静脉注射戈利木单抗治疗多关节病程幼年特发性关节炎患儿:一项开放标签的 3 期研究的长期扩展。

IF 3.6 2区 医学 Q2 RHEUMATOLOGY
Hermine I Brunner, César Pacheco-Tena, Ingrid Louw, Gabriel Vega-Cornejo, Ekaterina Alexeeva, Simone Appenzeller, Vyacheslav Chasnyk, Thomas Griffin, Carmen Navarrete Suarez, Sheila Knupp-Oliveira, Andrew Zeft, Yonatan Butbul Aviel, Deirdre De Ranieri, Beth S Gottlieb, Deborah M Levy, C Egla Rabinovich, Clóvis Artur Silva, Yury Spivakovsky, Yosef Uziel, Sarah Ringold, Xie L Xu, Jocelyn H Leu, Edwin Lam, Yuhua Wang, Daniel J Lovell, Alberto Martini, Nicolino Ruperto
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引用次数: 0

摘要

目的报告参加GO-VIVA研究开放标签长期延长(LTE)至第252周的活动性多关节病程幼年特发性关节炎(pcJIA)患儿静脉注射戈利木单抗的药代动力学、免疫原性、临床效果和安全性:纳入第52周后继续静脉注射戈利木单抗(每8周80毫克/平方米)的GO-VIVA参与者。药代动力学和安全性分别评估至第244周(最后一次给药)和第252周,临床反应评估至第116周。临床结果包括JIA美国风湿病学会(ACR)反应和基于10个关节的临床幼年关节炎疾病活动度评分(cJADAS-10)。二元结果采用非应答者估算;其他描述性分析采用观察数据:在112/127(88.2%)名进入LTE的参与者中,69人完成了第252周的访问。从第52周到第244周,戈利木单抗的中位稳态谷浓度基本保持不变(范围为0.3-0.6 μg/mL)。抗戈木单抗抗体发生率在第52周(39.2% [49/125])和第244周(44.8% [56/125])期间保持一致。第52周的JIA ACR 30/50/70/90应答率(分别为75.6% [96/127]/74.0% [94/127]/65.4% [83/127]/48.8% [62/127])在第116周基本保持不变(72.4% [92/127]/71.中位 cJADAS-10 为 1.6,56.7%(72/127)的参与者达到 JADAS-10 ≤5(最小疾病活动度)。截至第252周,严重不良事件和严重感染的发生率(每100名患者年)分别为7.7和3.9:GO-VIVA LTE参与者经历了充分的药代动力学暴露、稳定的安全性和免疫原性。结论:GO-VIVA LTE 参与者的药代动力学暴露充分,安全性和免疫原性稳定,大多数参与者的疾病活动残留不超过最低限度。数据表明,静脉注射戈利木单抗治疗可在第116周之前提供持久的临床应答,其获益-风险状况可接受。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Intravenous Golimumab in Children With Polyarticular-Course Juvenile Idiopathic Arthritis: Long-Term Extension of an Open-Label Phase III Study.

Objective: To report pharmacokinetics (PK), immunogenicity, clinical effect, and safety of intravenous (IV) golimumab in children with active polyarticular-course juvenile idiopathic arthritis (pcJIA) who participated in A Study to Evaluate the Pharmacokinetics, Efficacy and Safety of Intravenous Golimumab in Pediatric Participants With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate Therapy (GO-VIVA)'s open-label, long-term extension (LTE) through week 252.

Methods: GO-VIVA participants who continued IV golimumab (80 mg/m2 every 8 weeks) after week 52 were included. PK and safety were assessed through week 244 (last dose) and week 252, respectively, and clinical response through week 116. Clinical outcomes included JIA-American College of Rheumatology (ACR) responses and clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10). Binary outcomes used nonresponder imputation, and other descriptive analyses used observed data.

Results: Of 112/127 (88.2%) participants entering the LTE, 69 completed the week 252 visit. Median steady-state trough golimumab concentrations were generally maintained from week 52 through week 244 (range 0.3-0.6 μg/mL). Antigolimumab antibody rates were consistent through week 52 (39.2% [49/125]) and week 244 (44.8% [56/125]). Week 52 JIA-ACR 30/50/70/90 response rates (75.6% [96/127], 74% [94/127], 65.4% [83/127], and 48.8% [62/127], respectively) were generally maintained through week 116 (72.4% [92/127], 71.7% [91/127], 63.8% [81/127], and 50.4% [64/127], respectively), when the median cJADAS10 was 1.6 and 56.7% (72/127) of participants achieved cJADAS10 ≤ 5 (minimal disease activity). Rates (per 100 patient-years) of serious adverse events and serious infections through week 252 were 7.7 and 3.9, respectively.

Conclusion: GO-VIVA LTE participants experienced adequate PK exposure and stable safety and immunogenicity. The majority of participants experienced no more than minimal residual disease activity. Data suggest IV golimumab treatment provided durable clinical response through week 116, with an acceptable risk-benefit profile.

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来源期刊
Journal of Rheumatology
Journal of Rheumatology 医学-风湿病学
CiteScore
6.50
自引率
5.10%
发文量
285
审稿时长
1 months
期刊介绍: The Journal of Rheumatology is a monthly international serial edited by Earl D. Silverman. The Journal features research articles on clinical subjects from scientists working in rheumatology and related fields, as well as proceedings of meetings as supplements to regular issues. Highlights of our 41 years serving Rheumatology include: groundbreaking and provocative editorials such as "Inverting the Pyramid," renowned Pediatric Rheumatology, proceedings of OMERACT and the Canadian Rheumatology Association, Cochrane Musculoskeletal Reviews, and supplements on emerging therapies.
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