Arthritis Research & Therapy最新文献

{"title":"The impact of disease activity and interferon-α on the nervous system in systemic lupus erythematosus","authors":"Kristoffer A. Zervides, Elsa Grenmyr, Shorena Janelidze, Petrus Linge, Jessika Nystedt, Petra C. Nilsson, Pia C. Sundgren, Oskar Hansson, Anders A. Bengtsson, Andreas Jönsen","doi":"10.1186/s13075-025-03539-2","DOIUrl":"https://doi.org/10.1186/s13075-025-03539-2","url":null,"abstract":"Systemic lupus erythematosus (SLE) patients, with or without neuropsychiatric SLE (NPSLE), exhibit greater neuronal impairment compared to healthy individuals in terms of neuronal damage, magnet resonance imaging (MRI) changes and cognitive dysfunction. Interferon (IFN)-α is a key immunopathogenic driver of SLE, being persistently overexpressed in the majority of patients. This longitudinal study aimed to investigate whether disease activity and serum IFN-α levels over time were associated with objective findings of neuronal impairment regarding (i) higher plasma neurofilament light (NfL) concentrations, (ii) structural alterations on MRI, and (iii) cognitive dysfunction upon testing. Sixty-six consecutive female SLE outpatients were enrolled in a cross-sectional study. Retrospectively, prior visits with concomitant blood samples (n = 199) were selected from the Lund Lupus Cohort database and biobank. Serum IFN-α concentrations were measured using an electrochemiluminescence immunoassay. IFN-α lupus phenotypes were defined as high (n = 24) or low (n = 33) by considering persistent elevations in serum IFN-α concentrations despite low SLE Disease Activity Index-2000 (SLEDAI-2 K) scores. SLEDAI-2 K lupus phenotypes were defined as moderate-high (n = 31) or low (n = 35) based on SLEDAI-2 K scores from all 576 available visits prior to the study. Ongoing neuronal damage was assessed by plasma NfL concentration measurements using Simoa at the 199 visits. Structural MRI alterations and cognitive dysfunction according to the CNS-Vital Signs test battery were the additional outcomes. Multivariate linear mixed-effect, linear regression, and logistic regression models were used for the statistical analyses. Visits with higher disease activity were associated with higher plasma NfL concentrations (e.g. SLEDAI-2 K total: p = 1.5*10− 6). High compared with low IFN-α lupus phenotype patients displayed more cognitive dysfunction (odds ratio 11.0, p = 0.004), and smaller volumes of total grey matter, caudate nucleus, and thalamus (p = 0.036; p = 0.038; p = 0.023). Moderate-high compared with low SLEDAI-2 K lupus phenotype patients displayed larger white matter lesion volumes and smaller total grey matter and thalamus volumes (p = 0.011; p = 0.041; p = 0.005). The study suggests that disease activity and IFN-α may drive neuronal affliction in SLE, also in the absence of overt neuropsychiatric symptoms, and that controlling disease activity could improve the cerebral outcome.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"26 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661204","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}

{"title":"Efficacy of adipose stromal cells-enriched high-density fat graft combined with BTX-A for Raynaud’s phenomenon: a prospective cohort study","authors":"Chengliang Deng, Xin Liu, Miaomiao Wei, Bihua Wu, Tianhua Zhang, Shune Xiao, Peiru Min, Yixin Zhang","doi":"10.1186/s13075-025-03533-8","DOIUrl":"https://doi.org/10.1186/s13075-025-03533-8","url":null,"abstract":"Conventional treatments for Raynaud’s phenomenon (RP) often show limited effectiveness due to their inability to address both vascular and inflammatory aspects. This study evaluates the combination of high-density fat grafting (HDFG) with botulinum toxin A (BTX-A) for treating RP. Eleven patients with 20 affected hands diagnosed with RP were recruited and randomly assigned to receive either HDFG combined with BTX-A (intervention group, n = 11) or HDFG alone (control group, n = 9). Efficacy was assessed using Visual Analog Scale (VAS) pain scores and McCabe Cold Sensitivity Scores, along with finger ulcer healing time and infrared thermal imaging to evaluate blood perfusion improvements. The HDFG-BTX group showed significant improvements in hand symptoms. VAS pain scores decreased from a pre-treatment mean of 5.33 to 0.84 post-treatment (mean reduction of 4.49, p = 0.018), indicating effective pain relief. McCabe scores improved from 272.73 to 75.00 (mean reduction of 197.73, p = 0.001), demonstrating reduced cold sensitivity. Ulcer healing time was shorter in the HDFG-BTX group (14.25 days) compared to HDFG alone (25.6 days, p < 0.001), highlighting faster recovery. Infrared imaging indicated significant enhancements in blood perfusion. HDFG combined with BTX-A is a reliable and beneficial intervention for RP, leading to high patient satisfaction. • Combining high-density fat grafting with botulinum toxin A significantly improves symptoms in Raynaud’s phenomenon. • This novel therapy enhances pain relief, blood flow, and ulcer healing, demonstrating strong patient satisfaction.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"51 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653336","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}

{"title":"CRP-Albumin-Lymphocyte index (CALLYI) as a risk-predicting biomarker in association with osteoarthritis","authors":"Maosen Geng, Ke Zhang","doi":"10.1186/s13075-025-03530-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03530-x","url":null,"abstract":"As a novel biomarker, the C-reactive protein-Albumin-Lymphocyte Index (CALLYI) offers a comprehensive evaluation of the human body from three perspectives. However, the association between CALLYI and the incidence of osteoarthritis (OA) remains unclear. This cross-sectional study investigates the potential relationship between CALLYI and OA in US adults, develops a clinical prediction model, and validates its effectiveness. The study cohort consisted of 18,624 U.S. adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. The CALLYI was calculated using the formula: albumin * lymphocytes / CRP * 10. Three weighted multiple regression models were constructed to investigate the correlation between CALLYI and OA. Restricted cubic splines (RCS) were employed to evaluate the nonlinear relationship between these two variables. Subgroup analyses were conducted to examine interactions. Univariate logistic regression, binary logistic regression, and least absolute shrinkage and selection operator (LASSO) were utilized for variable selection in the prediction model. Decision curve analysis (DCA) and receiver operating characteristic (ROC) curve analysis were applied to assess the predictive performance of the models. The total sample size analyzed in this study was 18,624, of which 1,977 (10.62%) were diagnosed with OA. And the mean value of CALLYI was 5.13 (2.12,12.86). The multivariate logistic regression model revealed a negative correlation between elevated CALLYI and OA. The fully adjusted Model 3 demonstrated a significant 28% reduction in OA risk in the Q4 compared to the Q1 of CALLYI (OR = 0.72 95% CI: 0.59–0.88, p = 0.001). Subgroup analyses did not reveal any significant interactions (p > 0.05). Additionally, a significant non-linear relationship between CALLYI and OA using RCS (p < 0.0001). After variable screening, we constructed an OA prediction model incorporating CALLYI, and the results were visualized using a nomogram. The area under the curve (AUC) was 0.825 (95% CI: 0.817–0.834), and DCA indicated that the model holds clinical significance. This study, utilizing NHANES statistics, is the first to establish a nonlinear negative relationship between CALLYI and OA, with no significant interaction observed in subgroup analyses. In the OA prediction model incorporating CALLYI, we validated the effectiveness and clinical utility of this model, providing evidence that CALLYI can serve as a biomarker for OA risk prediction. Nevertheless, larger multicenter prospective cohort studies are necessary to mitigate the limitations inherent in cross-sectional designs and self-reported OA diagnoses.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"33 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653335","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}

{"title":"The needed daily dose of colchicine in patients with Familial Mediterranean Fever may be higher in women: a study on behalf of the JIR cohort","authors":"Ilenia Di Cola, Alessandra Bartoli, Léa Savey, Fatima Bensalek, Marion Delplanque, Rim Bourguiba, Zohra Aknouche, Isabelle Kone-Paut, Linda Rossi-Semerano, Isabelle Melki, Brigitte Bader-Meunier, Bénédicte Neven, Pierre Quartier, Guilaine Boursier, Laurence Cuisset, Gilles Grateau, Véronique Hentgen, Sophie Georgin-Lavialle","doi":"10.1186/s13075-024-03440-4","DOIUrl":"https://doi.org/10.1186/s13075-024-03440-4","url":null,"abstract":"At present, there are no data on the relationship between colchicine dose and weight in patients with Familial Mediterranean Fever (FMF). We aimed at describing the daily colchicine dose in a cohort of FMF patients. From 2016 to 2023, a retrospective evaluation of prospectively followed homozygous FMF patients at the French National Reference Centre was performed. Out of 272 patients, 149 were women (57.8%), with a mean age of 43 years old. The mean weight was 67.8 kg and body mass index 24,2 kg/m². Colchicine was taken by 96% of patients. A subgroup of 30 patients received 2.5 mg/day: they were mostly women (n = 23; 76.7%; p = 0.018), with a lower mean weight (p = 0.019); indeed, 26/30 (87%) weighed < 50 kg. Female sex correlated with higher values of daily colchicine dose (p = 0.0208); weight was not associated with colchicine dose (p = 0.4073). No toxicity has been noted in patients treated with 2.5 mg/day, including patients weighing < 50 kg, and most of these patients were women. We may speculate that the clinical picture of female patients requiring an increased dose of colchicine may be related to the hormonal background, with a possible exaggeration of pyrin activation. This is the first study to examine the question of colchicine dosage in relation to weight of FMF adult patients and to highlight a possible link with female gender. We advise clinicians to explain that colchicine treatment may be used daily up to 2.5 mg without toxicity.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"13 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653333","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}

{"title":"Accelerated Type VII collagen turnover in systemic sclerosis patients, reflected by serological neo-epitope fragment biomarkers","authors":"Yi He, Jannie M B Sand, Satoshi Kubo, Naoaki Ohkubo, Yusuke Miyazaki, Morten Karsdal, Yoshiya Tanaka, Anne-Christine Bay-Jensen","doi":"10.1186/s13075-025-03525-8","DOIUrl":"https://doi.org/10.1186/s13075-025-03525-8","url":null,"abstract":"Systemic sclerosis (SSc) is a rare autoimmune disease characterized by microvasculopathy, autoantibody production, and fibrosis of the skin and internal organs. Disrupted collagen turnover in SSc leads to excessive collagen accumulation, but the remodeling of type VII collagen, a key component of the skin’s basement membrane, is not well understood. This study investigates type VII collagen turnover in SSc by measuring serum levels of its formation (PRO-C7) and degradation (C7M) biomarkers and characterizing their association with other ECM biomarkers and clinical manifestations. An automated immunoassay, PRO-C7, was developed to quantify type VII collagen formation. Additionally, C7M, along with type III, IV, and VI collagen turnover biomarkers, were analyzed in a post-hoc study of SSc patients. The normality of all variables of interest was assessed using the Shapiro-Wilk test. Spearman’s correlation and Welch’s T-testtests were used to assess associations and differences in biomarker levels between SSc patients and healthy controls. A linear regression model was used to assess the relationship between biomarker levels and the modified Rodnan skin score (mRSS).To control the type I errors in multiple comparisons, the Bonferroni Correction was applied to adjust the significance levels. Results showed significantly elevated levels of type VII and VI collagen turnover biomarkers in SSc patients and controls. PRO-C3 and PRO-C6 levels were significantly correlated with mRSS score (R2 = 0.156, p = 0.0004; R2 = 0.222, p < 0.0001 respectively), while PRO-C7 and C7M were not. Moderate but significant correlations were observed between both PRO-C7 and C7M with C-reactive protein and Erythrocytes sedimentation rate, respectively (ρ = 0.39, p = 0.0006; ρ = 0.24 p = 0.045 for PRO-C7; ρ = 0.31, p = 0.0076; ρ = 0.28, p = 0.014 for C7M). C7M showed a significant correlation with type III, type IV, type VI collagen formation and degradation biomarkers, while PRO-C7 correlated significantly only with PRO-C6 and C6M. Furthermore, C7M levels were higher in SSc patients with renal dysfunction, and elevated PRO-C7 levels were associated with anti-dsDNA, while lower PRO-C7 levels were linked to capillary abnormalities in SSc. In conclusion, PRO-C7 and C7M, reflecting type VII collagen turnover, show promise as new serological biomarkers for SSc.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"9 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653334","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}

{"title":"Single-cell transcriptome analysis reveals cellular heterogeneity in the aortas of Takayasu arteritis","authors":"Na Gao, He Tang, Taotao Li, Yi Yang, Honglei Zhao, Longfei Wang, Yanqiu Guo, Bokang Qiao, Lili Pan","doi":"10.1186/s13075-025-03523-w","DOIUrl":"https://doi.org/10.1186/s13075-025-03523-w","url":null,"abstract":"Takayasu arteritis (TAK) is an inflammatory vasculitis that affects the aorta and its primary branches. The pathogenesis of TAK remains elusive, yet identifying key cell types in the aorta of TAK patients is crucial for uncovering cellular heterogeneity and discovering potential therapeutic targets. This study utilized single-cell transcriptome analysis on aortic specimens from three TAK patients, with control data sourced from a publicly available database (GSE155468). Additionally, bulk RNA sequencing was performed on peripheral CD4 + and CD8 + T cells from eight TAK patients and eight matched healthy volunteers. All participants were recruited at Anzhen Hospital, Capital Medical University, China, between January 2020 and December 2023. Single-cell transcriptome analysis identified 11 predominant cell types in aortic tissues, with notable differences in proportions between TAK patients and controls. T cells, B cells, macrophages, smooth muscle cells (SMCs), and fibroblasts exhibited subtype-specific gene expression signatures, with notable changes in interactions between T cells, B cells, and monocyte-macrophages, highlighting their active involvement in the pathogenesis of TAK. Bulk RNA-Seq analysis of peripheral blood T cells from TAK patients showed an upregulation of complement system genes, underscoring the significance of the complement signaling pathway in TAK’s immunopathogenesis. The findings underscore the active involvement of various immune and structural cells in the aortic tissues of TAK patients and reveal the presence of the complement signaling pathway in peripheral blood T cells. These insights are instrumental for identifying novel therapeutic targets and developing robust disease monitoring methods for TAK.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"28 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582819","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}

{"title":"Plasma levels of adhesion molecules are elevated in dermatomyositis-interstitial lung disease and associated with low paraoxonase-1 activity","authors":"Sangmee Sharon Bae, Ani Shahbazian, Jennifer Wang, Daniela Markovic, Tiffany De Leon, Yuna Lee, Srinivasa T. Reddy, Christina Charles-Schoeman","doi":"10.1186/s13075-025-03520-z","DOIUrl":"https://doi.org/10.1186/s13075-025-03520-z","url":null,"abstract":"To evaluate circulating levels of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) in patients with dermatomyositis (DM) and DM associated interstitial lung disease (DM-ILD). We performed a cross-sectional study in plasma samples from DM patients and matched healthy controls. Plasma ICAM-1 and VCAM-1 (CAM) levels were measured by ELISA. The activity of paraoxonase-1 (PON1), a high density lipoprotein (HDL) associated antioxidative enzyme was measured using paraoxonase, arylesterase and lactonase assays. Association analysis was performed between clinical predictors and CAM levels. We analyzed whether CAM levels have a mediating role in the association between PON1 activity and IIM outcomes using causal mediation analysis. Plasma samples from 83 DM patients with anti-Jo1 (n = 24), MDA5 (n = 29), and TIF1gamma (n = 30) and 28 age and sex matched healthy controls were analyzed. Plasma CAM levels were significantly higher in DM patients compared to controls. CAM levels were particularly higher in anti-MDA5 + DM patients compared to other autoantibody groups and in DM-ILD compared to DM without ILD. Higher ICAM-1 levels correlated low PON1 lactonase activity as well as worse restrictive lung physiology in multivariate models. Mediation analysis showed that 54% of the effect of low lactonase on worse DLCO was mediated through ICAM-1. Plasma CAM levels were higher in DM patients compared to healthy controls, particularly in DM patients with ILD. Our analyses support a pathway of low PON1 lactonase activity representing poor HDL function with low protective capacity of microvessels allowing increased endothelial activation leading to DM and DM-ILD. • Dermatomyositis (DM) patients had higher circulating ICAM-1 and VCAM-1 levels compared to healthy controls. • Plasma CAM levels were particularly higher in anti-MDA5 + patients and in DM with interstitial lung disease (ILD). • Our results support a potential pathway in which low PON1 associates with DM and DM-ILD partly mediated by increased endothelial activation.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"13 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575274","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}

{"title":"Quercetagetin alleviates inflammatory osteoclastogenesis and collagen antibody-induced arthritis via Nrf2 signaling and Pten/AKT/Nfatc1 axis","authors":"Haojue Wang, Tao Yuan, Jingpeng Wang, Dengju Li, Wayne Yuk-wai Lee, Ziqing Li, Shui Sun","doi":"10.1186/s13075-025-03522-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03522-x","url":null,"abstract":"Quercetagetin, a flavonoid derived from the natural herb Flos eriocauli, is used in traditional Chinese medicine for its fire-purging (anti-inflammation) and wind-expelling (pain-alleviating) properties. However, its potential effects concerning rheumatoid arthritis (RA) remain underexplored. This study was designed to elucidate the potential associations between Quercetagetin and RA, establishing the therapeutic potential of Quercetagetin and related mechanisms in RA treatment. Network pharmacology was conducted to decipher related targets and signaling pathways between Quercetagetin and RA. In vitro assays were then conducted to explore the effects of Quercetagetin on osteoclast cell behaviors and corresponding signaling pathways. In vivo study further validated the therapeutic effect of Quercetagetin in collagen antibody-induced arthritis (CAIA) mice. The network pharmacological analysis indicated an intimate correlation of Quercetagetin with RA-related inflammatory osteolysis treatment. Pertaining to biological validations, 2 µM of Quercetagetin successfully inhibited LPS-driven osteoclast differentiation and function. qPCR assay and Western blot analyses denoted parallel changes in osteoclastic marker genes and proteins. Further mechanism study uncovered the effect of Quercetagetin in stimulating the Nrf2/Keap1 signaling pathway and moderating the Pten/AKT/Nfatc1 axis in osteoclasts. In vivo study revealed 40 mg/kg Quercetagetin every day could significantly relief joint destruction in CAIA mice. Our study presents Quercetagetin ‘s therapeutic potential in treating RA, outlining its effects and potential mechanisms in suppressing LPS-induced osteoclast activity, and alleviating inflammatory bone destruction in CAIA model, thereby laying the groundwork for further translational research on Quercetagetin and Flos eriocauli in RA treatment. Quercetagetin extracted from Flos eriocauli displayed brilliant anti-osteoclast and anti-inflammation potential during rheumatoid arthritis. Quercetagetin significantly repressed lipopolysaccharide-stimulated osteoclast behavior from phenotypical and molecular level. Quercetagetin mitigated inflammatory bone destruction in collagen antibody-induced arthritis.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"20 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575093","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}

{"title":"Comparative effectiveness of subcutaneous sarilumab 200 mg biweekly, subcutaneous Tocilizumab 162 mg biweekly, and intravenous Tocilizumab 8 mg/kg every 4 weeks in patients with rheumatoid arthritis: a prospective cohort study","authors":"Akira Onishi, Masao Tanaka, Takayuki Fujii, Koichi Murata, Kosaku Murakami, Motomu Hashimoto, Ryu Watanabe, Yuji Nozaki, Chisato Ashida, Wataru Yamamoto, Hirotaka Yamada, Sho Sendo, Kosuke Ebina, Hidehiko Makino, Yonsu Son, Yumiko Wada, Kenichiro Hata, Shuichi Matsuda, Akio Morinobu","doi":"10.1186/s13075-025-03514-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03514-x","url":null,"abstract":"While targeting the interleukin-6 receptor (IL-6R) through the use of sarilumab (SAR) or tocilizumab (TCZ) has become a major therapeutic approach for rheumatoid arthritis (RA), direct comparisons between IL-6R inhibitors (IL-6Ris) for treating RA have not been conducted. We aimed to compare the effectiveness of subcutaneous sarilumab (SAR-SC), subcutaneous tocilizumab (TCZ-SC), and intravenous TCZ (TCZ-IV) against RA in a multicenter cohort study. Within the target trial emulation framework, an incident new-user and active-comparator cohort design was used. The source population was the entire cohort of a multicenter prospective study (the ANSWER cohort study) in Japan from 2009 to 2023. We consecutively included patients with IL-6Ri-naïve RA who initiated treatment with SAR-SC 200 mg biweekly, TCZ-SC 162 mg biweekly, or TCZ-IV 8 mg/kg every 4 weeks as the approved starting dose and dosing interval at baseline. The primary outcome of interest was the change in the clinical disease activity index (CDAI) at 24 weeks. In total, 1001 IL-6Ri-naïve patients were included (SAR-SC 200 mg biweekly, 201 patients; TCZ-SC 162 mg biweekly, 546; TCZ-IV 8 mg/kg every 4 week, 254). The improvement in CDAI at 24 weeks (primary outcome) was statistically significantly greater in the SAR-SC group than in the TCZ-SC group (-2.53, 95% confidence interval (CI): -4.38 to -0.69, p = 0.007), but that in TCZ-IV was not significantly different from that in TCZ-SC (1.00, 95% CI: -0.68 to 2.69, p = 0.243). Similar results were noted regarding the changes in CDAI at weeks 4, 12, and 48. The retention rates at 48 weeks in SAR-SC and TCZ-IV did not significantly differ from that in TCZ-SC. SAR-SC 200 mg biweekly initiation was associated with a statistically significantly greater decrease in disease activity than TCZ-SC 162 mg biweekly in IL-6Ri-naïve patients with RA. In contrast, no statistically significant differences were identified between TCZ-IV 8 mg/kg every 4 week and TCZ-SC 162 mg biweekly. However, the effect size of our findings should necessitate careful consideration of the cost difference between TCZ-SC 162 mg biweekly including its biosimilars and SAR-SC 200 mg biweekly.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569535","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}

{"title":"SDF-1 alleviates osteoarthritis by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathway","authors":"Yanping Zhao, Dan Lin, Xiaoying Zhu, Jingyao Yan, Yan Liang, Yanli Wang, Tianqi Dai, Zhiyi Zhang, Shuya Wang","doi":"10.1186/s13075-025-03509-8","DOIUrl":"https://doi.org/10.1186/s13075-025-03509-8","url":null,"abstract":"Osteoarthritis (OA) is the most common form of joint disease. Currently, OA treatment is limited to controlling symptoms. Our previous study showed that stromal cell-derived factor 1 (SDF-1) delayed the progression of OA to a certain extent. The aim of this study was to explore the specific mechanism of SDF-1 in OA. OA chondrocytes and a collagen-induced osteoarthritis (CIOA) mouse model were used as in vitro and in vivo models, respectively. SDF-1 was used to treat OA in vitro and in vivo. To explore the mechanism of SDF-1 in OA treatment, we pretreated chondrocytes with a Sirt 3 inhibitor and assessed mitochondrial function and then analysed related indicators of cartilage anabolic and cartilage metabolism. SOD2 and PGC-1α levels were significantly lower in OA chondrocytes and the cartilage of CIOA model mice than in normal chondrocytes, and mitochondrial dysfunction occurred in OA. After treating OA chondrocytes and CIOA model mice with exogenous SDF-1, mitochondrial dysfunction and abnormal biomarkers of OA normalized. The pretreatment of OA chondrocytes with a Sirt 3 inhibitor or mitochondrial function inhibitor before SDF-1 exposure reversed these changes. SDF-1 can alleviate OA by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathway, and therefore, SDF-1 may be a good candidate as a new treatment for OA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"85 4 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569532","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}