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青少年特发性关节炎中抗肿瘤坏死因子药物第一疗程和第二疗程的药物留存率

Drug survival of the first and second course of anti-tumour necrosis factor agents in juvenile idiopathic arthritis.

作者信息

Tynjälä P, Vähäsalo P, Honkanen V, Lahdenne P

机构信息

Department of Pediatric Rheumatology, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland.

出版信息

Ann Rheum Dis. 2009 Apr;68(4):552-7. doi: 10.1136/ard.2007.087130. Epub 2008 May 8.

Abstract

OBJECTIVES

To evaluate drug survival (continuation rates on drug) of anti-tumour necrosis factor (TNF) agents in juvenile idiopathic arthritis (JIA) and predictors for treatment discontinuation.

METHODS

A retrospective observational study on JIA patients taking etanercept (n = 105) or infliximab (n = 104) with at least one year follow-up. Kaplan-Meier curves and log-rank statistics were used to compare treatments and a proportional hazards model to assess risk factors for discontinuation.

RESULTS

Etanercept versus infliximab treatment survival at 12 months was 83% versus 80%, at 24 months 68% versus 68%, at 36 months 64% versus 53%, at 48 months 61% versus 48% (p = 0.194), respectively. Reasons for discontinuing the first biological treatment were inefficacy (etanercept 28% vs infliximab 20%, p = 0.445), adverse events (7% vs 22%, p = 0.002) or inactive disease (10% vs 16%, p = 0.068). Women (hazard ratio (HR) 2.8, 95% CI 1.3 to 5.8), patients with systemic JIA (HR 7.8, 95% CI 1.7 to 34.9) or those taking infliximab (HR 2.0, 95% CI 1.2 to 3.3) were at higher risk of treatment discontinuation. One-third of the patients were switched to the second anti-TNF therapy, which was discontinued less frequently than the first. At 12 months treatment survival of etanercept was 60%, infliximab 58% and adalimumab 66% as the second-line anti-TNF therapy.

CONCLUSIONS

Although infliximab was discontinued more often than etanercept because of adverse events, during a 48-month follow-up the overall treatment survival of etanercept and infliximab as the first biological agent in JIA was comparable. A switch from one anti-TNF agent to another appears a reasonable therapeutic option.

摘要

目的

评估抗肿瘤坏死因子(TNF)药物在幼年特发性关节炎(JIA)中的药物留存率(持续用药率)以及治疗中断的预测因素。

方法

对接受依那西普(n = 105)或英夫利昔单抗(n = 104)治疗且至少随访一年的JIA患者进行回顾性观察研究。采用Kaplan-Meier曲线和对数秩统计来比较治疗效果,并使用比例风险模型评估中断治疗的风险因素。

结果

依那西普与英夫利昔单抗在12个月时的治疗留存率分别为83%和80%,24个月时为68%和68%,36个月时为64%和53%,48个月时为61%和48%(p = 0.194)。中断首次生物治疗的原因包括无效(依那西普为28%,英夫利昔单抗为20%,p = 0.445)、不良事件(7%对22%,p = 0.002)或疾病缓解(10%对16%,p = 0.068)。女性(风险比(HR)2.8,95%置信区间1.3至5.8)、全身型JIA患者(HR 7.8,95%置信区间1.7至34.9)或使用英夫利昔单抗的患者(HR 2.0,95%置信区间1.2至3.3)中断治疗的风险更高。三分之一的患者换用了第二种抗TNF治疗药物,第二种药物的中断治疗频率低于第一种。作为二线抗TNF治疗药物,依那西普在12个月时的治疗留存率为60%,英夫利昔单抗为58%,阿达木单抗为66%。

结论

尽管英夫利昔单抗因不良事件中断治疗的频率高于依那西普,但在48个月的随访中,依那西普和英夫利昔单抗作为JIA的第一种生物制剂的总体治疗留存率相当。从一种抗TNF药物换用另一种药物似乎是一种合理的治疗选择。

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