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寡关节型和多关节型幼年特发性关节炎患者停用首支抗 TNF 药物后疾病复发的预测因素:意大利多中心经验。

Uveitis as predictor of disease flare after the first anti-TNF withdrawal in oligoarticular and polyarticular juvenile idiopathic arthritis: a multicentric Italian experience.

机构信息

Rheumatology Unit, ERN ReConnet Center, Meyer Children's Hospital IRCCS, Florence, and NeuroFARBA Department, University of Florence, Italy.

School of Health Human Science, University of Florence, Italy.

出版信息

Clin Exp Rheumatol. 2024 Sep;42(9):1867-1875. doi: 10.55563/clinexprheumatol/3mxsll. Epub 2024 Jul 4.

Abstract

OBJECTIVES

TNF inhibitors (TNFi) have dramatically changed the prognosis of juvenile idiopathic arthritis (JIA), but it is not clear how and when to stop therapy. We aim to describe a multicentric cohort of JIA treated with adalimumab or etanercept who discontinued the treatment for persistent inactivity and to identify factors associated with relapse.

METHODS

In a multicentric Italian retrospective cohort study, medical records of patients with oligoarticular and polyarticular JIA were evaluated if they stopped therapy for persistent inactivity after the first TNFi.

RESULTS

136 patients were enrolled (102 female, median age at onset 3 years (range 1-15), of whom 55.9% had oligoarticular JIA, 40.4% uveitis and 72.8% ANA positivity. Adalimumab (59.3%) and etanercept (40.7%) were started at a median age of 6 years (range 1-16), TNFi were discontinued after a median time of 30 months (range 6-90), increasing the interval (76.5%), reducing the dose (18.4%) and abrupt discontinuation (16.9%). 79.4% of patients relapsed after a median time of 5 months (range 0.5-66). Patients with uveitis relapsed earlier (log rank χ² 16.4 p<0.0001), while patients who lengthened the interval of administration showed a later relapse (log rank χ² 6.95 p=0.008). Uveitis (HR 2.11 CI 1.34-3.31), age at onset (HR 0.909 CI 0.836-0.987), duration of tapering (HR 0.938 CI 0.893-0.985) and to have a persistent oligoarticular JIA (HR 0.597 CI 0.368-0.968) are significant predictors of disease relapse (Mantel-Cox χ² 34.23 p<0.001).

CONCLUSIONS

Younger age at onset, uveitis, duration of tapering, and non-persistent oligoarticular JIA seem to be independent risk factors for earlier relapse after the first TNFi withdrawal.

摘要

目的

肿瘤坏死因子抑制剂(TNFi)显著改变了幼年特发性关节炎(JIA)的预后,但尚不清楚如何以及何时停止治疗。我们旨在描述一个接受阿达木单抗或依那西普治疗的 JIA 多中心队列,这些患者因持续不活动而停止治疗,并确定与复发相关的因素。

方法

在一项意大利多中心回顾性队列研究中,如果首发 TNFi 后因持续不活动而停止治疗的寡关节型和多关节型 JIA 患者的病历符合评估标准,则纳入研究。

结果

共纳入 136 例患者(102 例女性,发病年龄中位数为 3 岁(范围 1-15),其中 55.9%为寡关节型 JIA,40.4%有葡萄膜炎,72.8%抗核抗体阳性。阿达木单抗(59.3%)和依那西普(40.7%)分别在中位年龄 6 岁(范围 1-16)时开始治疗,TNFi 停药中位时间为 30 个月(范围 6-90),增加间隔(76.5%)、减少剂量(18.4%)和突然停药(16.9%)。79.4%的患者在中位时间 5 个月(范围 0.5-66)后复发。有葡萄膜炎的患者复发较早(对数秩 χ² 16.4,p<0.0001),而延长给药间隔的患者复发较晚(对数秩 χ² 6.95,p=0.008)。葡萄膜炎(HR 2.11,CI 1.34-3.31)、发病年龄(HR 0.909,CI 0.836-0.987)、减量时间(HR 0.938,CI 0.893-0.985)和持续存在寡关节型 JIA(HR 0.597,CI 0.368-0.968)是疾病复发的显著预测因素(Mantel-Cox χ² 34.23,p<0.001)。

结论

发病年龄较小、葡萄膜炎、减量时间以及非持续寡关节型 JIA 似乎是首发 TNFi 停药后早期复发的独立危险因素。

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