Arthritis Research & Therapy最新文献

{"title":"Serum GM-CSF level is a predictor of treatment response to tocilizumab in rheumatoid arthritis patients: a prospective observational cohort study","authors":"Jingbo Su, Wenlu Hu, Yanxia Ding, Panpan Zhang, Tianfang Li, Shengyun Liu, Lihua Xing","doi":"10.1186/s13075-024-03373-y","DOIUrl":"https://doi.org/10.1186/s13075-024-03373-y","url":null,"abstract":"The aim of this prospective observational cohort study was to unveil the predictors of treatment response to tocilizumab (TCZ) therapy in rheumatoid arthritis (RA) patients, in terms of clinical characteristics and serum proinflammatory cytokines, especially to explore the predictive value of granulocyte macrophage-colony stimulating factor (GM-CSF). Active adult RA patients with inadequate response to MTX intending to receive TCZ therapy were recruited prospectively in the study. A total of 174 severe RA patients were included for the identification of the associations between treatment response and the following characteristic features: demographics, medications, disease activity, serum proinflammatory cytokines and so on. Disease duration (OR = 0.996), tender joint count (TJC)/68 (OR = 0.943), neutrophil ratio (W4/baseline) (OR = 0.224), the high level of GM-CSF > 5 ng/ml (OR = 0.414) at baseline were the independent adverse predictors of good response assessed by clinical disease activity index (CDAI) at week 24 (W24) for TCZ therapy in RA patients. Moreover, DAS28-ESR (OR = 2.951, P = 0.002) and the high level of GM-CSF > 10 ng/ml at baseline (OR = 5.419, P = 0.002) were independent predictors of poor response, but not the high level of GM-CSF > 5 ng/ml (OR = 2.713, P = 0.054). The patients in the high GM-CSF group had significantly higher DAS28-ESR and serum levels of cytokines (IL-17A, IL-1β, IL-6, TNF-α) at baseline, as well as significantly higher rate of non-good response (62.8% vs. 39.4%, P = 0.010) and poor response (27.9% vs. 9.1%, P = 0.004) than the low GM-CSF group at W24. In addition, poor responders had significantly higher levels of GM-CSF with concomitant increase in the serum levels of IL-17A and IL-1β at baseline than those in moderate and good response groups, while serum levels of IL-6 and TNF-α at baseline were not significantly different in three response groups. The high levels of GM-CSF (> 5 ng/ml and > 10 ng/ml) at baseline were the independent predictors of non-good response and poor response to TCZ at W24 respectively. The high level of GM-CSF at baseline is a marker of high disease activity and a predictor of poor response to TCZ in severe RA patients, which may facilitate the development of individualized treatment strategies for refractory RA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597271","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 dual amylin and calcitonin receptor agonist KBP-336 elicits a unique combination of weight loss, antinociception and bone protection – a novel disease-modifying osteoarthritis drug","authors":"Khaled Elhady Mohamed, Anna Thorsø Larsen, Simone Melander, Frederik Andersen, Ellen Barendorff Kerrn, Morten Asser Karsdal, Kim Henriksen","doi":"10.1186/s13075-024-03361-2","DOIUrl":"https://doi.org/10.1186/s13075-024-03361-2","url":null,"abstract":"Despite the extensive research to provide a disease-modifying osteoarthritis drug (DMOAD), there is still no approved DMOAD. Dual amylin and calcitonin receptor agonists (DACRA) can provide metabolic benefits along with antinociceptive and potential structural preserving effects. In these studies, we tested a DACRA named KBP-336 on a metabolic model of OA in meniscectomised (MNX) rats. We evaluated KBP-336’s effect on pain-like symptoms in Sprague Dawley (SD) rats on high-fat diet (HFD) that underwent meniscectomy using the von Frey test to measure the 50% paw withdrawal threshold (PWT) and analyzed using one-way ANOVA. Short in vivo studies and in vitro cell receptor expression systems were used to illustrate receptor pharmacology. After 30 weeks on HFD, including an 8-week treatment, female MNX animals receiving KBP-336 4.5 nmol/Kg/72 h had lower body weight and smaller adipose tissues than their vehicle-treated counterparts. After 20 weeks on HFD, including an 8-week treatment, male rats receiving KBP-336 had lower body weight than the vehicle group. In both the female and male rats, the MNX groups on KBP-336 treatment had a higher PWT than the vehicle-treated MNX group. Aiming to identify the receptor influencing pain alleviation, KBP-336 was compared to the long-acting human calcitonin (hCTA). Single-dose studies on 12-week-old male rats showed that hCTA lowers CTX-I without affecting food intake, confirming its calcitonin receptor selectivity. On the metabolic OA model with 18 weeks of HFD, including 6-week treatment, hCTA at 100 nmol/Kg/24 h and KBP-336 at 0.5, 1.5, and 4.5 nmol/Kg/72 h produced significantly higher PWT in MNX animals compared to MNX animals on vehicle treatment. hCTA and KBP-336 at 0.5 nmol/Kg did not affect body weight and fat tissues. Overall, KBP-336 improved the pain observed in the metabolic OA model. Calcitonin receptor activation proved to be essential in this antinociceptive effect.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597272","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":"Correction: Rituximab in the treatment of progressive interstitial lung disease associated with the antisynthetase syndrome","authors":"Javier Narvaez, Elena Canadillas, Ivan Castellvi, Juan Jose Alegre, Vanesa Vicens‑Zygmunt, Guadalupe Bermudo, Paola Vidal-Montal, Maria Molina Molina, Joan Miquel Nolla","doi":"10.1186/s13075-024-03357-y","DOIUrl":"https://doi.org/10.1186/s13075-024-03357-y","url":null,"abstract":"<p><b>Correction: Arthritis Res Ther 26, 122 (2024)</b></p><p><b>https://doi.org/10.1186/s13075-024-03353-2</b></p><p>Following publication of the original article [1], the authors identified an error in the author name of Vanesa Vicens‑Zygmunt.</p><p> The incorrect author name is: Vanesa Vincens‑Zygmunt.</p><p> The correct author name is: Vanesa Vicens‑Zygmunt.</p><p> The author group has been updated above and the original article [1] has been corrected.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Narváez J, Cañadillas E, Castellví I, et al. Rituximab in the treatment of progressive interstitial lung disease associated with the antisynthetase syndrome. Arthritis Res Ther. 2024;26:122. https://doi.org/10.1186/s13075-024-03353-2.</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Department of Rheumatology, Hospital Universitario de Bellvitge. Bellvitge Biomedical Research Institute (IDIBELL), Feixa Llarga, s/n, Hospitalet de Llobregat, Barcelona, 08907, Spain</p><p>Javier Narvaez, Paola Vidal-Montal &amp; Joan Miquel Nolla</p></li><li><p>Department of Rheumatology, Hospital Cl?nico, Universitario Lozano Blesa, Zaragoza, Spain</p><p>Elena Canadillas</p></li><li><p>Department of Rheumatology. Hospital, Universitario de la Santa Creu i Sant Pau, Barcelona, Spain</p><p>Ivan Castellvi</p></li><li><p>Department of Rheumatology. Hospital, Universitario Dr Peset, Valencia, Spain</p><p>Juan Jose Alegre</p></li><li><p>Interstitial Lung Disease Unit, Department of Pneumology. Hospital, Universitario de Bellvitge. Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain</p><p>Vanesa Vicens‑Zygmunt, Guadalupe Bermudo &amp; Maria Molina Molina</p></li></ol><span>Authors</span><ol><li><span>Javier Narvaez</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Elena Canadillas</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Ivan Castellvi</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Juan Jose Alegre</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Vanesa Vicens‑Zygmunt</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Guadalupe Bermudo</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Paola Vidal-Mont","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561197","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 Relationship between the complement system and subclinical carotid atherosclerosis in patients with rheumatoid arthritis","authors":"Marta Hernández-Díaz, Dara Rodríguez-González, Elena Heras-Recuero, Fuensanta Gómez-Bernal, Juan Carlos Quevedo-Abeledo, Agustín F. González-Rivero, Elena González-López, J. Gonzalo Ocejo-Vinyals, Alejandro Jimenez-Sosa, Miguel Ángel González-Gay, Iván Ferraz-Amaro","doi":"10.1186/s13075-024-03360-3","DOIUrl":"https://doi.org/10.1186/s13075-024-03360-3","url":null,"abstract":"Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) events and CV mortality. Subclinical carotid atherosclerosis is independently associated with rates of incident CV events among patients with RA. The complement system has been related to both the etiopathogenesis of RA and CV disease. In this study, we aimed to evaluate the association between a comprehensive assessment of the complement system and carotid intima media thickness and carotid plaque in patients with RA. 430 patients with RA were recruited. Functional assays of the three pathways of the complement system, utilizing new-generation techniques, were assessed. Additionally, serum levels of individual components of the complement system belonging to the three pathways were measured: C1q (classical), lectin (lectin), C2, C4, and C4b (classical and lectin), factor D and properdin (alternative), C3 and C3a (common), C5, C5a, and C9 (terminal), as well as regulators factor I and C1-inhibitor. Subclinical carotid atherosclerosis was evaluated by ultrasonography. Multivariable linear regression analysis was conducted to investigate the association between the complement system and carotid intima media thickness and carotid plaque. After multivariable adjustment, which included traditional CV risk factors and disease-related data, C3a and C5a exhibited significant positive correlations with carotid intima media thickness. Additionally, higher values of C1-inhibitor, properdin, C3, C5, and C5a were independently associated with the presence of carotid plaque. The complement system and subclinical carotid atherosclerosis are linked in patients with RA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557184","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":"Investigation of ferroptosis-associated molecular subtypes and immunological characteristics in lupus nephritis based on artificial neural network learning","authors":"Li Zhang, Qing Yan, Miao Lin, Juanjuan He, Jie Tian, Zhihan Chen, Fuyuan Hong","doi":"10.1186/s13075-024-03356-z","DOIUrl":"https://doi.org/10.1186/s13075-024-03356-z","url":null,"abstract":"Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) with poor treatment outcomes. The role and underlying mechanisms of ferroptosis in LN remain largely unknown. We aimed to explore ferroptosis-related molecular subtypes and assess their prognostic value in LN patients. Molecular subtypes were classified on the basis of differentially expressed ferroptosis-related genes (FRGs) via the Consensus ClusterPlus package. The enriched functions and pathways, immune infiltrating levels, immune scores, and immune checkpoints were compared between the subgroups. A scoring algorithm based on the subtype-specific feature genes identified by artificial neural network machine learning, referred to as the NeuraLN, was established, and its immunological features, clinical value, and predictive value were evaluated in patients with LN. Finally, immunohistochemical analysis was performed to validate the expression and role of feature genes in glomerular tissues from LN patients and controls. A total of 10 differentially expressed FRGs were identified, most of which showed significant correlation. Based on the 10 FRGs, LN patients were classified into two ferroptosis subtypes, which exhibited significant differences in immune cell abundances, immune scores, and immune checkpoint expression. A NeuraLN-related protective model was established based on nine subtype-specific genes, and it exhibited a robustly predictive value in LN. The nomogram and calibration curves demonstrated the clinical benefits of the protective model. The high-NeuraLN group was closely associated with immune activation. Clinical specimens demonstrated the alterations of ALB, BHMT, GAMT, GSTA1, and HAO2 were in accordance with bioinformatics analysis results, GSTA1 and BHMT were negatively correlated with the severity of LN. The classification of ferroptosis subtypes and the establishment of a protective model may form a foundation for the personalized treatment of LN patients.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141495887","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":"S100 proteins as potential predictive biomarkers of abatacept response in polyarticular juvenile idiopathic arthritis","authors":"Hermine I Brunner, Grant S Schulert, Alyssa Sproles, Sherry Thornton, Gabriel Vega Cornejo, Jordi Antón, Ruben Cuttica, Michael Henrickson, Ivan Foeldvari, Daniel J Kingsbury, Margarita Askelson, Jinqi Liu, Sumanta Mukherjee, Robert L Wong, Daniel J Lovell, Alberto Martini, Nicolino Ruperto, Alexei A Grom","doi":"10.1186/s13075-024-03347-0","DOIUrl":"https://doi.org/10.1186/s13075-024-03347-0","url":null,"abstract":"Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of conditions that can cause marked disability and diminished quality of life. Data on predictors of clinical response are insufficient to guide selection of the appropriate biologic agent for individual patients. This study aimed to investigate the propensity of S100A8/9 and S100A12 as predictive biomarkers of abatacept response in polyarticular-course juvenile idiopathic arthritis (pJIA). Data from a phase 3 trial (NCT01844518) of subcutaneous abatacept in patients with active pJIA (n = 219) were used in this exploratory analysis. Association between biomarker levels at baseline and improvements in JIA-American College of Rheumatology (ACR) criteria responses or baseline disease activity (measured by Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein [JADAS27-CRP]) were assessed. Biomarker level changes from baseline to month 4 were assessed for disease outcome prediction up to 21 months. At baseline, 158 patients had available biomarker samples. Lower baseline S100A8/9 levels (≤ 3295 ng/mL) were associated with greater odds of achieving JIA-ACR90 (odds ratio [OR]: 2.54 [95% confidence interval (CI): 1.25–5.18]), JIA-ACR100 (OR: 3.72 [95% CI: 1.48–9.37]), JIA-ACR inactive disease (ID; OR: 4.25 [95% CI: 2.03–8.92]), JADAS27-CRP ID (OR: 2.34 [95% CI: 1.02–5.39]) at month 4, and JIA-ACR ID (OR: 3.01 [95% CI: 1.57–5.78]) at month 16. Lower baseline S100A12 levels (≤ 176 ng/mL) were associated with greater odds of achieving JIA-ACR90 (OR: 2.52 [95% CI: 1.23–5.13]), JIA-ACR100 (OR: 3.68 [95% CI: 1.46–9.28]), JIA-ACR ID (OR: 3.66 [95% CI: 1.76–7.61]), JIA-ACR90 (OR: 2.03 [95% CI: 1.07–3.87]), JIA-ACR100 (OR: 2.14 [95% CI: 1.10–4.17]), and JIA-ACR ID (OR: 4.22 [95% CI: 2.15–8.29]) at month 16. From baseline to month 4, decreases in S100A8/9 and S100A12 generally exceeded 50% among JIA-ACR90/100/ID responders. Lower baseline levels of S100A8/9 and S100A12 proteins predicted better response to abatacept treatment than higher levels and may serve as early predictive biomarkers in pJIA. Decreases in these biomarker levels may also predict longer-term response to abatacept in pJIA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141448148","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 impact of gastroesophageal reflux disease and its treatment on interstitial lung disease outcomes","authors":"A. Quinlivan, D. Neuen, D. Hansen, W. Stevens, L. Ross, N. Ferdowsi, S. M. Proudman, J. G. Walker, J. Sahhar, G-S. Ngian, D. Apostolopoulos, L. V. Host, G. Major, C. Basnayake, K. Morrisroe, M. Nikpour","doi":"10.1186/s13075-024-03355-0","DOIUrl":"https://doi.org/10.1186/s13075-024-03355-0","url":null,"abstract":"To determine the relationship between gastroesophageal reflux disease (GORD) and its treatment and interstitial lung disease in patients with systemic sclerosis (SSc). SSc patients from the Australian Scleroderma Cohort Study (ASCS) were included. GORD was defined as self-reported GORD symptoms, therapy with a proton pump inhibitor (PPI) or histamine 2 receptor antagonist (H2RA) and/or the presence of reflux oesophagitis diagnosed endoscopically. The impact of GORD and its treatment on ILD features (including severity and time to ILD development) and survival was evaluated. GORD was a common manifestation affecting 1539/1632 (94%) of SSc patients. GORD affected 450/469 (96%) of those with SSc-ILD cohort. In SSc-ILD, there was no relationship between the presence of GORD or its treatment and time to ILD development or ILD severity. However, GORD treatment was associated with improved survival in those with ILD (p = 0.002). Combination therapy with both a PPI and a H2RA was associated with a greater survival benefit than single agent therapy with PPI alone (HR 0.3 vs 0.5 p < 0.050 respectively). GORD is a common SSc disease manifestation. While the presence or treatment of GORD does not influence the development or severity of ILD, aggressive GORD treatment, in particular with a combination of PPI and H2RA, is associated with improved survival in those with SSc-ILD.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141448262","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 RA treatment strategies on lipids and vascular inflammation in rheumatoid arthritis: a secondary analysis of the TARGET randomized active comparator trial","authors":"Katherine P. Liao, Pamela Rist, Jon Giles, Leah Santacroce, Margery A. Connelly, Robert J. Glynn, Paul Ridker, Ahmed Tawakol, Joan Bathon, Daniel H. Solomon","doi":"10.1186/s13075-024-03352-3","DOIUrl":"https://doi.org/10.1186/s13075-024-03352-3","url":null,"abstract":"Treatments for rheumatoid arthritis (RA) are associated with complex changes in lipids and lipoproteins that may impact cardiovascular (CV) risk. The objective of this study was to examine lipid and lipoprotein changes associated with two common RA treatment strategies, triple therapy or tumor necrosis factor inhibitor (TNFi), and association with CV risk. In this secondary data analysis of the TARGET trial, methotrexate (MTX) inadequate responders with RA were randomized to either add sulfasalazine and hydroxychloroquine (triple therapy), or TNFi for 24-weeks. The primary trial outcome was the change in arterial inflammation measured in the carotid arteries or aorta by FDG-PET/CT at baseline and 24-weeks; this change was described as the target-to-background ratio (TBR) in the most diseased segment (MDS). Routine lipids and advanced lipoproteins were measured at baseline and 24-weeks; subjects on statin therapy at baseline were excluded. Comparisons between baseline and follow-up lipid measurements were performed within and across treatment arms, as well as change in lipids and change in MDS-TBR. We studied 122 participants, 61 in each treatment arm, with median age 57 years, 76% female, and 1.5 year median RA disease duration. When comparing treatment arms, triple therapy had on average a larger reduction in triglycerides (15.9 mg/dL, p = 0.01), total cholesterol to HDL-C ratio (0.29, p-value = 0.01), and LDL particle number (111.2, p = 0.02) compared to TNFi. TNFi had on average a larger increase in HDL particle number (1.6umol/L, p = 0.006). We observed no correlation between change in lipid measurements and change in MDS-TBR within and across treatment arms. Both treatment strategies were associated with improved lipid profiles via changes in different lipids and lipoproteins. These effects had no correlation with change in CV risk as measured by vascular inflammation by FDG-PET/CT. ClinicalTrials.gov ID NCT02374021.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141444902","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":"Rituximab in the treatment of progressive interstitial lung disease associated with the antisynthetase syndrome","authors":"Javier Narváez, Elena Cañadillas, Iván Castellví, Juan José Alegre, Vanesa Vincens-Zygmunt, Guadalupe Bermudo, Paola Vidal-Montal, María Molina Molina, Joan Miquel Nolla","doi":"10.1186/s13075-024-03353-2","DOIUrl":"https://doi.org/10.1186/s13075-024-03353-2","url":null,"abstract":"To assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with antisynthetase syndrome and progressive interstitial lung disease (ASS-ILD). Multicentre observational retrospective longitudinal study of a cohort of patients with ASS-ILD that started treatment with RTX due to recurrent or ongoing progressive ILD despite therapy with glucocorticoids and immunosuppressants. Twenty-eight patients were analyzed. Examining the entire study population, before treatment with RTX the mean decline in %pFVC and %pDLCO from the ASS-ILD diagnosis to the initiation of RTX treatment (T0) was -6.44% and -14.85%, respectively. After six months of treatment, RTX reversed the decline in pulmonary function test (PFT) parameters: ∆%pFVC +6.29% (95% CI: -10.07 to 2.51; p=0.002 compared to T0) and ∆%pDLCO +6.15% (95% CI: -10.86 to -1.43; p=0.013). Twenty-four patients completed one year of therapy and 22 two years, maintaining the response in PFT: ∆%pFVC: +9.93% (95% CI: -15.61 to -4.25; p=0.002) and ∆%pDLCO: +7.66% (95% CI: -11.67 to -3.65; p<0.001). In addition, there was a significant reduction in the median dose of prednisone, and it could be suspended in 18% of cases. In 33% of patients who required oxygen therapy at the start of treatment, it could be discontinued. The frequency of adverse events reached 28.5% of cases. Based on our results, RTX appears to be effective as rescue therapy in most patients with recurrent or progressive ASS-ILD unresponsive to conventional treatment. The use of RTX was well tolerated in the majority of patients.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334410","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":"Baricitinib ameliorates inflammatory and neuropathic pain in collagen antibody-induced arthritis mice by modulating the IL-6/JAK/STAT3 pathway and CSF-1 expression in dorsal root ganglion neurons","authors":"Kenta Makabe, Hiroyuki Okada, Naohiro Tachibana, Hisatoshi Ishikura, Norihito Ito, Masaru Tanaka, Ryota Chijimatsu, Asuka Terashima, Fumiko Yano, Meiko Asaka, Dai Yanagihara, Shuji Taketomi, Takumi Matsumoto, Sakae Tanaka, Yasunori Omata, Taku Saito","doi":"10.1186/s13075-024-03354-1","DOIUrl":"https://doi.org/10.1186/s13075-024-03354-1","url":null,"abstract":"Janus kinase (JAK) inhibitors, such as baricitinib, are widely used to treat rheumatoid arthritis (RA). Clinical studies show that baricitinib is more effective at reducing pain than other similar drugs. Here, we aimed to elucidate the molecular mechanisms underlying the pain relief conferred by baricitinib, using a mouse model of arthritis. We treated collagen antibody-induced arthritis (CAIA) model mice with baricitinib, celecoxib, or vehicle, and evaluated the severity of arthritis, histological findings of the spinal cord, and pain-related behaviours. We also conducted RNA sequencing (RNA-seq) to identify alterations in gene expression in the dorsal root ganglion (DRG) following baricitinib treatment. Finally, we conducted in vitro experiments to investigate the direct effects of baricitinib on neuronal cells. Both baricitinib and celecoxib significantly decreased CAIA and improved arthritis-dependent grip-strength deficit, while only baricitinib notably suppressed residual tactile allodynia as determined by the von Frey test. CAIA induction of inflammatory cytokines in ankle synovium, including interleukin (IL)-1β and IL-6, was suppressed by treatment with either baricitinib or celecoxib. In contrast, RNA-seq analysis of the DRG revealed that baricitinib, but not celecoxib, restored gene expression alterations induced by CAIA to the control condition. Among many pathways changed by CAIA and baricitinib treatment, the interferon-alpha/gamma, JAK-signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) pathways were considerably decreased in the baricitinib group compared with the celecoxib group. Notably, only baricitinib decreased the expression of colony-stimulating factor 1 (CSF-1), a potent cytokine that causes neuropathic pain through activation of the microglia–astrocyte axis in the spinal cord. Accordingly, baricitinib prevented increases in microglia and astrocytes caused by CAIA. Baricitinib also suppressed JAK/STAT3 pathway activity and Csf1 expression in cultured neuronal cells. Our findings demonstrate the effects baricitinib has on the DRG in relation to ameliorating both inflammatory and neuropathic pain.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141326854","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}