Arthritis Research & Therapy最新文献

{"title":"Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration","authors":"Christabel Thembela Dube, Hamish T. J. Gilbert, Niamh Rabbitte, Pauline Baird, Sonal Patel, Jeremy A. Herrera, Ivona Baricevic-Jones, Richard D. Unwin, Danny Chan, Kanna Gnanalingham, Judith A. Hoyland, Stephen M. Richardson","doi":"10.1186/s13075-025-03489-9","DOIUrl":"https://doi.org/10.1186/s13075-025-03489-9","url":null,"abstract":"Intervertebral disc (IVD) degeneration is a common cause of low back pain, and the most symptomatic patients with neural compression need surgical intervention to relieve symptoms. Current techniques used to diagnose IVD degeneration, such as magnetic resonance imaging (MRI), do not detect changes in the tissue extracellular matrix (ECM) as degeneration progresses. Improved techniques, such as a combination of tissue and blood biomarkers, are needed to monitor the progression of IVD degeneration for more effective treatment plans. To identify tissue and blood biomarkers associated with degeneration progression, we histologically graded 35 adult human degenerate IVD tissues and matched plasma from the individuals into two groups: mild degenerate and severe degenerate. Mass spectrometry was utilised to characterise proteomic differences in tissue and plasma between the two groups. Top differentially distributed proteins were further validated using immunohistochemistry and qRT-PCR. Additionally, correlational analyses were conducted to define similarities and differences between tissue and plasma protein changes in individuals with mild and severe IVD degeneration. Our data revealed that the abundance of 31 proteins was significantly increased in severe degenerated IVD tissues compared to mild. Functional analyses showed that more than 40% of these proteins were matrisome-related, indicating differences in ECM protein composition between severe and mild degenerate IVD tissues. We confirmed adipocyte enhancer-binding protein 1 (AEBP1) as one of the most significantly enriched core matrisome genes and proteins as degeneration progressed. Compared to others, AEBP1 protein levels best distinguished between mild and severe degenerated IVD tissues with an area under the curve score of 0.768 (95% CI: 0.60–0.93). However, we found that protein changes from associated plasma exhibited a weak relationship with histological grading and AEBP1 tissue levels. Given that systemic plasma changes are complex, a larger sample cohort may be required to identify patterns in blood relating to IVD degeneration progression. In this study, we have identified AEBP1 as a tissue marker for monitoring the severity of disc degeneration in humans. Further work to link alterations in tissue AEBP1 levels to changes in blood-related proteins will be beneficial for detailed monitoring of IVD degeneration thereby enabling more personalised treatment approaches.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"41 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375451","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":"Asthma, social isolation and loneliness, and risk of incident osteoarthritis","authors":"Ziyi Wu, Xukun Luo, Pengcheng Dou, Tang Liu, Jian Zhou","doi":"10.1186/s13075-025-03496-w","DOIUrl":"https://doi.org/10.1186/s13075-025-03496-w","url":null,"abstract":"Incidence of osteoarthritis (OA) was increased in patients with asthma, while no prospective cohort study has tested the association of asthma with OA, and the modified effect of social isolation and loneliness remains unclear. This prospective cohort study included 448,920 participants without OA at baseline from UK Biobank cohort. The evaluation of asthma was based on diagnosis and self-reported history. The outcome was OA including knee OA, hip OA and hand OA by referring to hospital admission records. Two Cox regression models were constructed to assess the relationship of asthma and risk of OA. With a median of 12.5 years of follow up, a total of 57,573 incident OA were recorded. Compared with participants without asthma, the hazard ratios (HRs) were 1.32 (95% CI: 1.29–1.35) for all OA, 1.21 (95% CI: 1.16–1.25) for knee OA, 1.12 (95% CI: 1.07–1.18) for hip OA and 1.62 (95% CI:1.42–1.85) for hand OA in participants with asthma. In addition, we found that social isolation and loneliness significantly modified the associations of asthma with OA (P-interaction < 0.001). Asthma was a stronger predictor of OA than lifestyle risk factors including smoking, alcohol and healthy diet. In this cohort study of UK Biobank participants, asthma was related to increased risk of OA; such association was more pronounced among those with higher social isolation or loneliness score.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"9 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375416","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":"Associations between age, red cell distribution width and 180-day and 1-year mortality in giant cell arteritis patients: mediation analyses and machine learning in a cohort study","authors":"Si Chen, Rui Nie, Xiaoran Shen, Yan Wang, Haixia Luan, Xiaoli Zeng, Yanhua Chen, Hui Yuan","doi":"10.1186/s13075-025-03477-z","DOIUrl":"https://doi.org/10.1186/s13075-025-03477-z","url":null,"abstract":"The aim of this study was to investigate the correlation between age, red cell distribution width (RDW) levels, and 180-day and 1-year mortality in giant cell arteritis (GCA) patients hospitalized or admitted to the ICU. Clinical data from GCA patients were extracted from the MIMIC-IV (3.0) database. Logistic and Cox regression analyses, Kaplan–Meier (KM) survival analysis, restricted cubic spline (RCS) analysis, and mediation effect analysis were employed to investigate the association between age, RDW levels, and 180-day and 1-year mortality in GCA patients hospitalized or admitted to the ICU. Predictive models were constructed using machine learning algorithms, and SHapley Additive exPlanations (SHAP) analysis was applied to evaluate the contributions of age and RDW levels to mortality in this patient population. A total of 228 GCA patients were eligible for analysis. Our study identified both age and RDW levels (both with OR > 1, P < 0.05) as significant predictors of 180-day and 1-year mortality in GCA patients hospitalized or admitted to the ICU using multivariate logistic regression analysis. In multivariate Cox regression analysis, both age and RDW (both with HR > 1, P < 0.05) also emerged as prognostic risk factors for 180-day and 1-year mortality in this patient population. KM survival analysis further showed that GCA patients hospitalized or admitted to the ICU with higher age or elevated RDW levels had significantly lower survival rates compared to younger patients or those with lower RDW levels (P < 0.0001). Moreover, RCS analysis indicated a strong nonlinear relationship between RDW levels (threshold: 17.53%) and 1-year mortality in this population. Additionally, RDW levels were found to modestly mediate the relationship between age (per 10-year increase) and 180-day or 1-year mortality in GCA patients hospitalized or admitted to the ICU. The results of the machine learning analysis indicated that the model built using the random forest algorithm performed the best, with an area under the curve of 0.879. Furthermore, SHAP analysis revealed that both age and RDW levels made significant contributions to the prediction of mortality in GCA patients hospitalized or admitted to the ICU. Older age and higher RDW levels were identified as independent risk factors for increased 180-day and 1-year mortality in GCA patients hospitalized or admitted to the ICU. Furthermore, elevated RDW levels modestly mediated the relationship between age and 180-day or 1-year mortality in this patient population.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"41 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367480","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":"Integrated analysis of dermatomyositis reveals heterogeneous immune infiltration and interstitial lung disease-associated endotype","authors":"Xinzhi Xu, Tianwen Qiu, Kexin Sun, Xue Han, Junxia Huang, Xiuyuan Wang, Jianchao Ge, Ji Yang","doi":"10.1186/s13075-025-03494-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03494-y","url":null,"abstract":"Dermatomyositis (DM) is an autoimmune disease with a high rate of disability and mortality especially in DM with concurrent interstitial lung disease (DM-ILD). Little is known about inflammatory signature and heterogeneous endotypes of DM. We aimed to illustrate the systemic inflammatory signature of DM and define an ILD-associated endotype. Olink proteomic analysis was performed on serum samples obtained from DM patients (n = 32), DM patients with ILD (n = 16), and healthy controls (n = 19). Transcriptomic data from skin samples was utilized to assess immune infiltration and investigate the correlation between protein and mRNA levels of biomarkers. Additionally, the prognostic value and clinical significance of identified biomarkers were validated through follow-up studies of DM patients and immunofluorescence analysis of skin tissues. Proteomic data revealed the inflammatory signature of DM, with GO and KEGG enrichment analyses identifying chemotaxis-related pathways. Transcriptomic analysis of skin samples indicated upregulated inflammatory responses and M1 macrophage infiltration in DM. Two chemokines, CXCL10 and CXCL11, were identified as highly associated with immune infiltration and DM progression. Our data suggest that serum CXCL10 and CXCL11 reflect the inflammatory burden of DM. The identified biomarkers hold promise for determining an ILD-associated endotype and predicting clinical outcomes, thereby paving the way for timely management of DM and prevention of complications. • Integrated analysis of serum proteomics and skin biopsy transcriptomics identified key analytes present in both protein and RNA transcripts that correlate with the degree of skin involvement in DM and the onset of ILD. • CXCL10 and CXCL11 were confirmed to reflect the local immune environment of the skin and hold the potential to assess ILD risk. • An ILD-associated endotype in DM was characterized by distinct inflammatory profiling and heterogeneous features, paving the way for early DM-ILD diagnoses and improved clinical management.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"21 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367259","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":"Blood molecular subtypes to guide precision treatment strategies in systemic juvenile idiopathic arthritis","authors":"In-Woon Baek, Jung Woo Rhim, Kyung-Su Park, Ki-Jo Kim","doi":"10.1186/s13075-025-03498-8","DOIUrl":"https://doi.org/10.1186/s13075-025-03498-8","url":null,"abstract":"Systemic juvenile idiopathic arthritis (sJIA) is the most severe subtype of JIA, with a combination of diverse clinical manifestations and a variable clinical course. A comprehensive understanding of molecular signatures at the systems level and the discovery of molecular subtypes are the initial steps toward personalized medicine in sJIA. A blood transcriptomic dataset was collected from patients with systemic JIA (sJIA) (n = 168), polyarticular JIA (n = 254), oligoarticular JIA (n = 96), enthesitis-related arthritis (n = 40), and healthy controls (n = 220). Gene expression profiles were filtered for differentially expressed genes and unsupervised clustering, gene set enrichment, and network-based centrality analyses. The molecular signatures of three novel sJIA subgroups (designated as C1, C2, and C3) were investigated, focusing on their distinct features and treatment responses. Neutrophil degranulation and the IL-1 signaling pathway were the shared key processes for the three subgroups. Proinflammatory signals, including TNF, IL-6, TLR, and G-CSF signaling pathways, were identified with variation across the subgroups. C1 was the most inflammatory subset with a high-risk profile for macrophage activation syndrome. The C2 subset had the most activated IL-1 and IL-18 signaling pathways. C2 and C3 have higher levels of interferon-stimulated signatures. In a canakinumab-treated dataset, treatment response was correlated with IL1B expression and NF-κB signaling pathway, and neutrophil activation-associated processes were effectively suppressed in a good responder group. GSK3B and p38 MAPK inhibitors showed a significant counteracting effect on the perturbed gene expression of sJIA. Neutrophil activation was the key feature in active sJIA. The three molecular subtype scheme enables the formulation of precision medicine strategies in sJIA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"48 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367479","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 rational use of glucocorticoids may reduce the risk of readmission in menopausal women with knee osteoarthritis: results from a five-year longitudinal study","authors":"Huang Xi, Hao Huiqin, Liu Hongqi, Zhang Ruqi, Zhang Junfeng","doi":"10.1186/s13075-025-03495-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03495-x","url":null,"abstract":"To investigate the effect of glucocorticoids (GCs) on the risk of readmission in menopausal women with knee osteoarthritis (OA). The study cohort comprised 80 menopausal women with knee OA treated at a tertiary hospital affiliated with Shanxi Medical University and who underwent follow-up between September 2018 and September 2023. Then the collected longitudinal monitoring data were used to construct a semi-variable coefficient shared Gamma frailty model (VCSGF). Based on the results of this model, we explored the impact of GCs on menopausal women with knee OA and made risk predictions. The mean patient age at study entry was 64.7 ± 9.3 (range 50–82 years). And during the research, patients were admitted to the hospital a mean of 2.4 ± 1.8 times (range 1–11 times). Compared to patients who have not used the drug, the risk of early readmission in patients who have used GCs was reduced by 96% (HR = 0.04, 95%CI: 0.006 ~ 0.284, $$:P<0.001$$ ). This protective effect diminished over time ( $$:{gamma:}_{2l}left({t}_{0}right)=0.629,P<0.001$$ ). In addition, the risk of hospital admission with recurrent symptoms was roughly 3.35-fold higher in patients who drink alcohol than in patients who do not (95%CI: 1.661~6.794, $$:P<0.001$$ ). GC use reduced the risk of readmission in menopausal women with knee OA, although this effect diminished over time. Therefore, in patients without further contraindications, GCs may be used in moderation to reduce the readmission risk. In clinical practice, additional research is needed to investigate the timing and appropriate use of GC in the treatment of menopausal women with knee OA, and to develop a more rational program for GC use.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"9 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191764","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":"Upadacitinib in active non-radiographic axial spondyloarthritis: 2-year data from the phase 3 SELECT-AXIS 2 study","authors":"Filip Van den Bosch, Atul Deodhar, Denis Poddubnyy, Walter P. Maksymowych, Désirée van der Heijde, Tae-Hwan Kim, Mitsumasa Kishimoto, Xenofon Baraliakos, Xianwei Bu, Ivan Lagunes-Galindo, In-Ho Song, Peter Wung, Koji Kato, Anna Shmagel","doi":"10.1186/s13075-024-03441-3","DOIUrl":"https://doi.org/10.1186/s13075-024-03441-3","url":null,"abstract":"In SELECT-AXIS 2, upadacitinib improved the signs and symptoms of active non-radiographic axial spondyloarthritis (nr-axSpA) through 52 weeks versus placebo and was well tolerated. Here, we evaluated the efficacy and safety of upadacitinib through 2 years. The study enrolled eligible adult patients with a clinical diagnosis of nr-axSpA who met the 2009 Assessment of SpondyloArthritis international Society (ASAS) classification criteria and had objective signs of active inflammation on magnetic resonance imaging (MRI) of sacroiliac joints and/or high-sensitivity C-reactive protein. Patients were randomized 1:1 to receive double-blinded treatment with upadacitinib 15 mg once daily (QD) or placebo for 52 weeks, after which all patients received open-label treatment with upadacitinib 15 mg QD. Efficacy results over 104 weeks were reported as observed (AO) and either AO with non-responder imputation (AO-NRI; binary endpoints) or AO with mixed-effect model for repeated measures (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized through week 104. Of 313 patients randomized and treated, 224 (continuous upadacitinib n = 117; placebo/upadacitinib n = 107) completed 104 weeks of treatment. In patients who received continuous upadacitinib, sustained improvement was observed through 2 years of treatment across efficacy endpoints including disease activity, pain, function, enthesitis, quality of life, and MRI measures of inflammation. At week 104, 57.1%, 59.0%, and 31.4% of patients achieved ASAS40 response, and low disease activity and inactive disease (as defined by Axial Spondyloarthritis Disease Activity Score), respectively (AO-NRI); week 104 outcomes were generally similar in patients who initially received placebo and were switched to upadacitinib at week 52. In total, 286 patients were exposed to ≥ 1 dose of upadacitinib, comprising 378.3 patient-years (PY) of exposure. Upadacitinib was generally well tolerated, with exposure-adjusted event rates (EAERs) for TEAEs, serious adverse events (AEs), and AEs leading to study drug discontinuation of 207.5, 8.7, and 5.3 events/100 PY, respectively. EAERs of TEAEs of special interest were broadly consistent with those reported through week 52. Treatment with upadacitinib demonstrated consistent improvement and maintenance of treatment effect across efficacy endpoints through 2 years; no new safety signals were identified with additional exposure. NCT04169373.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"1 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083493","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":"MiR-223 within neutrophil axis promotes Th17 expansion by PI3K-AKT pathway in systemic lupus erythematosus","authors":"Chengzhong Zhang, Yan Lu","doi":"10.1186/s13075-025-03487-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03487-x","url":null,"abstract":"Further investigation is required to determine the etiology of systemic lupus erythematosus (SLE). The aim of this study is to assess the presence of miR-223 within neutrophils in SLE and investigate its impact on the expansion of Th17 cells. Experiments were performed in MRL/lpr mice, which were divided into control and miR-223 knockdown (miR-223-) group. We assessed miR-223 expression within neutrophils and Th17 expansion in MRL/lpr mice and patients with SLE using RT-PCR, luciferase reporter assay, Elisa, flow cytometry analysis. Signaling pathway, RT-PCR and western blot were conducted to elucidate the mechanism by which miR-223 within neutrophils expands Th17. We initially identified miR-223 as a pivotal factor in the pathogenesis of SLE in both MRL/lpr mice and SLE patients. Subsequently, knockdown of miR-223 led to a significant reduction in Th17 expansion in MRL/lpr mice. Moreover, inhibition of miR-223 effectively attenuated the recruitment and activation of neutrophils in SLE. Furthermore, we found rb6-8c5 treatment alleviated lupus symptoms of MRL/lpr mice and reduce the level of Th17. Finally, we elucidated that neutrophils potentiate the induction of Th17 through the activation of thePI3K-AKT pathway mediated by miR-223 during SLE-associated Th17 expansion. MiR-223 within neutrophil axis contributes to Th17 expansion by PI3K-AKT pathway in SLE, and miR-223 could be a therapeutic target of SLE.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"34 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077489","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":"Long-term outcome of a treat-to-target strategy in late-onset rheumatoid arthritis with chronic lung disease: 5-year results of a prospective observational study","authors":"Manami Nomura, Takahiko Sugihara, Hiroyuki Baba, Tadashi Hosoya, Mari Kamiya, Tatsuro Ishizaki, Takumi Matsumoto, Kanae Kubo, Fumio Hirano, Masayo Kojima, Nobuyuki Miyasaka, Shinsuke Yasuda, Masayoshi Harigai","doi":"10.1186/s13075-025-03491-1","DOIUrl":"https://doi.org/10.1186/s13075-025-03491-1","url":null,"abstract":"Controlling disease activity and improving physical function would be more difficult in patients with late-onset rheumatoid arthritis (LORA) who have chronic lung disease (CLD) at baseline. Our aim was to evaluate 5-year outcomes of following a treat-to-target (T2T) strategy targeting low disease activity (LDA) in LORA with CLD. Data from 197 methotrexate (MTX)-naïve LORA patients (mean age 74.4 years) from a prospective, monocentric registry were analyzed. Patients were treated with MTX if they had one or more poor prognostic features. If they had interstitial lung disease (ILD), tacrolimus could be administered instead of MTX at the discretion of the attending physician. If patients exhibited no response according to the European League Against Rheumatism criteria at week 12 or had not achieved LDA by week 24, biological disease-modifying antirheumatic drugs (bDMARDs) were started targeting LDA. The primary outcomes were the 5-year simplified disease activity index (SDAI) remission and Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ 0.5 by non-responder imputation analysis. Secondary outcomes were serious adverse events (SAEs). Of the 197 LORA patients, 47 had CLD at baseline. The proportion of patients using MTX at baseline was significantly lower in those with than without CLD. Tacrolimus was initiated in 25.5% of the CLD group. The proportion of patients on bDMARDs was higher in those with CLD at year 5. Achievement of SDAI remission at year 5 was 29.8% in patients with CLD and 44.0% in those without CLD (p = 0.555). Achievement of HAQ-DI ≤ 0.5 at year 5 was 36.2% and 45.3% in patients with and without CLD, respectively (p = 0.939). Non-adherence to T2T due to comorbidities or adverse events was observed in 34.0% and 18.7% of the patients with and without CLD, respectively (p = 0.027). Infections requiring hospitalization, deterioration of extra-articular manifestations and fractures were more frequently reported as SAEs in patients with CLD, and multivariable analysis showed that patients with CLD had a higher risk of developing these SAEs (adjusted hazard ratio:2.53, 95% CI 1.60–4.00, p < 0.001). For LORA patients with CLD, the T2T strategy is effective, but comorbidities and SAEs make the implementation of the T2T more difficult.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"38 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077488","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":"Predicting abatacept retention using machine learning","authors":"Rieke Alten, Claire Behar, Pierre Merckaert, Ebenezer Afari, Virginie Vannier-Moreau, Anael Ohayon, Sean E. Connolly, Aurélie Najm, Pierre-Antoine Juge, Gengyuan Liu, Angshu Rai, Yedid Elbez, Karissa Lozenski","doi":"10.1186/s13075-025-03484-0","DOIUrl":"https://doi.org/10.1186/s13075-025-03484-0","url":null,"abstract":"The incorporation of machine learning is becoming more prevalent in the clinical setting. By predicting clinical outcomes, machine learning can provide clinicians with a valuable tool for refining precision medicine approaches and improving treatment outcomes. This was a post hoc analysis of pooled patient-level data from the global, real-world ACTION and ASCORE trials in patients with rheumatoid arthritis (RA) initiating abatacept. Patient demographic and disease characteristics were input across 10 machine learning models used to predict 12-month treatment retention. Retention was defined as treatment for > 365 days or ≤ 365 days in patients who achieved remission or major clinical response (based on European Alliance of Associations for Rheumatology response criteria). The pooled dataset was split into a training/validation cohort for model development and a test cohort for an unbiased evaluation of performance. SHapley Additive exPlanation (SHAP) values determined the level of importance and directionality for key patient features predicting abatacept retention. The pooled ACTION and ASCORE dataset included 5320 patients with RA (mean [standard deviation] age 57.7 [12.7] years; 79% female). The 12-month abatacept retention rate was 61% (n = 3236) with a discontinuation rate of 39% (n = 2037). In the training set (n = 4218), the gradient-boosting classifier model demonstrated the best performance (testing accuracy: 62%). This model had an area under the receiver operating characteristic curve (95% confidence interval) of 0.620 (0.586, 0.653) and F1 score of 0.659 (0.625, 0.689) in the test set of patients (n = 1055). Using this model, the five most important variables predicting 12-month abatacept retention were low body mass index (BMI), low American College of Rheumatology functional status class, anti-citrullinated protein antibody (ACPA) positivity, low Patient Global Assessment, and younger age. The gradient-boosting classifier model identified key patient features predictive of abatacept retention from this large, real-world study population. The SHAP values conveyed the directionality and importance of BMI, functional status, ACPA serostatus, Patient Global Assessment, and age for abatacept retention. Findings are consistent with previous observations and help validate the machine learning approach for predictive modelling in RA treatment, and may help inform clinical decision making. NCT02109666 (ACTION), NCT02090556 (ASCORE).","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"15 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072489","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}