Ann Rheum Dis :换用生物制剂治疗JIA疗效更小

　　　来自荷兰的一项研究表明，换用另一种生物制剂很常见，尤其是对于全身性青少年特发性关节炎（JIA）患者。第二个（和第三个）生物制剂比首个药物疗效更小。医师选择第二个生物制剂主要取决于（药物）利用率和JIA类型。该论文发表在2013年第5期《风湿病学年鉴》[Ann Rheum Dis 2013;72:721-727]。
　　儿童关节炎和生物制剂登记（ABC登记）目的是包括所有使用过生物制剂的荷兰JIA患者。有关病程的资料用于评估药品利用率（卡普兰-梅耶法）并计算不良事件率。
　　在307例无生物制剂使用史、开始使用依那西普的患者中，80例（26%）换用第二个生物制剂，22（7%）换用第三个生物制剂。在依那西普使用后随访1030患者-年期间，49例换用阿达木单抗，28例英夫利昔单抗，17例阿那白滞素，4例阿巴西普，并且评估了4种试验用药。与47%的患者换用第二个，51%患者换用第三个生物制剂相比，84%患者开始使用依那西普作为第一个生物制剂，12个月后仍使用依那西普。因基本无效而换药的患者连续使用第二种个药物少见（32%）。依那西普治疗失败后，对于非全身性JIA患者，阿达木单抗药物连用与英夫利昔单抗相似；对于全身性JIA，阿那白滞素优于另一种肿瘤坏死因子（TNF）阻滞剂。初始使用后第一个12个月里，不良事件生率在每个过程和每个生物制剂都具有可比性。
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Effectiveness and safety of a second and third biological agent after failing etanercept in juvenile idiopathic arthritis: results from the Dutch National ABC Register.
OBJECTIVE
To evaluate the effectiveness and safety of switching to a second or third biological agent in juvenile idiopathic arthritis (JIA) after etanercept failure.
METHODS
The Arthritis and Biologicals in Children Register aims to include all Dutch JIA patients who have used biological agents. Data on the disease course were used to estimate drug survival with Kaplan-Meier and calculate adverse event (AE) rates.
RESULTS
Of 307 biologically naive JIA patients who started etanercept, 80 (26%) switched to a second and 22 (7%) to a third biological agent. During 1030 patient-years of follow-up after the introduction of etanercept, 49 switches to adalimumab, 28 infliximab, 17 anakinra, four abatacept and four trial drugs were evaluated. 84% (95% CI 80% to 88%) of patients who started etanercept as a first biological agent were, after 12 months, still on the drug, compared with 47% (95% CI 35% to 60%) who started a second and 51% (95% CI 26% to 76%) who started a third biological agent. Patients who switched because of primary ineffectiveness continued the second agent less often (32%, 95% CI 12% to 53%). After etanercept failure, drug continuation of adalimumab was similar to infliximab for patients with non-systemic JIA; anakinra was superior to a second TNF-blocker for systemic JIA. AE rates within first 12 months after initiation were comparable for each course and each biological agent.
CONCLUSIONS
Switching to another biological agent is common, especially for systemic JIA patients. A second (and third) agent was less effective than the first. The choice of second biological agent by the physician mainly depends on availability and JIA category.