Tomas Walhelm, Ioannis Parodis, Charlotta Enerbäck, Elizabeth Arkema, Christopher Sjöwall
{"title":"Comorbid psoriasis in systemic lupus erythematosus: a cohort study from a tertiary referral centre and the National Patient Register in Sweden.","authors":"Tomas Walhelm, Ioannis Parodis, Charlotta Enerbäck, Elizabeth Arkema, Christopher Sjöwall","doi":"10.1136/lupus-2025-001504","DOIUrl":"10.1136/lupus-2025-001504","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the prevalence of psoriasis in SLE using a Swedish regional cohort and a nationwide cohort from the National Patient Register (NPR). Furthermore, we compared clinical features between patients with and without comorbid psoriasis.</p><p><strong>Methods: </strong>In total, 351 patients diagnosed with SLE based on the 1982 American College of Rheumatology and/or the 2012 Systemic Lupus International Collaborating Clinics criteria from Linköping University Hospital were evaluated. We obtained patient-reported and relevant clinical data extracted in 2024. Individuals with coexisting psoriasis were identified via the International Classification of Diseases code L40 and subsequent confirmation through chart review in the regional cohort. In the NPR, 7490 subjects with SLE living in Sweden in 2022 were identified, as well as therapies obtained from the Prescribed Drug Register.</p><p><strong>Results: </strong>We identified 12 subjects with SLE and coexisting psoriasis (3.4%) in the regional cohort and 367 patients (4.9%) in the nationwide cohort. Men were proportionally more common in the group with comorbid psoriasis in both cohorts. Patients with psoriasis reported more pain on a visual analogue scale (median 45.5/100 mm, IQR 23.3-58.3) compared with those without coexisting psoriasis (median 27.0/100 mm, IQR 7.0-50.5, p<0.04). We observed no differences in damage accrual or clinical phenotypes between the two groups. Subjects with psoriasis were more frequently prescribed methotrexate in the nationwide cohort.</p><p><strong>Conclusion: </strong>The prevalence of coexisting psoriasis in patients with SLE in Sweden was estimated to be 3.4-4.9%. Individuals with comorbid psoriasis reported more pain and were more likely to be prescribed methotrexate than those without psoriasis.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yinghua Xu, Xujie Deng, Tao Zhang, Minyi Zhang, Jiaxin Huo, You Peng, Qian Yin, Shujie Liu, Haotong Ouyang, Lien Ma, Ruiyan Liu, Jun Chen, Ruhao Xie, Guifang Hu, Haoyue Hu, Mei Zhong
{"title":"Pregnancy characteristics of patients with systemic lupus erythematosus with different onset times and their risk of adverse pregnancy outcomes: a retrospective cohort study.","authors":"Yinghua Xu, Xujie Deng, Tao Zhang, Minyi Zhang, Jiaxin Huo, You Peng, Qian Yin, Shujie Liu, Haotong Ouyang, Lien Ma, Ruiyan Liu, Jun Chen, Ruhao Xie, Guifang Hu, Haoyue Hu, Mei Zhong","doi":"10.1136/lupus-2025-001529","DOIUrl":"10.1136/lupus-2025-001529","url":null,"abstract":"<p><strong>Objective: </strong>SLE is prevalent among women of reproductive age, increasing the risk of adverse pregnancy outcomes (APOs). However, the correlation between the onset time of SLE and APOs remains unclear. This study aimed to analyse and compare pregnancy outcomes and clinical characteristics among three groups of patients with SLE: those with childhood onset, onset in adulthood before pregnancy and onset in adulthood during pregnancy.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on pregnant women with SLE admitted to Nanfang Hospital of Southern Medical University from 2010 to 2024. Patients were categorised based on the onset time of SLE. Clinical features, laboratory characteristics, medication and pregnancy outcomes were compared among three groups. Logistic regression analyses were used to explore the relationship between the onset time of SLE and APOs.</p><p><strong>Results: </strong>The study included a total of 251 pregnancies from 223 women. Pregnant women with SLE onset in adulthood during pregnancy had more pronounced multisystem disorders, higher disease activity and an increased incidence of APOs. SLE onset in adulthood during pregnancy was associated with a higher risk of fetal loss (OR=5.342, 95% CI 1.629 to 17.520, p=0.006) and premature birth (OR=6.390, 95% CI 1.244 to 32.828, p=0.026).</p><p><strong>Conclusions: </strong>Patients with SLE onset in adulthood during pregnancy exhibit more aggressive disease manifestations and higher rates of APOs, while women with childhood-onset or pre-pregnancy-onset SLE had a lower risk. The incidence of APOs does not correlate with disease duration if maternal disease is quiescent in the period before conception. Closer monitoring and tailored management strategies are needed for these patients.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marta Mosca, Laurent Arnaud, Anca Askanase, Coburn Hobar, Brandon Becker, Shalabh Singhal, Subhashis Banerjee, Samantha Pomponi, Jiyoon Choi, Vibeke Strand
{"title":"Deucravacitinib, an oral, selective, allosteric, tyrosine kinase 2 inhibitor, in patients with active SLE: efficacy on patient-reported outcomes in a phase II randomised trial.","authors":"Marta Mosca, Laurent Arnaud, Anca Askanase, Coburn Hobar, Brandon Becker, Shalabh Singhal, Subhashis Banerjee, Samantha Pomponi, Jiyoon Choi, Vibeke Strand","doi":"10.1136/lupus-2025-001517","DOIUrl":"10.1136/lupus-2025-001517","url":null,"abstract":"<p><strong>Objective: </strong>In PAISLEY, a 48-week, phase II, randomised controlled trial that assessed deucravacitinib in patients with active SLE, all primary and secondary endpoints were met with the deucravacitinib 3 mg two times per day dose. Changes in patient-reported outcomes, collected as exploratory endpoints, were evaluated in this study.</p><p><strong>Methods: </strong>Patients with SLE (n=363) were randomised to placebo (n=90) or deucravacitinib 3 mg two times per day (n=91), 6 mg two times per day (n=93) or 12 mg once daily (n=89). Patients assessed pain levels on a Numeric Rating Scale and completed the Patient-Reported Outcomes Measurement Information System Fatigue Short Form 7a and 36-Item Short Form Health Survey (SF-36) at scheduled intervals. These outcomes were stratified by Systemic Lupus Erythematosus Responder Index 4 (SRI-4) and British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response. Missing data were imputed using control-based pattern imputation.</p><p><strong>Results: </strong>At week 48, greater mean improvement in pain and fatigue scores from day 1 were reported across all deucravacitinib dose groups compared with placebo. Regardless of treatment group, SRI-4 and BICLA responders reported greater improvements in pain and fatigue than non-responders at week 48. Additionally, deucravacitinib-treated patients generally saw greater SRI-4 and BICLA response rates than placebo-treated patients. Pain decreased by 1.3 points vs 2.2-2.3 points and fatigue scores decreased by 3.4 points vs 5.9-7.3 points in the placebo versus deucravacitinib dose groups, respectively. Mean SF-36 physical scores were 41.5 vs ≥44.6 and mean SF-36 mental scores were 45.2 vs ≥46.3 with placebo versus deucravacitinib dose groups, respectively. A greater proportion of patients receiving deucravacitinib also reported clinically meaningful improvements in SF-36 scores compared with placebo.</p><p><strong>Conclusion: </strong>Patients with SLE experienced greater improvements in pain, fatigue and health-related quality-of-life scores at week 48 with deucravacitinib versus placebo treatment.</p><p><strong>Trial registration number: </strong>NCT03252587.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ozge Baba, Hakan Kısaoğlu, Dilara Unal, Umit Gul, Özge Basaran, Sezgin Sahin, Ozgur Kasapcopur, Seza Ozen, Mukaddes Kalyoncu
{"title":"Glucocorticoid tapering early in the course of juvenile SLE: association with lupus low disease activity state and outcomes.","authors":"Ozge Baba, Hakan Kısaoğlu, Dilara Unal, Umit Gul, Özge Basaran, Sezgin Sahin, Ozgur Kasapcopur, Seza Ozen, Mukaddes Kalyoncu","doi":"10.1136/lupus-2024-001415","DOIUrl":"10.1136/lupus-2024-001415","url":null,"abstract":"<p><strong>Objective: </strong>To determine the feasibility and risk of flares by achieving successful glucocorticoid (GC) tapering during the first year of juvenile SLE and the value of early achievement of childhood lupus low disease activity state (cLLDAS).</p><p><strong>Methods: </strong>The medical charts of children with moderate-to-severe SLE between 2012 and 2022 were retrospectively analysed. Successful tapering was defined as the employment of a prednisolone equivalent dose, lower dose of either ≤7.5 mg/day or ≤0.15 mg/kg/day, as per the cLLDAS definition. A linear mixed-effects model was used to determine the fixed effects affecting the GC dose over the first year. Cox regression analysis was used to identify whether successful tapering increased the risk of flares, and logistic regression was used to determine the odds of flares after the twelfth month of treatment.</p><p><strong>Results: </strong>Successful GC tapering was observed in 50 out of 80 patients (62.5%) within the first year of treatment, and flares were observed in 23 (28.8%) patients. The GC tapering trajectories over time were similar based on flare observations (p>0.05). Furthermore, successful tapering did not increase the risk of flares. Additionally, patients without flares received significantly higher GC doses as the initial treatment (p=0.046). Achievement of cLLDAS was observed in 40 (50%) patients at the twelfth month; however, achievement was not protective against future flares, and positive anti-double-stranded DNA antibodies at the twelfth month increased the odds of flares (OR: 4.8, p=0.008).</p><p><strong>Conclusion: </strong>Successful GC tapering is feasible and does not increase the risk of flares during the early disease phase. However, flares are common and adversely affect GC tapering. Thus, the identification of children with an increased risk of flares on GC tapering is needed to reduce the GC burden.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long-term efficacy and safety of the Lupus-Cruces Nephritis protocol: a propensity score study of the Lupus-Cruces and Lupus-Bordeaux cohorts.","authors":"Guillermo Ruiz-Irastorza, Beatriz Marín-García, Luis Dueña-Bartolomé, Diana Paredes Ruiz, Amaia Osorio, Estibaliz Lazaro","doi":"10.1136/lupus-2025-001562","DOIUrl":"10.1136/lupus-2025-001562","url":null,"abstract":"<p><strong>Objective: </strong>To assess the efficacy and toxicity of the Lupus-Cruces Nephritis (LCN) protocol compared with standard of care (SOC) with cyclophosphamide (CYC) or mycophenolate in patients with lupus nephritis (LN) during an extended follow-up time up to 10 years.</p><p><strong>Methods: </strong>Patients with biopsy-proven class III, IV or V LN treated with LCN were compared with SOC. Patients in the LCN were treated with a CYC plus repeated methylprednisolone pulse-based regimen. The achievement of complete renal response (CRR) and the progression to chronic kidney disease (CKD) were the two main outcomes. Glucocorticoid (GC)-related toxicity, major infections and damage accrual were also analysed. A propensity score (PS)-adjusted multivariate analysis was used to overcome the confounding-by-indication bias.</p><p><strong>Results: </strong>147 patients were included in this study (47 LCN and 100 SOC). CRR at 12 months was 85% vs 44%, respectively (p<0.001). Eventually, 96% patients in the LCN group achieved CRR vs 74% patients in the SOC (p=0.002). In the multivariate PS-adjusted Cox model, LCN patients were more likely to eventually achieve CRR (PS-adjusted HR 3.5, 95% CI 2.2 to 5.5, p<0.001). The risk of progression to CKD was lower in LCN patients (PS-adjusted HR 0.3, 95% CI 0.11 to 0.82, p=0.019). The risks of GC-induced toxicity, renal or GC-related damage accrual and major infections were also lower in the LCN group: adjusted HR 0.09, 95% CI 0.02 to 0.39; PS-adjusted HR 0.14, 95% CI 0.04 to 0.4; PS-adjusted HR 0.2, 95% CI 0.046 to 0.95; respectively.</p><p><strong>Conclusions: </strong>This study confirms the LCN protocol as an effective and safe, in addition to widely available and affordable, regimen for the induction therapy of LN.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anca D Askanase, Edward M Vital, Oliver Meier, Armando Turchetta, Huiyan Ashley Mao, Justine Maller, Jorge A Ross Terres, Maria Dall'Era
{"title":"Evaluating the concordance between BICLA and SRI4 in patients with systemic lupus erythematosus from the placebo arms of the EXPLORER and ATHOS trials.","authors":"Anca D Askanase, Edward M Vital, Oliver Meier, Armando Turchetta, Huiyan Ashley Mao, Justine Maller, Jorge A Ross Terres, Maria Dall'Era","doi":"10.1136/lupus-2024-001483","DOIUrl":"10.1136/lupus-2024-001483","url":null,"abstract":"<p><strong>Objective: </strong>The British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) and the Systemic Lupus Erythematosus Responder Index 4 (SRI4) responses are the most common primary endpoints in SLE clinical trials. We examined the concordance and the reasons for discordance in BICLA/SRI4 responses in participants with SLE receiving placebo and standard of care (SOC) in two randomised controlled trials.</p><p><strong>Methods: </strong>This post-hoc analysis included data from the placebo arm (participants treated with SOC) of the EXPLORER (n=87; NCT00137969) and ATHOS (n=80; NCT02908100) trials. Disease activity was measured using BILAG and SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index) in the EXPLORER trial and BILAG-2004 and SLEDAI-2000K in the ATHOS trial. For this analysis, participants were classified as responders or non-responders based on BICLA and SRI4 and the presence of intercurrent events. Concordance and discordance frequencies between BICLA and SRI4 were determined.</p><p><strong>Results: </strong>In EXPLORER, the BICLA response rates were lower than the SRI4 response rates (29.9% vs 41.4% at week 52, respectively), whereas in ATHOS the BICLA and SRI4 response rates were similar (41.2% vs 43.8% at week 48, respectively). The overall BICLA/SRI4 concordance (Cohen's κ score) was moderate (0.46 in EXPLORER and 0.54 in ATHOS at weeks 52 and 48, respectively). At weeks 52 and 48, BICLA+/SRI4- and BICLA-/SRI4+ discordance, respectively, was 6.9% and 18.4% in EXPLORER and 10.0% and 12.5% in ATHOS. In an analysis of ATHOS subgroups based on the presence or absence of rash at baseline, BICLA response was higher at week 48 in participants with arthritis only than in those with arthritis and mucocutaneous comanifestations (63.2% vs 33.9%, respectively). BICLA-/SRI4+ and BICLA+/SRI4- discordance was lower in participants with low compared with normal complement at baseline.</p><p><strong>Conclusions: </strong>BICLA and SRI4 may be discordant in SLE trials. Arthritis and rash were the primary drivers of the discordance, and serology influenced BICLA and SRI4 response, suggesting the need for evaluation of multiple efficacy endpoints rather than a single measure.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diogo Jesus, Ana Matos, Carla Henriques, Andrea Doria, Luis Sousa Ines
{"title":"SLE-DAS enables an accurate definition of severe lupus disease activity: derivation and validation in a post hoc study of anifrolumab phase II and III studies.","authors":"Diogo Jesus, Ana Matos, Carla Henriques, Andrea Doria, Luis Sousa Ines","doi":"10.1136/lupus-2025-001499","DOIUrl":"10.1136/lupus-2025-001499","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to derive and validate a cut-off for severe disease activity (SDA) using the SLE Disease Activity Score (SLE-DAS) and compare its accuracy and impact on health-related quality of life (HR-QoL) with the British Isles Lupus Assessment Group 2004 (BILAG-2004) and SLE Disease Activity Index 2000 (SLEDAI-2K).</p><p><strong>Methods: </strong>We performed a post hoc analysis of pooled placebo arm data from the MUSE (A Phase II, Randomized Study to Evaluate the Efficacy and Safety of MEDI-546 in Subjects with Systemic Lupus Erythematosus), TULIP-1 and TULIP-2 (Treatment of Uncontrolled Lupus via the Interferon Pathway) trials, including 438 patients with moderate-to-severe SLE. SLE-DAS was scored retrospectively, and a cut-off for SDA was derived using receiver operating characteristic (ROC) curves against the BILAG-2004 numerical score >11 as gold standard. Multiple linear regression analysis and Cohen's d effect size were applied to evaluate the effectiveness of SLE-DAS, BILAG-2004 and SLEDAI-2K SDA classifications in capturing HR-QoL patient-reported outcomes (PROs).</p><p><strong>Results: </strong>The optimal SLE-DAS cut-off for SDA was >9.90 (area under the ROC curve=0.847, sensitivity=77.8%, specificity=79.6%). Patients classified as SDA by both SLE-DAS and BILAG-2004 or only by SLE-DAS exhibited similar disease activity, while those classified by BILAG-2004 alone had less severe disease and better HR-QoL. The SLE-DAS cut-off was associated with worse HR-QoL across multiple PROs more consistently than BILAG-2004 or SLEDAI-2K.</p><p><strong>Conclusion: </strong>The SLE-DAS cut-off for SDA provides an accurate definition of SDA in SLE, with good discriminative power and consistent associations with worse HR-QoL. This SLE-DAS definition enhances disease activity classification and offers a practical tool for guiding treatment decisions in clinical practice, as well as selecting patients with SDA for inclusion in clinical trials.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
María Martínez-Urbistondo, Andrea Higuera-Gómez, Begoña de Cuevillas, Amanda Cuevas-Sierra, Susana Mellor-Pita, Victor Moreno-Torres, Juan-Antonio Vargas, Raquel Castejón, J Alfredo Martínez
{"title":"Visceral fat, cardiovascular risk factors and quality of life in lupus activity categorised via complement C3.","authors":"María Martínez-Urbistondo, Andrea Higuera-Gómez, Begoña de Cuevillas, Amanda Cuevas-Sierra, Susana Mellor-Pita, Victor Moreno-Torres, Juan-Antonio Vargas, Raquel Castejón, J Alfredo Martínez","doi":"10.1136/lupus-2024-001423","DOIUrl":"10.1136/lupus-2024-001423","url":null,"abstract":"<p><strong>Background: </strong>Patients with lupus face increased cardiovascular risk linked to their autoimmune status. This study assesses the relationships between cardiovascular risk factors, lifestyle and health-related quality of life (HRQoL) concerning SLE activity categorised by complement C3.</p><p><strong>Methods: </strong>74 patients with SLE were recruited and stratified as active (C3 <90 mg/dL) or inactive (C3 >90 mg/dL), alongside 74 controls with obesity-related low-grade inflammation, at Hospital Universitario Puerta de Hierro Majadahonda. Anthropometric measurements, clinical and demographic data were recorded, and participants completed validated questionnaires on physical activity, dietary intake and HRQoL. Fasting blood samples were collected for metabolic determinations. Comparative analyses between SLE groups and controls, along with regression models adjusted for variables associated with disease activity, were performed.</p><p><strong>Results: </strong>The inactive SLE group exhibited a less healthy adiposity profile compared with the active group (36.7% vs 33.2% total fat mass; 8.5 AU vs 6.5 AU visceral fat mass) and showed a higher prevalence of cardiovascular risk factors, including markers of obesity, hypertension, dyslipidaemia and increased waist circumference, along with worse HRQoL outcomes. Notably, age, body mass index and insulin resistance were associated with SLE inactivity, while fibrinogen correlated with disease activity as assessed by complement C3 levels. Interestingly, household composition as a sociodemographic variable (alone, couple/children/elderly or other) also showed an independent association with SLE activity.</p><p><strong>Conclusions: </strong>Inactive patients with SLE exhibited more adverse cardiovascular risk markers compared with active patients categorised by complement C3, even when glucocorticoid administration was accounted for. Additionally, this research highlights the potential influence of fibrinogen as well as metabolic and sociodemographic factors on disease activity. These findings emphasise the need for personalised precision management strategies such as measurement of fibrinogen levels and insulin resistance and sociodemographic considerations that address both cardiovascular risk and overall lifestyle plus exposome in patients with SLE and may partly explain SLE activity evolution.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erika Hubbard, Prathyusha Bachali, Amrie C Grammer, Peter E Lipsky
{"title":"Validation of eight endotypes of lupus based on whole-blood RNA profiles.","authors":"Erika Hubbard, Prathyusha Bachali, Amrie C Grammer, Peter E Lipsky","doi":"10.1136/lupus-2025-001526","DOIUrl":"10.1136/lupus-2025-001526","url":null,"abstract":"<p><strong>Objective: </strong>We previously described a classification system of persons with SLE based on whole blood RNA profiles and a random forest (RF) algorithm to predict individual patient endotypes. Here, we apply this algorithm prospectively in an independent set of patients to validate its use as a staging biomarker.</p><p><strong>Methods: </strong>Whole blood from 101 patients participating in three clinical trials (NCT03626311, NCT03180021 and NCT05845593) meeting American College of Rheumatology (ACR) or Systemic Lupus Collaborating Clinics (SLICC) criteria for SLE classification was obtained at baseline, and RNA isolated and sequenced. Gene expression values were used as input to gene set variation analysis (GSVA), and the RF algorithm was applied using GSVA enrichment scores of 32 informative gene sets as input. Composite scores summarising gene expression perturbations were assigned to each patient using a ridge logistic regression algorithm.</p><p><strong>Results: </strong>Patients with SLE were subset into eight endotypes identified by the algorithm. Patterns of gene enrichment in the identified endotypes mirrored those found in the previously reported endotypes. Differences in clinical characteristics, including serum complement levels, autoantibody positivity and the presence of nephritis, were observed between patients in various endotypes. Patients with active, concurrent nephritis were disproportionately assigned to the more molecularly perturbed endotypes. Composite scores were significantly, but modestly, inversely correlated with complement but not SLE Disease Activity Index (SLEDAI) or anti-double-stranded DNA antibody (anti-dsDNA) titre.</p><p><strong>Conclusions: </strong>The identification of eight molecular endotypes of lupus based on whole blood gene expression was validated in an independent data set of diverse patients. Endotyping patients with SLE based on transcriptional profiles can provide important status (presence of nephritis) information and provide novel molecular insights in support of personalised management.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiangning Yuan, Tong Li, Yudong Liu, Min Wang, Xiaoxia Zuo, Ying Jiang, Xuan Zhang
{"title":"Efficacy and safety of belimumab versus rituximab for refractory immune thrombocytopenia in patients with connective tissue disease.","authors":"Xiangning Yuan, Tong Li, Yudong Liu, Min Wang, Xiaoxia Zuo, Ying Jiang, Xuan Zhang","doi":"10.1136/lupus-2025-001501","DOIUrl":"10.1136/lupus-2025-001501","url":null,"abstract":"<p><strong>Objectives: </strong>Immune thrombocytopenia (ITP) is a haematological manifestation secondary to connective tissue disease (CTD). Many patients with CTD-ITP are refractory to glucocorticoids (GCs) plus immunosuppressant agents (ISAs); rituximab (RTX) is the recommended second-line therapy. Belimumab (BLM) shows efficacy against CTD. We compared the efficacy and safety of RTX and BLM.</p><p><strong>Methods: </strong>Data of patients with CTD-ITP refractory to GCs plus ISAs administered were collected. The data of 11 patients with refractory CTD-ITP who received BLM were compared with those of 15 patients treated with RTX.</p><p><strong>Results: </strong>At week 2, BLM resulted in a better overall response (OR) than RTX (72.7% vs 26.7%, p=0.045). The OR rate was 60.0% (9/15), 66.7% (10/15) and 73.3% (11/15) at week 4, 8 and 12, respectively, in the RTX group. It remained at 72.7% (8/11) during week 4-12 in the BLM group. Excluding the data of three deceased patients, the OR rate dropped at week 24 in both groups (RTX vs BLM, 61.5% (8/13) vs 70.0% (7/10), p=1.000). At week 24, four patients with OR in both groups successfully withdrew GCs to <15 mg prednisone (RTX vs BLM, 40% (4/10) vs 66.7% (4/6), p=0.608). The serum C3 level did not significantly change, whereas the serum immunoglobulin G level significantly decreased at week 4, 8 and 12 in both groups. There were three patients with serious adverse effects who died of severe pneumonia during weeks 12-24.</p><p><strong>Conclusions: </strong>BLM may be a safe and effective alternative to RTX for CTD-ITP refractory to GCs plus ISAs.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}