Tanaka Yoshiya, Takeuchi Tsutomu, Atsumi Tatsuya, Combe Bernard G, Aletaha Daniel, Kaise Toshihiko, Rajendran Vijay
The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu, 807-8555, Japan.
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Rheumatol Ther. 2023 Dec;10(6):1399-1415. doi: 10.1007/s40744-023-00590-w. Epub 2023 Sep 5.
Filgotinib is an oral preferential Janus kinase 1 inhibitor that demonstrated significant reductions in radiographic progression, with an acceptable tolerability and safety profile, vs placebo in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR; FINCH 1) and vs MTX in MTX-naïve patients with RA (FINCH 3). International treatment guidelines identify multiple poor prognostic factors (PPFs) associated with worse disease outcomes among patients with RA. However, questions remain both about the clinical utility of considering PPFs and about which PPFs should drive treatment decisions. Additionally, the role of radiographic findings in clinical practice continues to be discussed and to evolve. This review examines radiographic results from post hoc analyses of phase 3 trials of filgotinib that examined subgroups with 4 PPFs or with baseline estimated rapid radiographic progression (e-RRP). In MTX groups, there were trends toward greater progression among patients with 4 PPFs or e-RRP, suggesting these subgroups may comprise a higher-risk population. Results show general consistency for the efficacy of filgotinib 200 mg plus MTX vs placebo plus MTX/MTX monotherapy on radiographic assessments, including change from baseline in modified total Sharp score and proportions without radiographic progression, even among MTX-IR or MTX-naïve patients with 4 PPFs or e-RRP who may be at higher risk of bone damage. Multivariate analysis identified multiple factors associated with baseline e-RRP status. This summary of the current understanding of benefits associated with filgotinib on radiographic progression and the relevance of baseline factors to these benefits may help inform treatment decisions for patients facing high risk of radiographic progression.
非戈替尼是一种口服的选择性 Janus 激酶 1 抑制剂,在类风湿关节炎(RA)患者中,与安慰剂相比,它在影像学进展方面有显著降低,耐受性和安全性良好,这些患者对甲氨蝶呤反应不足(MTX-IR;FINCH 1);在初治 RA 患者中,与甲氨蝶呤相比(FINCH 3)。国际治疗指南确定了多个与 RA 患者疾病预后较差相关的不良预后因素(PPF)。然而,关于考虑 PPF 的临床实用性以及哪些 PPF 应驱动治疗决策仍存在疑问。此外,影像学检查结果在临床实践中的作用仍在讨论和不断演变。本综述检查了非戈替尼 3 期试验事后分析的影像学结果,这些试验研究了具有 4 种 PPF 或基线估计快速影像学进展(e-RRP)的亚组。在甲氨蝶呤组中,具有 4 种 PPF 或 e-RRP 的患者有更大进展的趋势,表明这些亚组可能构成更高风险人群。结果显示,在影像学评估方面,非戈替尼 200mg 加甲氨蝶呤与安慰剂加甲氨蝶呤/甲氨蝶呤单药治疗的疗效总体一致,包括改良总 Sharp 评分相对于基线的变化以及无影像学进展的比例,即使在可能有更高骨损伤风险的具有 4 种 PPF 或 e-RRP 的 MTX-IR 或初治患者中也是如此。多变量分析确定了与基线 e-RRP 状态相关的多个因素。对非戈替尼在影像学进展方面相关益处的当前理解以及基线因素与这些益处的相关性总结,可能有助于为面临影像学进展高风险的患者提供治疗决策依据。