Arthritis Research & Therapy最新文献

{"title":"Identifying two pathways to poor prognosis in patients with anti-MDA5 antibodies: insights from prognostic factor and cytokines analysis","authors":"Aya Shimizu, Kazuhiro Kurasawa, Tomoka Hiyama, Sara Komatsu, Azusa Kikuchi, Yuhi Yoshida, Anna Hasegawa, Tomoyuki Miyao, Ayae Tanaka, Satoko Arai, Reika Maezawa, Masafumi Arima, Kei Ikeda","doi":"10.1186/s13075-025-03558-z","DOIUrl":"https://doi.org/10.1186/s13075-025-03558-z","url":null,"abstract":"To identify pathways linking cytokine abnormalities to mortality via prognostic factors in patients with anti-melanoma differentiation-associated protein 5 antibodies (anti-MDA5 Ab). This study included patients with anti-MDA5 Ab whose serum was available. Serum cytokine levels were measured using a multiplex bead assay. Prognostic factors were identified using Cox regression and log-rank test. Prognostic factor groups were identified using principal component analysis (PCA) and factor and cluster analyses. The association between cytokine levels and prognostic factors (groups) was examined using PCA and correlation and path analyses. A prognosis-prediction model was developed using prognostic factors from the different groups. Thirty-five patients were included in this study, of whom 31 had rapidly progressive interstitial lung disease (RP-ILD), and 14 died. We identified white blood cell (WBC), gamma-glutamyl transpeptidase (γ-GTP), lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, and ILD-related factors (Krebs von den Lungen-6 [KL-6], surfactant protein D [SP-D], and CT score) as prognostic factors, in addition to von Willebrand factor and thrombomodulin. Two prognostic factor groups were found: Group 1 included WBC, CRP, and ILD-related factors, and Group 2 included ferritin, LDH, and γ-GTP. Both groups contributed to mortality. Group 1 was associated with IL-6, and Group 2 was related to IL-6, IL-10, and IP-10, and indirectly with TNF-α. A model using CRP (Group1) and γ-GTP (Group2) achieved an area under the curve of 0.84, which was not inferior to previously reported models. Two pathways leading to poor prognosis were identified in anti-MDA5-Ab-positive patients, each marked by specific cytokine abnormalities.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"114 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837077","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":"Impact of Mediterranean diet on mortality in vertebral compression fracture patients","authors":"Longyu Zhang, Yi Zhao, Jiao Xu, Shi Yin, Qiang Wang, Zhiwei Jia, Jingpei Ren, Cong Zhao, Xiaohong Mu","doi":"10.1186/s13075-025-03529-4","DOIUrl":"https://doi.org/10.1186/s13075-025-03529-4","url":null,"abstract":"Vertebral compression fractures (VCF) is a common fragility fracture with high mortality worldwide. The management and prevention of VCF start with a proper nutrition. The Mediterranean diet (MD) is rich in balanced nutrients and has been shown to be beneficial for several chronic diseases. However, the association of adherence to Mediterranean diet (aMED) and prognosis of VCF patients remains unclear. To explore the association between aMED and all-cause and cardiovascular disease (CVD)-cause morality in VCF patients. In present study, patients aged ≥ 40 years old and with the VCF patients measurement were extracted from the National Health and Nutrition Examination Survey (NHANES) 2013–2014. The bone mineral density (BMD) dual-energy X-ray absorptiometry (DXA) was used to diagnose VCF. We used the weighted univariable Cox proportional hazards model to screen the covariates related to the prognosis of VCF patients. We utilized the weighted multivariable Cox proportional hazards models to explore the association between aMED and the risk of mortality in VCF patients, and were described as hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses based on different complications were further assessed the association. A total of 2,730 eligible VCF patients were included. Until 12 December 2019, 218 (7.99%) deaths were documented. After adjusting for all VCFs, we found a high risk of all-cause mortality (HR = 1.75, 95%CI: 1.13–2.73, P = 0.041) and CVD-cause mortality (HR = 2.35, 95%CI: 1.12–4.91, P = 0.038); however, we found no significant association between aMED and all-cause mortality or CVD-cause mortality (all P > 0.05). Compared to patients without VCF and with aMED score ≥ 6, patients with VCF and aMED score < 6 has a higher risk of all-cause (HR = 2.27, 95%CI: 1.25–4.13, P = 0.025) and CVD-cause mortality (HR = 4.25, 95%CI: 1.64–11.06, P = 0.013). Our study also suggested that compared to patients with aMED ≥ 6, those patients with aMED < 6 has high all-cause (HR = 2.26, 95%CI: 1.22–4.17, P = 0.002) and CVD-cause mortality (HR = 3.31, 95%CI: 1.28–8.57, P = 0.018), this results suggested that aMED may have a moderating effect on the association of VCF and mortality. Subgroups analysis shown this moderating effect remain robust, especially in patients with dyslipidemia (HR: 2.49, 95%CI: 1.29–4.80, P = 0.009), CVD (HR: 3.48, 95%CI: 1.56–7.74, P < 0.001) and CKD (HR: 3.64, 95%CI: 1.50–8.78, P < 0.001). We found aMED have a moderating effect on the association between VCF patients and mortality. Our research further supports the importance of the MD as a potentially healthy eating pattern.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"2 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837108","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":"Hydroxychloroquine dose-dependently reduces the risk of incident diabetes in primary Sjögren syndrome patients on glucocorticoids: a nationwide population-based cohort study","authors":"Wei-Sheng Chen, Hui-Ching Hsu, Tzu-Min Lin, Yu-Sheng Chang, Yi-Chun Lin, Tzu-Tung Kuo, Yu-Chuan Shen, Shu-Chuan Chen, Jin-Hua Chen, Hsiang-Yen Lee, Chi-Ching Chang","doi":"10.1186/s13075-025-03542-7","DOIUrl":"https://doi.org/10.1186/s13075-025-03542-7","url":null,"abstract":"Hydroxychloroquine (HCQ) is commonly used to treat Sjögren syndrome (SS). Glucocorticoids, which are commonly applied for managing primary SS (pSS), can disrupt glucose metabolism and increase diabetes mellitus (DM) risk. HCQ reduces DM risk in systemic lupus erythematosus and rheumatoid arthritis. This study aimed to investigate the relationship between HCQ and glucocorticoids in the incidence of new-onset diabetes in pSS. This nationwide population-based cohort study identified patients diagnosed with pSS from the Taiwan’s National Health Insurance Research Database from 2006 to 2015. Multivariate and stratified analyses, Kaplan–Meier method, and Cox proportional hazard regression were used to evaluate DM risk associated with the use of HCQ and glucocorticoid, both individually and in combination. Among pSS patients (4,874 HCQ users and 2,437 HCQ nonusers), 497 patients developed DM over an average follow-up of 4.89 years. Multivariate analysis revealed significantly lower adjusted hazard ratios (aHRs) for DM in HCQ users in the 151–350 cumulative defined daily dose (cDDD) and ≥ 351 cDDD subgroups (0.600, 95% CI: 0.454–0.794 and 0.326, 95% CI: 0.246–0.433, respectively) compared with HCQ nonusers. High-dose glucocorticoids (≥ 151 cDDD) were linked to increased DM risk (aHR: 1.833, 95% CI: 1.410–2.383). However, high-dose HCQ (> 350 cDDD) mitigated this risk, even the risk caused by the use of high-dose glucocorticoids (≥ 151 cDDD) (aHR: 0.632, 95% CI: 0.421–0.948, P < 0.01). Our study demonstrated that HCQ exposure significantly reduces the risk of developing diabetes in patients with pSS. While higher doses of glucocorticoids are associated with an increased diabetes risk, concurrent HCQ use mitigates this risk in a dose-dependent manner.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837078","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 T-cell response to SARS-CoV- 2 vaccination persists beyond six months in rheumatoid arthritis patients treated with rituximab","authors":"Juliette Marin, Penelope Bourgoin, Noemie Saverna, Celia Cartagena, Pierre Lafforgue, Jean-Marc Busnel, Nathalie Balandraud","doi":"10.1186/s13075-025-03553-4","DOIUrl":"https://doi.org/10.1186/s13075-025-03553-4","url":null,"abstract":"The spike protein-specific humoral response observed after SARS-CoV- 2 vaccination is decreased in rheumatoid arthritis (RA) patients treated with rituximab (RTX). However, when analyzed immediately after vaccination, the spike-specific T-cell immune response appears to be preserved. The possible persistence of specific T cells over the long term is underexplored and could be a useful decision-making tool for deciding when to perform revaccination. This study aimed to assess the persistence of T-cell-mediated immunity after the last SARS-CoV- 2 vaccination or infection (named “SARS-CoV- 2 boost” in this study) in RA patients treated with RTX. Clinical and biological parameters that can influence this immune system were also explored. Our observational study cohort included 51 RA patients treated with RTX and 24 RA patients treated with other disease-modifying antirheumatic drugs (DMARDs) who had received at least one dose of the SARS-CoV- 2 mRNA vaccine. The T-cell immune response was assessed by flow cytometry, which focused on antigen-specific T-cell characterization between 3 and 18 months after the last SARS-CoV- 2 boost. T-cell activation was assessed by measuring CD69, CD154, CD137 and CD107a surface expression. As expected, even if a lower mean antibody titer was measured in RA patients receiving RTX (RA RTX) than in RA patients treated with therapies other than RTX (p = 0.034), all patients exhibited CD4 + and CD8 + T-cell spike protein-specific responses, with an even greater spike-specific CD8 + T-cell response in RA RTX patients (p < 0.001). The main finding of our study was that the T-cell response remarkably persisted up to 18 months after the last SARS-CoV- 2 boost and no difference was found in COVID- 19 severity between RTX- and non-RTX-treated patients (p = 0.770). Even if RTX treatment prevented the SARS-CoV- 2 vaccine-dependent antibody response in RA patients, a strong spike protein-specific T-cell-mediated response that persisted for up to 18 months after the last SARS-CoV- 2 boost was found in RA RTX patients. With respect to personalized medicine, analyzing the spike protein-specific T-cell response might be a valuable strategy for deciding when revaccination is necessary.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"34 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837107","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":"Neural network analysis as a novel skin outcome in a trial of belumosudil in patients with systemic sclerosis","authors":"Ilayda Gunes, Elana J. Bernstein, Shawn E. Cowper, Gauri Panse, Niki Pradhan, Lucy Duran Camacho, Nicolas Page, Elizabeth Bundschuh, Alyssa Williams, Mary Carns, Kathleen Aren, Sarah Fantus, Elizabeth R. Volkmann, Heather Bukiri, Chase Correia, Vijaya B. Kolachalama, F. Perry Wilson, Seamus Mawe, J. Matthew Mahoney, Monique Hinchcliff","doi":"10.1186/s13075-025-03508-9","DOIUrl":"https://doi.org/10.1186/s13075-025-03508-9","url":null,"abstract":"The modified Rodnan skin score (mRSS), a measure of systemic sclerosis (SSc) skin thickness, is agnostic to inflammation and vasculopathy. Previously, we demonstrated the potential of neural network-based digital pathology applied to SSc skin biopsies as a quantitative outcome. Here, we leverage deep learning and histologic analyses of clinical trial biopsies to decipher SSc skin features ‘seen’ by artificial intelligence (AI). Adults with diffuse cutaneous SSc ≤ 6 years were enrolled in an open-label trial of belumosudil [a Rho-associated coiled-coil containing protein kinase 2 (ROCK2) inhibitor]. Participants underwent serial mRSS and arm biopsies at week (W) 0, 24 and 52. Two blinded dermatopathologists scored stained sections (e.g., Masson’s trichrome, hematoxylin and eosin, CD3, α-smooth muscle actin) for 16 published SSc dermal pathological parameters. We applied our deep learning model to generate QIF signatures/biopsy and obtain ‘Fibrosis Scores’. Associations between Fibrosis Score and mRSS (Spearman correlation), and between Fibrosis Score and mRSS versus histologic parameters [odds ratios (OR)], were determined. Only ten patients were enrolled due to early study termination, and of those, five had available biopsies due to fixation issues. Median, interquartile range (IQR) for mRSS change (0–52 W) for the ten participants was -2 (-9—7.5) and for the five with biopsies was -2.5 (-11—7.5). The correlation between Fibrosis Score and mRSS was R = 0.3; p = 0.674. Per 1-unit mRSS change (0–52 W), histologic parameters with the greatest associated changes were (OR, 95% CI, p-value): telangiectasia (2.01, [(1.31—3.07], 0.001), perivascular CD3 + (0.99, [0.97—1.02], 0.015), and % of CD8 + among CD3 + (0.95, [0.89—1.01], 0.031). Likewise, per 1-unit Fibrosis Score change, parameters with greatest changes were (OR, p-value): hyalinized collagen (1.1, [1.04 – 1.16], < 0.001), subcutaneous (SC) fat loss (1.47, [1.19—1.81], < 0.001), thickened intima (1.21, [1.06—1.38], 0.005), and eccrine entrapment (1.14, [1—1.31], 0.046). Belumosudil was associated with non-clinically meaningful mRSS improvement. The histologic features that significantly correlated with Fibrosis Score changes (e.g., hyalinized collagen, SC fat loss) were distinct from those associated with mRSS changes (e.g., telangiectasia and perivascular CD3 +). These data suggest that AI applied to SSc biopsies may be useful for quantifying pathologic features of SSc beyond skin thickness.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"33 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819845","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":"CCL23 is a potential biomarker for antineutrophil cytoplasmic antibody–associated vasculitis","authors":"Weiwei Hao, Qianqian Liu, Xiaoping Li, Yiran Xu, Wenjuan Guan, Lei Zhang, Fang Dong, Wenjun Cao, Shengyun Liu, Wei Li","doi":"10.1186/s13075-025-03552-5","DOIUrl":"https://doi.org/10.1186/s13075-025-03552-5","url":null,"abstract":"The present cohort study aimed to evaluate the value of CCL23 in diagnosis, disease activity, and prognosis in patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV). CCL23 levels in serum samples from 317 patients with AAV and 83 healthy controls (HCs) were measured using a customized immune response kit. Patients with AAV had significantly elevated CL23 levels compared with HCs. CCL23 level was closely related to disease activity and was better than birmingham vasculitis activity score (BVAS) in distinguishing disease relapse from remission (area under curve: CCL23 = 0.942, BVAS = 0.84). Elevated CCL23 level was associated with poor prognosis within a 1 year follow-up period in patients with AAV (p = 0.0001). The ability of CCL23 to predict the poor prognosis of disease is better than that of five-factor score. Furthermore, elevated CCL23 levels were a risk factor for renal involvement (odds ratio = 1.722, p = 0.033), and were significantly related to serum creatinine (r = 0.381, p = 0.009) and eGFR (r = − 0.382, p = 0.01) at the time of diagnosis. High CCL23 level at diagnosis was associated with increased adverse outcomes during 1 year follow-up in patients with AAV with renal involvement (p = 0.0242). Elevated serum CCL23 level was closely related with disease activity and renal involvement in patients with AAV, can be a potential biomarker for diagnosis, and can predict prognosis in patients with AAV, especially adverse renal prognosis.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"39 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813645","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":"Achievement of treatment targets and maintenance of response with upadacitinib in patients with moderate-to-severe rheumatoid arthritis in real-world practice: 1-year outcomes from the UPHOLD observational study","authors":"Andrew Östör, Eugen Feist, Prodromos Sidiropoulos, Jérôme Avouac, Martin Rebella, Rajaie Namas, Erin McDearmon-Blondell, Tianming Gao, Ivan Lagunes-Galindo, Sander Strengholt, Devy Zisman, Suzan Attar","doi":"10.1186/s13075-025-03528-5","DOIUrl":"https://doi.org/10.1186/s13075-025-03528-5","url":null,"abstract":"Upadacitinib (UPA), an oral Janus kinase inhibitor, has shown efficacy with an acceptable safety profile in rheumatoid arthritis (RA) clinical trials. To assess the real-world effectiveness and safety of UPA in adults with moderate-to-severe RA in the UPHOLD observational study. Co-primary endpoints were: (i) proportion of patients achieving disease activity score in 28 joints using C-reactive protein (DAS28[CRP]) remission (< 2.6) at 6 months; and (ii) proportion of those patients maintaining remission at 12 months. Additional analyses included proportions of patients achieving and maintaining DAS28(CRP) low disease activity (LDA; ≤ 3.2), other composite measures of disease activity, and subgroup analyses by therapy strategy and prior treatment. Treatment-emergent adverse events (TEAEs) in the full analysis set (FAS; patients receiving ≥ 1 UPA dose) were reported through August 10, 2023. Co-primary and selected secondary endpoints were analyzed by modified non-responder imputation (mNRI) in modified (m)FAS1 (FAS patients who completed 6 months of treatment and had DAS28[CRP] data available, and those who discontinued before 6 months) and mFAS2 (mFAS1 patients who achieved remission at 6 months, completed 12 months of treatment, and had DAS28[CRP] data available, and those who discontinued between 6 and 12 months); and as observed (AO) in patients with non-missing data. Of 1719 participants, 1717 were enrolled; 1701 comprised the FAS. Overall, 400/1719 (23.3%) patients discontinued before 12 months. Of mFAS1 patients, 499 (mNRI: 499/1074 [46.5%]; AO: 499/902 [55.3%]) achieved DAS28(CRP) remission at 6 months; of mFAS2 patients, 269 (mNRI: 269/340 [79.1%]; AO: 269/317 [84.9%]) maintained remission at 12 months. DAS28(CRP) remission or LDA rates were consistent regardless of whether UPA was initiated and maintained as monotherapy or combination therapy. Similar responses were observed across prior treatment subgroups. Among selected TEAEs of special interest, herpes zoster and serious infection occurred at 3.12 and 2.62 events/100 patient-years, respectively. No new safety signals were identified. UPA demonstrated real-world effectiveness in moderate-to-severe RA, with approximately half of patients achieving DAS28(CRP) remission at 6 months and most maintaining remission through 12 months. The real-world benefit–risk profile of UPA remains favorable and is consistent with phase 3 clinical trial data. NCT04497597","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"3 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813598","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":"Methotrexate-related drug reactions on kidneys and liver in rheumatoid arthritis: an analysis of spontaneous reports in EudraVigilance","authors":"Kai Khoroshun, Carsten Bantel, Falk Hoffmann, Kathrin Jobski","doi":"10.1186/s13075-025-03551-6","DOIUrl":"https://doi.org/10.1186/s13075-025-03551-6","url":null,"abstract":"Methotrexate (MTX), a standard treatment for rheumatoid arthritis (RA), is known for its potential kidney and liver toxicity. Whether concomitant use of analgesics, possibly affecting the same organs, has an impact on the occurrence or course of adverse drug reactions (ADRs) remains unclear. We used all spontaneous reports (until 2022) of suspected ADRs associated with MTX in RA patients, from the EudraVigilance database, a spontaneous report system operated by the European Medicines Agency (EMA). We displayed case and treatment characteristics, stratified by the organ affected (kidneys, liver) and the outcome (fatal, non-fatal). We included a total of 10,319 reports (mean age: 62.3 years, 72.6% female). 365 and 1,082 were related to ADRs involving the kidneys and liver, respectively. Patients with ADRs on the kidneys were older and comedication (e.g. non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, metamizole and corticosteroids) was more common than in cases with ADRs on the liver. More patients with kidney- than liver-related ADRs had a fatal outcome (21.1% vs. 5.8%). In fatal cases with ADRs on the kidneys and with ADRs on the liver comedication was more common compared to non-fatal cases. Liver dysfunction was reported nearly three times more often than renal impairment. However, the kidneys need to be especially watched for, since a fatal outcome was considerably more common in renal failure. More precise and standardized recommendations on renal function tests might be necessary to support physicians in the complex treatment of RA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"37 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782585","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":"Discontinuation vs. continuation of concomitant methotrexate in patients with rheumatoid arthritis on certolizumab pegol: results from a randomised, controlled trial","authors":"Shuji Asai, Toshihisa Kojima, Hajime Ishikawa, Nobumasa Miyake, Masanari Kodera, Hisanori Hasegawa, Yasumori Sobue, Yasuhide Kanayama, Hiromi Shimada, Yuji Hirano, Toshihiko Hidaka, Takayoshi Fujibayashi, Takuya Matsumoto, Tomonori Kobayakawa, Hidekata Yasuoka, Takefumi Kato, Masahiro Hanabayashi, Yuko Kaneko, Masahiro Tada, Koichi Murata, Kenta Misaki, Masahiko Ando, Yachiyo Kuwatsuka, Mochihito Suzuki, Kenya Terabe, Shiro Imagama","doi":"10.1186/s13075-025-03548-1","DOIUrl":"https://doi.org/10.1186/s13075-025-03548-1","url":null,"abstract":"The present non-inferiority study was designed to compare the effect of discontinuing versus continuing methotrexate (MTX) alongside certolizumab pegol (CZP) on maintaining low disease activity (LDA) in rheumatoid arthritis (RA) patients already stable on combination therapy. This multicentre, open-label, randomised, controlled trial included RA patients with sustained LDA (Clinical Disease Activity Index [CDAI] ≤ 10) for ≥ 12 weeks with CZP + MTX. Patients were randomised 1:1 by computer to either continue MTX (CZP + MTX group) or discontinue MTX after a 12-week reduction period (CZP group) using a dynamic allocation strategy with the minimisation method. The primary endpoint was the proportion of patients maintaining LDA without a flare (i.e., a CDAI score > 10 or intervention with rescue treatments for any reason) at week 36 (24 weeks after MTX discontinuation). Non-inferiority is verified if the lower limit of the 90% confidence interval (CI) using normal approximation for the difference in the proportion of cases that maintained LDA at week 36 between the intervention group and control group exceeds the non-inferiority margin. All 84 screened patients were randomised to the CZP + MTX group (n = 41) and CZP group (n = 43), and were included in the efficacy analysis. Proportions (90% CI) of patients who maintained LDA at week 36 were 85.4% (76.3 to 94.4%) in the CZP + MTX group and 83.7% (74.5 to 93.0%) in the CZP group. The difference (90% CI) between the two groups was − 1.6% (-14.6 to 11.3%), with the lower limit of the 90% CI exceeding the non-inferiority margin of -18%. Reported adverse events were broadly similar between the two groups. The proportion of patients with gastrointestinal symptoms, as assessed by a self-administered questionnaire, was significantly lower in the CZP group than in the CZP + MTX group at week 36 (2.4% vs. 15.8%, P = 0.034). Discontinuing concomitant MTX in RA patients on CZP is clinically feasible for maintaining LDA. Japan Registry of Clinical Trials (jRCTs041200048).","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"8 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782572","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":"Cluster analysis reveals three clinical phenotypes of pulmonary artery hypertension associated with connective tissue diseases: insights into inflammation and immunity","authors":"Qianwen Wu, Dongyu Li, Huangshu Ye, Zhangdi Zhou, Yixin Zhang, Miaojia Zhang, Xiaoxuan Sun, Qiang Wang","doi":"10.1186/s13075-025-03545-4","DOIUrl":"https://doi.org/10.1186/s13075-025-03545-4","url":null,"abstract":"Inflammation and immune mechanisms play a crucial role in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), though they remain inadequately understood. This study aimed to identify specific clinical phenotypes in CTD-PAH using inflammatory and immune markers through hierarchical cluster analysis. We conducted a single-center, retrospective cohort study of CTD-PAH patients from 2009 to 2024. Clinical variables, including neutrophil lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complement C3 and C4, were analyzed to form clusters based on baseline characteristics, clinical outcomes, and treatment goals. Among 184 patients (95.1% female; median age 40.42 years), three distinct clusters were identified: Cluster 1 (vasculopathic phenotype) exhibited lower inflammatory activity but worse hemodynamic outcomes; Cluster 2 (vasculitic phenotype) had higher inflammatory activity with favorable hemodynamics; Cluster 3 (mixed phenotype) showed active inflammation and poor hemodynamic status. Most vasculitic patients were classified as systemic lupus erythematosus-associated PAH (SLE-PAH), which had a shorter course and higher prevalence of autoantibodies. The vasculopathic and mixed phenotypes were common in scleroderma-related PAH (SSc-PAH), undifferentiated CTD- related PAH (UCTD-PAH), and mixed CTD- related PAH (MCTD-PAH), associated with poorer treatment outcomes and survival rate. Distinct clinical phenotypes in CTD-PAH correlate with inflammatory activity and hemodynamic status, influencing treatment responses and prognosis. Inflammation and immune mechanisms are essential for the development of CTD-PAH. Three distinct phenotypes in CTD-PAH were identified through cluster analysis. Distinct phenotypes correlate with inflammatory and hemodynamic status, influencing treatment responses and prognosis. Identifying disease phenotypes might improve the management algorithm for CTD-PAH.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"108 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782587","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}