PMID- 36476479
OWN - NLM
STAT- MEDLINE
DCOM- 20221222
LR  - 20221222
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 24
IP  - 1
DP  - 2022 Dec 7
TI  - 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.
PG  - 264
LID - 10.1186/s13075-022-02957-w [doi]
LID - 264
AB  - BACKGROUND: This 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). METHODS: In 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. RESULTS: In 
      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%). CONCLUSIONS: Although 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 REGISTRATION: University 
      Hospital Medical Information Network Clinical Trials Registry, UMIN000030575. 
      Japan Registry for Clinical Trials, jRCTs071180018.
CI  - (c) 2022. The Author(s).
FAU - Iwamoto, Naoki
AU  - Iwamoto N
AD  - Department of Immunology and Rheumatology, Division of Advanced Preventive 
      Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 
      1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. naoki-iwa@nagasaki-u.ac.jp.
FAU - Chiba, Ko
AU  - Chiba K
AD  - Department of Orthopedic Surgery, Nagasaki University Graduate School of 
      Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
FAU - Sato, Shuntaro
AU  - Sato S
AD  - Clinical Research Center, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 
      852-8501, Japan.
FAU - Shiraishi, Kazuteru
AU  - Shiraishi K
AD  - Department of Orthopedic Surgery, Nagasaki University Graduate School of 
      Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
FAU - Watanabe, Kounosuke
AU  - Watanabe K
AD  - Department of Orthopedic Surgery, Nagasaki University Graduate School of 
      Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
FAU - Oki, Nozomi
AU  - Oki N
AD  - Department of Radiological Sciences, Nagasaki University Graduate School of 
      Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
FAU - Okada, Akitomo
AU  - Okada A
AD  - Department of Rheumatology, National Hospital Organization Nagasaki Medical 
      Center, 2-1001-1 Kubara, Omura, Nagasaki, 856-8562, Japan.
FAU - Koga, Tomohiro
AU  - Koga T
AD  - Department of Immunology and Rheumatology, Division of Advanced Preventive 
      Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 
      1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
FAU - Kawashiri, Shin-Ya
AU  - Kawashiri SY
AD  - Department of Immunology and Rheumatology, Division of Advanced Preventive 
      Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 
      1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
AD  - Departments of Community Medicine, Division of Advanced Preventive Medical 
      Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 
      Sakamoto, Nagasaki, 852-8501, Japan.
FAU - Tamai, Mami
AU  - Tamai M
AD  - Department of Immunology and Rheumatology, Division of Advanced Preventive 
      Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 
      1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
FAU - Hosogaya, Naoki
AU  - Hosogaya N
AD  - Clinical Research Center, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 
      852-8501, Japan.
FAU - Furuyama, Masako
AU  - Furuyama M
AD  - Department of Rheumatology, Nagasaki Kita Hospital, 800 Motomurago, 
      Nishisonogigun Togitsucho, Nagasaki, 851-2103, Japan.
FAU - Kobayashi, Makiko
AU  - Kobayashi M
AD  - Primary Medical Science Department, Medical Affairs Division, Daiichi Sankyo Co., 
      Ltd, 3-5-1 Nihonbashi-Honcho, Chuo-ku, Tokyo, 103-8426, Japan.
FAU - Saito, Kengo
AU  - Saito K
AD  - Primary Medical Science Department, Medical Affairs Division, Daiichi Sankyo Co., 
      Ltd, 3-5-1 Nihonbashi-Honcho, Chuo-ku, Tokyo, 103-8426, Japan.
FAU - Okubo, Naoki
AU  - Okubo N
AD  - Data Intelligence Department, Digital Transformation Management Division, Daiichi 
      Sankyo Co., Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
FAU - Uetani, Masataka
AU  - Uetani M
AD  - Department of Radiological Sciences, Nagasaki University Graduate School of 
      Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
FAU - Osaki, Makoto
AU  - Osaki M
AD  - Department of Orthopedic Surgery, Nagasaki University Graduate School of 
      Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
FAU - Kawakami, Atsushi
AU  - Kawakami A
AD  - Department of Immunology and Rheumatology, Division of Advanced Preventive 
      Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 
      1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20221207
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Antirheumatic Agents)
SB  - IM
MH  - Aged
MH  - Female
MH  - Humans
MH  - Male
MH  - *Antirheumatic Agents/therapeutic use
MH  - *Arthritis, Rheumatoid/diagnostic imaging/drug therapy
MH  - Japan
MH  - Tomography
PMC - PMC9727996
OTO - NOTNLM
OT  - Bone erosion
OT  - Denosumab
OT  - HR-pQCT
OT  - Rheumatoid arthritis
OT  - csDMARDs
COIS- Naoki Iwamoto and Atsushi Kawakami have received speaker's bureau fees and 
      grant/research support from Daiichi Sankyo Co., Ltd. Ko Chiba has received 
      speaker's bureau fees from Daiichi Sankyo Co., Ltd. Shuntaro Sato, Kazuteru 
      Shiraishi, Kounosuke Watanabe, Nozomi Oki, Akitomo Okada, Tomohiro Koga, Shin-ya 
      Kawashiri, Mami Tamai, Naoki Hosogaya, and Masako Furuyama declare that they have 
      no competing interests. Makiko Kobayashi was an employee of Daiichi Sankyo Co., 
      Ltd., during the conduct of this study. Kengo Saito and Naoki Okubo are employees 
      of Daiichi Sankyo Co., Ltd. Masataka Uetani and Makoto Osaki have received 
      lecture fees from Daiichi Sankyo Co., Ltd.
EDAT- 2022/12/09 06:00
MHDA- 2022/12/15 06:00
PMCR- 2022/12/07
CRDT- 2022/12/08 10:28
PHST- 2022/06/29 00:00 [received]
PHST- 2022/11/20 00:00 [accepted]
PHST- 2022/12/08 10:28 [entrez]
PHST- 2022/12/09 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/12/07 00:00 [pmc-release]
AID - 10.1186/s13075-022-02957-w [pii]
AID - 2957 [pii]
AID - 10.1186/s13075-022-02957-w [doi]
PST - epublish
SO  - Arthritis Res Ther. 2022 Dec 7;24(1):264. doi: 10.1186/s13075-022-02957-w.