2013年10月24日，罗氏（Roche）皮下注射剂型Actemra（通用名：tocilizumab）获FDA批准，用于既往经一种或多种疾病修饰抗风湿药物（DMARDs）治疗反应不足的中度至重度活动性类风湿性关节炎（RA）成人患者的治疗。此次批准，是Actemra在4年内获得的第6个FDA批准，此前FDA已批准Actemra用于中度至重度活动性类风湿性关节炎成人患者的治疗、用于2岁及以上活动性多关节幼年特发性关节炎和全身型幼年特发性关节炎的治疗。
与静脉注射剂型Actemra一样，皮下注射剂型Actemra可用作单药疗法，也可与甲氨蝶呤（MTX）或其他非生物类DMARDs联合用药。罗氏计划于11月初将皮下注射剂型配方Actemra推向市场。
FDA曾于2010年批准Actemra作为一种静脉注射（IV）药物，目前，该药是首个也是唯一一个获FDA批准可静脉滴注给药（IV）和皮下注射给药（SC）的人源化白细胞介素6受体拮抗剂单克隆抗体。
皮下注射剂型Actemra的获批，是基于III期临床试验SUMMACTA和BREVACTA研究的数据。
SUMMACTA是一项随机、双盲、活性药物对照、平行组、多中心III期临床研究，在1262例中度至重度活动性RA患者中开展。研究结果表明，皮下注射剂型（subcutaneous，SC）Actemra（162mg/周），达到了与静脉注射剂型（intravenous，IV）Actemra（8mg/kg/4周）相媲美的疗效，各组在24周时达到ACR20反应的患者比例相似（Actemra SC vs Actemra IV ：69% vs 73% ）。 24周时的安全性分析表明，除SC组注射部位反应外，SC组和IV组不良事件相当。
Brevacta是一项随机、双盲、平行组III期研究，调查了皮下注射剂型Actemra联合DMARDs用于治疗中度至重度活动性类风湿性关节炎患者时相对于安慰剂和DMARDs的疗效和安全性。研究结果表明，与安慰剂+DMARDs治疗组相比，Actemra SC+DMARDs治疗组有更多的患者达到ACR20反应（61% vs 32%）。该项研究中，除注射位点反应外，未发现临床意义的新安全信号
ACTEMRA Rx
Generic Name and Formulations:
Tocilizumab 20mg/mL (vial); soln for IV infusion after dilution; 162mg/0.9mL (prefilled syringe); soln for SC inj; both: preservative-free.
Company:
Genentech, Inc
Indications for ACTEMRA:
Moderately-to-severely active rheumatoid arthritis (RA) in patients who have had an inadequate response to ≥1 DMARDs; may be used as monotherapy or concomitantly with methotrexate or other non-biologic DMARDs. Active systemic juvenile idiopathic arthritis (SJIA) or active polyarticular juvenile idiopathic arthritis (PJIA) as monotherapy, or in combination with methotrexate.
Adult:
RA: IV regimen: give as a 60-min single IV drip. Initially 4mg/kg every 4 weeks, followed by an increase to 8mg/kg every 4 weeks based on clinical response. Doses >800mg per infusion: not recommended. SC regimen: <100kg: 162mg SC inj every other week, followed by an increase to once weekly based on clinical response. ≥100kg: 162mg SC inj once weekly. Rotate inj sites. Reduce IV dose to 4mg/kg or SC dose to every other week if elevated liver enzymes, neutropenia, or thrombocytopenia occur (see full labeling). Do not start if ANC <2000/mm3, platelets <100000/mm3, or ALT/AST >1.5xULN. Transitioning from IV to SC administration: give 1st SC dose instead of next scheduled IV dose.
Children:
RA: not established. SJIA, PJIA: <2yrs or SC administration: not studied. ≥2yrs: Give once every 2 weeks (SJIA) or once every 4 weeks (PJIA) as a 60-min IV infusion. SJIA: <30kg: 12mg/kg. PJIA: <30kg: 10mg/kg. Both: ≥30kg: 8mg/kg. May need to interrupt dose if elevated liver enzymes, neutropenia, or thrombocytopenia occur (see full labeling). Do not start if ANC <2000/mm3, platelets <100000/mm3, or ALT/AST >1.5xULN.
Pharmacological Class:
Interleukin-6 receptor inhibitor.
Warnings/Precautions:
Increased risk of serious or fatal infections (eg, TB, bacterial, invasive fungal, viral, and other opportunistic infections); if develop, interrupt until controlled. Active infections: do not give therapy. Consider risks/benefits prior to initiating: chronic or recurrent, or history of opportunistic infections, exposed to TB, travel to, or residence in, areas with endemic TB or mycoses, conditions that predispose to infection. Monitor closely for signs/symptoms of infection during and after therapy; interrupt if serious or opportunistic infection or sepsis develop. Test for and treat latent TB prior to starting therapy. HBV or HCV infection. ANC <500mm3, platelets <50000mm3, or ALT/AST >5xULN: not recommended. Monitor neutrophils, platelets, liver function tests: RA: every 4–8 weeks, then every 3 months; SJIA: at the time of the 2nd infusion and then every 2–4 weeks; PJIA: at the time of the 2nd infusion and then every 4–8 weeks. Monitor lipids 4–8 weeks after initiation, then every 6 months. Increased risk of GI perforation. Active hepatic disease or impairment: not recommended. Immunosuppression. Malignancies. CNS demyelinating disorders; monitor. Discontinue permanently if anaphylaxis or hypersensitivity reactions occur. Elderly. Pregnancy (Cat. C). Nursing mothers: not recommended.
Interactions:
Avoid live vaccines. Increased risk for infection with concomitant biological DMARDs (eg, TNF antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies, selective co-stimulation modulators); avoid. Caution with CYP3A4 substrate drugs (eg, oral contraceptives, lovastatin, atorvastatin, others). Monitor warfarin, cyclosporine, theophylline, other drugs that are CYP450 substrates with narrow therapeutic indices.
Adverse Reactions:
Upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT, inj site reactions; hypersensitivity reactions (may be severe and fatal), neutropenia, thrombocytopenia, GI perforation, increased lipids.
REMS:
YES
Note:
Register pregnant patients in Actemra pregnancy exposure registry by calling (877) 311-8972.
How Supplied:
Single-use vial (80mg/4mL, 200mg/10mL, 400mg/20mL)—1; Single-use prefilled syringe—1
