血清阳性青少年特发性关节炎的生物治疗:一项回顾性单中心研究的结果

M. Kaleda, Z. Kolkhidova, Irina Nikishina, V. A. N. Research, Каледа Мария Игоревна
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引用次数: 0

摘要

血清阳性的青少年特发性关节炎(JIA)是青少年关节炎中最罕见和最不利的亚型之一,其特点是治疗无效的频率增加。目的:研究血清JIA阳性患者的生物治疗特点,确定影响生物制剂(BA)选择和是否需要替代的因素,评价JADI损伤指数对预测BA疗效的价值。材料和方法。2010 - 2022年确诊JIA血清阳性92例,其中男孩占10.9%。研究组JIA发病的中位年龄为12.0 [7.7;14.0)年。研究组中有89.1%的患者服用了BA,其中31.7%的患者从发病开始服用的时间少于1年。BA起始时活动关节数中位数为15 [10];22],中位ESR - 29 [18;43] mm/h, CRP - 15.0 [5.3;31.0 mg / l。29.0%的患者在服用BA时出现关节外表现。对可能影响转BA需要的因素进行分析:发病年龄、诊断验证和BA开始的时间、性别、BA开始时活动关节数、ACCP阳性、RF、ACCP、ESR和CRP值-预约BA时、继发性Sjögren综合征的存在。自2021年起,检查复合体包括计算研究组所有入院患者的JADI (the Juvenile Arthritis Damage Index)损伤指数(共28例;17.9%——男孩)。其中JIA发病年龄中位数为10.5岁[6.31岁;13.0]年,81.2%获得学士学位。比较JADI指数与ACCP、RF、CRP、ESR及开药和切换BA的必要性。本研究设计为回顾性、开放标签、非随机、非对照研究。结果。在研究组中,29%的患者经历过1次以上的BA。Abatacept(45.1%)、tnf抑制剂(40.3%)最常被用作首选BA;托珠单抗和利妥昔单抗主要用于第2 - 4线治疗,近年来有更频繁使用的趋势。从一种BA切换到另一种BA的主要原因是治疗的继发性失败,4.9%的患者发生严重不良反应(AE)。总的来说,24.6%的患者记录了不需要停止治疗的不良事件。接受1次以上BA治疗的患者RF、ACCP值相对较高,CRP显著升高。JADI-A的平均值为2.39分,50%的患者JADI-A得分显著,92.8%的患者接受BA治疗,其中28.6%的患者有1次以上BA处方的经历。JADI指数与ACCP、ESR、CRP有直接相关性。结论。血清阳性JIA表现为对BA处方需求高,BA处方频率与JADI损伤指数显著指标相关。具体BA的选择首先取决于是否有系统性表现或继发性Sjögren综合征。在具有高替代指标活性(特别是CRP)的患者中,考虑到tnf抑制剂继发失败的高风险,tocilizumab在一线治疗中可能被认为是首选。我们的数据没有显示ACCP阳性对BA替代的首选或频率的影响。值得注意的是,在接受一个以上BA治疗的患者中,RF和ACCP值有升高的趋势。JADI指数与ACCP、ESR和CRP之间存在相关性,间接得出结论:为避免永久性损伤,提高治疗效果,该类患者应尽早开BA。BA的使用具有可接受的安全性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Biological therapy of seropositive juvenile idiopathic arthritis: Results of a retrospective single-center study
Seropositive juvenile idiopathic arthritis (JIA) is one of the rarest and most unfavorable subtypes of juvenile arthritis, characterized by an increased frequency of inefficacy of therapy. Objective – to characterize biologic therapy in patients with seropositive JIA, to identify factors influencing the choice of a biological agents (BA) and the need to replace it, to evaluate the value of the JADI damage index for predicting the response to BA.Material and methods. The diagnosis of seropositive JIA for the period from 2010 to 2022 was verified in 92 patients, 10.9% were boys. The median age of JIA onset in the study group was 12.0 [7.7; 14.0] years. BA were prescribed to 89.1% of patients in the study group, 31.7% of them for a period of less than 1 year from the onset. The median number of active joints at the time of BA initiation was 15 [10; 22], median ESR – 29 [18; 43] mm/h, CRP – 15.0 [5.3; 31.0] mg/l. Extra-articular manifestations at the time of prescribing BA occurred in 29.0% of patients. The analysis of factors that could influence the need to switch BA was carried out: age of onset, timing of diagnosis verification and initiation of BA, gender, the number of active joints at the start of BA, ACCP positivity, RF, ACCP, ESR and CRP values – at the time of BA appointment, the presence of secondary Sjögren’s syndrome. Since 2021, the complex of examinations included the calculation of the JADI (The Juvenile Arthritis Damage Index) damage index in all patients from the study group who were admitted to the hospital (28 in total; 17.9% – boys). The median age of JIA onset among them was 10.5 [6.31; 13.0] years, 81.2% received BA. The JADI index was compared with the ACCP, RF, CRP, ESR and the need to prescribe and switch BA. The design of the study was a retrospective, open-label, non-randomized, uncontrolled study. Results. In the study group of patients, 29% had experience with more than 1 BA. Abatacept (45.1%), TNF-inhibitors (40.3%) were most often used as the first BA; tocilizumab and rituximab were predominantly used in the 2nd–4th line of therapy, with a trend towards their more frequent prescription in recent years. The main reason for switching from one BA to another is the secondary failure of therapy, 4.9% of patients have serious adverse reactions (AE). In general, AEs that did not require discontinuation of therapy were recorded in 24.6% of patients. Patients who received more than 1 BA had relatively higher values of RF, ACCP and significantly higher CRP. The mean value of JADI-A was 2.39 points, 50% of patients had significant JADI-A scores, 92.8% of whom received BA with experience of more than 1 prescription of BA in 28.6% of them. A direct correlation of the JADI index with ACCP, ESR and CRP was revealed. Conclusions. Seropositive JIA is characterized by a high need for prescribing BA, the frequency of prescribing BA is associated with significant indicators of the JADI damage index. The choice of a specific BA is determined, first of all, by the presence of systemic manifestations or secondary Sjögren’s syndrome. In patients with high surrogate measures of activity (especially CRP), given the high risk of secondary failure of TNF-inhibitors, tocilizumab in the first line of therapy may be considered as the preferred choice. Our data did not reveal an effect of ACCP positivity on the preferred choice or frequency of BA replacement. Attention was drawn to the trend towards higher RF and ACCP values in patients treated with more than one BA. A correlation was established between the JADI index and ACCP, ESR, and CRP, which indirectly leads to the conclusion that it is necessary to prescribe BA earlier in this category of patients in order to avoid permanent damage and increase the effectiveness of thera py. The use of BA had an acceptable safety profile.
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