Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, and Deutsches Zentrum Immuntherapie, FAU Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Division of Rheumatology, Klinikum Nürnberg, Paracelsus Medical University, Nürnberg, Germany.
Arthritis Rheumatol. 2023 Nov;75(11):1923-1934. doi: 10.1002/art.42617. Epub 2023 Sep 21.
Rheumatoid arthritis (RA) is characterized by erosive joint damage, deterioration of bone mass, and biomechanics. Preclinical evidence suggests a beneficial effect of Janus kinase inhibition (JAKi) on bone properties, but clinical data are scarce to date. In this study, we evaluated the effect of JAKi through baricitinib (BARI) on 1) volumetric bone mineral density (vBMD), bone microstructure, biomechanics, and erosion repair and 2) synovial inflammation in RA patients.
Prospective, single-arm, interventional, open-label, single-center phase 4 study in RA patients with pathological bone status and clinical indication of JAKi (BARE BONE trial). Participants received BARI (4 mg/day) over 52 weeks. To assess bone properties and synovial inflammation, high-resolution computed tomography scans and magnetic resonance imaging were performed at baseline (BL), week 24, and week 52. Clinical response and safety were monitored.
Thirty RA patients were included. BARI significantly improved disease activity (Disease Activity Score in 28 joints using the erythrocyte sedimentation rate: 4.82 ± 0.90 to 2.71 ± 0.83) and synovial inflammation (RAMRIS synovitis score: 5.3 [4.2] to 2.7 [3.5]). We observed a significant improvement in trabecular vBMD with a mean change of 6.11 mgHA/mm (95% confidence interval [95% CI] 0.01-12.26). Biomechanical properties also improved with mean change from baseline in estimated stiffness of 2.28 kN/mm (95% CI 0.30-4.25) and estimated failure load of 98.8 N (95% CI 15.9-181.7). The number and size of erosions in the metacarpal joints remained stable. No new safety signals with BARI treatment were observed.
Bones of RA patients improve with BARI therapy, as shown by an increase in trabecular bone mass and an improvement of biomechanical properties.
类风湿关节炎（RA）的特征为侵蚀性关节损伤、骨质减少和生物力学改变。临床前证据表明，Janus 激酶抑制剂（JAKi）对骨骼特性有有益作用，但迄今为止临床数据仍然有限。在这项研究中，我们通过巴瑞替尼（BARI）评估了 JAKi 对 1）容积骨密度（vBMD）、骨微结构、生物力学和侵蚀修复以及 2）RA 患者滑膜炎症的影响。
RA 患者具有病理性骨骼状态和 JAKi 临床指征（BARE BONE 试验）的前瞻性、单臂、干预性、开放性、单中心 4 期研究。参与者接受 52 周的巴瑞替尼（4mg/天）治疗。基线（BL）、第 24 周和第 52 周时进行高分辨率计算机断层扫描和磁共振成像，以评估骨骼特性和滑膜炎症。监测临床反应和安全性。
共纳入 30 例 RA 患者。巴瑞替尼显著改善了疾病活动度（红细胞沉降率 28 关节疾病活动评分：4.82±0.90 至 2.71±0.83）和滑膜炎症（RAMRIS 滑膜炎评分：5.3[4.2]至 2.7[3.5]）。我们观察到小梁 vBMD 有显著改善，平均变化 6.11mgHA/mm（95%置信区间 [95%CI] 0.01-12.26）。生物力学性能也得到改善，从基线的平均刚度变化为 2.28kN/mm（95%CI 0.30-4.25）和估计的失效负荷为 98.8N（95%CI 15.9-181.7）。掌指关节的侵蚀数量和大小保持稳定。未观察到巴瑞替尼治疗的新的安全性信号。
RA 患者的骨骼在巴瑞替尼治疗下得到改善，表现为小梁骨量增加和生物力学性能改善。
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