美国食品和药品管理局（FDA）4月15日批准托珠单抗（Tocilizumab，商品名Actemra）单用或者与甲氨喋呤联合用于治疗2岁及以上儿童的活动期全身型幼年特发性关节炎（SJIA）。
    SJIA又称斯蒂尔病（Still’s disease），是在儿童中发病的一种罕见的、可能危及生命的、会导致全身性严重炎症的在儿童中发病的疾病。SJIA与其他类型幼年特发性关节炎（JIA）的区别在于其全身性的炎症特征突出，所述特征包括高烧，皮疹，淋巴结、肝、脾肿大和炎症，白细胞和血小板计数升高。JIA在儿童中的发病率估计为1-2‰，而SJIA的发病率约占总JIA患者的10%。
    托珠单抗是一种白介素-6受体阻断剂，曾于2010年1月8日获美国FDA批准用于治疗患中度至重度活动性风湿性关节炎的成年患者，所述患者对其他已批准药物没有充分应答。

    FDA药物评价和研究中心（Center for Drug Evaluation and Research）肺病、过敏症及风湿病药物部门（Division of Pulmonary, Allergy, and Rheumatology Products）主任Badrul Chowdhury博士表示，将托珠单抗的适用范围扩大为罹患SJIA这种罕见病的患儿提供了首个获批治疗方案。

    一项由112名SJIA患者参与的国际性、多中心、对照试验证实了该药的安全性和有效性。这些参与者是用非甾体类抗炎药物和类固醇类药物治疗效果不佳或不能适用这些药物的2-17岁SJIA患者，他们每两周接受一次托珠单抗输液或安慰剂输液治疗。

    有疗效是指至少改善美国风湿病学会JIA疗效变量的30%，并在改善前七天没有发烧。治疗组85%的患者对Actemra有应答，而安慰剂组只有24%。在该项试验的长期随访期间，治疗组出现3例巨噬细胞活化综合征（MAS）。MAS是儿童全身型炎症疾病的潜在致命并发症，据认为它是由某些免疫细胞的过度活化及增殖引起。
    托珠单抗有严重感染的黑框警告，如在使用过程中发生严重感染应立即停药，直到感染得到控制才可继续服药。药品说明书的顶端用黑框的形式警告故名黑框警告，它是一条简洁的信息概要，是处方权者应注意的关键信息，包括分配和使用禁忌。

    服用托珠单抗后不常见到肝功能、血细胞计数以及胆固醇水平的变化，因此应常进行血常规试验监测。试验中的SJIA患者最常见的不良反应有上呼吸道感染、头疼、咽痛以及腹泻等。

Actemra (tocilizumab) 日本包装

The US Food and Drug Administration (FDA) has approved tocilizumab intravenous infusion (Actemra, Roche) for the once-monthly treatment of moderately to severely active rheumatoid arthritis (RA) in adults who have had an inadequate response to 1 or more tumor necrosis factor antagonist therapies.

The first-in-class interleukin 6 receptor–inhibiting monoclonal antibody is the ninth biologic agent approved for the treatment of RA and may be used alone or in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARDS). It is expected to be available in the United States the week of January 18, 2010.

FDA approval was based on data from 5 multinational phase 3 clinical trials of more than 4000 patients, showing that tocilizumab therapy significantly decreased RA symptoms regardless of prior treatments.

Data from the RheumAtoiD ArthritIs Study in Anti-TNF FailurEs (RADIATE) trial showed that 50% and 30% of patients treated with methotrexate and tocilizumab 8 mg/kg and 4 mg/kg, respectively, achieved a 20% improvement in arthritis signs and symptoms (American College of Rheumatology [ACR] 20) at week 24 compared with 10% of those receiving methotrexate alone.

These findings were supported by data from the TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders (OPTION) and TociLIzumab Safety and THE Prevention of Structural Joint Damage (LITHE) studies, in which the addition of tocilizumab 8 mg/kg and 4 mg/kg to methotrexate likewise significantly improved ACR20 rates at week 24 relative to methotrexate alone (59% and 48% vs 27%; 56% and 51% vs 27%). In the Actemra versus Methotrexate double-Blind Investigative Trial In mONotherapy (AMBITION) trial, 70% of patients receiving tocilizumab 8 mg/kg with methotrexate achieved ACR20 at week 24 compared with 53% of those receiving methotrexate alone.

The fifth study, Tocilizumab in cOmbination With traditional DMARD therapy (TOWARD), showed that the addition of tocilizumab 8 mg/kg to methotrexate or other DMARDS significantly improved ACR20 rates at week 24 compared with DMARDS alone (61% vs 25%).

"For many RA patients, treatment with existing therapies does not resolve the painful and debilitating symptoms of the disease," said Mark Genovese, MD, study investigator and professor of medicine and cochief of the Division of Immunology and Rheumatology at Stanford University Medical Center, California, in a company news release. "Data from the clinical development program clearly establish Actemra and its unique mechanism of action as an important new option for RA patients who experience continued disease symptoms despite treatment with existing therapies."

Adverse events most commonly reported in tocilizumab-treated patients include upper respiratory tract infection, nasopharyngitis, headache, high blood pressure, and liver enzyme elevations that were generally mild and reversible. Serious adverse effects may include infection, gastrointestinal perforation, and hypersensitivity reactions.

Tocilizumab previously was approved for the treatment of RA in the European Union and several other countries, including Mexico, India, Brazil, Switzerland, Australia, and Japan. Additional indications in Japan include Castleman's disease and juvenile idiopathic arthritis.