Zeft Andrew, Hollister Roger, LaFleur Bonnie, Sampath Prahalad, Soep Jennifer, McNally Bernadette, Kunkel Gary, Schlesinger Margaret, Bohnsack John
Division of Immunology and Rheumatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah 84158, USA.
J Clin Rheumatol. 2009 Jun;15(4):161-4. doi: 10.1097/RHU.0b013e3181a4f459.
Poor outcomes in systemic juvenile arthritis have been associated with persistent thrombocytosis, increased sedimentation rates, anemia, polyarthritis, and prolonged steroid use. Off-label treatment with recombinant interleukin-1 receptor antagonist therapy (anakinra) has become more common since reports of its association with reduced systemic symptoms and arthritis scores, improved laboratory parameters of inflammation, and decreased corticosteroid requirements.
To examine the efficacy and safety of anakinra in a regional cohort of systemic juvenile arthritis patients.
We performed a retrospective case series of systemic juvenile arthritis patients (n = 33) treated with anakinra at 3 Pediatric Rheumatology centers. The effect of anakinra on corticosteroid dose, sedimentation rate, platelet count, albumin, hemoglobin, arthritis joint counts, and height Z score was determined using the paired t test. We evaluated differences in change in these variables between patient groups within the sample determined by: age of onset, anakinra dose, and duration from diagnosis until anakinra treatment.
Treatment was associated with decreases in corticosteroid dosage and sedimentation rate and increases in hemoglobin and albumin (P < 0.02). There were decreases in large joint arthritis counts (P < 0.04) but not small joint counts after 3 to 4 months. There were greater decreases in sedimentation rates from pre to post (1-2 months) in patients on high versus low dose anakinra (P < 0.001). Fever and rash, present in 7 cases before treatment, was resolved. Eight patients had periods of arthritis, 1 developed macrophage activation syndrome, and another Epstein Barr virus. Over half of patients reported localized pain or swelling at their injection site.
Treatment with anakinra was associated with short-term improvements in large joint counts and laboratory parameters of active disease. Higher anakinra doses may be more efficacious in treating the systemic inflammatory response in systemic onset juvenile idiopathic arthritis patients. A subset of patients had periods of arthritis during treatment, and local side-effects were frequent. Our experience supports the continued use of interleukin-1 inhibition in systemic juvenile arthritis and the search for more effective and more tolerable forms of interleukin-1 inhibition.
系统性幼年特发性关节炎预后不良与持续性血小板增多、血沉升高、贫血、多关节炎及长期使用类固醇有关。自有关重组白细胞介素-1受体拮抗剂疗法（阿那白滞素）与全身症状减轻、关节炎评分改善、炎症实验室指标改善及皮质类固醇需求减少相关的报道以来，其非标签治疗变得更为常见。
研究阿那白滞素在一组区域性系统性幼年特发性关节炎患者中的疗效和安全性。
我们对3家儿科风湿病中心接受阿那白滞素治疗的系统性幼年特发性关节炎患者（n = 33）进行了回顾性病例系列研究。使用配对t检验确定阿那白滞素对皮质类固醇剂量、血沉、血小板计数、白蛋白、血红蛋白、关节炎关节计数及身高Z评分的影响。我们评估了样本中不同患者组在这些变量变化方面的差异，这些患者组由以下因素确定：发病年龄、阿那白滞素剂量及从诊断到阿那白滞素治疗的持续时间。
治疗与皮质类固醇剂量和血沉降低以及血红蛋白和白蛋白升高相关（P < 0.02）。3至4个月后，大关节关节炎计数减少（P < 0.04），但小关节计数未减少。高剂量与低剂量阿那白滞素治疗的患者从治疗前到治疗后（1 - 2个月）血沉下降幅度更大（P < 0.001）。治疗前7例患者出现的发热和皮疹消退。8例患者出现关节炎发作期，1例发生巨噬细胞活化综合征，另1例感染爱泼斯坦-巴尔病毒。超过半数患者报告注射部位出现局部疼痛或肿胀。
阿那白滞素治疗与大关节计数及活动性疾病实验室指标的短期改善相关。较高剂量的阿那白滞素在治疗全身型幼年特发性关节炎患者的全身炎症反应方面可能更有效。一部分患者在治疗期间出现关节炎发作期，且局部副作用常见。我们的经验支持在系统性幼年特发性关节炎中继续使用白细胞介素-1抑制疗法，并寻找更有效且更耐受的白细胞介素-1抑制形式。
