PMID- 37658935 OWN - NLM STAT- MEDLINE DCOM- 20240109 LR - 20240130 IS - 1434-9949 (Electronic) IS - 0770-3198 (Linking) VI - 43 IP - 1 DP - 2024 Jan TI - Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis. PG - 117-128 LID - 10.1007/s10067-023-06735-0 [doi] AB - OBJECTIVE: Rheumatoid arthritis (RA) is characterized by localized bone loss, general osteoporosis and increased fracture risks. Tumour necrosis factor inhibitors (TNFi), non-tumour necrosis factor inhibitors (non-TNFi) biologic, Janus kinase inhibitors (JAKi) had shown the suppression effects to osteoclast activation and improvement of bone mineral density (BMD). Anti-cyclic citrullinated peptide antibody (ACPA) is associated with osteoclast activation and the resultant bone loss. However, few studies have compared BMD changes among patients with RA treated with targeted therapies that have different mechanisms of action. METHODS: This retrospective study recruited patients with RA who had undergone BMD testing twice. Changes in the BMD were compared using the generalized estimating equation (GEE) in treatment groups that received conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), TNFi, non-TNFi biologics, and JAKi. RESULTS: In total, 362 patients with RA were enrolled (csDMARDs, n = 153, TNFi, n = 71, non-TNFi biologics, n = 108, JAKi, n = 30). We observed greater changes in femoral BMD (left, 0.06, 95% CI 0.01-0.12, p = 0.016; right, 0.09, 95% CI 0.04-0.15, p = 0.001 by GEE) following JAKi treatment as compared with other treatments. Compared to the ACPA-negative group, patients with ACPA positivity exhibited greater improvement in the femoral BMD (left, 0.09, 95% CI 0.02-0.15, p = 0.008; right, 0.11, 95% CI 0.05-0.18, p = 0.001). CONCLUSION: Compared to other targeted therapies, JAKi might exert a more potent effect to prevent BMD loss, specifically in ACPA-positive patients with RA, and could be a potential therapeutic option to mitigate generalized bone loss. Key Points *JAKi therapy inhibits systemic bone loss in patients with RA. *ACPA-positive RA patients exhibited a greater BMD improvement than ACPA-negative RA patients. *JAKi might more potently prevent BMD decline than conventional synthetic or biological DMARDs. CI - (c) 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR). FAU - Chen, Yun-Wen AU - Chen YW AD - Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan. AD - Division of General Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Chen, Hsin-Hua AU - Chen HH AD - Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan. AD - Division of General Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. AD - Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan. AD - Faculty of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan. AD - Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan. AD - Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine & Big Data Center, Chung Hsing University, Taichung, Taiwan. AD - Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan. FAU - Huang, Wen-Nan AU - Huang WN AD - Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan. AD - Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan. AD - Faculty of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan. AD - College of Business and Management, Ling Tung University, Taichung, Taiwan. FAU - Chen, Jun-Peng AU - Chen JP AD - Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan. AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Chen, Yi-Hsing AU - Chen YH AD - Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan. AD - Faculty of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan. FAU - Chen, Yi-Ming AU - Chen YM AUID- ORCID: 0000-0001-7593-3065 AD - Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan. ymchen1@vghtc.gov.tw. AD - Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan. ymchen1@vghtc.gov.tw. AD - Faculty of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan. ymchen1@vghtc.gov.tw. AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. ymchen1@vghtc.gov.tw. AD - Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan. ymchen1@vghtc.gov.tw. LA - eng GR - NSTC -111-2634-F-A49-014/National Science and Technology Council/ GR - NSTC-111-2218-E-039-001/National Science and Technology Council/ GR - NSTC-111-2314-B-075A-003-MY3/National Science and Technology Council/ GR - TCVGH-1123801A/Taichung Veterans General Hospital/ GR - TCVGH-1127301C/Taichung Veterans General Hospital/ GR - TCVGH-1127302D/Taichung Veterans General Hospital/ GR - TCVGH-YM1120110/Taichung Veterans General Hospital/ PT - Journal Article DEP - 20230902 PL - Germany TA - Clin Rheumatol JT - Clinical rheumatology JID - 8211469 RN - 0 (Janus Kinase Inhibitors) RN - 0 (Antirheumatic Agents) RN - 0 (Tumor Necrosis Factor Inhibitors) RN - 0 (Biological Products) SB - IM MH - Humans MH - Bone Density MH - *Janus Kinase Inhibitors/therapeutic use MH - Retrospective Studies MH - *Arthritis, Rheumatoid MH - *Antirheumatic Agents/adverse effects MH - Tumor Necrosis Factor Inhibitors/therapeutic use MH - *Biological Products/therapeutic use OTO - NOTNLM OT - Bone loss OT - Bone mineral density OT - Janus kinase inhibitor OT - Non-tumour necrosis factor inhibitor OT - Osteoporosis OT - Rheumatoid arthritis OT - Tumour necrosis factor inhibitor EDAT- 2023/09/04 01:22 MHDA- 2024/01/09 06:41 CRDT- 2023/09/02 11:06 PHST- 2023/05/23 00:00 [received] PHST- 2023/08/04 00:00 [accepted] PHST- 2023/07/27 00:00 [revised] PHST- 2024/01/09 06:41 [medline] PHST- 2023/09/04 01:22 [pubmed] PHST- 2023/09/02 11:06 [entrez] AID - 10.1007/s10067-023-06735-0 [pii] AID - 10.1007/s10067-023-06735-0 [doi] PST - ppublish SO - Clin Rheumatol. 2024 Jan;43(1):117-128. doi: 10.1007/s10067-023-06735-0. Epub 2023 Sep 2.