背景:系统性幼年特发性关节炎(sJIA),多方面的自身炎症性疾病,可能因巨噬细胞活化综合征(MAS)和间质性肺病(ILD)等危及生命的疾病而复杂化。这些病症的管理提出了治疗挑战,强调需要创新的治疗方法。
目的:报道双特异性抗IL1β和IL-18单克隆抗体MAS825的可能作用,在多重耐药sJIA的治疗中。
方法:我们报告了两名患有严重和难治性MAS和高血清IL-18水平的sJIA患者,响应于IL-1β和IL-18的双重阻断。
结果:第一位患者是一名20岁的男性,出现严重的MAS并发血栓性微血管病,SARS-CoV-2感染后。他接受了MAS825治疗,病情迅速好转。十八个月后,患者仍在接受与MTX相关的MAS825双周治疗,环孢素和低剂量糖皮质激素,保持对疾病的系统特征的良好控制。第二个病人,一个10岁的女孩,提出了一个严重的MAS案例,并发后部可逆性脑病综合征(PRES),在耳乳突炎之后.尽管用静脉大剂量糖皮质激素治疗,但MAS仍未完全控制。Anakinra和环孢菌素.她开始每两周一次的MAS825,这导致MAS参数的迅速改善。10个月后,患者继续接受MAS825治疗,目前已完全缓解.
结论:鉴于IL-1β和IL-18在sJIA中的关键作用,MAS和ILD,MAS825可能是治疗耐药sJIA的一种可能的有效和安全的选择,特别是在血清IL-18水平较高的情况下。
BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA), a multifaceted autoinflammatory disorder, can be complicated by life-threatening conditions such as macrophage activation syndrome (MAS) and interstitial lung disease (ILD). The management of these conditions presents a therapeutic challenge, underscoring the need for innovative treatment approaches.
OBJECTIVE: to report the possible role of MAS825, a bispecific anti-IL1β and IL-18 monoclonal antibody, in the treatment of multi-drug-resistant sJIA.
METHODS: We report two patients affected by sJIA with severe and refractory MAS and high serum IL-18 levels, responding to dual blockade of IL-1β and IL-18.
RESULTS: The first patient is a 20-year-old man, presenting a severe MAS complicated by thrombotic microangiopathy, following SARS-CoV-2 infection. He was treated with MAS825, with quick improvement. Eighteen months later, the patient is still undergoing biweekly treatment with MAS825, associated with MTX, ciclosporin and low-dose glucocorticoids, maintaining good control over the systemic features of the disease.The second patient, a 10-year-old girl, presented a severe MAS case, complicated by posterior reversible encephalopathy syndrome (PRES), following an otomastoiditis. The MAS was not fully controlled despite treatment with IV high-dose glucocorticoids, anakinra and ciclosporin. She began biweekly MAS825, which led to a prompt amelioration of MAS parameters. After 10 months, the patient continues to receive MAS825 and is in complete remission.
CONCLUSIONS: In light of the pivotal role of IL-1β and IL-18 in sJIA, MAS and ILD, MAS825 might represent a possible valid and safe option in the treatment of drug-resistant sJIA, especially in the presence of high serum IL-18 levels.