Yokota Shumpei, Imagawa Tomoyuki, Mori Masaaki, Miyamae Takako, Takei Syuji, Iwata Naomi, Umebayashi Hiroaki, Murata Takuji, Miyoshi Mari, Tomiita Minako, Nishimoto Norihiro, Kishimoto Tadamitsu
From the Department of Pediatrics, Yokohama City University School of Medicine, and Department of Pediatrics, Yokohama City University Medical Center; Yokohama; School of Health Science, Faculty of Medicine, Kagoshima University, Kagoshima; Aichi Children's Health and Medical Center, Aichi; Miyagi Children's Hospital, Miyagi; Department of Pediatrics, Osaka Medical College, Osaka; Kobe Children's Hospital, Kobe; Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba; Department of Molecular Regulation for Intractable Diseases, Institute of Medical Science, Tokyo Medical University, Osaka; Immunology Frontier Research Center, Osaka University, Osaka, Japan.
J Rheumatol. 2014 Apr;41(4):759-67. doi: 10.3899/jrheum.130690. Epub 2014 Mar 15.
To assess the longterm safety and effectiveness of tocilizumab (TCZ) in systemic-onset juvenile idiopathic arthritis (sJIA).
The longterm extension phase of 2 pivotal studies (phase II with 11 patients and phase III with 56 patients) in patients with active sJIA was analyzed. Patients received open-label TCZ (8 mg/kg, every 2 weeks) without concomitant use of disease-modifying antirheumatic drugs.
In total, 67 patients were enrolled. All patients received corticosteroid at baseline. Median duration of exposure to TCZ was 3.4 years. Nine patients withdrew from the study [4 because of adverse events (AE), 4 because of the development of anti-TCZ antibodies, and 1 because of inadequate response]. Rates of AE and serious AE were 803.7/100 patient-years (PY) and 34.7/100 PY, respectively. The most common serious AE were infections (13.2/100 PY). No cases of malignancy or death were reported. Two serious infusion reactions were reported in patients testing negative for anti-TCZ antibodies. One definite macrophage activation syndrome (MAS) case and 1 potential MAS case were identified. American College of Rheumatology (ACR) response rates attained early in the TCZ treatment period were maintained throughout the study: at Week 168, JIA ACR 30, 50, 70, 90, and 100 response rates were 80.3%, 80.3%, 75.4%, 60.7%, and 18.0%, respectively. In total, 22 of 67 patients (32.8%) completely discontinued corticosteroids without flare.
TCZ has demonstrated durability of effectiveness in the longterm treatment of children with sJIA and has shown good tolerability and a low discontinuation rate associated with AE, development of anti-TCZ antibodies, or inadequate response. (ClinicalTrials.gov NCT00144599 and NCT00144612). (First Release March 15 2014; J Rheumatol 2014;41:759-67; doi:10.3899/jrheum.130690).
评估托珠单抗（TCZ）治疗全身型幼年特发性关节炎（sJIA）的长期安全性和有效性。
分析了2项关键研究（II期研究11例患者，III期研究56例患者）中活动性sJIA患者的长期延长期。患者接受开放标签的TCZ（8mg/kg，每2周一次），不联合使用改善病情抗风湿药物。
共纳入67例患者。所有患者在基线时均接受皮质类固醇治疗。TCZ的中位暴露时间为3.4年。9例患者退出研究[4例因不良事件（AE），4例因抗TCZ抗体产生，1例因反应不足]。AE和严重AE的发生率分别为803.7/100患者年（PY）和34.7/100 PY。最常见的严重AE是感染（13.2/100 PY）。未报告恶性肿瘤或死亡病例。抗TCZ抗体检测阴性的患者报告了2例严重输液反应。确定了1例明确的巨噬细胞活化综合征（MAS）病例和1例可能的MAS病例。在整个研究过程中，TCZ治疗早期达到的美国风湿病学会（ACR）反应率得以维持：在第168周时，幼年特发性关节炎ACR 30、50、70、90和100反应率分别为80.3%、80.3%、75.4%、60.7%和18.0%。67例患者中有22例（32.8%）完全停用皮质类固醇且未复发。
TCZ在sJIA患儿的长期治疗中已证明有效性持久，且显示出良好的耐受性以及与AE、抗TCZ抗体产生或反应不足相关的低停药率。（ClinicalTrials.gov标识符：NCT00144599和NCT00144612）。（首次发表于2014年3月15日；《风湿病学杂志》2014年；41：759 - 67；doi:10.3899/jrheum.130690）
