Pôle de Pathologies Rhumatismales Systémiques et Inflammatoires, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.
Department of Pediatric Hematology, Oncology, Immunology and Rheumatology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Rheumatology (Oxford). 2024 Mar 1;63(3):594-607. doi: 10.1093/rheumatology/kead490.
Biologic and targeted synthetic DMARDs (b/tsDMARDs) have revolutionized the management of multiple rheumatic inflammatory conditions. Among these, polyarticular JIA (pJIA) and RA display similarities in terms of disease pathophysiology and response pattern to b/tsDMARDs. Indeed, the therapeutic efficacy of novel targeted drugs is variable among individual patients, in both RA and pJIA. The mechanisms and determinants of this heterogeneous response are diverse and complex, such that the development of true 'precision'-medicine strategies has proven highly challenging. In this review, we will discuss pathophysiological, patient-specific, drug-specific and environmental factors contributing to individual therapeutic response in pJIA in comparison with what is known in RA. Although some biomarkers have been identified that stratify with respect to the likelihood of either therapeutic response or non-response, few have proved useful in clinical practice so far, likely due to the complexity of treatment-response mechanisms. Consequently, we propose a pragmatic, patient-centred and clinically based approach, i.e. personalized instead of biomarker-based precision medicine in JIA.
生物制剂和靶向合成 DMARDs（b/tsDMARDs）彻底改变了多种风湿性炎症性疾病的治疗管理。在这些疾病中，多关节型幼年特发性关节炎（pJIA）和类风湿关节炎（RA）在疾病病理生理学和对 b/tsDMARDs 的反应模式方面具有相似性。事实上，新型靶向药物在 RA 和 pJIA 中的个体患者中的治疗效果存在差异。这种异质性反应的机制和决定因素多种多样且复杂，因此开发真正的“精准”医学策略极具挑战性。在这篇综述中，我们将讨论导致 pJIA 中个体治疗反应的病理生理、患者特异性、药物特异性和环境因素，并将其与 RA 中的已知情况进行比较。尽管已经确定了一些生物标志物，这些标志物可以分层预测治疗反应或无反应的可能性，但迄今为止，很少有生物标志物在临床实践中被证明有用，这可能是由于治疗反应机制的复杂性所致。因此，我们提出了一种实用的、以患者为中心的、基于临床的方法，即在 JIA 中采用个性化而不是基于生物标志物的精准医学。
