制。

试验中的SJIA患者最常见的毒副作用包括上呼吸道感染、头痛、咽喉痛和腹泻。

ACTEMRA

Generic Name for ACTEMRA

Tocilizumab 20mg/mL; soln for IV infusion after dilution; preservative-free.

Legal Classification:

Rx

Pharmacological Class for ACTEMRA

Interleukin-6 receptor inhibitor.

Manufacturer of ACTEMRA

Genentech, Inc.

Indications for ACTEMRA

Moderately-to severely-active rheumatoid arthritis (RA) in patients who have had an inadequate response to ≥1 TNF blocker. May be used with methotrexate or DMARDs. Active systemic juvenile idiopathic arthritis (SJIA), as monotherapy or in combination with methotrexate.

Adult dose for ACTEMRA

RA: 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's dosing for ACTEMRA

RA: not recommended. SJIA: <2yrs: not recommended. ≥2yrs: Give once every 2 weeks as a 60-minute IV infusion. <30kg: 12mg/kg. ≥30kg: 8mg/kg. Do not start if ANC<2000/mm³, platelets <100000/mm³, or ALT/AST >1.5xULN. May need to interrupt dose if elevated liver enzymes, neutropenia, or thrombocytopenia occur.

Warnings/Precautions for ACTEMRA

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. ANC <500mm³, platelets <50000mm³, or ALT/AST >5xULN: not recommended. Monitor neutrophils, platelets, liver function tests: RA: every 4–8 weeks; SJIA: at the time of the 2^nd infusion and then every 2–4 weeks. Active hepatic disease or impairment: not recommended. HBV or HCV infection. Increased risk of GI perforation. Monitor lipids 4–8 weeks after initiation, then every 6 months. Immunosuppression. CNS demyelinating disorders. Malignancies. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions for ACTEMRA

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 Reactions for ACTEMRA

Upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT; infusion reactions (may be severe and fatal), neutropenia, thrombocytopenia, gastrointestinal perforations, increased lipids.

How is ACTEMRA supplied?

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