Pub Date : 2024-05-08DOI: 10.1136/lupus-2023-001118
Regina Rendas-Baum, Wen-Hung Chen, Kerry Gairy, Seth Anderson, Christine Henning, Anne Hammer, Mark Kosinski
Objective: Explore organ-specific SLE burden by assessing health-related quality of life (HRQoL) and fatigue changes associated with Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) organ system response (score improvement) and belimumab treatment.
Methods: Data from four phase III belimumab trials were pooled for post hoc analysis (GSK Study 217382): BLISS-52 (NCT00424476), BLISS-76 (NCT00410384), BLISS-SC (NCT01484496) and EMBRACE (NCT01632241). Patients with baseline organ system involvement were classed as organ system responders if SELENA-SLEDAI scores for that organ system decreased at any post-baseline visit. HRQoL (36-Item Short Form Health Survey version 2 (SF-36v2)) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)) changes over 52 weeks were compared between organ system responders and non-responders, and separately between belimumab versus placebo treatment arms among organ system responders. Group-level differences were compared using analysis of variance; differences were interpreted using published group-level minimal important difference (MID).
Results: In these post hoc analyses, musculoskeletal and mucocutaneous organ system responders had greater SF-36v2 improvements than non-responders across most SF-36v2 domains, but differences were largely MID), with FACIT-Fatigue also improving >MID for renal responders receiving belimumab.
Conclusions: SLE disease burden differs with the organ system(s) involved. While these analyses are limited by mutual inclusivity of organ system groupings, differing patient numbers between groups and small numbers in some groups, they suggest that mucocutaneous and musculoskeletal organ system response improves SF-36v2 domain scores; cardiovascular and respiratory organ system response may meaningfully improve fatigue; and belimumab may offer additional HRQoL or fatigue benefits beyond standard therapy for musculoskeletal and renal responders.
{"title":"SF-36v2 and FACIT-Fatigue quality of life improvements with organ-specific SELENA-SLEDAI response and belimumab treatment in patients with systemic lupus erythematosus.","authors":"Regina Rendas-Baum, Wen-Hung Chen, Kerry Gairy, Seth Anderson, Christine Henning, Anne Hammer, Mark Kosinski","doi":"10.1136/lupus-2023-001118","DOIUrl":"10.1136/lupus-2023-001118","url":null,"abstract":"<p><strong>Objective: </strong>Explore organ-specific SLE burden by assessing health-related quality of life (HRQoL) and fatigue changes associated with Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) organ system response (score improvement) and belimumab treatment.</p><p><strong>Methods: </strong>Data from four phase III belimumab trials were pooled for post hoc analysis (GSK Study 217382): BLISS-52 (NCT00424476), BLISS-76 (NCT00410384), BLISS-SC (NCT01484496) and EMBRACE (NCT01632241). Patients with baseline organ system involvement were classed as organ system responders if SELENA-SLEDAI scores for that organ system decreased at any post-baseline visit. HRQoL (36-Item Short Form Health Survey version 2 (SF-36v2)) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)) changes over 52 weeks were compared between organ system responders and non-responders, and separately between belimumab versus placebo treatment arms among organ system responders. Group-level differences were compared using analysis of variance; differences were interpreted using published group-level minimal important difference (MID).</p><p><strong>Results: </strong>In these post hoc analyses, musculoskeletal and mucocutaneous organ system responders had greater SF-36v2 improvements than non-responders across most SF-36v2 domains, but differences were largely <MID. Most organ system responders had improved FACIT-Fatigue scores versus non-responders, with cardiovascular and respiratory responders having improvements ≥MID. Musculoskeletal and renal responders receiving belimumab had greater improvements in several SF-36v2 domains than responders receiving placebo (>MID), with FACIT-Fatigue also improving >MID for renal responders receiving belimumab.</p><p><strong>Conclusions: </strong>SLE disease burden differs with the organ system(s) involved. While these analyses are limited by mutual inclusivity of organ system groupings, differing patient numbers between groups and small numbers in some groups, they suggest that mucocutaneous and musculoskeletal organ system response improves SF-36v2 domain scores; cardiovascular and respiratory organ system response may meaningfully improve fatigue; and belimumab may offer additional HRQoL or fatigue benefits beyond standard therapy for musculoskeletal and renal responders.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11086192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898747","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}
Pub Date : 2024-05-08DOI: 10.1136/lupus-2024-001204
Reyhan Bilici, Burcu Candemir, Hasan Satış, Gizem Tuğçe Alp, Funda Yıldırım Borazan, Olgun Deniz, Aslihan Avanoglu Guler, Hazan Karadeniz, Hacer Doğan Varan, Abdurrahman Tufan, Mehmet Akif Öztürk, Berna Goker
Objective: This study aimed to evaluate the prevalence of sarcopenia and its clinical significance in Turkish women with SLE, exploring the association between muscle mass, muscle strength and SLE disease activity.
Methods: A cross-sectional study was conducted at Gazi University Hospital's Department of Rheumatology from January to December 2020. It involved 82 patients with SLE, diagnosed according to the 2019 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria, and 69 healthy controls. Sarcopenia was assessed using hand grip dynamometry (hand grip strength (HGS)) and bioelectrical impedance analysis for muscle mass, with sarcopenia defined according to the 2018 European Working Group on Sarcopenia in Older People criteria and specific cut-offs for the Turkish population. The main outcomes measured were the presence of sarcopenia and probable sarcopenia, HGS values, skeletal muscle mass index and SLE Disease Activity Index 2000 (SLEDAI-2K).
Results: Among the patients with SLE, 51.2% met the criteria for probable sarcopenia and 12.9% were diagnosed with sarcopenia. The mean HGS was significantly lower in the SLE group (21.7±4.9 kg) compared with controls, indicating reduced muscle strength. The prevalence of anti-double-stranded DNA (anti-dsDNA) antibodies was 82.9%. Multivariate regression analysis identified height and levels of anti-dsDNA antibodies as independent predictors for developing probable sarcopenia. No significant association was found between clinical parameters, including SLEDAI-2K scores, and sarcopenia status.
Conclusions: Sarcopenia is prevalent among Turkish women with SLE, with a significant proportion showing reduced muscle strength. The study found no direct association between sarcopenia and SLE disease activity or clinical parameters. These findings underscore the importance of including muscle strength assessments in the routine clinical evaluation of patients with SLE to potentially improve management and quality of life.
{"title":"Frequency of sarcopenia in Turkish women with systemic lupus erythematosus.","authors":"Reyhan Bilici, Burcu Candemir, Hasan Satış, Gizem Tuğçe Alp, Funda Yıldırım Borazan, Olgun Deniz, Aslihan Avanoglu Guler, Hazan Karadeniz, Hacer Doğan Varan, Abdurrahman Tufan, Mehmet Akif Öztürk, Berna Goker","doi":"10.1136/lupus-2024-001204","DOIUrl":"10.1136/lupus-2024-001204","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the prevalence of sarcopenia and its clinical significance in Turkish women with SLE, exploring the association between muscle mass, muscle strength and SLE disease activity.</p><p><strong>Methods: </strong>A cross-sectional study was conducted at Gazi University Hospital's Department of Rheumatology from January to December 2020. It involved 82 patients with SLE, diagnosed according to the 2019 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria, and 69 healthy controls. Sarcopenia was assessed using hand grip dynamometry (hand grip strength (HGS)) and bioelectrical impedance analysis for muscle mass, with sarcopenia defined according to the 2018 European Working Group on Sarcopenia in Older People criteria and specific cut-offs for the Turkish population. The main outcomes measured were the presence of sarcopenia and probable sarcopenia, HGS values, skeletal muscle mass index and SLE Disease Activity Index 2000 (SLEDAI-2K).</p><p><strong>Results: </strong>Among the patients with SLE, 51.2% met the criteria for probable sarcopenia and 12.9% were diagnosed with sarcopenia. The mean HGS was significantly lower in the SLE group (21.7±4.9 kg) compared with controls, indicating reduced muscle strength. The prevalence of anti-double-stranded DNA (anti-dsDNA) antibodies was 82.9%. Multivariate regression analysis identified height and levels of anti-dsDNA antibodies as independent predictors for developing probable sarcopenia. No significant association was found between clinical parameters, including SLEDAI-2K scores, and sarcopenia status.</p><p><strong>Conclusions: </strong>Sarcopenia is prevalent among Turkish women with SLE, with a significant proportion showing reduced muscle strength. The study found no direct association between sarcopenia and SLE disease activity or clinical parameters. These findings underscore the importance of including muscle strength assessments in the routine clinical evaluation of patients with SLE to potentially improve management and quality of life.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"11 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11086267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898601","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}
Pub Date : 2024-04-01DOI: 10.1136/lupus-2023-001109
Luping Shen, Mo Han, Xuan Luo, Qixiang Zhang, Huanke Xu, Jing Wang, Ning Wei, Qing Liu, Guangji Wang, Fang Zhou
Objective Circadian rhythm disruption (CRD) has been associated with inflammation and immune disorders, but its role in SLE progression is unclear. We aimed to investigate the impact of circadian rhythms on immune function and inflammation and their contribution to SLE progression to lupus nephritis (LN). Methods This study retrospectively analysed the clinical characteristics and transcriptional profiles of 373 samples using bioinformatics and machine-learning methods. A flare risk score (FRS) was established to predict overall disease progression for patients with lupus. Mendelian randomisation was used to analyse the causal relationship between CRD and SLE progression. Results Abnormalities in the circadian pathway were detected in patients with SLE, and lower enrichment levels suggested a disease state (normalised enrichment score=0.6714, p=0.0062). The disruption of circadian rhythms was found to be closely linked to lupus flares, with the FRS showing a strong ability to predict disease progression (area under the curve (AUC) of 5-year prediction: 0.76). The accuracy of disease prediction was improved by using a prognostic nomogram based on FRS (AUC=0.77). Additionally, Mendelian randomisation analysis revealed an inverse causal relationship between CRD and SLE (OR 0.6284 (95% CI 0.3630 to 1.0881), p=0.0485) and a positive causal relationship with glomerular disorders (OR 0.0337 (95% CI 1.634e-3 to 6.934e-1), p=0.0280). Conclusion Our study reveals that genetic characteristics arising from CRD can serve as biomarkers for predicting the exacerbation of SLE. This highlights the crucial impact of CRD on the progression of lupus. Data are available on reasonable request.
目的 昼夜节律紊乱（CRD）与炎症和免疫紊乱有关，但其在系统性红斑狼疮进展中的作用尚不清楚。我们旨在研究昼夜节律对免疫功能和炎症的影响及其对系统性红斑狼疮进展为狼疮性肾炎（LN）的贡献。方法 本研究使用生物信息学和机器学习方法回顾性分析了 373 个样本的临床特征和转录特征。建立了狼疮发作风险评分（FRS）来预测狼疮患者的总体疾病进展。采用孟德尔随机法分析 CRD 与系统性红斑狼疮进展之间的因果关系。结果 在系统性红斑狼疮患者中检测到昼夜节律途径异常，较低的富集水平提示疾病状态（归一化富集分=0.6714，p=0.0062）。研究发现，昼夜节律的紊乱与狼疮复发密切相关，而昼夜节律评分（FRS）显示出预测疾病进展的强大能力（5年预测的曲线下面积（AUC）为0.76）：0.76).使用基于 FRS 的预后提名图（AUC=0.77）可提高疾病预测的准确性。此外，孟德尔随机分析显示，CRD 与系统性红斑狼疮之间存在反向因果关系（OR 0.6284 (95% CI 0.3630 to 1.0881)，p=0.0485），与肾小球疾病之间存在正向因果关系（OR 0.0337 (95% CI 1.634e-3 to 6.934e-1)，p=0.0280）。结论 我们的研究揭示了 CRD 的遗传特征可作为预测系统性红斑狼疮病情恶化的生物标志物。这凸显了 CRD 对红斑狼疮病情发展的重要影响。如有合理要求，可提供相关数据。
{"title":"Exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosus","authors":"Luping Shen, Mo Han, Xuan Luo, Qixiang Zhang, Huanke Xu, Jing Wang, Ning Wei, Qing Liu, Guangji Wang, Fang Zhou","doi":"10.1136/lupus-2023-001109","DOIUrl":"https://doi.org/10.1136/lupus-2023-001109","url":null,"abstract":"Objective Circadian rhythm disruption (CRD) has been associated with inflammation and immune disorders, but its role in SLE progression is unclear. We aimed to investigate the impact of circadian rhythms on immune function and inflammation and their contribution to SLE progression to lupus nephritis (LN). Methods This study retrospectively analysed the clinical characteristics and transcriptional profiles of 373 samples using bioinformatics and machine-learning methods. A flare risk score (FRS) was established to predict overall disease progression for patients with lupus. Mendelian randomisation was used to analyse the causal relationship between CRD and SLE progression. Results Abnormalities in the circadian pathway were detected in patients with SLE, and lower enrichment levels suggested a disease state (normalised enrichment score=0.6714, p=0.0062). The disruption of circadian rhythms was found to be closely linked to lupus flares, with the FRS showing a strong ability to predict disease progression (area under the curve (AUC) of 5-year prediction: 0.76). The accuracy of disease prediction was improved by using a prognostic nomogram based on FRS (AUC=0.77). Additionally, Mendelian randomisation analysis revealed an inverse causal relationship between CRD and SLE (OR 0.6284 (95% CI 0.3630 to 1.0881), p=0.0485) and a positive causal relationship with glomerular disorders (OR 0.0337 (95% CI 1.634e-3 to 6.934e-1), p=0.0280). Conclusion Our study reveals that genetic characteristics arising from CRD can serve as biomarkers for predicting the exacerbation of SLE. This highlights the crucial impact of CRD on the progression of lupus. Data are available on reasonable request.","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"10 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Lupus nephritis (LN) is a complication of SLE characterised by immune dysfunction and oxidative stress (OS). Limited options exist for LN. We aimed to identify LN-related OS, highlighting the need for non-invasive diagnostic and therapeutic approaches. Methods LN-differentially expressed genes (DEGs) were extracted from Gene Expression Omnibus datasets (GSE32591, GSE112943 and GSE104948) and Molecular Signatures Database for OS-associated DEGs (OSEGs). Functional enrichment analysis was performed for OSEGs related to LN. Weighted gene co-expression network analysis identified hub genes related to OS-LN. These hub OSEGs were refined as biomarker candidates via least absolute shrinkage and selection operator. The predictive value was validated using receiver operating characteristic (ROC) curves and nomogram for LN prognosis. We evaluated LN immune cell infiltration using single-sample gene set enrichment analysis and CIBERSORT. Additionally, gene set enrichment analysis explored the functional enrichment of hub OSEGs in LN. Results The study identified four hub genes, namely STAT1 , PRODH , TXN2 and SETX , associated with OS related to LN. These genes were validated for their diagnostic potential, and their involvement in LN pathogenesis was elucidated through ROC and nomogram. Additionally, alterations in immune cell composition in LN correlated with hub OSEG expression were observed. Immunohistochemical analysis reveals that the hub gene is most correlated with activated B cells and CD8 T cells. Finally, we uncovered that the enriched pathways of OSEGs were mainly involved in the PI3K-Akt pathway and the Janus kinase-signal transducer and activator of transcription pathway. Conclusion These findings contribute to advancing our understanding of the complex interplay between OS, immune dysregulation and molecular pathways in LN, laying a foundation for the identification of potential diagnostic biomarkers and therapeutic targets. Data are available upon reasonable request. The LN cohort’s transcriptional dataset (GSE32591, GSE112943 and GSE104948) was downloaded from the Gene Expression Omnibus (GEO) database ().
{"title":"Machine learning-based identification of novel hub genes associated with oxidative stress in lupus nephritis: implications for diagnosis and therapeutic targets","authors":"Huiqiong Zeng, Yu Zhuang, Xiaodong Yan, Xiaoyan He, Qianwen Qiu, Wei Liu, Ye Zhang","doi":"10.1136/lupus-2023-001126","DOIUrl":"https://doi.org/10.1136/lupus-2023-001126","url":null,"abstract":"Background Lupus nephritis (LN) is a complication of SLE characterised by immune dysfunction and oxidative stress (OS). Limited options exist for LN. We aimed to identify LN-related OS, highlighting the need for non-invasive diagnostic and therapeutic approaches. Methods LN-differentially expressed genes (DEGs) were extracted from Gene Expression Omnibus datasets (GSE32591, GSE112943 and GSE104948) and Molecular Signatures Database for OS-associated DEGs (OSEGs). Functional enrichment analysis was performed for OSEGs related to LN. Weighted gene co-expression network analysis identified hub genes related to OS-LN. These hub OSEGs were refined as biomarker candidates via least absolute shrinkage and selection operator. The predictive value was validated using receiver operating characteristic (ROC) curves and nomogram for LN prognosis. We evaluated LN immune cell infiltration using single-sample gene set enrichment analysis and CIBERSORT. Additionally, gene set enrichment analysis explored the functional enrichment of hub OSEGs in LN. Results The study identified four hub genes, namely STAT1 , PRODH , TXN2 and SETX , associated with OS related to LN. These genes were validated for their diagnostic potential, and their involvement in LN pathogenesis was elucidated through ROC and nomogram. Additionally, alterations in immune cell composition in LN correlated with hub OSEG expression were observed. Immunohistochemical analysis reveals that the hub gene is most correlated with activated B cells and CD8 T cells. Finally, we uncovered that the enriched pathways of OSEGs were mainly involved in the PI3K-Akt pathway and the Janus kinase-signal transducer and activator of transcription pathway. Conclusion These findings contribute to advancing our understanding of the complex interplay between OS, immune dysregulation and molecular pathways in LN, laying a foundation for the identification of potential diagnostic biomarkers and therapeutic targets. Data are available upon reasonable request. The LN cohort’s transcriptional dataset (GSE32591, GSE112943 and GSE104948) was downloaded from the Gene Expression Omnibus (GEO) database (<https://www.ncbi.nlm.nih.gov/geo/>).","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"39 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1136/lupus-2023-001096
Iñigo Rua-Figueroa, M Jesus García de Yébenes, Julia Martinez-Barrio, Maria Galindo Izquierdo, Jaime Calvo Alén, Antonio Fernandez-Nebro, Raúl Menor-Almagro, Loreto Carmona, Beatriz Tejera Segura, Eva Tomero, Mercedes Freire-González, Clara Sangüesa, Loreto Horcada, Ricardo Blanco, Esther Uriarte Itzazelaia, Javier Narváez, José Carlos Rosas Gómez de Salazar, Silvia Gómez-Sabater, Claudia Moriano Morales, Jose L Andreu, Vicente Torrente Segarra, Elena Aurrecoechea, Ana Perez, Javier Nóvoa Medina, Eva Salgado, Nuria Lozano-Rivas, Carlos Montilla, Esther Ruiz-Lucea, Marta Arevalo, Carlota Iñiguez, María Jesús García-Villanueva, Lorena Exposito, Mónica Ibáñez-Barceló, Gema Bonilla, Irene Carrión-Barberà, Celia Erausquin, Jorge Juan Fragio Gil, Angela Pecondón, Francisco J Toyos, Tatiana Cobo, Alejandro Muñoz-Jiménez, Jose Oller, Joan M Nolla, J M Pego-Reigosa
Objective To develop an improved score for prediction of severe infection in patients with systemic lupus erythematosus (SLE), namely, the SLE Severe Infection Score-Revised (SLESIS-R) and to validate it in a large multicentre lupus cohort. Methods We used data from the prospective phase of RELESSER (RELESSER-PROS), the SLE register of the Spanish Society of Rheumatology. A multivariable logistic model was constructed taking into account the variables already forming the SLESIS score, plus all other potential predictors identified in a literature review. Performance was analysed using the C-statistic and the area under the receiver operating characteristic curve (AUROC). Internal validation was carried out using a 100-sample bootstrapping procedure. ORs were transformed into score items, and the AUROC was used to determine performance. Results A total of 1459 patients who had completed 1 year of follow-up were included in the development cohort (mean age, 49±13 years; 90% women). Twenty-five (1.7%) had experienced ≥1 severe infection. According to the adjusted multivariate model, severe infection could be predicted from four variables: age (years) ≥60, previous SLE-related hospitalisation, previous serious infection and glucocorticoid dose. A score was built from the best model, taking values from 0 to 17. The AUROC was 0.861 (0.777–0.946). The cut-off chosen was ≥6, which exhibited an accuracy of 85.9% and a positive likelihood ratio of 5.48. Conclusions SLESIS-R is an accurate and feasible instrument for predicting infections in patients with SLE. SLESIS-R could help to make informed decisions on the use of immunosuppressants and the implementation of preventive measures. Data are available upon reasonable request.
{"title":"SLESIS-R: an improved score for prediction of serious infection in patients with systemic lupus erythematosus based on the RELESSER prospective cohort","authors":"Iñigo Rua-Figueroa, M Jesus García de Yébenes, Julia Martinez-Barrio, Maria Galindo Izquierdo, Jaime Calvo Alén, Antonio Fernandez-Nebro, Raúl Menor-Almagro, Loreto Carmona, Beatriz Tejera Segura, Eva Tomero, Mercedes Freire-González, Clara Sangüesa, Loreto Horcada, Ricardo Blanco, Esther Uriarte Itzazelaia, Javier Narváez, José Carlos Rosas Gómez de Salazar, Silvia Gómez-Sabater, Claudia Moriano Morales, Jose L Andreu, Vicente Torrente Segarra, Elena Aurrecoechea, Ana Perez, Javier Nóvoa Medina, Eva Salgado, Nuria Lozano-Rivas, Carlos Montilla, Esther Ruiz-Lucea, Marta Arevalo, Carlota Iñiguez, María Jesús García-Villanueva, Lorena Exposito, Mónica Ibáñez-Barceló, Gema Bonilla, Irene Carrión-Barberà, Celia Erausquin, Jorge Juan Fragio Gil, Angela Pecondón, Francisco J Toyos, Tatiana Cobo, Alejandro Muñoz-Jiménez, Jose Oller, Joan M Nolla, J M Pego-Reigosa","doi":"10.1136/lupus-2023-001096","DOIUrl":"https://doi.org/10.1136/lupus-2023-001096","url":null,"abstract":"Objective To develop an improved score for prediction of severe infection in patients with systemic lupus erythematosus (SLE), namely, the SLE Severe Infection Score-Revised (SLESIS-R) and to validate it in a large multicentre lupus cohort. Methods We used data from the prospective phase of RELESSER (RELESSER-PROS), the SLE register of the Spanish Society of Rheumatology. A multivariable logistic model was constructed taking into account the variables already forming the SLESIS score, plus all other potential predictors identified in a literature review. Performance was analysed using the C-statistic and the area under the receiver operating characteristic curve (AUROC). Internal validation was carried out using a 100-sample bootstrapping procedure. ORs were transformed into score items, and the AUROC was used to determine performance. Results A total of 1459 patients who had completed 1 year of follow-up were included in the development cohort (mean age, 49±13 years; 90% women). Twenty-five (1.7%) had experienced ≥1 severe infection. According to the adjusted multivariate model, severe infection could be predicted from four variables: age (years) ≥60, previous SLE-related hospitalisation, previous serious infection and glucocorticoid dose. A score was built from the best model, taking values from 0 to 17. The AUROC was 0.861 (0.777–0.946). The cut-off chosen was ≥6, which exhibited an accuracy of 85.9% and a positive likelihood ratio of 5.48. Conclusions SLESIS-R is an accurate and feasible instrument for predicting infections in patients with SLE. SLESIS-R could help to make informed decisions on the use of immunosuppressants and the implementation of preventive measures. Data are available upon reasonable request.","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"87 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140567184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1136/lupus-2023-001139
Eugene Krustev, John G Hanly, Ricky Chin, Katherine A Buhler, Murray B Urowitz, Caroline Gordon, Sang-Cheol Bae, Juanita Romero-Diaz, Jorge Sánchez-Guerrero, Sasha Bernatsky, Daniel J Wallace, David Isenberg, Anisur Rahman, Joan T Merrill, Paul R Fortin, Dafna D Gladman, Ian N Bruce, Michelle A Petri, Ellen M Ginzler, Mary Anne Dooley, Rosalind Ramsey-Goldman, Susan Manzi, Andreas Jönsen, Graciela S Alarcón, Ronald F van Vollenhoven, Cynthia Aranow, Meggan Mackay, Guillermo Ruiz-Irastorza, Sam Lim, Murat Inanc, Kenneth C Kalunian, Søren Jacobsen, Christine A Peschken, Diane L Kamen, Anca Askenase, Jill Buyon, Marvin J Fritzler, Ann E Clarke, May Y Choi
Background Cranial neuropathies (CN) are a rare neuropsychiatric SLE (NPSLE) manifestation. Previous studies reported that antibodies to the kinesin family member 20B (KIF20B) (anti-KIF20B) protein were associated with idiopathic ataxia and CN. We assessed anti-KIF20B as a potential biomarker for NPSLE in an international SLE inception cohort. Methods Individuals fulfilling the revised 1997 American College of Rheumatology (ACR) SLE classification criteria were enrolled from 31 centres from 1999 to 2011 and followed annually in the Systemic Lupus Erythematosus International Collaborating Clinics inception cohort. Anti-KIF20B testing was performed on baseline (within 15 months of diagnosis or first annual visit) samples using an addressable laser bead immunoassay. Logistic regression (penalised maximum likelihood and adjusting for confounding variables) examined the association between anti-KIF20B and NPSLE manifestations (1999 ACR case definitions), including CN, occurring over the first 5 years of follow-up. Results Of the 1827 enrolled cohort members, baseline serum and 5 years of follow-up data were available on 795 patients who were included in this study: 29.8% were anti-KIF20B-positive, 88.7% female, and 52.1% White. The frequency of anti-KIF20B positivity differed only for those with CN (n=10) versus without CN (n=785) (70.0% vs 29.3%; OR 5.2, 95% CI 1.4, 18.5). Compared with patients without CN, patients with CN were more likely to fulfil the ACR haematological (90.0% vs 66.1%; difference 23.9%, 95% CI 5.0%, 42.8%) and ANA (100% vs 95.7%; difference 4.3%, 95% CI 2.9%, 5.8%) criteria. In the multivariate analysis adjusting for age at baseline, female, White race and ethnicity, and ACR haematological and ANA criteria, anti-KIF20B positivity remained associated with CN (OR 5.2, 95% CI 1.4, 19.1). Conclusion Anti-KIF20B is a potential biomarker for SLE-related CN. Further studies are needed to examine how autoantibodies against KIF20B, which is variably expressed in a variety of neurological cells, contribute to disease pathogenesis. No data are available. All relevant data to this study are being published.
背景 颅神经病（CN）是一种罕见的神经精神系统性红斑狼疮（NPSLE）表现。先前的研究报告称，驱动蛋白家族成员20B（KIF20B）蛋白抗体（抗KIF20B）与特发性共济失调和颅神经病相关。我们在一个国际系统性红斑狼疮起始队列中评估了抗 KIF20B 作为非系统性红斑狼疮潜在生物标志物的作用。方法 从 1999 年到 2011 年，31 个中心招募了符合 1997 年美国风湿病学会（ACR）系统性红斑狼疮分类标准修订版的患者，并在系统性红斑狼疮国际合作诊所初始队列中进行了年度随访。使用可寻址激光磁珠免疫测定法对基线（诊断后 15 个月内或首次年检）样本进行抗 KIF20B 检测。逻辑回归（惩罚最大似然法并调整混杂变量）检验了抗-KIF20B与随访头5年中出现的NPSLE表现（1999年ACR病例定义）（包括CN）之间的关联。结果 在 1827 名登记的队列成员中，有 795 名患者的基线血清和 5 年随访数据被纳入本研究：29.8% 的患者抗 KIF20B 阳性，88.7% 为女性，52.1% 为白人。抗-KIF20B阳性的频率仅在有CN（10人）和无CN（785人）患者之间存在差异（70.0% vs 29.3%；OR 5.2，95% CI 1.4，18.5）。与无 CN 的患者相比，有 CN 的患者更有可能符合 ACR 血液学标准（90.0% vs 66.1%；差异为 23.9%，95% CI 为 5.0%，42.8%）和 ANA 标准（100% vs 95.7%；差异为 4.3%，95% CI 为 2.9%，5.8%）。在调整基线年龄、女性、白种人、ACR 血液学和 ANA 标准后进行的多变量分析中，抗 KIF20B 阳性仍与 CN 相关（OR 5.2，95% CI 1.4，19.1）。结论 抗 KIF20B 是与系统性红斑狼疮相关的 CN 的潜在生物标志物。KIF20B在多种神经细胞中的表达各不相同，需要进一步的研究来探讨针对KIF20B的自身抗体是如何导致疾病发病的。暂无相关数据。本研究的所有相关数据正在公布中。
{"title":"Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus","authors":"Eugene Krustev, John G Hanly, Ricky Chin, Katherine A Buhler, Murray B Urowitz, Caroline Gordon, Sang-Cheol Bae, Juanita Romero-Diaz, Jorge Sánchez-Guerrero, Sasha Bernatsky, Daniel J Wallace, David Isenberg, Anisur Rahman, Joan T Merrill, Paul R Fortin, Dafna D Gladman, Ian N Bruce, Michelle A Petri, Ellen M Ginzler, Mary Anne Dooley, Rosalind Ramsey-Goldman, Susan Manzi, Andreas Jönsen, Graciela S Alarcón, Ronald F van Vollenhoven, Cynthia Aranow, Meggan Mackay, Guillermo Ruiz-Irastorza, Sam Lim, Murat Inanc, Kenneth C Kalunian, Søren Jacobsen, Christine A Peschken, Diane L Kamen, Anca Askenase, Jill Buyon, Marvin J Fritzler, Ann E Clarke, May Y Choi","doi":"10.1136/lupus-2023-001139","DOIUrl":"https://doi.org/10.1136/lupus-2023-001139","url":null,"abstract":"Background Cranial neuropathies (CN) are a rare neuropsychiatric SLE (NPSLE) manifestation. Previous studies reported that antibodies to the kinesin family member 20B (KIF20B) (anti-KIF20B) protein were associated with idiopathic ataxia and CN. We assessed anti-KIF20B as a potential biomarker for NPSLE in an international SLE inception cohort. Methods Individuals fulfilling the revised 1997 American College of Rheumatology (ACR) SLE classification criteria were enrolled from 31 centres from 1999 to 2011 and followed annually in the Systemic Lupus Erythematosus International Collaborating Clinics inception cohort. Anti-KIF20B testing was performed on baseline (within 15 months of diagnosis or first annual visit) samples using an addressable laser bead immunoassay. Logistic regression (penalised maximum likelihood and adjusting for confounding variables) examined the association between anti-KIF20B and NPSLE manifestations (1999 ACR case definitions), including CN, occurring over the first 5 years of follow-up. Results Of the 1827 enrolled cohort members, baseline serum and 5 years of follow-up data were available on 795 patients who were included in this study: 29.8% were anti-KIF20B-positive, 88.7% female, and 52.1% White. The frequency of anti-KIF20B positivity differed only for those with CN (n=10) versus without CN (n=785) (70.0% vs 29.3%; OR 5.2, 95% CI 1.4, 18.5). Compared with patients without CN, patients with CN were more likely to fulfil the ACR haematological (90.0% vs 66.1%; difference 23.9%, 95% CI 5.0%, 42.8%) and ANA (100% vs 95.7%; difference 4.3%, 95% CI 2.9%, 5.8%) criteria. In the multivariate analysis adjusting for age at baseline, female, White race and ethnicity, and ACR haematological and ANA criteria, anti-KIF20B positivity remained associated with CN (OR 5.2, 95% CI 1.4, 19.1). Conclusion Anti-KIF20B is a potential biomarker for SLE-related CN. Further studies are needed to examine how autoantibodies against KIF20B, which is variably expressed in a variety of neurological cells, contribute to disease pathogenesis. No data are available. All relevant data to this study are being published.","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"49 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1136/lupus-2023-001065
Xinyi Zhu, Yashuo Chen, Zhihua Yin, Yutong Zhang, Yiwei Shen, Dai Dai, Xiaojing Lin, Ling-Hua Zou, Nan Shen, Zhizhong Ye, Huihua Ding, Guojun Hou
Objectives Systemic lupus erythematosus (SLE) is a highly heterogeneous disease, and B cell abnormalities play a central role in the pathogenesis of SLE. Long non-coding RNAs (lncRNAs) have also been implicated in the pathogenesis of SLE. The expression of lncRNAs is finely regulated and cell-type dependent, so we aimed to identify B cell-expressing lncRNAs as biomarkers for SLE, and to explore their ability to reflect the status of SLE critical pathway and disease activity. Methods Weighted gene coexpression network analysis (WGCNA) was used to cluster B cell-expressing genes of patients with SLE into different gene modules and relate them to clinical features. Based on the results of WGCNA, candidate lncRNA levels were further explored in public bulk and single-cell RNA-sequencing data. In another independent cohort, the levels of the candidate were detected by RT-qPCR and the correlation with disease activity was analysed. Results WGCNA analysis revealed one gene module significantly correlated with clinical features, which was enriched in type I interferon (IFN) pathway. Among non-coding genes in this module, lncRNA RP11-273G15.2 was differentially expressed in all five subsets of B cells from patients with SLE compared with healthy controls and other autoimmune diseases. RT-qPCR validated that RP11-273G15.2 was highly expressed in SLE B cells and positively correlated with IFN scores (r=0.7329, p<0.0001) and disease activity (r=0.4710, p=0.0005). Conclusion RP11-273G15.2 could act as a diagnostic and disease activity monitoring biomarker for SLE, which might have the potential to guide clinical management. Data are available in a public, open access repository. All data relevant to the study are included in the article or uploaded as supplementary information.
{"title":"Novel potential lncRNA biomarker in B cells indicates essential pathogenic pathway activation in patients with SLE","authors":"Xinyi Zhu, Yashuo Chen, Zhihua Yin, Yutong Zhang, Yiwei Shen, Dai Dai, Xiaojing Lin, Ling-Hua Zou, Nan Shen, Zhizhong Ye, Huihua Ding, Guojun Hou","doi":"10.1136/lupus-2023-001065","DOIUrl":"https://doi.org/10.1136/lupus-2023-001065","url":null,"abstract":"Objectives Systemic lupus erythematosus (SLE) is a highly heterogeneous disease, and B cell abnormalities play a central role in the pathogenesis of SLE. Long non-coding RNAs (lncRNAs) have also been implicated in the pathogenesis of SLE. The expression of lncRNAs is finely regulated and cell-type dependent, so we aimed to identify B cell-expressing lncRNAs as biomarkers for SLE, and to explore their ability to reflect the status of SLE critical pathway and disease activity. Methods Weighted gene coexpression network analysis (WGCNA) was used to cluster B cell-expressing genes of patients with SLE into different gene modules and relate them to clinical features. Based on the results of WGCNA, candidate lncRNA levels were further explored in public bulk and single-cell RNA-sequencing data. In another independent cohort, the levels of the candidate were detected by RT-qPCR and the correlation with disease activity was analysed. Results WGCNA analysis revealed one gene module significantly correlated with clinical features, which was enriched in type I interferon (IFN) pathway. Among non-coding genes in this module, lncRNA RP11-273G15.2 was differentially expressed in all five subsets of B cells from patients with SLE compared with healthy controls and other autoimmune diseases. RT-qPCR validated that RP11-273G15.2 was highly expressed in SLE B cells and positively correlated with IFN scores (r=0.7329, p<0.0001) and disease activity (r=0.4710, p=0.0005). Conclusion RP11-273G15.2 could act as a diagnostic and disease activity monitoring biomarker for SLE, which might have the potential to guide clinical management. Data are available in a public, open access repository. All data relevant to the study are included in the article or uploaded as supplementary information.","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"10 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1136/lupus-2023-001111
Guillaume Germain, Karen Worley, Sean D MacKnight, Bernard Rubin, Christopher F Bell, François Laliberté, Ana Urosevic, Mei Sheng Duh, Andrew Concoff
Objective To investigate the real-world impact of intravenous belimumab treatment among patients with SLE using rheumatoid arthritis-derived disease activity measures and SLE-related laboratory values. Methods This retrospective cohort study used US electronic medical record data from the United Rheumatology Normalised Integrated Community Evidence (UR-NICE) database. Adult patients with SLE who initiated intravenous belimumab between 1 January 2012 and 3 December 2019 (index), had 12 months of pre-index and 24 months of post-index clinical activity, and had ≥6 infusions of belimumab during the 24 months post-index were included. The primary outcome measure was time to first improvement of minimally important difference (MID) for Routine Assessment of Patient Index Data 3 (RAPID3), Patient Pain Index (PPI), swollen joint count, tender joint count (TJC), complement C3 and C4 and anti-double-stranded DNA antibodies during the on-treatment follow-up period of up to 24 months. The secondary outcome measure evaluated the trajectories of these outcome measures for up to 24 months of belimumab treatment. Results Of 495 patients included, between 21.0% and 52.1% had ≥1 record for each of the disease activity measures or laboratory values in the pre-index and post-index periods and were included in analyses for that measure. The proportion of patients achieving MID for each measure increased rapidly within 3 months, with continued gradual improvement throughout the remaining on-treatment period, up to 24 months. After 6 months, 52.3% and 55.3% of patients had achieved MID in RAPID3 and PPI, respectively. Outcome measure trajectories indicated improved disease activity with belimumab treatment, particularly in RAPID3, TJC and laboratory values. Conclusions In this real-world effectiveness study, belimumab therapy for SLE resulted in clinically meaningful improvements in rheumatoid arthritis-derived disease activity measures within 3 months of treatment, with patients who remained on belimumab therapy experiencing improvement even up to 24 months of observation. Data are available on reasonable request. Anonymised individual participant data and study documents can be requested for further research from .
{"title":"Evaluating the real-world effectiveness of belimumab in patients with SLE using SLE-related laboratory values and rheumatoid arthritis-derived disease activity measures: RAPID3, swollen joint count and tender joint count","authors":"Guillaume Germain, Karen Worley, Sean D MacKnight, Bernard Rubin, Christopher F Bell, François Laliberté, Ana Urosevic, Mei Sheng Duh, Andrew Concoff","doi":"10.1136/lupus-2023-001111","DOIUrl":"https://doi.org/10.1136/lupus-2023-001111","url":null,"abstract":"Objective To investigate the real-world impact of intravenous belimumab treatment among patients with SLE using rheumatoid arthritis-derived disease activity measures and SLE-related laboratory values. Methods This retrospective cohort study used US electronic medical record data from the United Rheumatology Normalised Integrated Community Evidence (UR-NICE) database. Adult patients with SLE who initiated intravenous belimumab between 1 January 2012 and 3 December 2019 (index), had 12 months of pre-index and 24 months of post-index clinical activity, and had ≥6 infusions of belimumab during the 24 months post-index were included. The primary outcome measure was time to first improvement of minimally important difference (MID) for Routine Assessment of Patient Index Data 3 (RAPID3), Patient Pain Index (PPI), swollen joint count, tender joint count (TJC), complement C3 and C4 and anti-double-stranded DNA antibodies during the on-treatment follow-up period of up to 24 months. The secondary outcome measure evaluated the trajectories of these outcome measures for up to 24 months of belimumab treatment. Results Of 495 patients included, between 21.0% and 52.1% had ≥1 record for each of the disease activity measures or laboratory values in the pre-index and post-index periods and were included in analyses for that measure. The proportion of patients achieving MID for each measure increased rapidly within 3 months, with continued gradual improvement throughout the remaining on-treatment period, up to 24 months. After 6 months, 52.3% and 55.3% of patients had achieved MID in RAPID3 and PPI, respectively. Outcome measure trajectories indicated improved disease activity with belimumab treatment, particularly in RAPID3, TJC and laboratory values. Conclusions In this real-world effectiveness study, belimumab therapy for SLE resulted in clinically meaningful improvements in rheumatoid arthritis-derived disease activity measures within 3 months of treatment, with patients who remained on belimumab therapy experiencing improvement even up to 24 months of observation. Data are available on reasonable request. Anonymised individual participant data and study documents can be requested for further research from <https://www.gsk-studyregister.com/en/>.","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"49 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140567181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1136/lupus-2023-001090
Stephen Balevic, Kai Sun, Jennifer L Rogers, Amanda Eudy, Rebecca Eli Sadun, Mithu Maheswaranathan, Jayanth Doss, Lisa Criscione-Schreiber, Tyler O'Malley, Megan Clowse, Daniel Weiner
Objective Characterise the relationship between hydroxychloroquine (HCQ) blood levels and the number of missed doses, accounting for dosage, dose timing and the large variability in pharmacokinetics (PK) between patients. Methods We externally validated a published PK model and then conducted dosing simulations. We developed a virtual population of 1000 patients for each dosage across a range of body weights and PK variability. Using the model, 10 Monte Carlo simulations for each patient were conducted to derive predicted whole blood concentrations every hour over 24 hours (240 000 HCQ levels at steady state). To determine the impact of missed doses on levels, we randomly deleted a fixed proportion of doses. Results For patients receiving HCQ 400 mg daily, simulated random blood levels <200 ng/mL were exceedingly uncommon in fully adherent patients (<0.1%). In comparison, with 80% of doses missed, approximately 60% of concentrations were <200 ng/mL. However, this cut-off was highly insensitive and would miss many instances of severe non-adherence. Average levels quickly dropped to <200 ng/mL after 2–4 days of missed doses. Additionally, mean levels decreased by 29.9% between peak and trough measurements. Conclusions We propose an algorithm to optimally interpret HCQ blood levels and approximate the number of missed doses, incorporating the impact of dosage, dose timing and pharmacokinetic variability. No single cut-off has adequate combinations of both sensitivity and specificity, and cut-offs are dependent on the degree of targeted non-adherence. Future studies should measure trough concentrations to better identify target HCQ levels for non-adherence and efficacy. Data are available upon reasonable request. The pharmacokinetic model used for dosing simulations is publicly available from the original publication.
{"title":"Interpreting hydroxychloroquine blood levels for medication non-adherence: a pharmacokinetic study","authors":"Stephen Balevic, Kai Sun, Jennifer L Rogers, Amanda Eudy, Rebecca Eli Sadun, Mithu Maheswaranathan, Jayanth Doss, Lisa Criscione-Schreiber, Tyler O'Malley, Megan Clowse, Daniel Weiner","doi":"10.1136/lupus-2023-001090","DOIUrl":"https://doi.org/10.1136/lupus-2023-001090","url":null,"abstract":"Objective Characterise the relationship between hydroxychloroquine (HCQ) blood levels and the number of missed doses, accounting for dosage, dose timing and the large variability in pharmacokinetics (PK) between patients. Methods We externally validated a published PK model and then conducted dosing simulations. We developed a virtual population of 1000 patients for each dosage across a range of body weights and PK variability. Using the model, 10 Monte Carlo simulations for each patient were conducted to derive predicted whole blood concentrations every hour over 24 hours (240 000 HCQ levels at steady state). To determine the impact of missed doses on levels, we randomly deleted a fixed proportion of doses. Results For patients receiving HCQ 400 mg daily, simulated random blood levels <200 ng/mL were exceedingly uncommon in fully adherent patients (<0.1%). In comparison, with 80% of doses missed, approximately 60% of concentrations were <200 ng/mL. However, this cut-off was highly insensitive and would miss many instances of severe non-adherence. Average levels quickly dropped to <200 ng/mL after 2–4 days of missed doses. Additionally, mean levels decreased by 29.9% between peak and trough measurements. Conclusions We propose an algorithm to optimally interpret HCQ blood levels and approximate the number of missed doses, incorporating the impact of dosage, dose timing and pharmacokinetic variability. No single cut-off has adequate combinations of both sensitivity and specificity, and cut-offs are dependent on the degree of targeted non-adherence. Future studies should measure trough concentrations to better identify target HCQ levels for non-adherence and efficacy. Data are available upon reasonable request. The pharmacokinetic model used for dosing simulations is publicly available from the original publication.","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"13 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1136/lupus-2024-001153
Víctor Moreno-Torres, María Martínez-Urbistondo, José Vázquez-Comendador, María Mateos Seirul-lo, Raquel Castejón, Ana Huerta, Pedro Durán-del Campo, Pablo Tutor, Susana Mellor-Pita
Objective To evaluate the impact of the different types of neoplasms and lineages on mortality of patients with SLE. Methods Retrospective and observational comparison of the neoplasm-related deaths in patients with SLE and the general Spanish population reported in the Spanish Hospital Discharge Database. To determine the impact of SLE on the risk of dying from each neoplasm lineage, a binary logistic regression considering age, female sex, tobacco and alcohol consumption, was performed. Results During 2016–2019, 139 531 in-hospital deaths from neoplasms were certified in Spain (91 in patients with SLE). Patients with SLE presented a lower mortality rate from solid organ neoplasms, (80.2% vs 91.1%, OR 0.393), linked to their lower risk of colorectal carcinoma (1.1% vs 10.8%, OR 0.110). By contrast, gynaecological neoplasms presented a higher risk (8.8% vs 3%, OR 3.039) in the deceased patients with SLE, associated with the higher frequency of vulvar neoplasms (2% vs 0.2%, OR 14.767) and cervical carcinomas (3.3% vs 0.5%, OR 3.809). Haematological neoplasm-related deaths were also more prevalent in patients with SLE (19.8% vs 8.9%, OR 2.546), mostly attributable to the higher proportion of deaths due to non-Hodgkin’s lymphoma (11% vs 2.9%, OR 4.060) of B cell lineage (9.9% vs 2.5%, OR 4.133). Conclusions Patients with SLE present a higher risk of death from vulvar neoplasms, cervical carcinomas and B-cell non-Hodgkin’s lymphoma in comparison with the general Spanish population. In addition to developing strategies that might help to attenuate their occurrence and impact, such as decreasing the immunosuppressive burden, specific early detection programmes for these conditions should be investigated and considered carefully. Data are available in a public, open access repository. The data analysed are extracted from the Spanish Hospital Discharge Database (SNHDD)—a public access registry belonging to the Spanish Government.
目的 评估不同类型的肿瘤和肿瘤系对系统性红斑狼疮患者死亡率的影响。方法 对西班牙医院出院数据库中报告的系统性红斑狼疮患者和西班牙普通人群中与肿瘤相关的死亡病例进行回顾性观察比较。为了确定系统性红斑狼疮对每种肿瘤死亡风险的影响，我们进行了考虑年龄、女性性别、烟酒消费的二元逻辑回归。结果 2016-2019 年间，西班牙共有 139 531 例肿瘤住院死亡病例（其中 91 例为系统性红斑狼疮患者）。系统性红斑狼疮患者死于实体器官肿瘤的死亡率较低（80.2% vs 91.1%，OR 0.393），这与他们患结直肠癌的风险较低（1.1% vs 10.8%，OR 0.110）有关。相比之下，已故系统性红斑狼疮患者患妇科肿瘤的风险较高（8.8% vs 3%，OR 3.039），这与外阴肿瘤（2% vs 0.2%，OR 14.767）和宫颈癌（3.3% vs 0.5%，OR 3.809）发生率较高有关。血液肿瘤相关死亡在系统性红斑狼疮患者中也更常见（19.8% vs 8.9%，OR 2.546），主要原因是B细胞系非霍奇金淋巴瘤（11% vs 2.9%，OR 4.060）（9.9% vs 2.5%，OR 4.133）导致的死亡比例较高。结论 与西班牙普通人群相比，系统性红斑狼疮患者死于外阴肿瘤、宫颈癌和B细胞非霍奇金淋巴瘤的风险更高。除了制定可能有助于减少这些疾病的发生和影响的策略（如减轻免疫抑制负担）外，还应仔细研究和考虑针对这些疾病的特定早期检测方案。数据可在公开、开放的资料库中获取。所分析的数据来自西班牙医院出院数据库（SNHDD），这是一个属于西班牙政府的公共访问登记系统。
{"title":"Higher mortality risk from gynaecological neoplasms and non-Hodgkin’s lymphoma in patients with systemic lupus erythematosus: an observational study from the Spanish National Registry","authors":"Víctor Moreno-Torres, María Martínez-Urbistondo, José Vázquez-Comendador, María Mateos Seirul-lo, Raquel Castejón, Ana Huerta, Pedro Durán-del Campo, Pablo Tutor, Susana Mellor-Pita","doi":"10.1136/lupus-2024-001153","DOIUrl":"https://doi.org/10.1136/lupus-2024-001153","url":null,"abstract":"Objective To evaluate the impact of the different types of neoplasms and lineages on mortality of patients with SLE. Methods Retrospective and observational comparison of the neoplasm-related deaths in patients with SLE and the general Spanish population reported in the Spanish Hospital Discharge Database. To determine the impact of SLE on the risk of dying from each neoplasm lineage, a binary logistic regression considering age, female sex, tobacco and alcohol consumption, was performed. Results During 2016–2019, 139 531 in-hospital deaths from neoplasms were certified in Spain (91 in patients with SLE). Patients with SLE presented a lower mortality rate from solid organ neoplasms, (80.2% vs 91.1%, OR 0.393), linked to their lower risk of colorectal carcinoma (1.1% vs 10.8%, OR 0.110). By contrast, gynaecological neoplasms presented a higher risk (8.8% vs 3%, OR 3.039) in the deceased patients with SLE, associated with the higher frequency of vulvar neoplasms (2% vs 0.2%, OR 14.767) and cervical carcinomas (3.3% vs 0.5%, OR 3.809). Haematological neoplasm-related deaths were also more prevalent in patients with SLE (19.8% vs 8.9%, OR 2.546), mostly attributable to the higher proportion of deaths due to non-Hodgkin’s lymphoma (11% vs 2.9%, OR 4.060) of B cell lineage (9.9% vs 2.5%, OR 4.133). Conclusions Patients with SLE present a higher risk of death from vulvar neoplasms, cervical carcinomas and B-cell non-Hodgkin’s lymphoma in comparison with the general Spanish population. In addition to developing strategies that might help to attenuate their occurrence and impact, such as decreasing the immunosuppressive burden, specific early detection programmes for these conditions should be investigated and considered carefully. Data are available in a public, open access repository. The data analysed are extracted from the Spanish Hospital Discharge Database (SNHDD)—a public access registry belonging to the Spanish Government.","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"64 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140614375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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