Baricitinib Improves Bone Properties and Biomechanics in Patients With Rheumatoid Arthritis: Results of the Prospective Interventional BARE BONE Trial

IF 11.4 1区医学 Q1 RHEUMATOLOGY Arthritis & Rheumatology Pub Date : 2023-05-25 DOI:10.1002/art.42617

David Simon, Ioanna Minopoulou, Stephan Kemenes, Sara Bayat, Koray Tascilar, Melek Yalcin Mutlu, Larissa Valor-Méndez, Gerhard Krönke, Axel J. Hueber, Georg Schett, Arnd Kleyer

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引用次数: 2

Abstract

Objective

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.

Methods

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.

Results

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/mm³ (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.

Conclusion

Bones of RA patients improve with BARI therapy, as shown by an increase in trabecular bone mass and an improvement of biomechanical properties.

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巴里西替尼改善类风湿性关节炎患者的骨特性和生物力学：前瞻性裸骨介入试验的结果。

目的：类风湿性关节炎（RA）以侵蚀性关节损伤、骨量和生物力学恶化为特征。临床前证据表明Janus激酶抑制（JAKi）对骨骼特性有有益影响，但迄今为止临床数据很少。在本研究中，我们评估了JAKi通过巴里西替尼（BARI）对1）RA患者的体积骨密度（vBMD）、骨微观结构、生物力学和侵蚀修复以及2）滑膜炎症的影响。方法：前瞻性、单臂、介入、开放标签、单中心4期研究RA患者的病理骨状态和JAKi的临床指征（裸骨试验）。52岁以上的参与者接受BARI（4 mg/天）周。为了评估骨特性和滑膜炎症，在基线（BL）、第24周和第52周进行了高分辨率计算机断层扫描和磁共振成像。监测临床反应和安全性。结果：纳入RA患者30例。BARI显著改善了疾病活动性（使用红细胞沉降率的28个关节的疾病活动性得分：4.82± 0.90至2.71± 0.83）和滑膜炎症（RAMRIS滑膜炎评分：5.3[4.2]-2.7[3.5]（95%CI 15.9-181.7）。掌骨关节侵蚀的数量和大小保持稳定。BARI治疗未观察到新的安全信号。结论：BARI治疗RA患者的骨骼得到改善，表现为骨小梁质量的增加和生物力学性能的改善。

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来源期刊

Arthritis & Rheumatology RHEUMATOLOGY-

CiteScore

20.90

自引率

3.00%

发文量

371

期刊介绍： Arthritis & Rheumatology is the official journal of the American College of Rheumatology and focuses on the natural history, pathophysiology, treatment, and outcome of rheumatic diseases. It is a peer-reviewed publication that aims to provide the highest quality basic and clinical research in this field. The journal covers a wide range of investigative areas and also includes review articles, editorials, and educational material for researchers and clinicians. Being recognized as a leading research journal in rheumatology, Arthritis & Rheumatology serves the global community of rheumatology investigators and clinicians.