Abstract：
BACKGROUND: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine is the primary treatment, around 10% of FMF patients do not respond to it, necessitating alternative therapies. Biologic treatments, such as interleukin-1β (IL-1β), TNF-α, and interleukin-6 (IL-6) inhibitors, have been considered. However, the accessibility and cost of IL-1β inhibitors may limit their use in certain regions. Tocilizumab (TCZ), an IL-6 receptor inhibitor, offers an alternative, but its efficacy in FMF is not well-documented.
OBJECTIVE: To evaluate the efficacy and safety of tocilizumab in the treatment of FMF.
METHODS: Following PRISMA guidelines, we identified 237 articles on the use of TCZ in FMF.
RESULTS: After selection, 14 articles were included: 2 double-blind RCTs, 2 retrospective studies, and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in pediatric FMF.
CONCLUSIONS: This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1β inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors.
OBJECTIVE: To evaluate the efficacy and safety of tocilizumab in the treatment of FMF.
METHODS: Following PRISMA guidelines, we identified 237 articles on the use of TCZ in FMF.
RESULTS: After selection, 14 articles were included: 2 double-blind RCTs, 2 retrospective studies, and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in pediatric FMF.
CONCLUSIONS: This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1β inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors.
摘要：
背景：家族性地中海热（FMF）是最常见的单基因自身炎性疾病，其特征是反复发热和浆膜炎症。虽然秋水仙碱是主要的治疗方法，大约10%的FMF患者对它没有反应，需要替代疗法。生物治疗,如白细胞介素-1β（IL-1β），TNF-α,和白细胞介素-6（IL-6）抑制剂，已经考虑过了。然而,IL-1β抑制剂的可及性和成本可能会限制其在某些地区的使用。Tocilizumab（TCZ），IL-6受体抑制剂，提供了另一种选择，但其在FMF中的功效并没有得到很好的证明。
目的：评价托珠单抗治疗FMF的疗效和安全性。
方法：遵循PRISMA指南，我们确定了237篇关于TCZ在FMF中使用的文章。
结果：选择后，包括14篇文章：2个双盲RCT，2个回顾性研究，10例病例报告。由于现有研究的遗传/分类异质性，多中心双盲随机对照试验报告了无AA淀粉样变性的FMF患者的混合结果。可能误诊的FMF患者和研究设计。回顾性研究表明，TCZ可能有利于FMF患者的肾脏AA淀粉样变性，潜在的预防进展和更有效地管理耀斑。TCZ显示出安全的情况，没有特定的不良事件，但是缺乏有关其在怀孕或母乳喂养期间使用的数据。没有关于在儿科FMF中使用TCZ的可用数据。
结论：这篇综述总结了研究的现状，TCZ在FMF中的安全性和有效性。虽然IL1β抑制剂仍然是秋水仙碱耐药或不耐受的FMF患者的首选，TCZ可能在某些已确定的AA淀粉样变性且对秋水仙碱和白介素1抑制剂具有抗性的选定FMF患者中引起关注。
目的：评价托珠单抗治疗FMF的疗效和安全性。
方法：遵循PRISMA指南，我们确定了237篇关于TCZ在FMF中使用的文章。
结果：选择后，包括14篇文章：2个双盲RCT，2个回顾性研究，10例病例报告。由于现有研究的遗传/分类异质性，多中心双盲随机对照试验报告了无AA淀粉样变性的FMF患者的混合结果。可能误诊的FMF患者和研究设计。回顾性研究表明，TCZ可能有利于FMF患者的肾脏AA淀粉样变性，潜在的预防进展和更有效地管理耀斑。TCZ显示出安全的情况，没有特定的不良事件，但是缺乏有关其在怀孕或母乳喂养期间使用的数据。没有关于在儿科FMF中使用TCZ的可用数据。
结论：这篇综述总结了研究的现状，TCZ在FMF中的安全性和有效性。虽然IL1β抑制剂仍然是秋水仙碱耐药或不耐受的FMF患者的首选，TCZ可能在某些已确定的AA淀粉样变性且对秋水仙碱和白介素1抑制剂具有抗性的选定FMF患者中引起关注。
