Sibley Cailin H, Plass Nikki, Snow Joseph, Wiggs Edythe A, Brewer Carmen C, King Kelly A, Zalewski Christopher, Kim H Jeffrey, Bishop Rachel, Hill Suvimol, Paul Scott M, Kicker Patrick, Phillips Zachary, Dolan Joseph G, Widemann Brigitte, Jayaprakash Nalini, Pucino Frank, Stone Deborah L, Chapelle Dawn, Snyder Christopher, Butman John A, Wesley Robert, Goldbach-Mansky Raphaela
Translational Autoinflammatory Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland.
Arthritis Rheum. 2012 Jul;64(7):2375-86. doi: 10.1002/art.34409.
Blocking interleukin-1 with anakinra in patients with the autoinflammatory syndrome neonatal-onset multisystem inflammatory disease (NOMID) reduces systemic and organ-specific inflammation. However, the impact of long-term treatment has not been established. This study was undertaken to evaluate the long-term effect of anakinra on clinical and laboratory outcomes and safety in patients with NOMID.
We conducted a cohort study of 26 NOMID patients ages 0.80-42.17 years who were followed up at the NIH and treated with anakinra 1-5 mg/kg/day for at least 36 months. Disease activity was assessed using daily diaries, questionnaires, and C-reactive protein level. Central nervous system (CNS) inflammation, hearing, vision, and safety were evaluated.
Sustained improvements in diary scores, parent's/patient's and physician's global scores of disease activity, parent's/patient's pain scores, and inflammatory markers were observed (all P<0.001 at 36 and 60 months). At 36 and 60 months, CNS inflammation was suppressed, with decreased cerebrospinal fluid white blood cell counts (P=0.0026 and P=0.0076, respectively), albumin levels, and opening pressures (P=0.0012 and P<0.001, respectively). Most patients showed stable or improved hearing. Cochlear enhancement on magnetic resonance imaging correlated with continued hearing loss. Visual acuity and peripheral vision were stable. Low optic nerve size correlated with poor visual field. Bony lesions progressed. Adverse events other than viral infections were rare, and all patients continued to receive the medication.
These findings indicate that anakinra provides sustained efficacy in the treatment of NOMID for up to 5 years, with the requirement of dose escalation. Damage progression in the CNS, ear, and eye, but not bone, is preventable. Anakinra is well tolerated overall.
在患有自身炎症综合征新生儿期多系统炎症性疾病（NOMID）的患者中，使用阿那白滞素阻断白细胞介素-1可减轻全身和器官特异性炎症。然而，长期治疗的影响尚未明确。本研究旨在评估阿那白滞素对NOMID患者临床和实验室结果及安全性的长期影响。
我们对26例年龄在0.80至42.17岁之间的NOMID患者进行了队列研究，这些患者在美国国立卫生研究院接受随访，并接受阿那白滞素1 - 5毫克/千克/天的治疗至少36个月。使用每日日记、问卷和C反应蛋白水平评估疾病活动度。评估中枢神经系统（CNS）炎症、听力、视力和安全性。
观察到日记评分、家长/患者和医生的疾病活动度总体评分、家长/患者的疼痛评分以及炎症标志物持续改善（在36个月和60个月时均P<0.001）。在36个月和60个月时，CNS炎症得到抑制，脑脊液白细胞计数降低（分别为P = 0.0026和P = 0.0076）、白蛋白水平和开放压降低（分别为P = 0.0012和P<0.001）。大多数患者听力稳定或改善。磁共振成像上的耳蜗强化与持续听力损失相关。视力和周边视力稳定。视神经尺寸小与视野差相关。骨病变进展。除病毒感染外的不良事件罕见，所有患者继续接受药物治疗。
这些发现表明，阿那白滞素在治疗NOMID方面可提供长达5年的持续疗效，但需要增加剂量。中枢神经系统、耳朵和眼睛而非骨骼的损伤进展是可预防的。阿那白滞素总体耐受性良好。
