Comparative study of the inhibitory effect on bone erosion progression with denosumab treatment and conventional treatment in rheumatoid arthritis patients: study protocol for an open-label randomized controlled trial by HR-pQCT
Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints, causes joint destruction, and leads to physical disability. Advances in the treatment of RA, such as biologic disease-modifying anti-rheumatic drugs (DMARDs), have provided better clinical outcomes, includ...
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Trials |
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| Online Access: | http://link.springer.com/article/10.1186/s13063-019-3589-8 |
| _version_ | 1811322692173824000 |
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| author | Naoki Iwamoto Shuntaro Sato Remi Sumiyoshi Ko Chiba Nanami Miyamoto Kumiko Arinaga Makiko Kobayashi Hiroshi Yamamoto Makoto Osaki Atsushi Kawakami |
| author_facet | Naoki Iwamoto Shuntaro Sato Remi Sumiyoshi Ko Chiba Nanami Miyamoto Kumiko Arinaga Makiko Kobayashi Hiroshi Yamamoto Makoto Osaki Atsushi Kawakami |
| author_sort | Naoki Iwamoto |
| collection | DOAJ |
| description | Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints, causes joint destruction, and leads to physical disability. Advances in the treatment of RA, such as biologic disease-modifying anti-rheumatic drugs (DMARDs), have provided better clinical outcomes, including the achievement of remission for patients with RA, but some patients cannot receive these treatments because of their side effects and high cost, and not all patients achieve remission. Although the efficacy of denosumab, which is a human IgG2 monoclonal antibody with a high affinity for the receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), in the treatment of RA has been reported in clinical trials, the efficacy of denosumab in both preventing joint destruction and improving disease activity has not been evaluated in a real-world setting. Methods/design This open-label, randomized, parallel-group study will compare the continued use of conventional synthetic DMARDs (csDMARDs) alone with the combined use of csDMARDs and denosumab in patients whose RA is treated with csDMARDs. In total, 44 patients with RA will be randomly assigned to receive additional treatment with denosumab or to continue RA treatment without additional denosumab. The duration of the intervention will be 12 months. To analyze bone erosion and bone micro-architecture precisely, high-resolution peripheral quantitative computed tomography (HR-pQCT) will be performed every 6 months. The primary endpoint is changes in the depth of bone erosion as measured by HR-pQCT from baseline to 6 months. Important secondary endpoints are the changes from baseline in the width and volume of bone erosion as measured by HR-pQCT and changes from baseline in the depth of bone erosion at 12 months. Changes in bone micro-architecture will also be analyzed as an exploratory endpoint. Discussion The results of this study are expected to provide strong evidence regarding the usefulness of denosumab for the treatment of RA. Moreover, by using HR-pQCT, this study will also reveal the effect of denosumab not only on bone erosion but also on bone micro-architecture. Trial registration This study was registered with the University Hospital Medical Information Network Clinical Trials Registry as UMIN000030575 on December 26, 2017. |
| first_indexed | 2024-04-13T13:40:36Z |
| format | Article |
| id | doaj.art-d11b28ac95ff439b90cd468e6be4045f |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-04-13T13:40:36Z |
| publishDate | 2019-08-01 |
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| series | Trials |
| spelling | doaj.art-d11b28ac95ff439b90cd468e6be4045f2022-12-22T02:44:39ZengBMCTrials1745-62152019-08-012011810.1186/s13063-019-3589-8Comparative study of the inhibitory effect on bone erosion progression with denosumab treatment and conventional treatment in rheumatoid arthritis patients: study protocol for an open-label randomized controlled trial by HR-pQCTNaoki Iwamoto0Shuntaro Sato1Remi Sumiyoshi2Ko Chiba3Nanami Miyamoto4Kumiko Arinaga5Makiko Kobayashi6Hiroshi Yamamoto7Makoto Osaki8Atsushi Kawakami9Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical SciencesNagasaki University Hospital, Clinical Research CenterDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical SciencesDepartment of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical SciencesNagasaki University Hospital, Clinical Research CenterNagasaki University Hospital, Clinical Research CenterMedical Science Department, Daiichi Sankyo Co., LtdNagasaki University Hospital, Clinical Research CenterDepartment of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical SciencesDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical SciencesAbstract Background Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints, causes joint destruction, and leads to physical disability. Advances in the treatment of RA, such as biologic disease-modifying anti-rheumatic drugs (DMARDs), have provided better clinical outcomes, including the achievement of remission for patients with RA, but some patients cannot receive these treatments because of their side effects and high cost, and not all patients achieve remission. Although the efficacy of denosumab, which is a human IgG2 monoclonal antibody with a high affinity for the receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), in the treatment of RA has been reported in clinical trials, the efficacy of denosumab in both preventing joint destruction and improving disease activity has not been evaluated in a real-world setting. Methods/design This open-label, randomized, parallel-group study will compare the continued use of conventional synthetic DMARDs (csDMARDs) alone with the combined use of csDMARDs and denosumab in patients whose RA is treated with csDMARDs. In total, 44 patients with RA will be randomly assigned to receive additional treatment with denosumab or to continue RA treatment without additional denosumab. The duration of the intervention will be 12 months. To analyze bone erosion and bone micro-architecture precisely, high-resolution peripheral quantitative computed tomography (HR-pQCT) will be performed every 6 months. The primary endpoint is changes in the depth of bone erosion as measured by HR-pQCT from baseline to 6 months. Important secondary endpoints are the changes from baseline in the width and volume of bone erosion as measured by HR-pQCT and changes from baseline in the depth of bone erosion at 12 months. Changes in bone micro-architecture will also be analyzed as an exploratory endpoint. Discussion The results of this study are expected to provide strong evidence regarding the usefulness of denosumab for the treatment of RA. Moreover, by using HR-pQCT, this study will also reveal the effect of denosumab not only on bone erosion but also on bone micro-architecture. Trial registration This study was registered with the University Hospital Medical Information Network Clinical Trials Registry as UMIN000030575 on December 26, 2017.http://link.springer.com/article/10.1186/s13063-019-3589-8Rheumatoid arthritisRANKLDenosumabBone erosionBone micro-architectureHR-pQCT |
| spellingShingle | Naoki Iwamoto Shuntaro Sato Remi Sumiyoshi Ko Chiba Nanami Miyamoto Kumiko Arinaga Makiko Kobayashi Hiroshi Yamamoto Makoto Osaki Atsushi Kawakami Comparative study of the inhibitory effect on bone erosion progression with denosumab treatment and conventional treatment in rheumatoid arthritis patients: study protocol for an open-label randomized controlled trial by HR-pQCT Trials Rheumatoid arthritis RANKL Denosumab Bone erosion Bone micro-architecture HR-pQCT |
| title | Comparative study of the inhibitory effect on bone erosion progression with denosumab treatment and conventional treatment in rheumatoid arthritis patients: study protocol for an open-label randomized controlled trial by HR-pQCT |
| title_full | Comparative study of the inhibitory effect on bone erosion progression with denosumab treatment and conventional treatment in rheumatoid arthritis patients: study protocol for an open-label randomized controlled trial by HR-pQCT |
| title_fullStr | Comparative study of the inhibitory effect on bone erosion progression with denosumab treatment and conventional treatment in rheumatoid arthritis patients: study protocol for an open-label randomized controlled trial by HR-pQCT |
| title_full_unstemmed | Comparative study of the inhibitory effect on bone erosion progression with denosumab treatment and conventional treatment in rheumatoid arthritis patients: study protocol for an open-label randomized controlled trial by HR-pQCT |
| title_short | Comparative study of the inhibitory effect on bone erosion progression with denosumab treatment and conventional treatment in rheumatoid arthritis patients: study protocol for an open-label randomized controlled trial by HR-pQCT |
| title_sort | comparative study of the inhibitory effect on bone erosion progression with denosumab treatment and conventional treatment in rheumatoid arthritis patients study protocol for an open label randomized controlled trial by hr pqct |
| topic | Rheumatoid arthritis RANKL Denosumab Bone erosion Bone micro-architecture HR-pQCT |
| url | http://link.springer.com/article/10.1186/s13063-019-3589-8 |
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