Tocilizumab reduced production of scleroderma-related autoantibodies and anti-cyclic citrullinated protein antibodies in two patients overlapping scleroderma and rheumatoid arthritis
Tocilizumab reduced production of scleroderma-related autoantibodies and anti-cyclic citrullinated protein antibodies in two patients overlapping scleroderma and rheumatoid arthritis
复制标题
托珠单抗减少了两名患有硬皮病和类风湿性关节炎的患者的硬皮病相关自身抗体和抗环瓜氨酸蛋白抗体的产生
DOI：
10.1080/03009742.2017.1297482
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发表时间：
2018
影响因子：
2.1
通讯作者：
Atsumi T
中科院分区：
文献类型：
--
作者：
Kono M;Yasuda S;Kono M;Atsumi T
系统性硬化症(SSC)是一种罕见的结缔组织疾病，以皮肤和器官的纤维化为特征。白介素6(IL-6)在SSC(1，2)发病机制中的作用已有许多报道。最近，抗IL-6受体抗体tocilizumab(TCZ)治疗皮肤硬化症的疗效在SSC的一个小病例系列中被报道(3)，随后进行的皮下TCZ治疗的第二阶段试验显示皮肤僵硬减轻的信号(4)。在这里，我们报告两例类风湿关节炎(RA)合并SSc成功地使用TCZ治疗，与RA和SS相关的自身抗体滴度降低。患者1，25岁，女性，多关节痛，抗环瓜氨酸肽抗体(ACPAs)阳性，诊断为RA。她接受了甲氨蝶呤(MTX)和依那西普(ETN)的治疗，导致临床缓解。当时，她没有SSc的表现，尽管检测到了带有斑点图案的抗核抗体(ANA)和抗拓扑异构酶I抗体(ATA)。两年后，由于她计划怀孕，MTX被停用。在那之后不久，她的双手和前臂迅速出现皮肤僵硬，并出现了新的间质性肺炎。随后，她被诊断为SSc合并类风湿关节炎。28个关节疾病活动度-血沉(DAS28-ESR)和改良Rodnan总皮肤评分(RSS)分别为2.92和25。用强的松龙(PSL)30 mg/d，静脉注射环磷酰胺(IVCY)和他克莫司(TAC)治疗，起初改善了临床表现，但在PSL逐渐减少的过程中，关节压痛和皮肤硬化复发。我们在PSL和TAC的同时使用TCZ，导致皮肤硬化和关节炎的迅速改善。治疗1年后，DAS28-ESR和RSS分别降至1.76和8。ACPA和ATA的滴度也显著下降(图1 A)。
Systemic sclerosis (SSc) is a rare connective tissue disease, characterized by fibrosis in the skin and organs. There are many reports on the roles of interleukin 6 (IL-6) in the pathogenesis of SSc (1, 2). Recently, the efficacy of tocilizumab (TCZ), an anti-IL-6 receptor antibody, for skin sclerosis has been reported in a small case series in SSc (3), followed by a phase 2 trial of subcutaneous TCZ therapy showing the signal of reduction in skin stiffness (4). Here, we report two cases with rheumatoid arthritis (RA) accompanied by SSc successfully treated using TCZ, with reduction in the titres of autoantibodies related to both RA and SSc.Patient 1, a 25-year-old woman, presented with polyarthralgia and positive anti-cyclic citrullinated peptide antibodies (ACPAs), and was diagnosed as having RA. She was treated with methotrexate (MTX) and etanercept (ETN), resulting in clinical remission. At that time, she had no manifestations of SSc, although anti-nuclear antibodies (ANAs) with a speckled pattern and antitopoisomerase I antibodies (ATAs) were detected. Two years later, MTX was discontinued because she was planning for pregnancy. Shortly after that, skin stiffness rapidly developed in her both hands and forearms, with newly developed interstitial pneumonia. Then, she was diagnosed as having SSc complicated with RA. The 28-joint Disease Activity Score–erythrocyte sedimentation rate (DAS28-ESR) and modified Rodnan total skin score (RSS) were 2.92 and 25, respectively. She was treated with prednisolone (PSL) at 30 mg/day, intravenous cyclophosphamide (IVCY), and tacrolimus (TAC), which at first improved the clinical manifestations, but during PSL tapering, joint tenderness and skin sclerosis recurred. We administered TCZ concurrently with PSL and TAC, resulting in the rapid improvement of skin sclerosis and arthritis. After 1 year of TCZ treatment, the DAS28-ESR and RSS were decreased to 1.76 and 8, respectively. The titres of ACPAs and ATAs were also significantly decreased (Figure 1 A).