M.L. Mannion, MD, MSPH, Assistant Professor, T. Beukelman, MD, MSCE, Associate Professor, Division of Pediatric Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama;
F. Xie, PhD, MS, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama.
J Rheumatol. 2021 Aug;48(8):1322-1329. doi: 10.3899/jrheum.200437. Epub 2020 Sep 15.
Biologic medications have significantly improved disease control and outcomes of patients with juvenile idiopathic arthritis (JIA). Current treatment recommendations suggest escalating therapy, including changing biologics if needed, when inactive or low disease activity is not attained. The patterns and reasons for switching biologics in clinical practice in North America are not well described.
We used the Childhood Arthritis and Rheumatology Research Alliance Registry and included individuals with JIA if they newly started a biologic after January 1, 2008, and had at least 12 months of subsequent observable time. Subjects with systemic JIA were excluded. We compared characteristics of switchers and nonswitchers using chi-square for categorical variables and Wilcoxon rank-sum test for continuous variables, and used linear regression for time analysis.
Of the eligible children, 1361 with JIA in the registry started a biologic (94% tumor necrosis factor inhibitors [TNFi]). Median followup time was 30 months and 349 (26%) switched biologics. Among biologic switchers, ineffectiveness/disease flare was the most common reason for switch (202, 58%). The most common documented switch was from etanercept to another TNFi (221, 63%). The median time to switch to a second biologic decreased substantially from 55.2 months in 2008 to 7.2 months in 2016.
In a multicenter cohort of patients with JIA starting a biologic, one-quarter switched to a second biologic, and the time to switching decreased in recent years. Additional studies should evaluate the outcomes and optimal timing of switching and preferred sequence of biologic use.
生物制剂显著改善了幼年特发性关节炎（JIA）患者的疾病控制和预后。目前的治疗建议建议逐步升级治疗，如果未达到无活动或低疾病活动度，则包括更换生物制剂。在北美的临床实践中，生物制剂的转换模式和原因尚不清楚。
我们使用了儿童关节炎和风湿病研究联盟注册中心，并纳入了自 2008 年 1 月 1 日起新开始使用生物制剂且随后有至少 12 个月可观察时间的 JIA 患者。排除了患有全身型 JIA 的患者。我们使用卡方检验比较了转换者和非转换者的特征，对于连续变量使用 Wilcoxon 秩和检验，使用线性回归进行时间分析。
在符合条件的儿童中，注册中心有 1361 名 JIA 患者开始使用生物制剂（94%为肿瘤坏死因子抑制剂[TNFi]）。中位随访时间为 30 个月，349 名（26%）患者更换了生物制剂。在生物制剂转换者中，无效/疾病发作是最常见的转换原因（202 例，58%）。最常见的记录转换是从依那西普转换为另一种 TNFi（221 例，63%）。转换为第二种生物制剂的中位时间从 2008 年的 55.2 个月显著缩短至 2016 年的 7.2 个月。
在开始使用生物制剂的 JIA 患者多中心队列中，有四分之一的患者转换为第二种生物制剂，近年来转换时间缩短。应进一步研究评估转换的结果和最佳时机以及生物制剂使用的首选顺序。
