Neven Bénédicte, Marvillet Isabelle, Terrada Celine, Ferster Alice, Boddaert Nathalie, Couloignier Vincent, Pinto Graziella, Pagnier Anne, Bodemer Christine, Bodaghi Bahram, Tardieu Marc, Prieur Anne Marie, Quartier Pierre
Assistance Publique Hôpitaux de Paris, Hôpital Necker-Enfants-Malades, INSERM U768, Université René Descartes-Paris 5, Paris, France.
Arthritis Rheum. 2010 Jan;62(1):258-67. doi: 10.1002/art.25057.
Cryopyrin-associated periodic syndromes (CAPS) are a group of rare autoinflammatory diseases. Neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic, cutaneous, articular syndrome (CINCA syndrome) is the most severe phenotype, with fever, rash, articular manifestations, and neurologic and neurosensory involvement. CAPS are caused by mutations in CIAS1, the gene encoding NLRP3, which plays a critical role in interleukin-1 (IL-1) processing. Anakinra, an IL-1 receptor antagonist, has been shown to be an effective treatment; however, data on long-term efficacy and safety have been sparse. This study was undertaken to assess the long-term efficacy and safety of anakinra treatment in patients with NOMID/CINCA syndrome.
We retrospectively analyzed the medical records of NOMID/CINCA syndrome patients referred to 2 centers, who had started anakinra treatment before June 2007.
There were 10 patients with NOMID/CINCA syndrome who had been treated with anakinra. The patients' ages at the time anakinra treatment was initiated ranged from 3 months to 20 years. They had been followed up for 26-42 months. Sustained efficacy in the treatment of systemic inflammation and, in some cases, neurologic involvement and growth parameters, was achieved. The dosage of anakinra required for efficacy ranged from 1 to 3 mg/kg/day in the 8 oldest patients and from 6 to 10 mg/kg/day in the 2 youngest. Residual central nervous system inflammation and deafness persisted in some patients, especially if there had been a delay in diagnosis and treatment. Secondary amyloidosis persisted in cases in which it was present at treatment initiation, but no new lesions developed. No effect on overgrowth arthropathy was observed. Adverse events consisted of mild injection-site reactions.
The present results indicate that anakinra treatment is effective over the long term in NOMID/CINCA syndrome. However, treatment has to be initiated before irreversible lesions develop, and, particularly in very young patients, dosage adjustment is required.
冷吡啉相关周期性综合征（CAPS）是一组罕见的自身炎症性疾病。新生儿期起病的多系统炎症性疾病（NOMID）/慢性婴儿神经、皮肤、关节综合征（CINCA综合征）是最严重的表型，有发热、皮疹、关节表现以及神经和神经感觉受累。CAPS由编码NLRP3的CIAS1基因突变引起，NLRP3在白细胞介素-1（IL-1）加工过程中起关键作用。阿那白滞素，一种IL-1受体拮抗剂，已被证明是一种有效的治疗药物；然而，关于其长期疗效和安全性的数据一直很少。本研究旨在评估阿那白滞素治疗NOMID/CINCA综合征患者的长期疗效和安全性。
我们回顾性分析了转诊至2个中心的NOMID/CINCA综合征患者的病历，这些患者在2007年6月之前开始接受阿那白滞素治疗。
有10例NOMID/CINCA综合征患者接受了阿那白滞素治疗。开始阿那白滞素治疗时患者的年龄为3个月至20岁。他们接受了26 - 42个月的随访。在治疗全身炎症以及某些情况下的神经受累和生长参数方面取得了持续疗效。8例年龄较大的患者疗效所需的阿那白滞素剂量为1至3 mg/kg/天，2例年龄最小的患者为6至10 mg/kg/天。一些患者残留中枢神经系统炎症和耳聋，尤其是在诊断和治疗延迟的情况下。继发性淀粉样变性在治疗开始时存在的病例中持续存在，但没有出现新的病变。未观察到对过度生长性关节病的影响。不良事件包括轻度注射部位反应。
目前的结果表明，阿那白滞素治疗NOMID/CINCA综合征长期有效。然而，必须在不可逆病变出现之前开始治疗，特别是对于非常年幼的患者，需要调整剂量。
