Anakinra as First-Line Disease-Modifying Therapy in Systemic Juvenile Idiopathic Arthritis Report of Forty-Six Patients From an International Multicenter Series
Anakinra as First-Line Disease-Modifying Therapy in Systemic Juvenile Idiopathic Arthritis Report of Forty-Six Patients From an International Multicenter Series
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DOI：
10.1002/art.30128
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发表时间：
2011-02-01
影响因子：
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通讯作者：
Higgins, Gloria C.
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文献类型：
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作者：
Nigrovic, Peter A.;Mannion, Melissa;Higgins, Gloria C.
Objective.研究白细胞介素-1（IL-1）受体拮抗剂阿那白滞素作为系统性幼年特发性关节炎（JIA）一线治疗的安全性和有效性。从4个国家的11个中心确定了接受阿那白滞素作为初始疾病缓解抗风湿药物（DMARD）治疗的一部分的全身性JIA患者。使用标准化工具提取病历，分析所得数据以描述伴随治疗、临床病程、不良事件和预后预测因素。在46例符合入选标准的患者中，10例（22%）使用阿那白滞素单药治疗，67%接受皮质类固醇治疗，33%接受额外的DMARD治疗。在中位随访间隔14.5个月时评价结局。>95%的患者发热和皮疹在1个月内消退，而>80%的患者C反应蛋白和铁蛋白在此期间恢复正常。39%的患者在1个月时仍有活动性关节炎，27%的患者在3个月时仍有活动性关节炎，11%的患者在随访>6个月时仍有活动性关节炎。大约60%的患者，包括10名接受阿那白滞素单药治疗的患者中的8名，在没有升级治疗的情况下获得了完全缓解。部分和完全应答者的疾病特征和治疗相似，除了部分应答者在发病时明显更年轻（中位年龄5.2岁vs 10.2岁; P = 0.004）。相关不良事件包括2例患者记录的细菌感染和1例患者的肝炎。快速耐受性未被消除。阿那白滞素作为全身性JIA的一线治疗与全身症状的快速缓解和几乎90%的患者在检查期间预防难治性关节炎相关。这些结果证明进一步研究IL-1抑制作为一线，而不是补救，治疗全身性JIA。
Objective. To examine the safety and efficacy of the interleukin-1 (IL-1) receptor antagonist anakinra as first-line therapy for systemic juvenile idiopathic arthritis (JIA).Methods. Patients with systemic JIA receiving anakinra as part of initial disease-modifying antirheumatic drug (DMARD) therapy were identified from 11 centers in 4 countries. Medical records were abstracted using a standardized instrument, and resulting data were analyzed to characterize concomitant therapies, clinical course, adverse events, and predictors of outcome.Results. Among 46 patients meeting inclusion criteria, anakinra monotherapy was used in 10 patients (22%), while 67% received corticosteroids and 33% received additional DMARDs. Outcomes were evaluated at a median followup interval of 14.5 months. Fever and rash resolved within 1 month in >95% of patients, while C-reactive protein and ferritin normalized within this interval in >80% of patients. Active arthritis persisted at 1 month in 39% of patients, at 3 months in 27%, and at >6 months of followup in 11%. Approximately 60% of patients, including 8 of 10 receiving anakinra monotherapy, attained a complete response without escalation of therapy. Disease characteristics and treatment were similar in partial and complete responders, except that partial responders were markedly younger at onset (median age 5.2 years versus 10.2 years; P = 0.004). Associated adverse events included documented bacterial infection in 2 patients and hepatitis in 1 patient. Tachyphylaxis was not observed.Conclusion. Anakinra as first-line therapy for systemic JIA was associated with rapid resolution of systemic symptoms and prevention of refractory arthritis in almost 90% of patients during the interval examined. These results justify further study of IL-1 inhibition as first-line, rather than rescue, therapy in systemic JIA.