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Time trends of variability in disease activity in systemic lupus erythematosus.
IF 3.7 2区 医学
Lupus Science & Medicine Pub Date : 2025-02-12 DOI: 10.1136/lupus-2024-001335
Ning Li, Alberta Hoi, Shue-Fen Luo, Yeong-Jian Jan Wu, Worawit Louthrenoo, Vera Golder, Sargunan Sockalingam, Jiacai Cho, Aisha Lateef, Sean O'Neill, Chak Sing Lau, Laniyati Hamijoyo, Mandana Nikpour, Shereen Oon, Yanjie Hao, Madelynn Chan, Zhanguo Li, Sandra Navarra, Leonid Zamora, Yasuhiro Katsumata, Masayoshi Harigai, Fiona Goldblatt, Sang-Cheol Bae, Zhuoli Zhang, Tsutomu Takeuchi, Jun Kikuchi, Kristine Ng, Nicola Tugnet, Yoshiya Tanaka, Naoaki Ohkubo, Yi-Hsing Chen, B M D B Basnayake, Annie Law, Sunil Kumar, Cherica Tee, Michael Lucas Tee, Jiyoon Choi, Rangi Kandane-Rathnayake, Eric Morand
{"title":"Time trends of variability in disease activity in systemic lupus erythematosus.","authors":"Ning Li, Alberta Hoi, Shue-Fen Luo, Yeong-Jian Jan Wu, Worawit Louthrenoo, Vera Golder, Sargunan Sockalingam, Jiacai Cho, Aisha Lateef, Sean O'Neill, Chak Sing Lau, Laniyati Hamijoyo, Mandana Nikpour, Shereen Oon, Yanjie Hao, Madelynn Chan, Zhanguo Li, Sandra Navarra, Leonid Zamora, Yasuhiro Katsumata, Masayoshi Harigai, Fiona Goldblatt, Sang-Cheol Bae, Zhuoli Zhang, Tsutomu Takeuchi, Jun Kikuchi, Kristine Ng, Nicola Tugnet, Yoshiya Tanaka, Naoaki Ohkubo, Yi-Hsing Chen, B M D B Basnayake, Annie Law, Sunil Kumar, Cherica Tee, Michael Lucas Tee, Jiyoon Choi, Rangi Kandane-Rathnayake, Eric Morand","doi":"10.1136/lupus-2024-001335","DOIUrl":"10.1136/lupus-2024-001335","url":null,"abstract":"<p><strong>Objective: </strong>Disease activity both between and within patients with SLE is highly variable, yet factors driving this variability remain unclear. This study aimed to identify predictors of variability in SLE disease activity over time.</p><p><strong>Methods: </strong>We analysed data from 2930 patients with SLE across 13 countries, collected over 38 754 clinic visits between 2013 and 2020. Clinic visit records were converted to panel data with 1-year intervals. The time-adjusted mean disease activity, termed <i>AMS</i>, was calculated. The yearly change in [Formula: see text], denoted as [Formula: see text], was regressed onto [Formula: see text] and other potential predictors using random-effects models. Some variables were split into a person-mean component to assess between-patient differences and a demeaned component to assess within-patient variability.</p><p><strong>Results: </strong>Overall, variability in SLE disease activity exhibited stabilisation over time. A significant inverse relationship emerged between a patient's disease activity in a given year and variability in disease activity in the subsequent year: a 1-point increase in person-mean disease activity was associated with a 0.27-point decrease (95% CI -0.29 to -0.26, p<0.001) in subsequent variability. Additionally, a 1-point increase in within-patient disease activity variability was associated with a 0.56-point decrease (95% CI -0.57 to -0.55, p<0.001) in the subsequent year. Furthermore, each 1-point increase in the annual average time-adjusted mean Physician Global Assessment was associated with a 0.08-point decrease (90% CI -0.13 to -0.03, p=0.002) in disease activity variability for the following year. Prednisolone dose and the duration of activity in specific organ systems exhibited negative and positive associations, respectively, with disease activity variability in the subsequent year. Patients from less affluent countries displayed greater disease activity variability compared with those from wealthier nations.</p><p><strong>Conclusion: </strong>Disease activity tends to be less variable among patients with higher or more variable disease activity in the previous year. Within-patient variability in disease activity has a stronger impact on subsequent fluctuations than differences between individual patients.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408805","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}
引用次数: 0
Characteristics and clinical outcomes of patients with systemic lupus erythematosus initiating anifrolumab in a real-world setting in Spain (AZAHAR study): an observational study protocol.
IF 3.7 2区 医学
Lupus Science & Medicine Pub Date : 2025-02-12 DOI: 10.1136/lupus-2024-001486
María Galindo-Izquierdo, Noemí Bahamontes-Rosa, Berta Sarto-Ferres, Marta Galvez-Fernandez, Josefina Cortés-Hernández
{"title":"Characteristics and clinical outcomes of patients with systemic lupus erythematosus initiating anifrolumab in a real-world setting in Spain (AZAHAR study): an observational study protocol.","authors":"María Galindo-Izquierdo, Noemí Bahamontes-Rosa, Berta Sarto-Ferres, Marta Galvez-Fernandez, Josefina Cortés-Hernández","doi":"10.1136/lupus-2024-001486","DOIUrl":"10.1136/lupus-2024-001486","url":null,"abstract":"<p><strong>Introduction: </strong>Anifrolumab (Saphnelo) is approved for adult patients with moderate-severe systemic lupus erythematosus (SLE). Considering its commercialisation in Spain in 2023, observational studies describing the use of anifrolumab in routine clinical practice are limited. The aim of the AZAHAR study is to describe the characteristics and clinical outcomes of patients with SLE who initiated anifrolumab during its first year of marketing in Spain.</p><p><strong>Methods and analysis: </strong>This is an observational retrospective study including ~120 patients with moderate-severe SLE who received anifrolumab in Spain in 20 centres from 1 June 2023 to 31 May 2024. Patients will be followed up every 6 months after the first infusion of anifrolumab for a period between 6 and 18 months until the end of the study (31 December 2024). Data will be obtained through the review of medical records, considering as primary outcomes disease activity measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000, clinical SLEDAI, Physician Global Assessment and Lupus Low Disease Activity State and remission, defined by Definitions of Remission in SLE-21, and as secondary outcomes, SLE treatment, flare incidence, anifrolumab adherence and persistence (time on treatment) and healthcare resources utilisation.</p><p><strong>Ethics and dissemination: </strong>The final protocol of the study will be approved by ethics committees/institutional review boards (IRB)/independent ethics committees at each site.</p><p><strong>Trial registration number: </strong>NCT06626945.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408797","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}
引用次数: 0
Rare and common single nucleotide variants in childhood-onset systemic lupus erythematosus.
IF 3.7 2区 医学
Lupus Science & Medicine Pub Date : 2025-02-11 DOI: 10.1136/lupus-2024-001436
Ahmed Sayadi, Johanna K Sandling, Maija-Leena Eloranta, Andreas Jönsen, Iva Gunnarsson, Solbritt Rantapää-Dahlqvist, Christopher Sjöwall, Anders A Bengtsson, Elisabet Svenungsson, Kerstin Lindblad-Toh, Dag Leonard, Lars Rönnblom
{"title":"Rare and common single nucleotide variants in childhood-onset systemic lupus erythematosus.","authors":"Ahmed Sayadi, Johanna K Sandling, Maija-Leena Eloranta, Andreas Jönsen, Iva Gunnarsson, Solbritt Rantapää-Dahlqvist, Christopher Sjöwall, Anders A Bengtsson, Elisabet Svenungsson, Kerstin Lindblad-Toh, Dag Leonard, Lars Rönnblom","doi":"10.1136/lupus-2024-001436","DOIUrl":"10.1136/lupus-2024-001436","url":null,"abstract":"<p><strong>Background: </strong>SLE is a systemic autoimmune disease with a large number of common risk gene variants, but several rare gene variants can cause monogenic SLE. The relationship between common and rare variants in SLE is unclear. We therefore investigated the occurrence of rare deleterious variants in patients with childhood-onset SLE (cSLE) and adult-onset SLE (aSLE) and compared the frequency of these variants with their individual SLE polygenic risk score (PRS).</p><p><strong>Materials and methods: </strong>Targeted sequencing of 1832 gene regions, including coding regions of 31 genes associated with monogenic SLE, was performed in 958 patients with SLE and 1026 healthy individuals. A total of 116 patients with SLE had disease onset before the age of 18 (cSLE). An SLE common variant PRS was created from 37 SLE genome-wide association study single nucleotide variants (SNVs).</p><p><strong>Results: </strong>Rare coding deleterious SNVs (RD SNVs) were observed in 23 of the monogenic SLE-associated genes. Six per cent of patients with cSLE, compared with 3.2% of controls and 4.6% of patients with aSLE, carried rare deleterious alleles. In cSLE, RD SNVs were observed in the <i>C1S</i>, <i>DDX58</i>, <i>IFIH1</i>, <i>IKZF1</i>, <i>RNASEH2A</i> and <i>C8A</i> genes. A PRS analysis showed that patients with cSLE with any of these gene variants had a similar average PRS as control individuals.</p><p><strong>Conclusion: </strong>RD SNVs were observed in a small proportion of cSLE and carriers of these RD SNVs had a PRS similar to healthy individuals, suggesting the importance of rare coding heterozygous variants in driving disease risk in a subset of children with SLE.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399496","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}
引用次数: 0
Association of race and ethnicity with mortality in adults with SLE: a systematic literature review and meta-analysis.
IF 3.7 2区 医学
Lupus Science & Medicine Pub Date : 2025-02-11 DOI: 10.1136/lupus-2024-001383
Samir Patel, Zijing Yang, Deepak Nagra, Maryam Adas, Mark Russell, Sam Norton, Chris Wincup, James Galloway, Kate Bramham, Patrick Gordon
{"title":"Association of race and ethnicity with mortality in adults with SLE: a systematic literature review and meta-analysis.","authors":"Samir Patel, Zijing Yang, Deepak Nagra, Maryam Adas, Mark Russell, Sam Norton, Chris Wincup, James Galloway, Kate Bramham, Patrick Gordon","doi":"10.1136/lupus-2024-001383","DOIUrl":"10.1136/lupus-2024-001383","url":null,"abstract":"<p><strong>Objectives: </strong>Ethnicity and health outcomes are intrinsically interrelated, although mechanisms are complex. SLE is a disease with higher incidence in Asian, Black, Hispanic and Indigenous populations than in White populations. SLE is associated with premature mortality, but it is unclear if ethnicity impacts on health outcomes as studies are frequently underpowered. We aimed to describe the association between SLE and mortality across different racial and ethnic groups using meta-analysis.</p><p><strong>Methods: </strong>We identified studies of adults with SLE that reported mortality, stratified by racial and ethnic group, through a systematic literature review. We used a pairwise meta-analysis to determine the pooled odds ratio (OR) of death for those from underserved groups compared with those of White race and ethnicity.</p><p><strong>Results: </strong>Thirty-seven studies, comprising 85 578 patients with SLE, were included. Mortality was higher in Black patients (OR 1.30 (95% CI 1.16 to 1.46)) and Indigenous patients (OR 1.47 (95% CI 1.11 to 1.94)), while Asian and Hispanic patients showed no significant differences compared with White patients with SLE. Seventy per cent of included studies were conducted in the USA and when excluded, the significant difference in mortality between Black and White individuals with SLE was no longer seen (OR 0.84 (95% CI 0.54 to 1.31)).</p><p><strong>Conclusion: </strong>Overall, patients with SLE from Black or Indigenous racial and ethnic groups had higher mortality than those of White race and ethnicity. We observed no significant association in the mortality of Black patients compared with White patients from non-USA cohorts, but a scarcity of data outside of the USA was highlighted. We promote caution in the use of race and ethnicity as a factor in determining mortality risk until more generalisable data are available.</p><p><strong>Prospero registration number: </strong>CRD42023379034.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399388","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}
引用次数: 0
Intermediate monocytes in blood correlate with subclinical vascular changes in lupus nephritis.
IF 3.7 2区 医学
Lupus Science & Medicine Pub Date : 2025-02-06 DOI: 10.1136/lupus-2024-001432
Shivani Garg, Sara S McCoy, Izzy Hartel, Abigail Muhlstock, Amish N Raval, Christie Bartels
{"title":"Intermediate monocytes in blood correlate with subclinical vascular changes in lupus nephritis.","authors":"Shivani Garg, Sara S McCoy, Izzy Hartel, Abigail Muhlstock, Amish N Raval, Christie Bartels","doi":"10.1136/lupus-2024-001432","DOIUrl":"10.1136/lupus-2024-001432","url":null,"abstract":"","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365239","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}
引用次数: 0
Lower circulating mitochondrial DNA and increased mitokines suggest significant mitochondrial dysfunction in systemic lupus erythematosus with renal involvement.
IF 3.7 2区 医学
Lupus Science & Medicine Pub Date : 2025-02-03 DOI: 10.1136/lupus-2024-001368
Matthieu Halfon, Ashfaque A Memon, Anna Hedelius, Manuel Pascual, Kristina Sundquist, Camillo Ribi
{"title":"Lower circulating mitochondrial DNA and increased mitokines suggest significant mitochondrial dysfunction in systemic lupus erythematosus with renal involvement.","authors":"Matthieu Halfon, Ashfaque A Memon, Anna Hedelius, Manuel Pascual, Kristina Sundquist, Camillo Ribi","doi":"10.1136/lupus-2024-001368","DOIUrl":"10.1136/lupus-2024-001368","url":null,"abstract":"<p><strong>Background: </strong>SLE is associated with significant morbidity, especially in the case of renal involvement. Mitochondrial dysfunction plays a significant role in SLE and may be assessed by measuring mitochondrial DNA (mtDNA) and cytokines reflecting mitochondrial stress (mitokines). Circulating mtDNA is a promising biomarker in SLE and appears to be reduced in severe SLE. However, measuring circulating mtDNA is challenging and reported methods are heterogenous. Our study aimed at evaluating whole blood mtDNA to nuclear DNA (nucDNA) ratio using droplet-digital PCR and circulating mitokines, growth differentiation factor 15 (GDF-15) and fibroblast growth factor 21 in SLE with and without renal involvement.</p><p><strong>Methods: </strong>Cross-sectional study involving 195 patients with SLE and age-matched healthy volunteers (HV) as control. Biomarkers were compared in patients with and without renal involvement (defined by estimated glomerular filtration rate <60 mL/min or proteinuria >0.5 g/day) and in those with active and inactive SLE.</p><p><strong>Results: </strong>Compared with HV, patients with SLE displayed lower mtDNA/nucDNA ratios, especially in the case of renal involvement. Accordingly, mitokines were increased in patients with SLE with renal involvement. We found no correlation between mtDNA/nucDNA ratio and global disease activity. Mitokine levels, on the other hand, correlated with disease activity, in particular GDF-15 even after adjusting for renal involvement.</p><p><strong>Conclusion: </strong>Our findings suggest that lower whole blood mtDNA/nucDNA ratio, a surrogate marker for mitochondrial dysfunction, reflects renal damage, while GDF-15 may also reflect disease activity in SLE. Further studies are needed to assess the clinical value of these markers as predictors for active lupus nephritis.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123201","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}
引用次数: 0
Medication-related hospitalisations in patients with SLE.
IF 3.7 2区 医学
Lupus Science & Medicine Pub Date : 2025-01-30 DOI: 10.1136/lupus-2024-001362
Michèle Stanciu, Joo-Young Esther Lee, Emily G McDonald, Gregory Clark, Christian A Pineau, Fares Kalache, Louis-Pierre Grenier, Évelyne Vinet, Sasha Bernatsky, Arielle Mendel
{"title":"Medication-related hospitalisations in patients with SLE.","authors":"Michèle Stanciu, Joo-Young Esther Lee, Emily G McDonald, Gregory Clark, Christian A Pineau, Fares Kalache, Louis-Pierre Grenier, Évelyne Vinet, Sasha Bernatsky, Arielle Mendel","doi":"10.1136/lupus-2024-001362","DOIUrl":"10.1136/lupus-2024-001362","url":null,"abstract":"<p><strong>Objectives: </strong>Patients with SLE take multiple medications. Within a large prospective longitudinal SLE cohort, we characterised medication-related hospitalisations and their preventability.</p><p><strong>Methods: </strong>We identified consecutive admissions to our tertiary hospitals between 2015 and 2020. Two independent adjudicators evaluated if medication-related events contributed to the hospitalisation, considering (1) adverse drug events (ADEs) and (2) events from medication non-adherence, using the Leape and Bates method. We classified ADEs as potentially preventable/ameliorable if we identified modifiable factors. Logistic regressions with generalised estimating equations evaluated associations between participant characteristics and medication-related hospitalisations, accounting for repeat hospitalisations within the same participant.</p><p><strong>Results: </strong>We studied 68 hospitalisations among 45 participants (91% female). At first hospitalisation, the median age was 38 years (IQR 26.5-53.0) and median SLE duration was 12 years (IQR 5.5-19.5). One or more ADEs contributed to 20 (29%) hospitalisations (11/23 (48%) ADEs being preventable/ameliorable), and SLE flares associated with medication non-adherence contributed to 7 (10%) hospitalisations. Adjusting for age and sex, current prednisone use (adjusted OR (aOR) 3.7, 95% CI 1.1 to 13.0) or ≥1 current immunosuppressant (aOR 11.5, 95% CI 2.7 to 50.0), renal involvement at SLE diagnosis (aOR 6.5, 95% CI 2.7 to 15.7) and polypharmacy (≥5 medications; aOR 11.3, 95% CI 1.2 to 103.8) were associated with having an ADE-related (vs non-ADE) hospitalisation. Age at SLE diagnosis<18 years (OR 5.9, 95% CI 1.3 to 26.6) was associated with hospitalisation for a flare related to non-adherence.</p><p><strong>Conclusion: </strong>Forty per cent of SLE hospitalisations were medication-related, while half were potentially preventable/ameliorable. Renal involvement, polypharmacy, prednisone and immunosuppressant use were associated with hospitalisation related to an ADE, highlighting a vulnerable group.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066449","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}
引用次数: 0
Metabolic profiles of cutaneous lupus have abnormalities in the nicotinamide adenine dinucleotide pathway.
IF 3.7 2区 医学
Lupus Science & Medicine Pub Date : 2025-01-25 DOI: 10.1136/lupus-2024-001401
Laila F Abbas, Grant Barber, Grace Lu, Bahir Chamseddin, Hieu Vu, Ling Cai, Divya Srivastava, Rajiv L Nijhawan, Richard C Wang, Benjamin F Chong
{"title":"Metabolic profiles of cutaneous lupus have abnormalities in the nicotinamide adenine dinucleotide pathway.","authors":"Laila F Abbas, Grant Barber, Grace Lu, Bahir Chamseddin, Hieu Vu, Ling Cai, Divya Srivastava, Rajiv L Nijhawan, Richard C Wang, Benjamin F Chong","doi":"10.1136/lupus-2024-001401","DOIUrl":"10.1136/lupus-2024-001401","url":null,"abstract":"<p><strong>Objective: </strong>Metabolic reprogramming plays a critical role in modulating the innate and adaptive immune response, but its role in cutaneous autoimmune diseases, such as cutaneous lupus erythematosus (CLE), is less well studied. An improved understanding of the metabolic pathways dysregulated in CLE may lead to novel treatment options, biomarkers and insights into disease pathogenesis. The objective was to compare metabolomic profiles in the skin and sera of CLE and control patients using liquid chromatography-mass spectrometry (LC-MS).</p><p><strong>Methods: </strong>This was a cross-sectional pilot study comparing metabolomic sera and skin profiles of patients with CLE and normal controls. Patients were recruited from outpatient dermatology clinics at the University of Texas Southwestern and Parkland Health in Dallas, Texas, from January 2019 to October 2020. Skin and serum samples underwent LC-MS analysis. Disease sample metabolite levels were compared with controls, with significance levels adjusted for multiple hypothesis testing.</p><p><strong>Results: </strong>17 serum samples (9 CLE, 8 control) and 11 skin samples (5 CLE, 6 control) were analysed using LC-MS, yielding 313 known unique metabolic structures from CLE samples. Patients with CLE were found to have 11 metabolites of differential abundance in the skin, but only 2 in the sera. CLE skin showed increased levels of citrulline (log<sub>2</sub> fold change (FC)=1.15, p=0.02) and uracil (log<sub>2</sub>FC=1.79, p=0.04), and downregulation of cyclic ADP ribose (cADPr) (log<sub>2</sub>FC=0.83, p=0.04), nicotinamide mononucleotide (NMN) (log<sub>2</sub>FC=0.75, p=0.016) and nicotinamide adenine dinucleotide (NAD<sup>+</sup>) (log<sub>2</sub>FC=0.86, p=0.016) versus control skin. CLE sera had increased arabinose (log<sub>2</sub>FC=1.17, p=0.02) and cystine (log<sub>2</sub>FC=1.04, p=0.03) compared with control sera.</p><p><strong>Conclusions: </strong>Metabolites associated with the NAD<sup>+</sup> pathway may be dysregulated in the skin of patients with CLE. Available treatments including nicotinamide supplementation and anti-CD38 biologics that can correct these abnormalities can be further investigated in patients with CLE.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039632","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}
引用次数: 0
Real-world treatment patterns and clinical characteristics in patients with moderate-to-severe systemic lupus erythematosus: an analysis of the SLE Prospective Observational Cohort Study (SPOCS).
IF 3.7 2区 医学
Lupus Science & Medicine Pub Date : 2025-01-23 DOI: 10.1136/lupus-2024-001336
Martin Aringer, Laurent Arnaud, Richard A Furie, Eric F Morand, Christine Peschken, Alberta Hoi, Barnabas Desta, Jonatan Hedberg, Tina Grünfeld Eén, Alessandro Sorrentino, Danuta Kielar, Raj Tummala, Stephanie Chen, Bo Ding
{"title":"Real-world treatment patterns and clinical characteristics in patients with moderate-to-severe systemic lupus erythematosus: an analysis of the SLE Prospective Observational Cohort Study (SPOCS).","authors":"Martin Aringer, Laurent Arnaud, Richard A Furie, Eric F Morand, Christine Peschken, Alberta Hoi, Barnabas Desta, Jonatan Hedberg, Tina Grünfeld Eén, Alessandro Sorrentino, Danuta Kielar, Raj Tummala, Stephanie Chen, Bo Ding","doi":"10.1136/lupus-2024-001336","DOIUrl":"10.1136/lupus-2024-001336","url":null,"abstract":"<p><strong>Objectives: </strong>Systemic lupus erythematosus (SLE) is a disease with heterogeneous treatment patterns largely based on organ involvement and disease severity. The SLE Prospective Observational Cohort Study (SPOCS) collected data worldwide over 3 years from patients with moderate-to-severe SLE. We report real-world patterns of medication use in patients enrolled in SPOCS.</p><p><strong>Methods: </strong>Data were collected at study entry; patients were followed twice annually according to local practice. Disease activity (SLE Disease Activity Index 2000 (SLEDAI-2K)), average oral glucocorticoid dose and use of other treatments-specifically antimalarials, biologics and immunosuppressants-were measured over time. Subgroup analyses were stratified by baseline interferon gene signature (IFNGS) status and disease activity (SLEDAI-2K) status.</p><p><strong>Results: </strong>Patient demographics and baseline characteristics were similar among subgroups; the majority of patients were on antimalarials (n=670; 81.1%), followed by glucocorticoids (n=537; 65.0%), immunosuppressants (n=453; 54.8%) and biologics (n=175; 21.2%). In the overall population, median (IQR) SLEDAI-2K scores decreased within 12 months (baseline: 8.0 (6.0-12.0); 12 months: 4.0 (2.0-8.0)) and remained stable thereafter. The mean (SD) daily oral glucocorticoid dose increased by 6 months (baseline: 6.0 (7.09); 6 months: 9.8 (8.67)) and remained stable thereafter. The proportion of patients who were on glucocorticoid doses >5 mg/day ranged from ~20% to 33% throughout the study. In subgroup analyses, patients with high IFNGS and high disease activity state (HDAS) at baseline used more immunosuppressants and glucocorticoids compared with those with low IFNGS and non-HDAS at baseline.</p><p><strong>Conclusions: </strong>These findings underscore that SLE therapy is still often unable to reach goals as recommended by the European Alliance of Associations for Rheumatology, both with regard to glucocorticoid use and disease activity, suggesting that there is an unmet need for new treatment options for patients with SLE.</p><p><strong>Trial registration number: </strong>NCT03189875; 16 June 2017.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039634","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}
引用次数: 0
Factors influencing therapeutic efficacy of denosumab against osteoporosis in systemic lupus erythematosus.
IF 3.7 2区 医学
Lupus Science & Medicine Pub Date : 2025-01-22 DOI: 10.1136/lupus-2024-001438
Jiwon Yang, Youngjae Park, Jennifer Jooha Lee, Seung-Ki Kwok, Ji Hyeon Ju, Wan-Uk Kim, Sung-Hwan Park
{"title":"Factors influencing therapeutic efficacy of denosumab against osteoporosis in systemic lupus erythematosus.","authors":"Jiwon Yang, Youngjae Park, Jennifer Jooha Lee, Seung-Ki Kwok, Ji Hyeon Ju, Wan-Uk Kim, Sung-Hwan Park","doi":"10.1136/lupus-2024-001438","DOIUrl":"10.1136/lupus-2024-001438","url":null,"abstract":"<p><strong>Objective: </strong>Osteoporosis is a common comorbidity in patients with SLE, and bone loss in patients with SLE has a multifactorial aetiology. This study aimed to evaluate the therapeutic efficacy of denosumab in patients with SLE with osteoporosis and to analyse the factors influencing therapeutic efficacy.</p><p><strong>Methods: </strong>A total of 166 patients with SLE with osteoporosis who initiated denosumab between January 2016 and December 2023 were included. Changes in the T-score and areal bone mineral density (BMD) at the lumbar spine, total hip and femur neck from denosumab initiation to 12 months were measured. Correlation analysis was performed between the degree of BMD improvement and covariates including SLE-specific factors such as SLE duration, SLE Disease Activity Index 2000 (SLEDAI-2K) score, glucocorticoid dose and hydroxychloroquine use. Multiple linear regression analysis was conducted to identify predictors of the therapeutic efficacy of denosumab.</p><p><strong>Results: </strong>Denosumab significantly increased BMD and decreased bone turnover markers at 12 months compared with baseline. The degree of BMD improvement revealed a significant negative correlation with SLEDAI-2K score, hydroxychloroquine use, prior osteoporosis treatment and baseline BMD values. In contrast, body mass index and c-telopeptide of collagen type 1 levels were positively correlated with the degree of BMD improvement. Higher baseline BMD values, SLEDAI-2K scores and hydroxychloroquine use were significant predictors of attenuated BMD improvement.</p><p><strong>Conclusions: </strong>Our study suggests that denosumab is an effective treatment option for osteoporosis in patients with SLE. The therapeutic efficacy of denosumab can be predicted by baseline BMD values, SLEDAI-2K scores and hydroxychloroquine use.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023036","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}
引用次数: 0
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