Horneff Gerd, Klein Ariane, Klotsche Jens, Minden Kirsten, Huppertz Hans-Iko, Weller-Heinemann Frank, Kuemmerle-Deschner Jasmin, Haas Johannes-Peter, Hospach Anton
Department of Pediatrics, Centre of General Pediatrics and Neonatology, Asklepios Clinic Sankt Augustin, 53757, Sankt Augustin, Germany.
German Rheumatism Research Centre Berlin, and Children's University Hospital Charité, Berlin, Germany.
Arthritis Res Ther. 2016 Nov 24;18(1):272. doi: 10.1186/s13075-016-1170-3.
Treatment response, remission rates and compliance in patients with polyarticular juvenile idiopathic arthritis (polyJIA) treated with adalimumab, etanercept, or tocilizumab were analyzed in clinical practice.
Data collected in the German BIKER registry were analyzed in patients with polyJIA who started treatment with approved biologics, adalimumab, etanercept or tocilizumab, from 2011 to 2015. Baseline patient characteristics, treatment response, safety and drug survival were compared.
Two hundred thirty-six patient started adalimumab, 419 etanercept and 74 tocilizumab, with differences in baseline patient characteristics. Baseline Juvenile Disease Activity Score (JADAS)10 (mean ± SD) in the adalimumab/etanercept/tocilizumab cohorts was 12.1+/-7.6, 13.8 ± 7.1 and 15.1 ± 7.4, respectively (adalimumab vs etanercept, p = 0.01), and Childhood Health Assessment Questionnaire (CHAQ)-disability index scores was 0.43 ± 0.58, 0.59 ± 0.6 and 0.63 ± 0.55, respectively (adalimumab vs etanercept, p < 0.001). Uveitis history was more frequent in the adalimumab cohort (OR 5.73; p < 0.001). Balanced patients' samples were obtained by a generalized propensity score to adjust for baseline differences. Pediatric ACR30/50/70/90 criterion improvement after 3 months treatment was achieved by 68%/60%/42%/24% in the etanercept cohort, 67%/59%/43%/27% in the adalimumab cohort and 61%/52%/35%/26% in the tocilizumab cohort. At 24 months, JADAS minimal disease activity was achieved in 52.4%/61.3%/52.4% and JADAS remission in 27.9%/34.8%/27.9% patients in the adalimumab/etanercept/tocilizumab cohorts, respectively. Etanercept was used in 95.5% of patients as a first biologic, adalimumab in 50.8% and tocilizumab in 20.2%. There were no important differences in efficacy between first-line and second-line use of biologics. In total 60.4%/49.4%/31.1% patients discontinued adalimumab/etanercept/tocilizumab, respectively (HR for adalimumab 1.67; p < 0.001; HR for tocilizumab 0.35; p = 0.001). Drug survival rates did not differ significantly in patients on biologic monotherapy compared with combination therapy with methotrexate. Over 4 years observation under etanercept/adalimumab/tocilizumab, 996/386/103 adverse events, and 148/119/26 serious adverse events, respectively, were reported.
In clinical practice, etanercept is most frequently used as first-line biologic. Adalimumab/etanercept/tocilizumab showed comparable efficacy toward polyJIA. Overall, tolerance was acceptable. Interestingly, compliance was highest with tocilizumab and lowest with adalimumab. This study provides the first indication for the comparison of different biologic agents in polyarticular JIA based on observational study data with all their weaknesses and demonstrates the need for well-controlled head-to-head studies for confirmation.
在临床实践中,分析了接受阿达木单抗、依那西普或托珠单抗治疗的多关节型幼年特发性关节炎(polyJIA)患者的治疗反应、缓解率和依从性。
对德国BIKER注册中心收集的数据进行分析,研究对象为2011年至2015年开始使用已获批生物制剂阿达木单抗、依那西普或托珠单抗治疗的polyJIA患者。比较了患者的基线特征、治疗反应、安全性和药物生存率。
236例患者开始使用阿达木单抗,419例使用依那西普,74例使用托珠单抗,患者基线特征存在差异。阿达木单抗/依那西普/托珠单抗队列的基线青少年疾病活动评分(JADAS)10(均值±标准差)分别为12.1±7.6、13.8±7.1和15.1±7.4(阿达木单抗与依那西普比较,p = 0.01),儿童健康评估问卷(CHAQ)残疾指数评分分别为0.43±0.58、0.59±0.6和0.63±0.55(阿达木单抗与依那西普比较,p < 0.001)。葡萄膜炎病史在阿达木单抗队列中更为常见(比值比5.73;p < 0.001)。通过广义倾向评分获得平衡的患者样本,以调整基线差异。依那西普队列在治疗3个月后达到儿科ACR30/50/70/90标准改善的比例分别为该队列的68%/60%/42%/24%,阿达木单抗队列的67%/59%/43%/27%,托珠单抗队列的61%/52%/35%/26%。在24个月时,阿达木单抗/依那西普/托珠单抗队列中分别有52.4%/61.3%/52.4%的患者达到JADAS最小疾病活动度,27.9%/34.8%/27.9%的患者达到JADAS缓解。95.5%的患者将依那西普作为第一种生物制剂使用,50.8%使用阿达木单抗,20.2%使用托珠单抗。生物制剂一线和二线使用的疗效无重要差异。分别有60.4%/49.4%/31.1%的患者停用阿达木单抗/依那西普/托珠单抗(阿达木单抗的风险比为1.67;p < 0.001;托珠单抗的风险比为0.35;p = 0.001)。与甲氨蝶呤联合治疗相比,生物单药治疗患者的药物生存率无显著差异。在依那西普/阿达木单抗/托珠单抗治疗的4年观察期内,分别报告了996/386/103例不良事件和148/119/26例严重不良事件。
在临床实践中,依那西普最常作为一线生物制剂使用。阿达木单抗/依那西普/托珠单抗对polyJIA显示出相当的疗效。总体而言,耐受性尚可。有趣的是,托珠单抗的依从性最高,阿达木单抗最低。本研究基于观察性研究数据(存在所有这些弱点)首次对不同生物制剂在多关节型幼年特发性关节炎中的比较提供了指征,并表明需要进行严格对照的头对头研究以进行确认。