Efficacy of Tocilizumab in Conventional Treatment-Refractory Adult-Onset Still's Disease
Efficacy of Tocilizumab in Conventional Treatment-Refractory Adult-Onset Still's Disease
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DOI：
10.1002/art.38398
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发表时间：
2014-06-01
影响因子：
13.3
通讯作者：
Gonzalez-Gay, Miguel A.
中科院分区：
文献类型：
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作者：
Ortiz-Sanjuan, Francisco;Blanco, Ricardo;Gonzalez-Gay, Miguel A.
Objective.成人斯蒂尔病（AOSD）通常对标准治疗无效。托珠单抗（TCZ）已在单个病例和小系列AOSD患者中证明了疗效。这项多中心研究的目的是评估TCZ在常规治疗难治性AOSD患者中的疗效。这是一项回顾性开放标签研究，在34例AOSD患者中进行TCZ治疗，这些患者对皮质类固醇和至少1种标准合成免疫抑制剂反应不佳，在许多情况下还使用生物制剂。患者（8名男性和26名女性）的平均+/- SD年龄为38.7 +/- 16.1岁。开始TCZ治疗前AOSD的中位持续时间为4.2年（四分位距[IQR] 1-9年）。TCZ初始剂量为8 mg/kg，每4周一次，2例为4 mg/kg，每4周一次，10例为8 mg/kg，每2周一次。TCZ治疗导致临床和实验室参数的快速和持续改善。TCZ治疗1年后，关节表现的发生率从基线时的97.1%降至32.4%，皮肤表现和发热的发生率从58.8%降至5.9%，淋巴结肿大的发生率从29.4%降至0%。实验室炎症标志物，包括C反应蛋白水平、红细胞沉降率和铁蛋白水平显著降低。泼尼松的中位剂量也从TCZ开始时的13.8 mg/天（IQR 5-45）减少到12个月时的2.5 mg/天（IQR 0-30）。中位随访19个月（IQR 12-31个月）后，仅有2例患者因严重感染而永久性停用TCZ治疗。TCZ治疗与标准治疗难治性AOSD患者的快速和持续临床和实验室改善相关。然而，与全身表现相比，关节表现似乎更难治疗。
Objective. Adult-onset Still's disease (AOSD) is frequently refractory to standard therapy. Tocilizumab (TCZ) has demonstrated efficacy in single cases and in small series of patients with AOSD. The aim of this multicenter study was to assess the efficacy of TCZ in patients with AOSD refractory to conventional treatment.Methods. This was a retrospective open-label study of TCZ treatment in 34 patients with AOSD who had experienced an inadequate response to corticosteroids and at least 1 standard synthetic immunosuppressive drug and also, in many cases, biologic agents.Results. The mean +/- SD age of the patients (8 men and 26 women) was 38.7 +/- 16.1 years. The median duration of AOSD before TCZ was initiated was 4.2 years (interquartile range [IQR] 1-9 years). The initial dosages of intravenous TCZ were 8 mg/kg every 4 weeks in 22 patients, 4 mg/kg every 4 weeks in 2 patients, and 8 mg/kg every 2 weeks in 10 patients. TCZ treatment resulted in rapid and maintained improvement in both clinical and laboratory parameters. After 1 year of TCZ therapy, the incidence of joint manifestations had decreased from 97.1% at baseline to 32.4%, the incidence of both cutaneous manifestations and fever had decreased from 58.8% to 5.9%, and the incidence of lymphadenopathy had decreased from 29.4% to 0%. A dramatic reduction in laboratory markers of inflammation, including the C-reactive protein level, the erythrocyte sedimentation rate, and the ferritin level, was achieved. The median dosage of prednisone was also reduced, from 13.8 mg/day (IQR 5-45) at the initiation of TCZ to 2.5 mg/day (IQR 0-30) at 12 months. After a median followup of 19 months (IQR 12-31 months), only 2 patients required permanent discontinuation of TCZ therapy because of severe infections.Conclusion. TCZ treatment was associated with rapid and maintained clinical and laboratory improvement in patients with AOSD refractory to standard treatment. However, joint manifestations seem to be more refractory to treatment compared with systemic manifestations.