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儿童大动脉炎抗TNF和抗IL-6治疗的系统评价:解决治疗困境

A Systematic Review of Anti-TNF and Anti-IL-6 Treatments for Pediatric Takayasu Arteritis: Addressing a Therapeutic Dilemma.

作者信息

Batu Ezgi Deniz, Sener Seher

机构信息

Department of Pediatrics, Division of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, 06100, Ankara, Turkey.

Department of Pediatrics, Division of Pediatric Rheumatology, Adana City Research and Training Hospital, Adana, Turkey.

出版信息

Paediatr Drugs. 2025 Jun 18. doi: 10.1007/s40272-025-00706-5.

Abstract

BACKGROUND AND OBJECTIVES

Takayasu arteritis (TAK) is a rare large-vessel vasculitis primarily affecting young female patients, with pediatric cases being even rarer. Biologic therapies, such as anti-tumor necrosis factor (anti-TNF) and anti-interleukin-6 (anti-IL-6) agents, have become integral to TAK treatment; however, their use in children is not well supported by robust data due to the rarity of the disease. This systematic review aimed to evaluate the use, effectiveness, and safety of anti-TNF drugs and tocilizumab in the treatment of pediatric TAK.

METHODS

We conducted a systematic literature search in PubMed/MEDLINE and Scopus databases from their inception until 15 December 2024. Studies were eligible if they included pediatric patients with TAK (diagnosed before 18 years of age) treated with anti-TNF or anti-IL-6 drugs and reported clinical outcomes. Clinical trials, observational studies, case series, and reports were included. Data were extracted independently by two reviewers. Only English articles were analyzed. Due to heterogeneity in study designs and reporting, a narrative synthesis was performed.

RESULTS

A total of 94 reports involving 225 pediatric patients with TAK who received 262 treatment courses of biologic treatment were included. Anti-TNF drugs were more frequently used than tocilizumab (74.2% versus 36.9%, p < 0.001). Both groups showed comparable effectiveness, with clinical improvement observed in 64.9% of anti-TNF drug and 70.9% of tocilizumab treatment courses (p = 0.438). The frequency of relapse was also similar between the two groups (~50% in both groups, p = 0.472). Hypertension was more prevalent in the anti-TNF group (p = 0.004), while concurrent glucocorticoid administration was more frequent in the tocilizumab group (p = 0.024). Infliximab was the most frequently used anti-TNF drug, with a higher proportion of patients showing improvement compared with adalimumab (71.1% versus 45.5%). Adverse events were only reported with infliximab (n = 3), including allergic and infusion reactions.

LIMITATIONS

The evidence is primarily based on case reports and series, which might have introduced selection and publication bias. Additionally, heterogeneity in diagnostic criteria, treatment protocols, and outcome definitions limits the comparability of results across studies.

CONCLUSION

Despite the higher frequency of anti-TNF drug use, both therapies exhibit similar clinical outcomes, highlighting the potential of tocilizumab as an equally effective alternative in pediatric TAK management. Long-term head-to-head studies are needed to optimize the data regarding biologic treatment strategies in pediatric TAK.

摘要

背景与目的

大动脉炎(TAK)是一种罕见的大血管血管炎,主要影响年轻女性患者,儿科病例更为罕见。生物疗法,如抗肿瘤坏死因子(抗TNF)和抗白细胞介素-6(抗IL-6)药物,已成为TAK治疗的重要组成部分;然而,由于该疾病的罕见性,关于其在儿童中的应用缺乏有力数据支持。本系统评价旨在评估抗TNF药物和托珠单抗在儿科TAK治疗中的应用、有效性和安全性。

方法

我们在PubMed/MEDLINE和Scopus数据库中进行了系统的文献检索,检索时间从数据库建立至2024年12月15日。纳入的研究需包括接受抗TNF或抗IL-6药物治疗的儿科TAK患者(18岁前确诊)并报告临床结局。包括临床试验、观察性研究、病例系列和报告。由两名审阅者独立提取数据。仅分析英文文章。由于研究设计和报告的异质性,进行了叙述性综合分析。

结果

共纳入94篇报告,涉及225例接受262个疗程生物治疗的儿科TAK患者。抗TNF药物的使用频率高于托珠单抗(74.2%对36.9%,p<0.001)。两组显示出相当的有效性,抗TNF药物治疗疗程中有64.9%、托珠单抗治疗疗程中有70.9%观察到临床改善(p = 0.438)。两组的复发频率也相似(两组均约为50%,p = 0.472)。抗TNF组高血压更常见(p = 0.004),而托珠单抗组同时使用糖皮质激素更频繁(p = 0.024)。英夫利昔单抗是最常用的抗TNF药物,与阿达木单抗相比,显示改善的患者比例更高(71.1%对45.5%)。仅英夫利昔单抗报告了不良事件(n = 3),包括过敏和输注反应。

局限性

证据主要基于病例报告和病例系列,可能存在选择和发表偏倚。此外,诊断标准、治疗方案和结局定义的异质性限制了各研究结果的可比性。

结论

尽管抗TNF药物使用频率更高,但两种疗法均显示出相似的临床结局,突出了托珠单抗在儿科TAK管理中作为同样有效的替代方案的潜力。需要进行长期的头对头研究,以优化儿科TAK生物治疗策略的数据。

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