Bayesian trial of adalimumab versus secukinumab for children with juvenile idiopathic arthritis associated uveitis or chronic anterior uveitis.

IF 2.8 3区医学 Q1 PEDIATRICS

Pediatric Rheumatology Pub Date : 2025-05-19 DOI:10.1186/s12969-025-01107-1

Athimalaipet V Ramanan, Andrew D Dick, Thomas Jaki, Gianmarco Caruso, David S Robertson, Ashley P Jones, Ben Hardwick, Sian Drake, Balini Balasubramaniam, Coziana Ciurtin, Ivan Foeldvari, Elke O Kreps, Alice Leahy, Kristina May, Pierre Quartier, Matthieu P Robert, Gabriele Simonini, Catherine Guly, Michael W Beresford

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引用次数: 0

Abstract

Background: Juvenile idiopathic arthritis (JIA)-associated uveitis and chronic anterior uveitis in children may result in permanent sight loss. Currently, the only licensed and approved treatment for JIA-uveitis is adalimumab. However, even in patients where adalimumab may be initially effective, therapeutic response may subside for example, due to neutralising drug antibodies. Further treatment options are necessary to prevent sight loss in children with uveitis. Interleukin 17 is elevated in uveitis. Inhibition of interleukin 17 ameliorates inflammation in mouse models of uveitis. Secukinumab, an antibody which neutralizes interleukin 17 A, has been shown to be partially effective in adult uveitis. The objective of the Bayesian consensus meeting was to quantify prior expert opinion about the potential utility of secukinumab in treatment of uveitis in JIA.

Methods: Nine international experts in paediatric rheumatology, paediatric ophthalmology and/or paediatric uveitis took part in a structured Bayesian prior elicitation meeting.

Results: The final consensus was that adalimumab is expected to yield a higher response rate than secukinumab (mean 0.67 vs. 0.55). The uncertainty in the response rate on secukinumab is somewhat larger than for adalimumab. The equivalent sample size for the prior distribution of adalimumab is 15.7 and 13.1 for secukinumab. The decisions based on the combined evidence would still be driven by the trial data, yet substantial enhancement of the power of the study can be expected by adding information from the equivalent of almost 30 patients.

Conclusions: The Bayesian analysis adds substantial enhancement of the power of the study and supports a head-to-head trial of adalimumab and secukinumab for JIA-associated uveitis and chronic anterior uveitis.

Trial registration: ISRCTN 12,427,150 Registration date 14/02/2023. EudraCT 2022-003068-26 Registration date 07/09/2022.

查看原文本刊更多论文

阿达木单抗与secukinumab治疗儿童特发性关节炎相关性葡萄膜炎或慢性前葡萄膜炎的贝叶斯试验

背景：儿童特发性关节炎（JIA）相关的葡萄膜炎和慢性前葡萄膜炎可导致永久性视力丧失。目前，唯一获得许可和批准的治疗jia -葡萄膜炎的药物是阿达木单抗。然而，即使在阿达木单抗最初可能有效的患者中，治疗反应也可能减弱，例如，由于中和药物抗体。为了防止葡萄膜炎儿童的视力丧失，需要进一步的治疗选择。葡萄膜炎患者白细胞介素17升高。抑制白细胞介素17可改善葡萄膜炎小鼠模型的炎症。Secukinumab是一种中和白细胞介素17a的抗体，已被证明对成人葡萄膜炎部分有效。贝叶斯共识会议的目的是量化先前专家对secukinumab在JIA中治疗葡萄膜炎的潜在效用的意见。方法：9位国际儿科风湿病学、儿科眼科和/或儿科葡萄膜炎专家参加了一个结构化的贝叶斯先验启发会议。结果：最终共识是阿达木单抗的应答率有望高于secukinumab（平均0.67 vs 0.55）。secukinumab应答率的不确定性比阿达木单抗要大一些。阿达木单抗的等效样本量为15.7，而secukinumab的等效样本量为13.1。基于综合证据的决策仍将由试验数据驱动，然而，通过增加相当于近30名患者的信息，可以预期该研究的效力将大幅增强。结论：贝叶斯分析大大增强了该研究的有效性，并支持阿达木单抗和secukinumab治疗jia相关性葡萄膜炎和慢性前葡萄膜炎的正面试验。试验注册：ISRCTN 12,427,150注册日期14/02/2023。EudraCT 2022-003068-26注册日期2022年9月7日。

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来源期刊

Pediatric Rheumatology PEDIATRICS-RHEUMATOLOGY

CiteScore

4.10

自引率

8.00%

发文量

审稿时长

>12 weeks

期刊介绍： Pediatric Rheumatology is an open access, peer-reviewed, online journal encompassing all aspects of clinical and basic research related to pediatric rheumatology and allied subjects. The journal’s scope of diseases and syndromes include musculoskeletal pain syndromes, rheumatic fever and post-streptococcal syndromes, juvenile idiopathic arthritis, systemic lupus erythematosus, juvenile dermatomyositis, local and systemic scleroderma, Kawasaki disease, Henoch-Schonlein purpura and other vasculitides, sarcoidosis, inherited musculoskeletal syndromes, autoinflammatory syndromes, and others.