Rheumatoid arthritis (RA) is a systemic disease that primarily manifests as chronic synovitis of the symmetric small joints. Despite the availability of various targeted drugs for RA, these treatments are limited by adverse reactions, warranting new treatment approaches. Suberosin (SBR), isolated from Plumbago zeylanica—a medicinal plant traditionally used to treat RA in Asia—possesses notable biological activities. This study aimed to investigate the effects and potential underlying pathways of SBR on RA. Tumor necrosis factor-alpha (TNF-α) induced inflammation in RA-derived fibroblast-like synoviocytes (RA-FLS), and the expression of proinflammatory mediators was assessed using q-RT PCR and ELISA after treatment with various SBR concentrations. Bone marrow-derived macrophages (BMDMs) were induced to differentiate into M1 and M2 macrophages, followed by treatment with various SBR concentrations and macrophage polarization assessment. Low-dose (0.5 mg/kg/d) and high-dose (2 mg/kg/d) SBR regimens were administered to a collagen-induced arthritis (CIA) mouse model for 21 days, and the anti-arthritic effects of SBR were evaluated. Network pharmacology and molecular docking analyses were used to predict the anti-arthritic targets of SBR. The effect of SBR on the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway was evaluated. SBR suppressed macrophage polarization toward the M1 phenotype while enhancing their polarization toward the M2 phenotype. SBR reduced the levels of proinflammatory mediators in TNF-α-induced RA-FLS. Mechanistically, SBR inhibited the phosphorylation of the JAK1/STAT3 signaling pathway in RA-FLS and M1 macrophages and promoted the phosphorylation of the JAK1/STAT6 pathway in M2 macrophages, enhancing M2 polarization. In vivo, prophylactic treatment of low-dose SBR reduced M1 macrophage infiltration into synovial tissue, increased the proportion of M2 macrophages, and decreased the expression of inflammatory mediators in the serum and synovial tissue, alleviating synovial inflammation. SBR significantly alleviated arthritis in CIA mice through macrophage repolarization and inhibition of inflammation. SBR significantly reduced clinical symptoms, joint pathological damage, and expression inflammatory cytokine expression in CIA mice. SBR exhibited anti-arthritic effects via the JAK1/STAT3 and JAK1/STAT6 signaling pathways, inhibiting synovial tissue inflammation and M1 macrophage polarization while promoting M2 macrophage polarization. Therefore, SBR may be an effective candidate for RA treatment.
类风湿性关节炎（RA）是一种全身性疾病，主要表现为对称小关节的慢性滑膜炎。尽管有各种针对类风湿性关节炎的靶向药物，但这些治疗受到不良反应的限制，需要新的治疗方法。从亚洲传统上用于治疗类风湿性关节炎的药用植物白花苜蓿中分离得到的紫红素（SBR）具有显著的生物活性。本研究旨在探讨SBR对RA的作用及其可能的潜在途径。肿瘤坏死因子-α (TNF-α)诱导ra源性成纤维细胞样滑膜细胞（RA-FLS）发生炎症，用不同浓度SBR处理后采用q-RT PCR和ELISA检测促炎介质的表达。诱导骨髓源性巨噬细胞（bmdm）分化为M1和M2巨噬细胞，然后用不同浓度的SBR处理并评估巨噬细胞极化。采用低剂量（0.5 mg/kg/d）和高剂量（2 mg/kg/d） SBR方案治疗胶原性关节炎（CIA）小鼠模型21 d，观察SBR的抗关节炎作用。采用网络药理学和分子对接分析预测SBR的抗关节炎靶点。研究了SBR对Janus kinase/signal transducer and activator of transcription （JAK/STAT）通路的影响。SBR抑制巨噬细胞向M1表型极化，同时增强其向M2表型极化。SBR可降低TNF-α-诱导的RA-FLS中促炎介质的水平。机制上，SBR抑制了RA-FLS和M1巨噬细胞中JAK1/STAT3信号通路的磷酸化，促进了M2巨噬细胞中JAK1/STAT6信号通路的磷酸化，增强了M2极化。在体内，低剂量SBR预防性治疗可减少M1巨噬细胞向滑膜组织的浸润，增加M2巨噬细胞的比例，降低血清和滑膜组织中炎症介质的表达，减轻滑膜炎症。SBR通过巨噬细胞复极化和抑制炎症显著缓解CIA小鼠关节炎。SBR可显著减轻CIA小鼠的临床症状、关节病理损伤和炎症细胞因子表达。SBR通过JAK1/STAT3和JAK1/STAT6信号通路发挥抗关节炎作用，抑制滑膜组织炎症和M1巨噬细胞极化，促进M2巨噬细胞极化。因此，SBR可能是治疗RA的有效候选药物。
{"title":"Suberosin attenuates rheumatoid arthritis by repolarizing macrophages and inhibiting synovitis via the JAK/STAT signaling pathway","authors":"Huan Liu, Qianwei Li, Yuehong Chen, Min Dong, Hongjiang Liu, Jiaqian Zhang, Leiyi Yang, Geng Yin, Qibing Xie","doi":"10.1186/s13075-025-03481-3","DOIUrl":"https://doi.org/10.1186/s13075-025-03481-3","url":null,"abstract":"Rheumatoid arthritis (RA) is a systemic disease that primarily manifests as chronic synovitis of the symmetric small joints. Despite the availability of various targeted drugs for RA, these treatments are limited by adverse reactions, warranting new treatment approaches. Suberosin (SBR), isolated from Plumbago zeylanica—a medicinal plant traditionally used to treat RA in Asia—possesses notable biological activities. This study aimed to investigate the effects and potential underlying pathways of SBR on RA. Tumor necrosis factor-alpha (TNF-α) induced inflammation in RA-derived fibroblast-like synoviocytes (RA-FLS), and the expression of proinflammatory mediators was assessed using q-RT PCR and ELISA after treatment with various SBR concentrations. Bone marrow-derived macrophages (BMDMs) were induced to differentiate into M1 and M2 macrophages, followed by treatment with various SBR concentrations and macrophage polarization assessment. Low-dose (0.5 mg/kg/d) and high-dose (2 mg/kg/d) SBR regimens were administered to a collagen-induced arthritis (CIA) mouse model for 21 days, and the anti-arthritic effects of SBR were evaluated. Network pharmacology and molecular docking analyses were used to predict the anti-arthritic targets of SBR. The effect of SBR on the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway was evaluated. SBR suppressed macrophage polarization toward the M1 phenotype while enhancing their polarization toward the M2 phenotype. SBR reduced the levels of proinflammatory mediators in TNF-α-induced RA-FLS. Mechanistically, SBR inhibited the phosphorylation of the JAK1/STAT3 signaling pathway in RA-FLS and M1 macrophages and promoted the phosphorylation of the JAK1/STAT6 pathway in M2 macrophages, enhancing M2 polarization. In vivo, prophylactic treatment of low-dose SBR reduced M1 macrophage infiltration into synovial tissue, increased the proportion of M2 macrophages, and decreased the expression of inflammatory mediators in the serum and synovial tissue, alleviating synovial inflammation. SBR significantly alleviated arthritis in CIA mice through macrophage repolarization and inhibition of inflammation. SBR significantly reduced clinical symptoms, joint pathological damage, and expression inflammatory cytokine expression in CIA mice. SBR exhibited anti-arthritic effects via the JAK1/STAT3 and JAK1/STAT6 signaling pathways, inhibiting synovial tissue inflammation and M1 macrophage polarization while promoting M2 macrophage polarization. Therefore, SBR may be an effective candidate for RA treatment.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"9 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-21DOI: 10.1186/s13075-024-03466-8
Alyssa Howren, Eric C. Sayre, J. Antonio Avina-Zubieta, Joseph H. Puyat, Deborah Da Costa, Hui Xie, Eileen Davidson, Amit Gupta, Mary A. De Vera
Describe patterns of pharmacotherapy and psychological treatment and evaluate receipt of minimally adequate treatment for incident depression and anxiety in individuals with inflammatory arthritis (IA). We used population-based linked administrative health databases from British Columbia, Canada to evaluate pharmacotherapy and psychological treatments for incident depression and/or anxiety among individuals with IA and without IA (‘IA-free controls’). We defined minimally adequate pharmacotherapy as antidepressant prescriptions filled with ≥ 84 days’ supply and adequate psychological treatment as ≥ 4 counselling/psychotherapy services. Multivariable logistic regression models were used to evaluate the odds of individuals with IA receiving minimally adequate pharmacotherapy and/or psychological treatment compared to IA-free controls. 6,951 (mean age 54.8 ± 18.3 years; 65.5% female) individuals with IA had incident depression and 3,701 (mean age 52.9 ± 16.8 years; 74.3% female) had incident anxiety. Minimally adequate pharmacotherapy and psychological treatment for depression was respectively observed in 50.5% and 19.6% of those with IA, proportions similar to IA-free controls (pharmacotherapy: aOR 1.10, 95% CI 1.00 to 1.21; psychological: aOR 1.07, 95% CI 0.94 to 1.21). Results were similar regarding anxiety treatment. Individuals with IA had a significantly greater likelihood of dispensing ≥ 1 benzodiazepine (anxiety: IA 45.0%, IA-free controls 39.0%, p-value < 0.001) and ≥ 1 tricyclic antidepressant prescription (anxiety: IA 12.8%, IA-free controls 7.8%, p-value < 0.001). Significantly higher average days’ supply of benzodiazepines was observed for IA (anxiety: IA 123.7 days, controls 112.4 days, p-value = 0.003). A substantial proportion of individuals with IA were not receiving adequate mental health treatment for depression and anxiety, a finding similar for IA-free controls. The undertreatment of mental disorders for people with IA has well-known negative implications for the provision of effective rheumatology care. It remains fundamental to expand publicly funded health care to include mental health services in an effort to address unmet counselling needs.
描述药物治疗和心理治疗的模式，并评估炎症性关节炎（IA）患者对偶发抑郁和焦虑的最低限度适当治疗的接受情况。我们使用了来自加拿大不列颠哥伦比亚省的以人群为基础的相关行政卫生数据库来评估IA患者和非IA患者（“无IA对照”）的药物治疗和心理治疗对突发抑郁和/或焦虑的影响。我们将最低限度适当的药物治疗定义为抗抑郁药处方≥84天的供应，适当的心理治疗定义为≥4次咨询/心理治疗服务。使用多变量logistic回归模型来评估IA患者与无IA患者相比接受最低限度药物治疗和/或心理治疗的几率。6951人（平均年龄54.8±18.3岁）；65.5%女性)IA患者有抑郁症，3701例(平均年龄52.9±16.8岁；74.3%的女性)有偶发性焦虑。在IA患者中，分别有50.5%和19.6%的患者接受了最低限度的药物治疗和心理治疗，比例与无IA对照组相似(药物治疗：aOR 1.10, 95% CI 1.00 ~ 1.21；心理：aOR 1.07, 95% CI 0.94 ~ 1.21)。焦虑治疗的结果相似。IA患者配用≥1种苯二氮卓类药物（焦虑组：IA 45.0%，无IA对照组39.0%，p值< 0.001）和≥1种三环类抗抑郁药物（焦虑组：IA 12.8%，无IA对照组7.8%，p值< 0.001）的可能性显著增加。IA组苯二氮卓类药物平均供给量显著增加（焦虑组：IA 123.7天，对照组112.4天，p值= 0.003）。相当大比例的IA患者没有接受足够的抑郁症和焦虑症心理健康治疗，这一发现与没有IA的对照组相似。众所周知，IA患者的精神障碍治疗不足对提供有效的风湿病治疗具有负面影响。扩大公共资助的卫生保健，使其包括精神卫生服务，以努力解决未得到满足的咨询需求，这仍然是至关重要的。
{"title":"Do individuals with inflammatory arthritis receive minimally adequate treatment for incident depression and anxiety: A population-based study","authors":"Alyssa Howren, Eric C. Sayre, J. Antonio Avina-Zubieta, Joseph H. Puyat, Deborah Da Costa, Hui Xie, Eileen Davidson, Amit Gupta, Mary A. De Vera","doi":"10.1186/s13075-024-03466-8","DOIUrl":"https://doi.org/10.1186/s13075-024-03466-8","url":null,"abstract":"Describe patterns of pharmacotherapy and psychological treatment and evaluate receipt of minimally adequate treatment for incident depression and anxiety in individuals with inflammatory arthritis (IA). We used population-based linked administrative health databases from British Columbia, Canada to evaluate pharmacotherapy and psychological treatments for incident depression and/or anxiety among individuals with IA and without IA (‘IA-free controls’). We defined minimally adequate pharmacotherapy as antidepressant prescriptions filled with ≥ 84 days’ supply and adequate psychological treatment as ≥ 4 counselling/psychotherapy services. Multivariable logistic regression models were used to evaluate the odds of individuals with IA receiving minimally adequate pharmacotherapy and/or psychological treatment compared to IA-free controls. 6,951 (mean age 54.8 ± 18.3 years; 65.5% female) individuals with IA had incident depression and 3,701 (mean age 52.9 ± 16.8 years; 74.3% female) had incident anxiety. Minimally adequate pharmacotherapy and psychological treatment for depression was respectively observed in 50.5% and 19.6% of those with IA, proportions similar to IA-free controls (pharmacotherapy: aOR 1.10, 95% CI 1.00 to 1.21; psychological: aOR 1.07, 95% CI 0.94 to 1.21). Results were similar regarding anxiety treatment. Individuals with IA had a significantly greater likelihood of dispensing ≥ 1 benzodiazepine (anxiety: IA 45.0%, IA-free controls 39.0%, p-value < 0.001) and ≥ 1 tricyclic antidepressant prescription (anxiety: IA 12.8%, IA-free controls 7.8%, p-value < 0.001). Significantly higher average days’ supply of benzodiazepines was observed for IA (anxiety: IA 123.7 days, controls 112.4 days, p-value = 0.003). A substantial proportion of individuals with IA were not receiving adequate mental health treatment for depression and anxiety, a finding similar for IA-free controls. The undertreatment of mental disorders for people with IA has well-known negative implications for the provision of effective rheumatology care. It remains fundamental to expand publicly funded health care to include mental health services in an effort to address unmet counselling needs.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"37 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-20DOI: 10.1186/s13075-025-03475-1
Shuning Guo, Jiehan Li, Shurui Pang, Jing Li, Xinping Tian
Advances in treatment have swiftly alleviated systemic inflammation of Takayasu’s arteritis (TAK), while subclinical vascular inflammation and the ensuing arterial remodeling continue to present unresolved challenges in TAK. The phenotypic switching of vascular smooth muscle cells (VSMC) is regarded as the first step in vascular pathology and contributes to arterial remodeling. Exosomes facilitate the transfer and exchange of proteins and specific nucleic acids, thereby playing a significant role in intercellular communication. Little is known about the modulatory role of serum exosomes in phenotypic switching of VSMC and vascular remodeling in TAK. Serum exosomes isolated from TAK patients were co-cultured with VSMC to identify the modulatory role of exosomes. VSMC were transfected with miR-199a-5p mimic and inhibitor. CCK8 assays and EdU assays were performed to measure proliferative ability. The migration of VSMC was evaluated by scratch assays and transwell migration assays. The flow cytometry was employed to identify apoptosis of VSMC. Dual-luciferase reporter assay, RNA immunoprecipitation assay and fluorescence in situ hybridization were utilized to validate the target gene of miR-199a-5p. The correlational analysis was conducted among exosome miRNA, serum MMP2, TIMP2 and clinical parameters in TAK patients. The coculture of VSMC with serum exosome mediated dedifferentiation of VSMC. Through gain- and loss-of-function approaches, miR-199a-5p over-expression significantly increased expression of VSMC marker genes and inhibited VSMC proliferation and migration, whilst the opposite effect was observed when endogenous miR-199a-5p was knocked down. The overexpression of miR-199a-5p suppressed VSMC apoptosis. Further, MMP2 serves as functional target gene of miR-199a-5p. The correlation analyses revealed an inverse correlation between Vasculitis Damage Index and exosome miR-199a-5p level or serum MMP2, which requires validation in a larger cohort. Our study indicated that the miR-199a-5p/MMP2 pathway played a role in inhibiting the migration, proliferation and apoptosis of VSMC. The decreased secretion of MMP2 may potentially prompt the intimal infiltration of inflammatory cells within the vascular wall, offering a novel therapeutic opportunity by tackling both inflammatory responses and the neointimal overgrowth associated with TAK arterial damage. Moreover, exosome miR-199a-5p and MMP2 derived from serum possess potential as future biomarkers for vascular injury.
{"title":"Exosome miR-199a-5p modulated vascular remodeling and inflammatory infiltration of Takayasu’s arteritis","authors":"Shuning Guo, Jiehan Li, Shurui Pang, Jing Li, Xinping Tian","doi":"10.1186/s13075-025-03475-1","DOIUrl":"https://doi.org/10.1186/s13075-025-03475-1","url":null,"abstract":"Advances in treatment have swiftly alleviated systemic inflammation of Takayasu’s arteritis (TAK), while subclinical vascular inflammation and the ensuing arterial remodeling continue to present unresolved challenges in TAK. The phenotypic switching of vascular smooth muscle cells (VSMC) is regarded as the first step in vascular pathology and contributes to arterial remodeling. Exosomes facilitate the transfer and exchange of proteins and specific nucleic acids, thereby playing a significant role in intercellular communication. Little is known about the modulatory role of serum exosomes in phenotypic switching of VSMC and vascular remodeling in TAK. Serum exosomes isolated from TAK patients were co-cultured with VSMC to identify the modulatory role of exosomes. VSMC were transfected with miR-199a-5p mimic and inhibitor. CCK8 assays and EdU assays were performed to measure proliferative ability. The migration of VSMC was evaluated by scratch assays and transwell migration assays. The flow cytometry was employed to identify apoptosis of VSMC. Dual-luciferase reporter assay, RNA immunoprecipitation assay and fluorescence in situ hybridization were utilized to validate the target gene of miR-199a-5p. The correlational analysis was conducted among exosome miRNA, serum MMP2, TIMP2 and clinical parameters in TAK patients. The coculture of VSMC with serum exosome mediated dedifferentiation of VSMC. Through gain- and loss-of-function approaches, miR-199a-5p over-expression significantly increased expression of VSMC marker genes and inhibited VSMC proliferation and migration, whilst the opposite effect was observed when endogenous miR-199a-5p was knocked down. The overexpression of miR-199a-5p suppressed VSMC apoptosis. Further, MMP2 serves as functional target gene of miR-199a-5p. The correlation analyses revealed an inverse correlation between Vasculitis Damage Index and exosome miR-199a-5p level or serum MMP2, which requires validation in a larger cohort. Our study indicated that the miR-199a-5p/MMP2 pathway played a role in inhibiting the migration, proliferation and apoptosis of VSMC. The decreased secretion of MMP2 may potentially prompt the intimal infiltration of inflammatory cells within the vascular wall, offering a novel therapeutic opportunity by tackling both inflammatory responses and the neointimal overgrowth associated with TAK arterial damage. Moreover, exosome miR-199a-5p and MMP2 derived from serum possess potential as future biomarkers for vascular injury.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"56 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-16DOI: 10.1186/s13075-025-03479-x
Xuegang Li, Haijian Jiang, Xu Wang, Shuping Zhong
Currently, the pathophysiology of new bone formation in radiographic axial spondyloarthritis (r-axSpA) remains unclear. Cellular elements and their secreted bone turnover markers might be one of the underlying mechanisms that drive the new bone formation. Our study aimed to investigate the role of bone turnover markers in r-axSpA patients with fatty lesions. 73 r-axSpA patients were enrolled in this study. 48 and 25 patients were divided into r-axSpA group with and without fatty lesions. Clinical variables were collected and all patients received comprehensive rheumatologic assessment for disease activity, including Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Axial Spondyloarthritis Disease Activity Score (ASDAS). Fatty lesions in the sacroiliac joints (SIJs) were scored independently by two radiologists. Serum levels of bone turnover markers, including sclerostin, osteoprotegerin (OPG), procollagen I N-terminal propeptide (PINP), cross linked C-telopeptide of type I collagen (CTX-I), osteocalcin (OC), were measured using enzyme-linked immunosorbent assays. There were no significant differences between two groups in terms of gender, age, body mass index (BMI), duration, smoking, HLA-B27 positivity rate, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), BASDAI, ASDAS-ESR, ASDAS-CRP, biological disease-modifying anti-rheumatic drugs (bDMARDs) rate. No significant differences were observed in terms of OPG, PINP, CTX-I or OC between two groups. The mSASSS were higher in fatty lesions group than in those without fatty lesions (p < 0.001). The serum sclerostin levels were significantly lower in r-axSpA patients with fatty lesions than in those without fatty lesions (p < 0.001). There were correlations between BMI, mSASSS and sclerostin with the comprehensive Berlin scoring method (CBM) scores in the univariate analysis (ρ = 0.311, ρ = 0.306, ρ = -0.920, respectively). However, only sclerostin had correlation with the CBM scores in multivariate analysis (ρ = -0.040, p < 0.001). In the r-axSpA patients with fatty lesions, serum sclerostin levels are declined. Serum sclerostin might be useful as a biomarker to predict the progression of the chronic inflammation in SIJs in r-axSpA.
{"title":"The serum level of sclerostin decreases in radiographic axial spondyloarthritis patients with fatty lesions","authors":"Xuegang Li, Haijian Jiang, Xu Wang, Shuping Zhong","doi":"10.1186/s13075-025-03479-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03479-x","url":null,"abstract":"Currently, the pathophysiology of new bone formation in radiographic axial spondyloarthritis (r-axSpA) remains unclear. Cellular elements and their secreted bone turnover markers might be one of the underlying mechanisms that drive the new bone formation. Our study aimed to investigate the role of bone turnover markers in r-axSpA patients with fatty lesions. 73 r-axSpA patients were enrolled in this study. 48 and 25 patients were divided into r-axSpA group with and without fatty lesions. Clinical variables were collected and all patients received comprehensive rheumatologic assessment for disease activity, including Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Axial Spondyloarthritis Disease Activity Score (ASDAS). Fatty lesions in the sacroiliac joints (SIJs) were scored independently by two radiologists. Serum levels of bone turnover markers, including sclerostin, osteoprotegerin (OPG), procollagen I N-terminal propeptide (PINP), cross linked C-telopeptide of type I collagen (CTX-I), osteocalcin (OC), were measured using enzyme-linked immunosorbent assays. There were no significant differences between two groups in terms of gender, age, body mass index (BMI), duration, smoking, HLA-B27 positivity rate, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), BASDAI, ASDAS-ESR, ASDAS-CRP, biological disease-modifying anti-rheumatic drugs (bDMARDs) rate. No significant differences were observed in terms of OPG, PINP, CTX-I or OC between two groups. The mSASSS were higher in fatty lesions group than in those without fatty lesions (p < 0.001). The serum sclerostin levels were significantly lower in r-axSpA patients with fatty lesions than in those without fatty lesions (p < 0.001). There were correlations between BMI, mSASSS and sclerostin with the comprehensive Berlin scoring method (CBM) scores in the univariate analysis (ρ = 0.311, ρ = 0.306, ρ = -0.920, respectively). However, only sclerostin had correlation with the CBM scores in multivariate analysis (ρ = -0.040, p < 0.001). In the r-axSpA patients with fatty lesions, serum sclerostin levels are declined. Serum sclerostin might be useful as a biomarker to predict the progression of the chronic inflammation in SIJs in r-axSpA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"118 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-15DOI: 10.1186/s13075-024-03470-y
Alberto Floris, Maria Maddalena Angioni, Mattia Fadda, Micaela Rita Naitza, Mattia Congia, Elisabetta Chessa, Matteo Piga, Alberto Cauli
To explore the role of newly emerging autoantibodies (AAbs) - peptidyl-arginine deiminase 4 (aPAD4), carbamylated proteins (aCarP), and anti-RA33 (aRA33) - alongside the traditionally assessed rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), in predicting the response to abatacept (ABT) and its retention rate in rheumatoid arthritis (RA) patients. Data from 121 consecutive ABT-treated RA patients were recorded. The RF and ACPA status were retrospectively assessed by reviewing the patients’ clinical records. Positivity for aPAD4, aCarP and aRA33 were determined by Enzyme-Linked Immunosorbent Assay (ELISA). The achievement of a moderate or good EULAR response at 6 months and the 3-years retention were analyzed as treatment outcomes. Multiple logistic regression models and Cox regression hazard analysis models were built to identify the association between such outcomes and the different AAbs, after adjustment for different confounders. The AAbs were assessed both individually and in different combinations to identify the most robust predictive model. In the studied cohort, RF, ACPA, aPAD4, aCarP and aRA33-Ab tested positive in 74.4%, 69.4%, 43.8%, 23.9%, 14.9% patients, respectively. A moderate or good EULAR response at 6 months was achieved by 64.5% of subjects and the cumulative 3-years retention rate was 56.6%. A higher EULAR response rate was recorded in patient with positivity for RF (67% in subjects tested positive vs. 58% in negative), ACPA (68% vs. 57%), aPAD4 (68% vs. 62%), and aCarP (72% vs. 62%), although statistical significance was not reached likely due to sample size limitations. Similarly, ACPA, aPAD4, aCarP were associated with higher 3-year retention rates, though not statistically significant individually. The combined analysis revealed that positivity for ACPA and/or aPAD4 predicted a significantly higher EULAR response rate at 6 months compared with double negativity (adjusted OR 2.7, p 0.026). Furthermore, positivity for at least one of ACPA, aPAD4, or aCarP predicted a significantly higher 3-year ABT retention rate compared to triple negativity (62.1% single or double positive vs. 33.5% triple negative, adjusted HR 0.48, p 0.022). This study highlights the potential benefits of using a combined assessment of ACPA aPAD4 and aCarP in predicting effectiveness of ABT in RA.
探讨新出现的自身抗体（AAbs）——肽基精氨酸脱亚胺酶4 （aPAD4）、氨甲酰化蛋白（aCarP）和抗ra33 （aRA33）——与传统评估的类风湿因子（RF）和抗瓜氨酸化蛋白抗体（ACPA）一起，在预测类风湿关节炎（RA）患者对阿巴肽接受（ABT）的反应及其保留率中的作用。记录了121例连续接受abt治疗的RA患者的数据。通过回顾患者的临床记录对RF和ACPA状态进行回顾性评估。酶联免疫吸附试验（ELISA）检测aPAD4、aCarP和aRA33的阳性表达。在6个月时达到中度或良好的EULAR反应和3年的保留率作为治疗结果进行分析。在调整不同混杂因素后，建立多元logistic回归模型和Cox回归风险分析模型，以确定这些结果与不同自身抗体之间的关联。对抗体进行单独和不同组合的评估，以确定最可靠的预测模型。在研究队列中，RF、ACPA、aPAD4、aCarP和aRA33-Ab的阳性检出率分别为74.4%、69.4%、43.8%、23.9%、14.9%。64.5%的受试者在6个月时达到中度或良好的EULAR反应，累计3年保留率为56.6%。RF阳性患者（阳性67%对阴性58%）、ACPA（68%对57%）、aPAD4（68%对62%）和aCarP（72%对62%）的ular反应率较高，但由于样本量的限制，可能没有达到统计学意义。同样，ACPA, aPAD4， aCarP与较高的3年保留率相关，尽管单独没有统计学意义。联合分析显示，与双阴性相比，ACPA和/或aPAD4阳性预测6个月时EULAR反应率显著更高（调整or为2.7,p 0.026）。此外，与三阴性相比，至少一种ACPA、aPAD4或aCarP阳性预测3年ABT保留率显著更高（62.1%单或双阳性vs. 33.5%三阴性，调整HR 0.48, p 0.022）。本研究强调了联合评估ACPA、aPAD4和aCarP在预测RA中ABT疗效方面的潜在益处。
{"title":"The role of Anti-PAD4, Anti-CarP, and Anti-RA33 antibodies combined with RF and ACPA in predicting abatacept response in rheumatoid arthritis","authors":"Alberto Floris, Maria Maddalena Angioni, Mattia Fadda, Micaela Rita Naitza, Mattia Congia, Elisabetta Chessa, Matteo Piga, Alberto Cauli","doi":"10.1186/s13075-024-03470-y","DOIUrl":"https://doi.org/10.1186/s13075-024-03470-y","url":null,"abstract":"To explore the role of newly emerging autoantibodies (AAbs) - peptidyl-arginine deiminase 4 (aPAD4), carbamylated proteins (aCarP), and anti-RA33 (aRA33) - alongside the traditionally assessed rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), in predicting the response to abatacept (ABT) and its retention rate in rheumatoid arthritis (RA) patients. Data from 121 consecutive ABT-treated RA patients were recorded. The RF and ACPA status were retrospectively assessed by reviewing the patients’ clinical records. Positivity for aPAD4, aCarP and aRA33 were determined by Enzyme-Linked Immunosorbent Assay (ELISA). The achievement of a moderate or good EULAR response at 6 months and the 3-years retention were analyzed as treatment outcomes. Multiple logistic regression models and Cox regression hazard analysis models were built to identify the association between such outcomes and the different AAbs, after adjustment for different confounders. The AAbs were assessed both individually and in different combinations to identify the most robust predictive model. In the studied cohort, RF, ACPA, aPAD4, aCarP and aRA33-Ab tested positive in 74.4%, 69.4%, 43.8%, 23.9%, 14.9% patients, respectively. A moderate or good EULAR response at 6 months was achieved by 64.5% of subjects and the cumulative 3-years retention rate was 56.6%. A higher EULAR response rate was recorded in patient with positivity for RF (67% in subjects tested positive vs. 58% in negative), ACPA (68% vs. 57%), aPAD4 (68% vs. 62%), and aCarP (72% vs. 62%), although statistical significance was not reached likely due to sample size limitations. Similarly, ACPA, aPAD4, aCarP were associated with higher 3-year retention rates, though not statistically significant individually. The combined analysis revealed that positivity for ACPA and/or aPAD4 predicted a significantly higher EULAR response rate at 6 months compared with double negativity (adjusted OR 2.7, p 0.026). Furthermore, positivity for at least one of ACPA, aPAD4, or aCarP predicted a significantly higher 3-year ABT retention rate compared to triple negativity (62.1% single or double positive vs. 33.5% triple negative, adjusted HR 0.48, p 0.022). This study highlights the potential benefits of using a combined assessment of ACPA aPAD4 and aCarP in predicting effectiveness of ABT in RA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"24 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-14DOI: 10.1186/s13075-024-03465-9
Andreas Haidmayer, Gabriel Adelsmayr, Christopher Spreizer, Eva Valentina Klocker, Franz Quehenberger, Michael Fuchsjaeger, Jens Thiel, Josef Hermann
Axial spondyloarthritis (SpA) leads to structural bone lesions in every part of the vertebral column. These lesions are only partially visualized on conventional radiographs, omitting posterior parts of the vertebral column and the thoracic spine, that may nevertheless contribute to impaired spinal mobility and function in patients with axial SpA. In this prospective and blinded investigation, we assessed the distribution of structural spinal lesions using magnetic resonance imaging (MRI) of the whole spine in 55 patients with axial SpA classified according to the Assessment in Spondyloarthritis International Society (ASAS) criteria. After assessment of spinal mobility and function two blinded radiologists independently evaluated MRIs of 23 vertebral units in every patient. Non-parametric statistical methods, Spearman‘s correlation and linear regression models were used to analyze structural lesion distribution and the relationship with clinical spinal mobility and function parameters. In 55 patients with axial SpA (13 females, average disease duration 14.9 years) 657 ventral and 139 dorsal vertebral body structural bone lesions and, notably, 534 facet joint lesions could be visualized. The median number of lesions per patient was higher in the thoracic (8.5, range 1.0–41.0) than in the lumbar (7.5, range 0.0-27.5) and the cervical spine (3.5, range 0.0-24.5). A negative correlation was noted between the number of osteoproliferative structural bone lesions and impairment of spinal mobility and function in univariate, but not in multivariate analyses. MRI of the whole spine revealed a high prevalence of lesions in dorsal parts of the vertebral column and in the thoracic spine in patients with axial SpA that may not be adequately visualized on conventional radiographs. These findings could further contribute to a better understanding of reduced mobility of the spine typically associated with axial SpA and assist diagnostics.
{"title":"Distribution of spinal damage in patients with axial spondyloarthritis as assessed by MRI: a prospective and blinded study","authors":"Andreas Haidmayer, Gabriel Adelsmayr, Christopher Spreizer, Eva Valentina Klocker, Franz Quehenberger, Michael Fuchsjaeger, Jens Thiel, Josef Hermann","doi":"10.1186/s13075-024-03465-9","DOIUrl":"https://doi.org/10.1186/s13075-024-03465-9","url":null,"abstract":"Axial spondyloarthritis (SpA) leads to structural bone lesions in every part of the vertebral column. These lesions are only partially visualized on conventional radiographs, omitting posterior parts of the vertebral column and the thoracic spine, that may nevertheless contribute to impaired spinal mobility and function in patients with axial SpA. In this prospective and blinded investigation, we assessed the distribution of structural spinal lesions using magnetic resonance imaging (MRI) of the whole spine in 55 patients with axial SpA classified according to the Assessment in Spondyloarthritis International Society (ASAS) criteria. After assessment of spinal mobility and function two blinded radiologists independently evaluated MRIs of 23 vertebral units in every patient. Non-parametric statistical methods, Spearman‘s correlation and linear regression models were used to analyze structural lesion distribution and the relationship with clinical spinal mobility and function parameters. In 55 patients with axial SpA (13 females, average disease duration 14.9 years) 657 ventral and 139 dorsal vertebral body structural bone lesions and, notably, 534 facet joint lesions could be visualized. The median number of lesions per patient was higher in the thoracic (8.5, range 1.0–41.0) than in the lumbar (7.5, range 0.0-27.5) and the cervical spine (3.5, range 0.0-24.5). A negative correlation was noted between the number of osteoproliferative structural bone lesions and impairment of spinal mobility and function in univariate, but not in multivariate analyses. MRI of the whole spine revealed a high prevalence of lesions in dorsal parts of the vertebral column and in the thoracic spine in patients with axial SpA that may not be adequately visualized on conventional radiographs. These findings could further contribute to a better understanding of reduced mobility of the spine typically associated with axial SpA and assist diagnostics.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"16 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10DOI: 10.1186/s13075-024-03472-w
Siying Deng, Bei Wang, Ziwei Hu, Shaozhe Cai, Lingli Dong
The objective of this study was to investigate the therapeutic effectiveness and safety profile of Eltrombopag, a thrombopoietin receptor agonist, as prolonged therapy in refractory CTD-ITP patients. We conducted a pilot observational study of Eltrombopag in CTD-ITP patients who were unresponsive to or intolerant of conventional medications. Eltrombopag was administered orally at 25–75 mg/qd and adjusted on the basis of tolerance and efficacy until a minimum dosage of 25 mg/qd was reached. Clinical and laboratory data were collected and analysed monthly. The therapeutic response, relapse, and adverse events during the follow-up were also reviewed and evaluated. Fifty-two patients were enrolled and followed monthly for a median of 6 months. Thirty-six (90%) patients achieved durable overall remission. The remission rates were 67.5% at month 1, 87.5% at month 2, 97.5% at month 3, and 95% at month 6. The platelet count of the patients improved significantly, with the median reaching 50 × 109/L within 2 weeks (p = 0.003). Disease activity indices were reduced in SLE and pSS patients (p = 0.016), allowing glucocorticoid tapering (p = 0.004). One patient had no response, four relapsed, and fifteen (28.8%) experienced clinically relevant adverse events. In the analyses, protopathy, comorbidity, and prior treatment were associated with efficacy. For refractory CTD-ITP patients, Eltrombopag demonstrated significant clinical improvement, safety, and a steroid-sparing effect with prolonged use. Patient characteristics at baseline may affect treatment efficacy. First-line treatment with immunosuppressant therapy has a poor effect on ITP secondary to connective tissue disease and brings unignorable side effects on patients. Few studies have sufficiently elucidated the effects of Eltrombopag, a thrombopoietin receptor agonist, in refractory ITP secondary to CTD. Here, we report a series of refractory ITP-CTD patients treated with Eltrombopag. A 90% durable overall remission rate was observed at week 24, and remission rates promptly increased from 67.5% at month 1 to 89.5% at month 2. Eltrombopag had a rapid onset of action and permitted a steroid-sparing effect as the response was sustained. A 28.8% adverse event rate was observed. The baseline characteristics of patients may influence drug efficacy. This study may provide important supporting information for developing a treatment strategy for refractory CTD-ITP patients based on Eltrombopag.
{"title":"Eltrombopag for the treatment of refractory connective tissue disease-related thrombocytopenia: a pilot study of 52 cases","authors":"Siying Deng, Bei Wang, Ziwei Hu, Shaozhe Cai, Lingli Dong","doi":"10.1186/s13075-024-03472-w","DOIUrl":"https://doi.org/10.1186/s13075-024-03472-w","url":null,"abstract":"The objective of this study was to investigate the therapeutic effectiveness and safety profile of Eltrombopag, a thrombopoietin receptor agonist, as prolonged therapy in refractory CTD-ITP patients. We conducted a pilot observational study of Eltrombopag in CTD-ITP patients who were unresponsive to or intolerant of conventional medications. Eltrombopag was administered orally at 25–75 mg/qd and adjusted on the basis of tolerance and efficacy until a minimum dosage of 25 mg/qd was reached. Clinical and laboratory data were collected and analysed monthly. The therapeutic response, relapse, and adverse events during the follow-up were also reviewed and evaluated. Fifty-two patients were enrolled and followed monthly for a median of 6 months. Thirty-six (90%) patients achieved durable overall remission. The remission rates were 67.5% at month 1, 87.5% at month 2, 97.5% at month 3, and 95% at month 6. The platelet count of the patients improved significantly, with the median reaching 50 × 109/L within 2 weeks (p = 0.003). Disease activity indices were reduced in SLE and pSS patients (p = 0.016), allowing glucocorticoid tapering (p = 0.004). One patient had no response, four relapsed, and fifteen (28.8%) experienced clinically relevant adverse events. In the analyses, protopathy, comorbidity, and prior treatment were associated with efficacy. For refractory CTD-ITP patients, Eltrombopag demonstrated significant clinical improvement, safety, and a steroid-sparing effect with prolonged use. Patient characteristics at baseline may affect treatment efficacy. First-line treatment with immunosuppressant therapy has a poor effect on ITP secondary to connective tissue disease and brings unignorable side effects on patients. Few studies have sufficiently elucidated the effects of Eltrombopag, a thrombopoietin receptor agonist, in refractory ITP secondary to CTD. Here, we report a series of refractory ITP-CTD patients treated with Eltrombopag. A 90% durable overall remission rate was observed at week 24, and remission rates promptly increased from 67.5% at month 1 to 89.5% at month 2. Eltrombopag had a rapid onset of action and permitted a steroid-sparing effect as the response was sustained. A 28.8% adverse event rate was observed. The baseline characteristics of patients may influence drug efficacy. This study may provide important supporting information for developing a treatment strategy for refractory CTD-ITP patients based on Eltrombopag.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"204 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-09DOI: 10.1186/s13075-025-03473-3
Zhongsheng Zhou, Shuhui Wu, Yang Li, Pu Shao, Jinlan Jiang
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, tissue damage, and fibrosis, significantly affecting the quality of life. While there are currently some effective treatments available, they often come with side effects. There is an urgent need to find new treatments that can further improve therapeutic outcomes and reduce side effects. Our study investigates the role of Mesenchymal Stem Cell exosomes (MSC-exo) combined with Ginsenoside Rh2 (Rh2) in the treatment of RA. We specifically focus on how this combined strategy influences macrophage polarization and pyroptosis. This research utilized a collagen-induced rat arthritis model. The study findings reveal that the combination of MSC-exo combined with Rh2 can inhibit the polarization of M1 macrophages, increase the proportion of M2-like macrophages, and suppress M1-like macrophage pyroptosis via the NLRP3/Caspase11/GSDMD-N pathway. In the rat arthritis model, the combination of MSC-exo and Rh2 showed synergistic therapeutic effects. This research contributes to a deeper understanding of RA’s pathogenesis and presents new potential targeted therapeutic interventions. The combined application of MSC-exo and Rh2 offers promising insights for future innovative strategies in RA treatment, paving the way for more effective management of this autoimmune disease.
{"title":"Inhibition of macrophage polarization and pyroptosis in collagen-induced arthritis through MSC-exo and ginsenoside Rh2","authors":"Zhongsheng Zhou, Shuhui Wu, Yang Li, Pu Shao, Jinlan Jiang","doi":"10.1186/s13075-025-03473-3","DOIUrl":"https://doi.org/10.1186/s13075-025-03473-3","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, tissue damage, and fibrosis, significantly affecting the quality of life. While there are currently some effective treatments available, they often come with side effects. There is an urgent need to find new treatments that can further improve therapeutic outcomes and reduce side effects. Our study investigates the role of Mesenchymal Stem Cell exosomes (MSC-exo) combined with Ginsenoside Rh2 (Rh2) in the treatment of RA. We specifically focus on how this combined strategy influences macrophage polarization and pyroptosis. This research utilized a collagen-induced rat arthritis model. The study findings reveal that the combination of MSC-exo combined with Rh2 can inhibit the polarization of M1 macrophages, increase the proportion of M2-like macrophages, and suppress M1-like macrophage pyroptosis via the NLRP3/Caspase11/GSDMD-N pathway. In the rat arthritis model, the combination of MSC-exo and Rh2 showed synergistic therapeutic effects. This research contributes to a deeper understanding of RA’s pathogenesis and presents new potential targeted therapeutic interventions. The combined application of MSC-exo and Rh2 offers promising insights for future innovative strategies in RA treatment, paving the way for more effective management of this autoimmune disease.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"101 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-08DOI: 10.1186/s13075-024-03471-x
Tatiana Cobo-Ibáñez, Ivan Castellví, Ana Pros, Marta Domínguez-Álvaro, Laura Nuño-Nuño, Julia Martínez-Barrio, Vega Jovaní, Fredeswinda Romero-Bueno, Esther Ruiz-Lucea, Eva Tomero, Ernesto Trallero-Araguás, Javier Narváez, Jordi Camins-Fàbregas, Alberto Ruiz-Román, Jesús Loarce-Martos, Susana Holgado-Pérez, V Miguel Flores-Rodríguez, Francisca Sivera, Carolina Merino-Argumanez, Antonio Juan-Mas, Irene Altabás-González, María Martín-López, Joaquín María Belzunegui-Otano, Carmen Carrasco-Cubero, Mercedes Freire-González, Iñigo Rúa-Figueroa, Nuria Lozano-Rivas, Julio David Suarez-Cuba, Olga Martínez, Rafaela Ortega-Castro, Patricia Alcocer, Alejandro Gómez-Gómez, Olga Sánchez-Pernaute, José Luis Tandaipan, Irene Carrión-Barberà, Chamaida Plasencia-Rodríguez, Oihane Ibarguengoitia-Barrena, Paola Vidal-Montal, Vera Ortiz-Santamaria, Noemi Garrido-Puñal, Anne Riveros, Esmeralda Delgado-Frías, Juan Miguel López-Gómez, Carmen Barbadillo, José María Pego-Reigosa, Beatriz E. Joven-Ibáñ..
To evaluate the main outcomes of disease activity and their association with other measures of activity, damage, and quality of life in patients with idiopathic inflammatory myopathy (IIM) according to time since diagnosis and positivity to antisynthetase autoantibodies (ASAs). Cross-sectional multicenter study within the Spanish Myo-Spain registry. Cases were classified as incident (≤ 12 months since diagnosis) and prevalent. The main outcomes of disease activity were the Myositis Disease Activity Assessment visual analogue scale (MYOACT), the Manual Muscle Test 8 (MMT-8), physician global activity (PhGA), and extramuscular activity. Other measures of activity, damage, and quality of life included patient global disease activity, MYOACT muscular, creatine phosphokinase, Health Assessment Questionnaire, physician and patient global damage, global damage of the Myositis Damage Index, and the 12-item Short-Form Health Survey (SF-12). We analyzed associations using a multivariate generalized linear model and a simple linear regression model. A total of 554 patients with different diagnostic subgroups of IIM were included (136 incident and 418 prevalent cases), with 215 ASA-positive patients (58 incident and 157 prevalent cases). All measures of disease activity were higher in the incident cases (p < 0.05), except for MYOACT muscular and creatine phosphokinase, for which no differences were recorded in ASA-positive patients. No differences were found between incident and prevalent cases for measures of damage. Values for the physical component of the SF-12 were higher in the prevalent cases (p < 0.05). The multivariate model was initially significant overall for the main activity outcomes. Positivity to ASAs was positively and negatively associated with the MYOACT index and MMT-8, respectively (p < 0.05), although no association was recorded with PhGA and extramuscular activity. Prevalent cases were negatively associated with the main outcomes of activity, except with MMT-8, for which the association was positive (p < 0.05). The main activity outcomes validated in polymyositis and dermatomyositis could also be used in other subtypes of IIM, such as antisynthetase syndrome. Recent diagnosis is associated with greater disease activity, as assessed based on these activity outcomes. PhGA and extramuscular activity are not modified by ASA positivity, thus supporting their preferred use for assessing treatment response in IIM with ASAs.
{"title":"Disease activity in patients with idiopathic inflammatory myopathy according to time since diagnosis and positivity to antisynthetase autoantibodies: data from the Myo-Spain registry","authors":"Tatiana Cobo-Ibáñez, Ivan Castellví, Ana Pros, Marta Domínguez-Álvaro, Laura Nuño-Nuño, Julia Martínez-Barrio, Vega Jovaní, Fredeswinda Romero-Bueno, Esther Ruiz-Lucea, Eva Tomero, Ernesto Trallero-Araguás, Javier Narváez, Jordi Camins-Fàbregas, Alberto Ruiz-Román, Jesús Loarce-Martos, Susana Holgado-Pérez, V Miguel Flores-Rodríguez, Francisca Sivera, Carolina Merino-Argumanez, Antonio Juan-Mas, Irene Altabás-González, María Martín-López, Joaquín María Belzunegui-Otano, Carmen Carrasco-Cubero, Mercedes Freire-González, Iñigo Rúa-Figueroa, Nuria Lozano-Rivas, Julio David Suarez-Cuba, Olga Martínez, Rafaela Ortega-Castro, Patricia Alcocer, Alejandro Gómez-Gómez, Olga Sánchez-Pernaute, José Luis Tandaipan, Irene Carrión-Barberà, Chamaida Plasencia-Rodríguez, Oihane Ibarguengoitia-Barrena, Paola Vidal-Montal, Vera Ortiz-Santamaria, Noemi Garrido-Puñal, Anne Riveros, Esmeralda Delgado-Frías, Juan Miguel López-Gómez, Carmen Barbadillo, José María Pego-Reigosa, Beatriz E. Joven-Ibáñ..","doi":"10.1186/s13075-024-03471-x","DOIUrl":"https://doi.org/10.1186/s13075-024-03471-x","url":null,"abstract":"To evaluate the main outcomes of disease activity and their association with other measures of activity, damage, and quality of life in patients with idiopathic inflammatory myopathy (IIM) according to time since diagnosis and positivity to antisynthetase autoantibodies (ASAs). Cross-sectional multicenter study within the Spanish Myo-Spain registry. Cases were classified as incident (≤ 12 months since diagnosis) and prevalent. The main outcomes of disease activity were the Myositis Disease Activity Assessment visual analogue scale (MYOACT), the Manual Muscle Test 8 (MMT-8), physician global activity (PhGA), and extramuscular activity. Other measures of activity, damage, and quality of life included patient global disease activity, MYOACT muscular, creatine phosphokinase, Health Assessment Questionnaire, physician and patient global damage, global damage of the Myositis Damage Index, and the 12-item Short-Form Health Survey (SF-12). We analyzed associations using a multivariate generalized linear model and a simple linear regression model. A total of 554 patients with different diagnostic subgroups of IIM were included (136 incident and 418 prevalent cases), with 215 ASA-positive patients (58 incident and 157 prevalent cases). All measures of disease activity were higher in the incident cases (p < 0.05), except for MYOACT muscular and creatine phosphokinase, for which no differences were recorded in ASA-positive patients. No differences were found between incident and prevalent cases for measures of damage. Values for the physical component of the SF-12 were higher in the prevalent cases (p < 0.05). The multivariate model was initially significant overall for the main activity outcomes. Positivity to ASAs was positively and negatively associated with the MYOACT index and MMT-8, respectively (p < 0.05), although no association was recorded with PhGA and extramuscular activity. Prevalent cases were negatively associated with the main outcomes of activity, except with MMT-8, for which the association was positive (p < 0.05). The main activity outcomes validated in polymyositis and dermatomyositis could also be used in other subtypes of IIM, such as antisynthetase syndrome. Recent diagnosis is associated with greater disease activity, as assessed based on these activity outcomes. PhGA and extramuscular activity are not modified by ASA positivity, thus supporting their preferred use for assessing treatment response in IIM with ASAs.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"11 3 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-07DOI: 10.1186/s13075-024-03468-6
Juan Molina-Collada, Marta Domínguez-Álvaro, Rafael B. Melero-González, Eugenio de Miguel, Maite Silva-Díaz, Jesús Alejandro Valero Jaimes, Ismael González, Julio Sánchez Martín, Javier Narváez, Joan Calvet, Ivette Casafont-Solé, Jose A Román Ivorra, Selene Labrada Arrabal, Margarida Vasques Rocha, Carlota L Iñiguez, María Sagrario Bustabad Reyes, Cristina Campos Fernández, María Alcalde Villar, Antonio Juan Mas, Ricardo Blanco
To compare mortality rates between GCA patients and the general population in Spain, and to identify associated factors influencing mortality. ARTESER, a multicenter registry by the Spanish Society of Rheumatology, includes GCA patients from June 2013 to March 2019. Demographic, clinical, imaging, histological and mortality data were collected retrospectively. Only patients with at least one year of follow-up were included for analysis. The mortality rates were expressed as the number of deaths per 1000 person-years, with 95% confidence interval (CI) by sex and age group. Kaplan-Meier method was performed for survival analysis. The factors influencing mortality were analyzed using Cox regression model. A total of 1200 patients with GCA were analyzed, with a mean (SD) follow-up of 2.18 (1.53) years. The overall five-year cumulative mortality rate (95%CI) was 37.86 (31.75-43.96) per 1000 patients/year. The cumulative mortality rate was significantly higher in males than females (59.04vs29.06; p<0.001). The age- and sex-adjusted cumulative mortality rate was similar to the Spanish general population (19.75vs20.72;p=0.559). In the multivariate analysis, older age (HR 1.11, 95%CI 1.073-1.142) and male sex (HR 1.775, 95%CI 1.214-2.594) were associated with increased mortality. Headache (HR 0.55, 95%CI 0.362-0.843) and high hemoglobin levels (HR 0.85, 95%CI 0.744-0.970) were protective factors against death. The overall five-year age- and sex-adjusted cumulative mortality rate in GCA is similar compared to the general population. Older age and male sex appear to be associated with an increased risk of mortality, whereas headache and high hemoglobin levels might serve as protective factors against death.
{"title":"Mortality in patients with giant cell arteritis in Spain: results from the ARTESER registry","authors":"Juan Molina-Collada, Marta Domínguez-Álvaro, Rafael B. Melero-González, Eugenio de Miguel, Maite Silva-Díaz, Jesús Alejandro Valero Jaimes, Ismael González, Julio Sánchez Martín, Javier Narváez, Joan Calvet, Ivette Casafont-Solé, Jose A Román Ivorra, Selene Labrada Arrabal, Margarida Vasques Rocha, Carlota L Iñiguez, María Sagrario Bustabad Reyes, Cristina Campos Fernández, María Alcalde Villar, Antonio Juan Mas, Ricardo Blanco","doi":"10.1186/s13075-024-03468-6","DOIUrl":"https://doi.org/10.1186/s13075-024-03468-6","url":null,"abstract":"To compare mortality rates between GCA patients and the general population in Spain, and to identify associated factors influencing mortality. ARTESER, a multicenter registry by the Spanish Society of Rheumatology, includes GCA patients from June 2013 to March 2019. Demographic, clinical, imaging, histological and mortality data were collected retrospectively. Only patients with at least one year of follow-up were included for analysis. The mortality rates were expressed as the number of deaths per 1000 person-years, with 95% confidence interval (CI) by sex and age group. Kaplan-Meier method was performed for survival analysis. The factors influencing mortality were analyzed using Cox regression model. A total of 1200 patients with GCA were analyzed, with a mean (SD) follow-up of 2.18 (1.53) years. The overall five-year cumulative mortality rate (95%CI) was 37.86 (31.75-43.96) per 1000 patients/year. The cumulative mortality rate was significantly higher in males than females (59.04vs29.06; p<0.001). The age- and sex-adjusted cumulative mortality rate was similar to the Spanish general population (19.75vs20.72;p=0.559). In the multivariate analysis, older age (HR 1.11, 95%CI 1.073-1.142) and male sex (HR 1.775, 95%CI 1.214-2.594) were associated with increased mortality. Headache (HR 0.55, 95%CI 0.362-0.843) and high hemoglobin levels (HR 0.85, 95%CI 0.744-0.970) were protective factors against death. The overall five-year age- and sex-adjusted cumulative mortality rate in GCA is similar compared to the general population. Older age and male sex appear to be associated with an increased risk of mortality, whereas headache and high hemoglobin levels might serve as protective factors against death.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"15 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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