Inhibition of bone erosion, determined by high-resolution peripheral quantitative computed tomography (HR-pQCT), in rheumatoid arthritis patients receiving a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) plus denosumab vs csDMARD therapy alone: an open-label, randomized, parallel-group study

Arthritis Research & Therapy

Research

Naoki Hosogaya¹  Shuntaro Sato¹  Naoki Okubo²  Mami Tamai³  Atsushi Kawakami³  Tomohiro Koga³  Naoki Iwamoto³  Shin-ya Kawashiri⁴  Ko Chiba⁵  Kounosuke Watanabe⁵  Kazuteru Shiraishi⁵  Makoto Osaki⁵  Masataka Uetani⁶  Nozomi Oki⁶  Masako Furuyama⁷  Akitomo Okada⁸  Makiko Kobayashi⁹  Kengo Saito⁹ 

[1] Clinical Research Center, Nagasaki University Hospital, 1-7-1 Sakamoto, 852-8501, Nagasaki, Japan;Data Intelligence Department, Digital Transformation Management Division, Daiichi Sankyo Co., Ltd, 1-2-58, Hiromachi, Shinagawa-ku, 140-8710, Tokyo, Japan;Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, 852-8501, Nagasaki, Japan;Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, 852-8501, Nagasaki, Japan;Departments of Community Medicine, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, 852-8501, Nagasaki, Japan;Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, 852-8501, Nagasaki, Japan;Department of Radiological Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, 852-8501, Nagasaki, Japan;Department of Rheumatology, Nagasaki Kita Hospital, 800 Motomurago, Nishisonogigun Togitsucho, 851-2103, Nagasaki, Japan;Department of Rheumatology, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, Omura, 856-8562, Nagasaki, Japan;Primary Medical Science Department, Medical Affairs Division, Daiichi Sankyo Co., Ltd, 3-5-1 Nihonbashi-Honcho, Chuo-ku, 103-8426, Tokyo, Japan;

关键词: Bone erosion;    csDMARDs;    Denosumab;    HR-pQCT;    Rheumatoid arthritis;   

DOI  :  10.1186/s13075-022-02957-w

 received in 2022-06-29, accepted in 2022-11-20,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThis exploratory study compared the inhibition of bone erosion progression in rheumatoid arthritis (RA) patients treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) plus denosumab versus csDMARD therapy alone and investigated the effects of denosumab on bone micro-architecture and other bone-related parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT).MethodsIn this open-label, randomized, parallel-group study, patients with RA undergoing treatment with a csDMARD were randomly assigned (1:1) to continue csDMARD therapy alone or to continue csDMARDs with denosumab (60-mg subcutaneous injection once every 6 months) for 12 months. The primary endpoint was the change from baseline in the depth of bone erosion, measured by HR-pQCT, in the second and third metacarpal heads at 6 months after starting treatment. Exploratory endpoints were also evaluated, and adverse events (AEs) were monitored for safety.ResultsIn total, 46 patients were enrolled, and 43 were included in the full analysis set (csDMARDs plus denosumab, N = 21; csDMARD therapy alone, N = 22). Most patients were female (88.4%), and the mean age was 65.3 years. The adjusted mean (95% confidence interval) change from baseline in the depth of bone erosion, measured by HR-pQCT, in the 2–3 metacarpal heads at 6 months was − 0.57 mm (− 1.52, 0.39 mm) in the csDMARDs plus denosumab group vs − 0.22 mm (− 0.97, 0.53 mm) in the csDMARD therapy alone group (between-group difference: − 0.35 mm [− 1.00, 0.31]; P = 0.2716). Similar results were shown for the adjusted mean between-group difference in the width and volume of bone erosion of the 2–3 metacarpal heads. Significant improvements in bone micro-architecture parameters were shown. The incidence of AEs and serious AEs was similar between the csDMARDs plus denosumab and the csDMARD therapy alone groups (AEs: 52.2% vs 56.5%; serious AEs: 4.3% vs 8.7%).ConclusionsAlthough the addition of denosumab to csDMARDs did not find statistically significant improvements in bone erosion after 6 months of treatment, numerical improvements in these parameters suggest that the addition of denosumab to csDMARDs may be effective in inhibiting the progression of bone erosion and improving bone micro-architecture.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry, UMIN000030575. Japan Registry for Clinical Trials, jRCTs071180018

【 授权许可】

CC BY   
© The Author(s) 2022

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