阿达木单抗与司库奇尤单抗治疗幼年特发性关节炎相关葡萄膜炎或慢性前葡萄膜炎儿童的贝叶斯试验。
Bayesian trial of adalimumab versus secukinumab for children with juvenile idiopathic arthritis associated uveitis or chronic anterior uveitis.
作者信息
Ramanan Athimalaipet V, Dick Andrew D, Jaki Thomas, Caruso Gianmarco, Robertson David S, Jones Ashley P, Hardwick Ben, Drake Sian, Balasubramaniam Balini, Ciurtin Coziana, Foeldvari Ivan, Kreps Elke O, Leahy Alice, May Kristina, Quartier Pierre, Robert Matthieu P, Simonini Gabriele, Guly Catherine, Beresford Michael W
机构信息
Bristol Royal Hospital for Children, Upper Maudlin Street, Bristol, BS2 8BJ, UK.
Translational Health Sciences, University of Bristol, Bristol, UK.
出版信息
Pediatr Rheumatol Online J. 2025 May 19;23(1):55. doi: 10.1186/s12969-025-01107-1.
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.
背景
青少年特发性关节炎（JIA）相关葡萄膜炎和儿童慢性前葡萄膜炎可能导致永久性视力丧失。目前，JIA-葡萄膜炎唯一获得许可和批准的治疗方法是阿达木单抗。然而，即使在阿达木单抗最初可能有效的患者中，治疗反应也可能消退，例如由于中和药物抗体。需要进一步的治疗选择来预防葡萄膜炎患儿的视力丧失。白细胞介素17在葡萄膜炎中升高。抑制白细胞介素17可改善葡萄膜炎小鼠模型中的炎症。司库奇尤单抗是一种中和白细胞介素17A的抗体，已被证明在成人葡萄膜炎中部分有效。贝叶斯共识会议的目的是量化专家之前关于司库奇尤单抗在治疗JIA葡萄膜炎中的潜在效用的意见。
方法
九位儿科风湿病学、儿科眼科和/或儿科葡萄膜炎领域的国际专家参加了一次结构化的贝叶斯先验诱导会议。
结果
最终共识是，预计阿达木单抗的缓解率高于司库奇尤单抗（平均0.67对0.55）。司库奇尤单抗缓解率的不确定性比阿达木单抗略大。阿达木单抗先验分布的等效样本量为15.7，司库奇尤单抗为13.1。基于综合证据的决策仍将由试验数据驱动，但通过添加近30名患者的等效信息，预计可大幅提高研究效能。
结论
贝叶斯分析大幅提高了研究效能，并支持对阿达木单抗和司库奇尤单抗治疗JIA相关葡萄膜炎和慢性前葡萄膜炎进行头对头试验。
试验注册
ISRCTN 12427150，注册日期2023年2月14日。EudraCT 2022-003068-26，注册日期2022年9月7日。
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