静脉注射戈利木单抗治疗多关节型幼年特发性关节炎患儿：一项开放性 III 期研究的长期扩展。
Intravenous Golimumab in Children With Polyarticular-Course Juvenile Idiopathic Arthritis: Long-Term Extension of an Open-Label Phase III Study.
机构信息
H.I. Brunner, MD, MSc, MBA, D.J. Lovell, MD, MPH, Cincinnati Children's Hospital Medical Center, Division of Rheumatology, University of Cincinnati, Cincinnati, Ohio, USA;
C. Pacheco-Tena, MD, MSc, PhD, Investig y Biomedicina de Chihuahua, Facultad de Medicina, Universidad Autónoma de Chihuahua, Circuito Universitario Campus II, Chihuahua, México.
出版信息
J Rheumatol. 2024 Nov 1;51(11):1125-1134. doi: 10.3899/jrheum.2024-0298.
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/m 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.
目的
报告参加评价静脉注射戈利木单抗治疗儿童活动性多关节型幼年特发性关节炎（pcJIA）的药代动力学（PK）、免疫原性、临床疗效和安全性的开放标签、长期扩展（LTE）研究的参与者的 PK、免疫原性、临床疗效和安全性，GO-VIVA 的 LTE 参与者在第 52 周后继续接受静脉注射戈利木单抗（80mg/m 每 8 周）。
方法
纳入继续接受静脉注射戈利木单抗（80mg/m 每 8 周）治疗的 GO-VIVA 参与者。通过第 244 周（最后一剂）评估 PK 和安全性，通过第 116 周评估临床反应。临床结局包括幼年特发性关节炎-美国风湿病学会（JIA-ACR）反应和 10 个关节的临床幼年特发性关节炎疾病活动评分（cJADAS10）。采用非应答者插补法评估二分类结局，采用观察数据进行其他描述性分析。
结果
在进入 LTE 的 127 名参与者中，有 112 名（88.2%）完成了第 252 周的就诊。从第 52 周到第 244 周，稳态谷浓度的戈利木单抗浓度普遍保持稳定（范围为 0.3-0.6μg/ml）。从第 52 周（39.2%[49/125]）到第 244 周（44.8%[56/125]），抗戈利木单抗抗体的发生率保持一致。第 52 周 JIA-ACR30/50/70/90 反应率（分别为 75.6%[96/127]、74%[94/127]、65.4%[83/127]和 48.8%[62/127]）在第 116 周（分别为 72.4%[92/127]、71.7%[91/127]、63.8%[81/127]和 50.4%[64/127]）时基本保持不变，在第 116 周时，中位数 cJADAS10 为 1.6，56.7%（72/127）的参与者达到 cJADAS10≤5（最小疾病活动度）。第 252 周时，严重不良事件和严重感染的发生率（每 100 患者年）分别为 7.7%和 3.9%。
结论
GO-VIVA LTE 参与者具有足够的 PK 暴露和稳定的安全性和免疫原性。大多数参与者的疾病活动度不超过最小残留疾病活动度。数据表明，静脉注射戈利木单抗治疗在第 116 周时具有持久的临床疗效，具有可接受的风险效益比。
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