Annals of the Rheumatic Diseases最新文献

{"title":"Systematic literature review and meta-analysis informing the EULAR points to consider on the initiation of targeted therapies in patients with inflammatory arthritis and a history of cancer.","authors":"Eden Sebbag, Juan Molina-Collada, Ramatoulaye Ndoye, Daniel Aletaha, Johan Askling, Karolina Gente, Heidi Bertheussen, Samuel Bitoun, Ertugrul Cagri Bolek, Maya H Buch, Gerd R Burmester, Helena M Canhão, Katerina Chatzidionysiou, Jeffrey R Curtis, Francois-Xavier Danlos, Vera Guimarães, Merete Lund Hetland, Florenzo Iannone, Marie Kostine, Tue Wenzel Kragstrup, Tore K Kvien, Anne Constanze Regierer, Hendrik Schulze-Koops, Nathanaël Sedmak, Lucía Silva-Fernández, Zoltan Szekanecz, Kim Lauper, Axel Finckh, Jacques-Eric Gottenberg","doi":"10.1136/ard-2024-225981","DOIUrl":"10.1136/ard-2024-225981","url":null,"abstract":"<p><strong>Background: </strong>Targeted therapies have been associated with potential risk of malignancy, which is a common concern in daily rheumatology practice in patients with inflammatory arthritis (IA) and a history of cancer.</p><p><strong>Objectives: </strong>To perform a systematic literature review to inform a Task Force formulating EULAR points to consider on the initiation of targeted therapies in patients with IA and a history of cancer.</p><p><strong>Methods: </strong>Specific research questions were defined within the Task Force before formulating the exact research queries with a librarian. We included studies reporting a relative risk measure of patients with a history of cancer initiating a targeted therapy or a conventional synthetic disease-modifying antirheumatic drug (csDMARD), regardless of the time since diagnosis of cancer. All relevant studies included in PubMed or Embase up to 15 July 2022 were included. Two reviewers independently performed standardised article selection, data extraction, synthesis and risk of bias assessment.</p><p><strong>Results: </strong>14 published articles and one ACR abstract fulfilled the inclusion criteria. All studies were high-quality observational studies, representing a median follow-up from treatment initiation of 4.52 years among 4428 patients and 15 062 patient-years of follow-up for new or recurrent cancer.All patients had a history of cancer, most frequently solid cancer, most frequently receiving treatment for rheumatoid arthritis and most frequently treated with tumour necrosis factor-alpha inhibitors. Across these studies, the overall HR of cancer recurrence was 0.92 (95% CI 0.74 to 1.15) for patients receiving a targeted therapy versus a csDMARD.</p><p><strong>Conclusion: </strong>Overall, the targeted therapies and clinical contexts covered by the included studies were not associated with an increased risk of cancer recurrence as compared with csDMARDs.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2024 EULAR points to consider on the initiation of targeted therapies in patients with inflammatory arthritis and a history of cancer.","authors":"Eden Sebbag, Kim Lauper, Juan Molina-Collada, Daniel Aletaha, Johan Askling, Karolina Gente, Heidi Bertheussen, Samuel Bitoun, Ertugrul Cagri Bolek, Gerd R Burmester, Helena M Canhão, Katerina Chatzidionysiou, Jeffrey R Curtis, Francois-Xavier Danlos, Vera Guimarães, Merete Lund Hetland, Florenzo Iannone, Marie Kostine, Tue Wenzel Kragstrup, Tore K Kvien, Anne Constanze Regierer, Hendrik Schulze-Koops, Lucía Silva-Fernández, Zoltan Szekanecz, Maya H Buch, Axel Finckh, Jacques-Eric Gottenberg","doi":"10.1136/ard-2024-225982","DOIUrl":"10.1136/ard-2024-225982","url":null,"abstract":"<p><strong>Background: </strong>Potential associations between targeted therapies and a new cancer in patients with inflammatory arthritis (IA) and a previous malignancy are a frequent concern in daily rheumatology practice.</p><p><strong>Objectives: </strong>To develop points to consider (PTC) to assist rheumatologists when initiating a targeted therapy in the context of a previous malignancy.</p><p><strong>Methods: </strong>Following EULAR standardised operating procedures, a task force met to define the research questions for a systematic literature review and to formulate the overarching principles (OPs) and the PTC.</p><p><strong>Results: </strong>The group formulated five OPs; seven PTC were formulated concerning the initiation of targeted therapies in patients with active IA and a previous malignancy in remission and one PTC concerning patients with active IA who were not in cancer remission. Major themes included (a) the need to assess the individualised risk of cancer recurrence based on the characteristics of the patient, cancer and the underlying disease; (b) the importance of engaging with specialists caring for cancer and defining treatment based on a shared decision between the patient and the rheumatologist; (c) the value of initiating without delay an appropriate targeted therapy for the treatment of the IA in patients in remission of their cancer; (d) the proposal to use Janus kinase inhibitors and abatacept with caution and in the absence of therapeutic alternatives, based on the absence of any data concerning their use in the context of previous malignancy.</p><p><strong>Conclusion: </strong>The 2024 EULAR points to consider provide guidance on the management of targeted therapies in patients with IA and a previous malignancy.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expert consensus recommendations for the diagnosis and treatment of chronic non-bacterial osteitis (CNO) in adults.","authors":"Elizabeth M Winter, Olaf M Dekkers, Caroline M Andreasen, Salvatore D'Angelo, Natasha M Appelman-Dijkstra, Simone Appenzeller, Gunter Assmann, Judith S Bubbear, Oana O Bulaicon, Roland Chapurlat, Varvara Choida, Gavin Peter Ross Clunie, Dimitrios Daoussis, Torsten Diekhoff, Marcel Flendrie, Olivier Fogel, Roba Ghossan, Hermann Girschick, Femke van Haalen, Neveen A T Hamdy, Barbara Hauser, Christian M Hedrich, Philip S Helliwell, Kay Geert Hermann, Antonella Insalaco, Anne Grethe Jurik, Mitsumasa Kishimoto, Willem Lems, Paivi Miettunen, Burkhard Muche, Ana Navas Cañete, Natalia Palmou-Fontana, Frits Smit, James Teh, Charlotte Verroken, Kurt de Vlam, Daniel Wendling, Wei Zhou, Hans-Georg Zmierczak, Anne T Leerling","doi":"10.1136/ard-2024-226446","DOIUrl":"10.1136/ard-2024-226446","url":null,"abstract":"<p><strong>Background: </strong>There is considerable practice variation in labelling, diagnosis and treatment of adults with sterile bone inflammation. We developed a expert consensus recommendations on the disease definition, diagnosis and treatment of this rare condition.</p><p><strong>Methods: </strong>Systematic literature review and Grading of Recommendations, Assessment, Development and Evaluations-based appraisal of evidence, two Delphi surveys and three digital and in-person consensus meetings with a multidisciplinary expert panel and patient representatives.</p><p><strong>Results: </strong>A consensus disease definition was developed and the term 'chronic non-bacterial osteitis' (CNO) is proposed to describe adults with sterile bone inflammation. For initial imaging evaluation of adults with suspected CNO, the panel recommends MRI or otherwise CT combined with nuclear imaging. Whole-body imaging at initial evaluation can be considered for diagnostic and prognostic purposes. Suggested first-line treatment in adults with active CNO includes non-steroidal anti-inflammatory drugs/cyclooxygenase 2-inhibitors. Second-line treatment preferably consists of intravenous bisphosphonates, and otherwise tumour necrosis factor-α inhibitors. Choice between them should be individualised, considering the presence of additional inflammatory features. The panel further discusses outcome measures, follow-up and management of adverse events and complications.</p><p><strong>Conclusions and future perspectives: </strong>These expert consensus recommendations are intended to support healthcare professionals worldwide in their care for adults with CNO. They also lay the groundwork for establishing international patient registries, translational research lines and multicentre trials, all of which are urgently required.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ivarmacitinib, a selective Janus kinase 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis and inadequate response to conventional synthetic DMARDs: results from a phase III randomised clinical trial.","authors":"Jinjing Liu, Ying Jiang, Shangzhu Zhang, Shengyun Liu, Jingbo Su, Changsong Lin, Xiaohong He, Rui Wu, Lei Yang, Huaxiang Liu, Xinwang Duan, Shengqian Xu, Hui Luo, Jing Liu, Qibing Xie, Cundong Mi, Lin Chen, Ning Zhang, Huiping Gong, Jing Zhu, Yasong Li, Hua Wei, Long Qian, Jian Wang, Xiaofei Shi, Hongtao Jin, Zhenyu Jiang, Xi Xie, Feng Zhan, Xiuqin Geng, Zhaohui Zheng, Zhengfu Du, Guangchao Dong, Yuqi Sun, Xiaofeng Zeng","doi":"10.1136/ard-2024-226385","DOIUrl":"10.1136/ard-2024-226385","url":null,"abstract":"<p><strong>Objective: </strong>To assess the efficacy/safety of ivarmacitinib, a selective Janus kinase (JAK) 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).</p><p><strong>Methods: </strong>Patients were randomised (1:1:1) to receive either placebo (n=188), ivarmacitinib 4 mg (n=189) or ivarmacitinib 8 mg (n=189) once daily, with background csDMARDs allowed. After 24 weeks, patients on placebo switched to ivarmacitinib 4 mg for an additional 28 weeks, while those on ivarmacitinib continued their initial dosage. The primary endpoint was the proportion of patients achieving a 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24.</p><p><strong>Results: </strong>At week 24, ACR20 response rates were significantly higher in the ivarmacitinib 4 mg (70.4%) and 8 mg (75.1%) groups compared with the placebo group (40.4%; both p<0.0001). Both ivarmacitinib doses achieved numerically higher Disease Activity Score 28-joint count C reactive protein of <2.6/≤3.2 response rates compared with placebo. Improvements in efficacy and patient-reported outcomes were sustained through 52 weeks and were noted in patients who switched from placebo after week 24. During the placebo-controlled period, treatment-emergent adverse events (TEAEs) occurred in 81.5% and 90.5% of patients in the ivarmacitinib 4 mg and 8 mg groups, versus 79.3% in the placebo group. Infection-related TEAEs were slightly higher in the ivarmacitinib groups.</p><p><strong>Conclusions: </strong>Ivarmacitinib may offer a potential therapeutic option for patients with RA who have an inadequate response to csDMARDs, with a safety profile that was generally manageable over 1 year of treatment and similar to other JAK inhibitors.</p><p><strong>Trial registration number: </strong>NCT04333771.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Olokizumab plus methotrexate: safety and efficacy over 106 weeks of treatment.","authors":"","doi":"10.1136/ard-2023-225473corr1","DOIUrl":"10.1136/ard-2023-225473corr1","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD-19 CAR-T cells for polyrefractory rheumatoid arthritis.","authors":"Merav Lidar, Doron Rimar, Paula David, Elad Jacoby, Ronnie Shapira-Frommer, Orit Itzhaki, Gleb Slobodin, Myriam D Stern, Iris Eshed, Tamer Sanalla, Ronit Marcus, Avichai Shimoni, Ronit Yerushalmi, Noga Shem Tov, Ivetta Danylesko, Abraham Avigdor","doi":"10.1136/ard-2024-226437","DOIUrl":"10.1136/ard-2024-226437","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacodynamics of the S1P₁ receptor modulator cenerimod in a phase 2b randomised clinical trial in patients with moderate to severe SLE.","authors":"Madeleine Suffiotti, Pijus Brazauskas, Marcel Peter Keller, Ouali Berkani, Gustavo Seifer, Peter Cornelisse, Mark Joseph Murphy, Daniel Stefan Strasser","doi":"10.1136/ard-2024-226547","DOIUrl":"10.1136/ard-2024-226547","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterised by autoreactive T and B lymphocytes. Sphingosine-1-phosphate (S1P) is involved in lymphocyte egress from peripheral lymphoid organs into the circulation. In phase 2a clinical trial, the potent, selective S1P₁ receptor modulator cenerimod reduced circulating antibody-secreting cells and interferon (IFN)-associated biomarkers.</p><p><strong>Objectives: </strong>Pharmacodynamic effects of 2 and 4 mg cenerimod were evaluated in the phase 2b clinical trial (CARE) in moderate to severe patients with SLE (NCT03742037).</p><p><strong>Methods: </strong>Blood samples were collected at baseline and after 6 months of treatment with cenerimod or placebo from CARE. The gene expression signatures for type 1 interferon (IFN-1), IFN-γ and plasma cells were used to assess dose-dependent pharmacodynamic effects of cenerimod. Cell-type deconvolution was performed to estimate cell abundance.</p><p><strong>Results: </strong>Cenerimod 4 mg reduced IFN-associated protein and gene signature biomarkers after 6 months compared with placebo. A larger decrease of IFN proteins was evident in IFN-1 high patients compared with IFN-1 low patients. The median IFN-1 score in the IFN-1 high patients was reduced after 6 months of cenerimod 4 mg and the transition from IFN-1 low to high status compared with placebo was prevented. Cenerimod 4 mg exhibited a larger effect size on the pharmacodynamic biomarkers IFN-1, IFN-γ and plasma cells compared with cenerimod 2 mg.</p><p><strong>Conclusions: </strong>This study further characterised the mechanism of action of cenerimod in patients with SLE and substantiated the scientific rationale for cenerimod 4 mg in the phase 3 clinical trials in moderate to severe SLE (OPUS-1/-2).</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psoriatic arthritis phenotype clusters and their association with treatment response: a real-world longitudinal cohort study from the psoriatic arthritis research consortium.","authors":"Paras Karmacharya, Leslie J Crofford, Daniel W Byrne, Alisa Stephens-Shields, M Elaine Husni, Jose U Scher, Ethan Craig, Robert Fitzsimmons, Soumya M Reddy, Marina N Magrey, Jessica A Walsh, Alexis Ogdie","doi":"10.1136/ard-2024-226150","DOIUrl":"10.1136/ard-2024-226150","url":null,"abstract":"<p><strong>Objectives: </strong>To identify phenotype clusters and their trajectories in psoriatic arthritis (PsA) and examine the association of the clusters with treatment response in a real-world setting.</p><p><strong>Methods: </strong>In the multicentre PsA Research Consortium (PARC) study, we applied factor analysis of mixed data to reduce dimensionality and collinearity, followed by hierarchical clustering on principal components. We then evaluated the transition of PsA clusters and their response to new immunomodulatory therapy and tumour necrosis factor inhibitor (TNFi).</p><p><strong>Results: </strong>Among 627 patients with PsA, three clusters were identified: mild PsA and psoriasis only (PsO) (Cluster 1, 47.4%), severe PsA and mild PsO (Cluster 2, 34.3%) and severe PsA and severe PsO (Cluster 3, 18.3%). Among 339 patients starting or changing, significant differences in response were observed (mean follow-up of 0.7 years, SD 0.8), with Cluster 3 showing the largest improvements in cDAPSA and PsAID. No differences were found among those starting TNFi (n=218). cDAPSA remission and PsAID patient acceptable symptom state were achieved in 10% and 54%, respectively. Clusters remained stable over time despite treatment changes, though some transitions occurred, notably from Cluster 3 to milder clusters.</p><p><strong>Conclusion: </strong>Data-driven clusters with distinct therapy responses identified in this real-world study highlight the extensive heterogeneity in PsA and the central role of psoriasis and musculoskeletal severity in treatment outcomes. Concurrently, these findings underscore the need for better outcome measures, particularly for individuals with lower disease activity.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-life use of the PEXIVAS reduced-dose glucocorticoid regimen in granulomatosis with polyangiitis and microscopic polyangiitis.","authors":"Sophie Nagle, Yann Nguyen, Mary-Jane Guerry, Thomas Quemeneur, Dimitri Titeca-Beauport, Thomas Crépin, Rafik Mesbah, Idris Boudhabhay, Grégory Pugnet, Céline Lebas, Antoine Néel, Alexandre Karras, Eric Hachulla, Juliette Woessner, Vincent Pestre, Raphaël Borie, Stephane Vinzio, Jean-Baptiste Gouin, Sara Melboucy-Belkhir, Roderau Outh, Benjamin Subran, Mathieu Gerfaud-Valentin, Sebastien Humbert, Philippe Kerschen, Yurdagul Uzunhan, Tiphaine Goulenok, Maxime Beydon, Nathalie Costedoat-Chalumeau, Xavier Puechal, Benjamin Terrier","doi":"10.1136/ard-2024-226339","DOIUrl":"10.1136/ard-2024-226339","url":null,"abstract":"<p><strong>Background: </strong>The PEXIVAS (Plasma exchange and glucocorticoids in severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis) trial showed that a reduced-dose glucocorticoid regimen (redGC) was non-inferior to a standard-dose regimen (standGC) with respect to death or end-stage kidney disease (ESKD) in patients with ANCA-associated vasculitis (AAV). However, the primary endpoint did not include disease progression or relapse, cyclophosphamide was the main induction therapy and rituximab (RTX)-treated patients tended to have a higher risk of death or ESKD with redGC. We aimed to evaluate the real-world use of redGC.</p><p><strong>Methods: </strong>We conducted a retrospective, multicentre study comparing PEXIVAS redGC with standGC in patients with AAV. The primary composite outcome was the occurrence of death, ESKD, AAV progression before remission or relapse within the 12 months following induction. Inverse probability of treatment weighting was used to correct for baseline imbalance between groups. Factors associated with the occurrence of the primary outcome were estimated.</p><p><strong>Results: </strong>A total of 234 patients were included. The primary composite outcome occurred in 42/126 (33%) patients with redGC versus 20/108 (19%) with standGC. In unweighted multivariable analysis and in weighted analysis, redGC was independently associated with the primary outcome but not with death or ESKD. Among redGC-treated patients, those with serum creatinine>300 µmol/L were more likely to achieve the primary outcome. RTX-treated patients who received redGC were more likely to experience death or ESKD and to achieve the primary outcome.</p><p><strong>Conclusion: </strong>In this study of patients with AAV primarily treated with RTX, redGC was associated with an increased risk of the primary outcome consisting of death, ESKD, AAV progression before remission or relapse.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma proteome profiling in giant cell arteritis.","authors":"Kevin Y Cunningham, Benjamin Hur, Vinod K Gupta, Matthew J Koster, Cornelia M Weyand, David Cuthbertson, Nader A Khalidi, Curry L Koening, Carol A Langford, Carol A McAlear, Paul A Monach, Larry W Moreland, Christian Pagnoux, Rennie L Rhee, Philip Seo, Peter A Merkel, Kenneth J Warrington, Jaeyun Sung","doi":"10.1136/ard-2024-225868","DOIUrl":"10.1136/ard-2024-225868","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to identify plasma proteomic signatures that differentiate active and inactive giant cell arteritis (GCA) from non-disease controls. By comprehensively profiling the plasma proteome of both patients with GCA and controls, we aimed to identify plasma proteins that (1) distinguish patients from controls and (2) associate with disease activity in GCA.</p><p><strong>Methods: </strong>Plasma samples were obtained from 30 patients with GCA in a multi-institutional, prospective longitudinal study: one captured during active disease and another while in clinical remission. Samples from 30 age-matched/sex-matched/race-matched non-disease controls were also collected. A high-throughput, aptamer-based proteomics assay, which examines over 7000 protein features, was used to generate plasma proteome profiles from study participants.</p><p><strong>Results: </strong>After adjusting for potential confounders, we identified 537 proteins differentially abundant between active GCA and controls, and 781 between inactive GCA and controls. These proteins suggest distinct immune responses, metabolic pathways and potentially novel physiological processes involved in each disease state. Additionally, we found 16 proteins associated with disease activity in patients with active GCA. Random forest models trained on the plasma proteome profiles accurately differentiated active and inactive GCA groups from controls (95.0% and 98.3% in 10-fold cross-validation, respectively). However, plasma proteins alone provided limited ability to distinguish between active and inactive disease states within the same patients.</p><p><strong>Conclusions: </strong>This comprehensive analysis of the plasma proteome in GCA suggests that blood protein signatures integrated with machine learning hold promise for discovering multiplex biomarkers for GCA.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1762-1772"},"PeriodicalIF":20.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}