{"title":"Old techniques still have relevance in personalised predictive medicine.","authors":"Kristina E N Clark,Christopher P Denton","doi":"10.1002/art.43402","DOIUrl":"https://doi.org/10.1002/art.43402","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"68 21-22 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133908","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}
April Jorge,Aakash V Patel,Baijun Zhou,Lingxiao Zhang,Hyon Choi
{"title":"Glucagon-Like Peptide-1 Receptor Agonist Use and the Risk of Adverse Cardiac and Kidney Outcomes Among Patients with Systemic Lupus Erythematosus and Lupus Nephritis.","authors":"April Jorge,Aakash V Patel,Baijun Zhou,Lingxiao Zhang,Hyon Choi","doi":"10.1002/art.43403","DOIUrl":"https://doi.org/10.1002/art.43403","url":null,"abstract":"OBJECTIVEGlucagon-like peptide-1 receptor agonists (GLP-1RA) have cardioprotective and kidney-protective benefits among patients with type 2 diabetes (T2D). We sought to determine whether GLP-1RA use improves cardiovascular (CV) and kidney outcomes among patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN).METHODSWe emulated a pragmatic target trial to evaluate the impact of GLP-1RA vs. comparator hypoglycemic agents, dipeptidyl peptidase 4 inhibitors (DPP4i), on CV and kidney outcomes among patients with SLE and T2D using a large, US multi-center electronic health record database. We used propensity score overlap weighting to emulate randomization between treatment groups. Outcomes included major adverse cardiovascular events, venous thrombosis (VTE), kidney disease progression (eGFR decline ≥ 30% or new-onset end-stage kidney disease), and all-cause mortality. We used Cox regression to compare hazard ratios (HR) based on the weighted populations. In a secondary analysis, we only included patients with LN.RESULTSThere were 910 and 1004 initiators of GLP-1RA and DPP4i, respectively, including 267 and 324 patients with LN, respectively. Baseline covariates were balanced after propensity score overlap weighting. The risks of MACE (HR 0.66 [95% CI 0.48-0.91]), VTE (HR 0.49 [0.24-0.97]), kidney disease progression (HR 0.77 [0.60-0.98]), and all-cause mortality (HR 0.26 [CI 0.10-0.68]) were lower with GLP-1RA vs. DPP4i use. GLP-1RA use was similarly associated with lower risks of MACE and kidney disease progression among patients with LN.CONCLUSIONWe found lower risks of adverse CV and kidney outcomes and mortality with GLP-1RA use compared with DPP4i use among patients with lupus and T2D.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"86 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133910","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}
Nico Wittmann,Dominik Nell,Magdalena Mohs,Marie C Grude,Neha Mishra,Almut Meyer-Bahlburg,Lukas Bossaller
{"title":"Long-term remission with ustekinumab in a patient with PAPA syndrome suggests the importance of IL-12/IL-23 cytokines in PSTPIP1-associated inflammatory diseases.","authors":"Nico Wittmann,Dominik Nell,Magdalena Mohs,Marie C Grude,Neha Mishra,Almut Meyer-Bahlburg,Lukas Bossaller","doi":"10.1002/art.43399","DOIUrl":"https://doi.org/10.1002/art.43399","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"20 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103462","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}
Parameswaran K Nair,Bernhard Hellmich,Arnaud Bourdin,David R W Jayne,Florence Roufosse,Nader Khalidi,Lena Börjesson Sjö,Ying Fan,Christopher McCrae,Sofia Necander,Eva Rodríguez-Suárez,Anat Shavit,Claire Walton,Peter A Merkel,Michael E Wechsler
{"title":"The Effect of Benralizumab and Mepolizumab on Use of Oral Glucocorticoids in Patients with Eosinophilic Granulomatosis with Polyangiitis.","authors":"Parameswaran K Nair,Bernhard Hellmich,Arnaud Bourdin,David R W Jayne,Florence Roufosse,Nader Khalidi,Lena Börjesson Sjö,Ying Fan,Christopher McCrae,Sofia Necander,Eva Rodríguez-Suárez,Anat Shavit,Claire Walton,Peter A Merkel,Michael E Wechsler","doi":"10.1002/art.43398","DOIUrl":"https://doi.org/10.1002/art.43398","url":null,"abstract":"OBJECTIVEThe Phase 3 MANDARA study demonstrated non-inferiority of benralizumab versus mepolizumab for remission in patients with eosinophilic granulomatosis with polyangiitis (EGPA). More benralizumab-treated patients achieved complete withdrawal of oral glucocorticoids (OGCs). These post-hoc analyses further elucidate the efficacy of benralizumab and mepolizumab in facilitating reductions in OGCs.METHODSAdults with EGPA requiring ≥7.5 mg/day OGC ±immunosuppressive therapy were randomized to benralizumab 30mg (n=70) or mepolizumab 300mg (n=70) subcutaneously every 4 weeks for 52 weeks. Investigators tapered OGCs for patients with stable EGPA based on clinical judgment. Reductions in OGC use (to ≤4mg/day, by ≥50%, or complete withdrawal) were considered sustained if achieved by Week 40 and maintained through Week 52.RESULTSThe 12-month cumulative dose of OGC was ~1,800 mg in both groups. At Weeks 49-52, the median (minimum-maximum) OGC dose was 1.16 (0.0-16.6) and 3.00 (0.0-25.7) mg/day for benralizumab and mepolizumab, respectively. Time to first or sustained OGC reduction to ≤4mg/day or by ≥50%, and accrued OGC-free duration, were similar between groups. More benralizumab- than mepolizumab-treated patients completely withdrew OGCs (33/70 vs 20/70; HR for time to first complete withdrawal 1.84 [95% CI, 1.06, 3.27], unstratified log-rank test p=0.0291) and sustained complete withdrawal (17/70 vs 7/70; HR for time to reduction 2.97 [95%CI: 1.26,7.77], unstratified log-rank test p=0.0268). In both groups, complete OGC withdrawal was similar across patient subgroups, including by ANCA status and immunosuppressive use.CONCLUSIONTargeting the interleukin-5 receptor with benralizumab, or circulating interleukin-5 with mepolizumab, are effective OGC-sparing strategies in patients with EGPA.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"39 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103485","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}
Jelleke B de Jonge,Sytze de Roock,Dieneke Schonenberg-Meinema,J Merlijn van den Berg,Deborah A Marshall,Sebastiaan J Vastert,Rae S M Yeung,Joost F Swart,Susanne M Benseler,
{"title":"Effect of time to start of biologic therapy on treatment response in childhood arthritis: Results from the UCAN CAN-DU study.","authors":"Jelleke B de Jonge,Sytze de Roock,Dieneke Schonenberg-Meinema,J Merlijn van den Berg,Deborah A Marshall,Sebastiaan J Vastert,Rae S M Yeung,Joost F Swart,Susanne M Benseler, ","doi":"10.1002/art.43401","DOIUrl":"https://doi.org/10.1002/art.43401","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"162 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103464","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":"Comparative efficacy and safety of anakinra and canakinumab in patients with VEXAS syndrome - an international multicenter study.","authors":"Tali Eviatar,Dafne Capelusnik,Corrado Campochiaro,Valentin Lacombe,Vincent Jachiet,Michael Zisapel,Iftach Sagy,Oshrat E Tayer-Shifman,David Ozeri,Shaye Kivity,Alessandro Tomelleri,Benjamin Terrier,Hagit Peleg,Thibault Comont,Karim Sacre,Pascal Woaye-Hune,Laurent Arnaud,Estibaliz Lazaro,Vincent Grobost,Francois Lifermann,Maxime Samson,Samuel Ardois,Alice Garnier,Alexandre Maria,Alain Cantagrel,Aurore Meyer,Jean-David Bouaziz,Mael Heiblig,Lorenzo Dagna,Elisa Diral,Olivier Kosmider,Ori Elkayam,Jérôme Hadjadj,Sophie Georgin-Lavialle,Olivier Fain,Arsene Mekinian","doi":"10.1002/art.43384","DOIUrl":"https://doi.org/10.1002/art.43384","url":null,"abstract":"OBJECTIVESThe aim of this study was to compare differences in clinical response, drug survival, and adverse event rates between anakinra and canakinumab in VEXAS syndrome.METHODSThis multicenter international study includes VEXAS patients from France, Israel, and Italy treated with IL1 inhibition (IL1i). Global response (GR) was defined as the absence of inflammatory symptoms, 50% or greater decrease in steroid dose and C-reactive protein. Multiple regression analysis was performed to identify associated variables. Drug survival was analyzed using Kaplan-Meier plots and log-rank test, with Cox-regression models for associated factors.RESULTSWe included 47 male VEXAS patients; 44 received anakinra, and 9 received canakinumab, with 6 patients using both at different time points. GR at 1 month was 34% for anakinra and 100% for canakinumab (p<0.001), 22% and 78% at 3 months, respectively (p=0.001). Treatment with canakinumab was associated with higher odds ratio (OR) of achieving GR at 3 months (OR 28.8, 95%CI 3·0-273·9, p=0.004) in a multivariable analysis. Median drug survival was 54 (30-56) months for canakinumab at 300 mg/month, compared to 7 (4-8) months for canakinumab 150 mg/month and 1 (1-2.5) months for anakinra (p=0.01). Injection site reactions were only recorded for the anakinra group (47 vs 0%; p=0.006), whereas infections were more frequent in the anakinra group (31% and 11%; p=0·3).CONCLUSIONSCanakinumab demonstrated superior clinical response and drug survival with fewer adverse events compared to anakinra. Monthly Canakinumab 300 mg may be considered as an effective steroid-sparing therapeutic option for VEXAS patients.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"196 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103463","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}
Monica M Yang,Shuo Liu,Michael Wax,Seoyeon Lee,Sarah French,Paul J Wolters,Francesco Boin
{"title":"Telomere Length of Peripheral Blood Leukocytes Predicts Disease Severity and Worse Survival in Systemic Sclerosis.","authors":"Monica M Yang,Shuo Liu,Michael Wax,Seoyeon Lee,Sarah French,Paul J Wolters,Francesco Boin","doi":"10.1002/art.43400","DOIUrl":"https://doi.org/10.1002/art.43400","url":null,"abstract":"OBJECTIVEPeripheral blood leukocyte telomere length (PBL-TL) shortening is associated with systemic sclerosis related interstitial lung disease (SSc-ILD). However, its association with other organ involvement, disease severity, and survival remains unclear. This study aimed to define the relationship of TL with SSc-specific disease manifestations and outcomes.METHODPBL-TL was measured by quantitative PCR in 244 patients with SSc and 314 healthy controls. Multivariate modeling was utilized to assess the association of PBL-TL with disease severity and event-free survival. Longitudinal changes in PBL-TL were measured in a subset of patients. Telomere length was quantified in SSc skin and lung tissues by telomere fluorescence in situ hybridization.RESULTSPBL-TL was significantly shorter in patients with SSc than healthy controls. Shortened PBL-TL was associated with presence and severity of ILD and pulmonary hypertension (PH) with the shortest PBL-TL found in subjects with concurrent ILD and PH (p=0.04). PBL-TL was not associated with skin disease or peripheral vascular disease. Shorter PBL-TL was associated with hospitalizations (p<0.01) and worse event-free survival (p=0.03). Patients with early SSc had a faster rate of PBL-TL shortening compared to patients with longer disease duration (p = 0.04). TL was shorter in SSc-ILD lung epithelial cells (p=0.01) while no difference was found in epithelial cells of SSc skin (p=0.82).CONCLUSIONShort PBL-TL is associated with pulmonary disease severity and predicts worse SSc clinical outcomes. This study provides rationale to further investigate the role of telomere dysfunction in SSc pathogenesis and validate TL as a prognostic biomarker in SSc.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"63 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077853","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}
Hanna Graßhoff,Sara Comdühr,Henry Nording,Jacob von Esebeck,Philine Letz,Miriam Prohaczka,Handan Gedik,Henner Zirpel,Elisabeth Spallek,Linh Ha-Wissel,El-Baraa Adjailia,Sabrina Arnold,Konstantinos Fourlakis,Sebastian Klapa,Ingo Eitel,Oliver J Müller,Jens Y Humrich,Gabriela Riemekasten,Diamant Thaçi,Peter Lamprecht
{"title":"Transition from psoriasis to psoriatic arthritis is characterized by distinct alterations in peripheral blood Tc17, Th17 and CD4+ TEM cells.","authors":"Hanna Graßhoff,Sara Comdühr,Henry Nording,Jacob von Esebeck,Philine Letz,Miriam Prohaczka,Handan Gedik,Henner Zirpel,Elisabeth Spallek,Linh Ha-Wissel,El-Baraa Adjailia,Sabrina Arnold,Konstantinos Fourlakis,Sebastian Klapa,Ingo Eitel,Oliver J Müller,Jens Y Humrich,Gabriela Riemekasten,Diamant Thaçi,Peter Lamprecht","doi":"10.1002/art.43396","DOIUrl":"https://doi.org/10.1002/art.43396","url":null,"abstract":"OBJECTIVECellular mechanisms driving transition from psoriasis to psoriatic arthritis have remained largely elusive. Thus, we investigated changes within the peripheral blood T cell compartment associated with the transition phase.METHODSIn an observational study, 116 patients were examined and categorized into subgroups including psoriasis with at least one risk factor for transition to psoriatic arthritis, subclinical psoriatic arthritis according to EULAR taskforce recommendations from 2023, and definitive psoriatic arthritis meeting the CASPAR criteria. Demographic and clinical characteristics of patient subgroups were analyzed. Deep T cell phenotyping using multicolor flow cytometry and machine learning techniques were applied.RESULTSOverlapping T cell endotypes were found among patients with subclinical psoriatic arthritis exhibiting the most notable divergence from the others. Frequencies of effector memory CD4+ T (TEM) cells, T helper 17 (Th17) and T cytotoxic 17 (Tc17) cells differed between psoriasis with at least one risk factor for transition, subclinical psoriatic arthritis and psoriatic arthritis. Transition-associated changes of Tc17 cell frequencies were confirmed by machine learning-assisted unsupervised clustering analysis. Moreover, patients with enthesitis could be distinguished from those without, with Tc17 cells being the main distinctive feature.CONCLUSIONTransition from psoriasis to psoriatic arthritis was associated with distinct alterations of the peripheral blood T cell compartment with Tc17 cells exhibiting the greatest discriminatory power. These findings provide insight into pathomechanisms driving disease progression during transition from psoriasis to psoriatic arthritis and identify Tc17 cells as foremost novel potential therapeutic target for the prevention of transition.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"77 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068242","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}
Brent A Luedders,Daniel Kass,Joshua F Baker,Michael J Duryee,Yangyuna Yang,Punyasha Roul,Halie Frideres,Katherine D Wysham,Paul A Monach,Andreas Reimold,Gail S Kerr,Gary Kunkel,Grant W Cannon,Scott M Matson,Jill A Poole,Geoffrey M Thiele,Ted R Mikuls,Bryant R England,Dana P Ascherman
{"title":"Performance of an Idiopathic Pulmonary Fibrosis Derived Multibiomarker Panel for Rheumatoid Arthritis-Associated Interstitial Lung Disease.","authors":"Brent A Luedders,Daniel Kass,Joshua F Baker,Michael J Duryee,Yangyuna Yang,Punyasha Roul,Halie Frideres,Katherine D Wysham,Paul A Monach,Andreas Reimold,Gail S Kerr,Gary Kunkel,Grant W Cannon,Scott M Matson,Jill A Poole,Geoffrey M Thiele,Ted R Mikuls,Bryant R England,Dana P Ascherman","doi":"10.1002/art.43383","DOIUrl":"https://doi.org/10.1002/art.43383","url":null,"abstract":"OBJECTIVETo assess whether a panel of peripheral blood biomarkers associated with idiopathic pulmonary fibrosis (IPF) is also associated with interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) utilizing three independent cohorts.METHODSWe first assessed the association of a panel of IPF-associated biomarkers with prevalent ILD among two separate RA cohorts (n=93 and n=71). Concentrations of eight IPF-related biomarkers (eotaxin, Flt-3L, IL-8, MDC, MCP-1, and MMP-2/7/9) were measured, standardized, and summed to generate a multibiomarker score. We subsequently validated the association of this score (minus MMP-2) with prevalent and incident ILD in an independent multicenter, prospective cohort of US Veterans with RA (n=2,507). Multivariable regression models were adjusted for relevant covariates in the validation cohort.RESULTSIn both development cohorts, participants with RA-ILD had significantly higher IPF multibiomarker scores than those with RA alone. In the independent validation cohort, participants with the highest quartile multibiomarker scores had a significantly higher likelihood of prevalent ILD (adjusted odds ratio 2.14 [95% CI 1.18-3.87]) and incident ILD (adjusted hazard ratio 2.45 [95% CI 1.55-3.88]) than those in the lowest quartile. The cumulative hazard of incident ILD approached 20% by 15 years for those in the highest quartile compared to <10% for all other quartiles.CONCLUSIONA multibiomarker panel derived from IPF-associated biomarkers was associated with RA-ILD in separate development and validation cohorts. This overlap supports the concept of shared etiopathogenesis of IPF and RA-ILD and illustrates the potential for peripheral blood biomarker panels to stratify ILD risk among RA patients.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"19 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068248","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}