General Pediatric Department, French National Reference Center for Autoinflammatory Diseases (CEREMAIA), Versailles Hospital, Versailles, France.
Internal Medicine Department, French National Reference Center for Autoinflammatory Diseases (CEREMAIA), Tenon Hospital, Sorbonne University, Paris, France.
Front Immunol. 2020 May 28;11:971. doi: 10.3389/fimmu.2020.00971. eCollection 2020.
Familial Mediterranean fever (FMF) is the most common monogenic auto-inflammatory disease characterized by recurrent attacks of fever and serositis. It is associated with mutation in pyrin inflammasome leading to interleukin-1 (IL-1) over secretion. Although colchicine is the first line treatment in FMF, 5-10% of patients are reported in literature as non-responders. Colchicine is not always well-tolerated due either to its direct toxicity or to co-morbidities that preclude the administration of its proper dosage. For these patients an alternative or additional treatment to colchicine is necessary. This literature review reports the published data regarding the use of IL-1 inhibitors in Familial Mediterranean Fever. There is no uniform definition of colchicine resistance, but the different studies of treatment with IL-1 inhibitors provide evidence of IL-1 pathogenic role in colchicine-resistant FMF. IL-1 inhibition is an efficacious option for controlling and preventing flares -at least at the short term- in FMF patients who are insufficiently controlled with colchicine alone. Although canakinumab is the only approved drug in Europe for colchicine resistant FMF treatment, experience with anakinra is also substantial. In the absence of comparative studies both treatments seem to be an equal option for the management of these patients. Overall the safety profile of IL-1 inhibitors seems not different in FMF patients than in the other diseases and can be considered as globally safe. The main side effects are local injection site reactions and infections. IL-1 inhibitors have the potential to improve patient outcome even in FMF patients with co-morbidities or severe complications in whom inflammation control is difficult to achieve with colchicine alone. Nevertheless, current data are limited and further evaluation of long-term efficacy and safety of IL-1 inhibitors are necessary, in order to provide robust evidence in this domain.
家族性地中海热（FMF）是最常见的单基因自身炎症性疾病，其特征是反复发热和浆膜炎发作。它与 pyrin 炎症小体的突变有关，导致白细胞介素-1（IL-1）过度分泌。尽管秋水仙碱是 FMF 的一线治疗药物，但文献报道有 5-10%的患者对此无反应。由于其直接毒性或因共存疾病而无法给予适当剂量，秋水仙碱并非总是能很好耐受。对于这些患者，需要秋水仙碱的替代或附加治疗。本文献综述报告了关于在家族性地中海热中使用白细胞介素-1 抑制剂的已发表数据。对于秋水仙碱耐药性没有统一的定义，但使用白细胞介素-1 抑制剂的不同研究提供了证据表明白细胞介素-1 在秋水仙碱耐药性 FMF 中具有致病性作用。白细胞介素-1 抑制是控制和预防 FMF 患者发作的有效选择 -至少在短期内-，这些患者仅用秋水仙碱治疗效果不足。虽然在欧洲，只有坎卡奴单抗被批准用于治疗秋水仙碱耐药性 FMF，但阿那白滞素的经验也相当丰富。在没有比较研究的情况下，这两种治疗方法似乎都是这些患者的同等治疗选择。总体而言，白细胞介素-1 抑制剂在 FMF 患者中的安全性与其他疾病中的安全性似乎没有不同，可以被认为是整体安全的。主要的副作用是局部注射部位反应和感染。白细胞介素-1 抑制剂有可能改善患者的预后，即使是在 FMF 患者中有合并症或严重并发症的情况下，这些患者单独使用秋水仙碱很难控制炎症。然而，目前的数据有限，需要进一步评估白细胞介素-1 抑制剂的长期疗效和安全性，以便在这一领域提供有力的证据。
