背景:甲羟戊酸激酶缺乏症(MKD)和TNF受体相关周期性综合征(TRAPS)被归类为全身性自身炎症性疾病(SAIDs),以早期发病为特征的罕见疾病,条件恶劣,具有挑战性的诊断和治疗。虽然不同的SAIDs有不同的标准治疗方法,一些SAIDs在常规治疗后控制不佳,严重影响儿童的生长发育和生活质量。本研究旨在为SAIDs提供更多的治疗策略。
方法:我们介绍了两名患有MKD和TRAPS的中国患者,他们对TNF-(肿瘤坏死因子-)α阻断具有抗性。使用依那西普之后,baricitinib,和糖皮质激素,MKD和TRAPS患者仍有周期性发热和皮疹.由于IL-1拮抗剂在中国大陆的不可用,我们开始以每3周240mg的剂量静脉注射托珠单抗(TCZ).他们在接受一或两剂TCZ后没有发烧或皮疹。在MKD患者接受TCZ治疗之前,白细胞(WBC)计数,TNF-α水平正常,血沉(ESR)和C反应蛋白(CRP)显著升高,IL-6略有增加。用TCZ治疗后,ESR和CRP水平恢复正常;然而,IL-6偶尔增加。在陷阱患者中,ESR,CRP,WBC,IL-6和TNF-α水平显著升高。TCZ治疗后,ESR,CRP,WBC,IL-6和TNF-α水平恢复正常。两名患者接受TCZ治疗超过6个月,并获得临床和血清学缓解。此外,注射TCZ后无不良反应。
结论:在中国大陆没有IL-1拮抗剂的情况下,托珠单抗作为抗TNF-α阻断的SAID的替代药物出现。
BACKGROUND: Mevalonate kinase deficiency (MKD) and TNF receptor-associated periodic syndrome (TRAPS) are categorized as systemic autoinflammatory diseases (SAIDs), which are rare diseases characterized by early onset, severe conditions, and challenging diagnosis and treatment. Although different SAIDs have varying standard treatments, some SAIDs are poorly controlled after routine treatment, seriously affecting the growth and development of children and their quality of life. This study aims to provide more treatment strategies for SAIDs.
METHODS: We present two Chinese patients with MKD and TRAPS who were resistant to TNF- (tumor necrosis factor-) α blockade. After using etanercept, baricitinib, and glucocorticoid, patients with MKD and TRAPS still had periodic fever and rash. Due to the unavailability of IL-1 antagonists in the Chinese Mainland, we started administering intravenous tocilizumab (TCZ) at a dosage of 240 mg every three weeks. They had not experienced fever or rash after receiving one or two doses of TCZ. Before treatment with TCZ in the MKD patient, white blood cell (WBC) count, and TNF-α level were normal, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) increased significantly, and IL-6 increased slightly. After treatment with TCZ, ESR and CRP levels returned to normal; however, IL-6 increased occasionally. In the TRAPS patient, ESR, CRP, WBC, IL-6, and TNF-α levels were increased significantly. After TCZ treatment, ESR, CRP, WBC, IL-6, and TNF-α levels returned to normal. The two patients were treated with TCZ for more than six months and achieved clinical and serological remission. Furthermore, they had no adverse reactions after injection of TCZ.
CONCLUSIONS: In the absence of IL-1 antagonists in mainland China, tocilizumab emerges as an alternative drug in SAIDs that are resistant to TNF-α blockade.