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BACKGROUND: Since the development of the OMERACT Systemic Lupus Erythematosus (SLE) Core Outcome Set (COS) in 1998, many new SLE domains have been identified and measures developed, creating a need to update the SLE COS. To revisit the 1998 SLE COS and research agenda domains, and generate new candidate domains, we conducted this study of patients with SLE and collaborators. OBJECTIVE: (1) To evaluate existing candidate SLE domains for inclusion in the SLE COS. (2) To generate additional candidate SLE domains for COS consideration. (3) To engage SLE collaborators, including patients, in developing the updated SLE COS. METHODS: The OMERACT SLE Working Group's steering committee developed a survey to assess the importance of candidate SLE domains and generate additional domains for consideration towards the SLE COS. Patients with SLE followed at the University of Toronto Lupus Clinic (patient group) and members of the OMERACT SLE Working Group (collaborator group) were invited to complete the survey between August 2022 and February 2023. RESULTS: A total of 175 patients were invited and 100 completed the survey. Of 178 collaborators invited, 145 completed the survey. Patients tended to prioritize life-impact domains while collaborators prioritized clinical domains. Both patients and collaborators recommended additional domains to those included in the 1998 SLE COS and research agenda. CONCLUSION: The domain inclusion and importance results demonstrate that patients and collaborators prioritize different domains, so capturing the perspectives of both groups is essential to ensure a holistic assessment of SLE. The results of the study identify domains that already have a high level of agreement for potential inclusion in the SLE COS, domains that require further explanation, and novel domains that warrant consideration.
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OBJECTIVE: To investigate the association between neuropsychiatric systemic lupus erythematosus (NPSLE) and SLICC/ACR damage index (SDI) items, especially non-neuropsychiatric items. METHODS: Baseline data from five phase III trials (BLISS-52, BLISS-76, BLISS-SC, BLISS-NEA, EMBRACE) were analysed. NPSLE involvement was defined as NP BILAG A/B/C/D (n = 272); NP BILAG E denoted non-neuropsychiatric SLE (n = 3273). We employed multivariable logistic regression analysis adjusting for age, sex, disease duration, and ethnicity. RESULTS: The median (IQR) and mean ± SD SDI scores were 0 (0-1) and 0.62 ± 1.09. Compared with the non-neuropsychiatric SLE group, NPSLE patients were more likely to develop damage (adjusted (a)OR = 2.86; 95% CI = 2.28-3.59). This held true also after suppression of the NP SDI items (aOR = 1.70; 95% CI = 1.36-2.12). Beyond the neuropsychiatric domain, NPSLE was associated with damage in the cardiovascular (aOR = 2.63; 95% CI = 1.75-3.95), musculoskeletal (aOR = 1.90; 95% CI = 1.43-2.52), and skin (aOR = 1.54; 95% CI = 1.06-2.22) SDI domains. Dissecting domains into items, NPSLE was associated with coronary artery disease (aOR = 3.08; 95% CI = 1.44-6.58), myocardial infraction (aOR = 3.11; 95% CI = 1.54-6.27), muscle atrophy (aOR = 3.34; 2.16-5.16), scarring alopecia (aOR = 1.79; 95% CI = 1.19-2.70), bowel infarction (aOR = 1.98; 95% CI = 1.20-3.26), retinopathy (aOR = 2.23; 95% CI = 1.15-4.32), and premature gonadal failure (aOR = 2.10; 95% CI = 1.11-3.90). CONCLUSION: The intricate association between NPSLE and damage accrual extends beyond the nervous system to also comprise the musculoskeletal, skin, and cardiovascular organ systems.
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Lupus Vasculitis, Central Nervous System , Humans , Female , Lupus Vasculitis, Central Nervous System/psychology , Male , Adult , Middle Aged , Randomized Controlled Trials as Topic , Severity of Illness Index , Clinical Trials, Phase III as Topic , Lupus Erythematosus, Systemic/psychology , Lupus Erythematosus, Systemic/complications , Logistic Models , Risk FactorsABSTRACT
OBJECTIVE: To determine the occurrence of breakthrough COVID-19 infections (BIs) in patients with systemic lupus erythematosus (SLE) compared with patients with other rheumatic autoimmune diseases (rAIDs), patients with non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs). METHODS: The study was based on data from 7035 fully vaccinated respondents to the online COVAD questionnaire with SLE (N = 852), rAIDs (N = 3098), or nrAIDs (N = 414), and HCs (N = 2671). BI was defined as COVID-19 infection occurring in individuals vaccinated with ≥ 2 doses (or 1 dose of J&J) ≥ 14 days after vaccination and not after 6 months since the last vaccine dose. Data were analysed using linear and logistic regression models. RESULTS: A total of 91/852 (10.7%) SLE patients reported at least one BI. The frequency of BIs in SLE patients was comparable to that among HCs (277/2671; p = 0.847) and patients with nrAID (39/414; p = 0.552) but higher than that among patients with other rAIDs (235/3098; p = 0.005). No demographic factors or treatments were associated with BIs in SLE patients (p ≥ 0.05 for all). Joint pain was more frequent in SLE patients than in HCs (odds ratio [OR]: 3.38; 95% confidence interval [CI]: 1.89-6.04; p < 0.001) or nrAID patients (OR: 2.44; 95% CI: 1.04-5.75; p = 0.041). Patient with SLE did not report a higher frequency of hospitalisation or need for advanced treatment for COVID-19 infection compared with disease controls and HCs, respectively. CONCLUSION: COVID-19 vaccination conferred similar protection against COVID-19 infection in terms of frequency and severity in patients with SLE to that reported by healthy individuals.
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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterised by a wide range of symptoms and a risk for irreversible organ damage, leading to increased morbidity and mortality. To improve long-term outcomes, innovative therapeutic goals have been explored, including attainment and maintenance of remission or low disease activity, with minimal use of glucocorticoids. Other goals encompass early diagnosis, potent yet less toxic therapies, appropriate glucocorticoid tapering, and better quality of life for the patients. Implementing a treat-to-target (T2T) approach involves treatment adjustments to achieve predefined objectives. Evidence from other chronic diseases, like hypertension and diabetes, supports the success of target-based approaches. In rheumatic diseases, the multitude of clinical features adds complexity to T2T strategies, but in rheumatoid arthritis, T2T has yielded improved outcomes. The application of T2T in SLE requires realistic therapeutic goals and practical tools for their measurement. International task forces have developed T2T recommendations for SLE, focusing on limiting disease activity, preventing organ damage, and minimising glucocorticoid use, while considering patients' quality of life. Advancements in defining clinically meaningful remission and low disease activity states, coupled with promising novel therapies, have spurred progress in the management of SLE.
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Monitoring belimumab concentrations in patients can be a valuable tool for assessing treatment response and for personalizing drug doses. Various assay formats may be used to measure concentrations of therapeutic monoclonal antibodies. A particularly useful format involves the use of anti-idiotype monoclonal antibodies, selected to be highly specific to the antibody of interest. Here, we describe the development of a specific, high-affinity anti-idiotype antibody to belimumab, and the application of this antibody in a homologous sandwich ELISA to measure belimumab concentrations.
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Antibodies, Anti-Idiotypic , Antibodies, Monoclonal, Humanized , Drug Monitoring , Enzyme-Linked Immunosorbent Assay , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/immunology , Humans , Enzyme-Linked Immunosorbent Assay/methods , Drug Monitoring/methods , Antibodies, Anti-Idiotypic/immunology , Animals , Immunosuppressive Agents/bloodABSTRACT
Introduction: Current therapeutic management of lupus nephritis (LN) fails to induce long-term remission in over 50% of patients, highlighting the urgent need for additional options. Methods: We analyzed differentially expressed genes (DEGs) in peripheral blood from patients with active LN (n = 41) and active nonrenal lupus (n = 62) versus healthy controls (HCs) (n = 497) from the European PRECISESADS project (NTC02890121), and dysregulated gene modules in a discovery (n = 26) and a replication (n = 15) set of active LN cases. Results: Replicated gene modules qualified for correlation analyses with serologic markers, and regulatory network and druggability analysis. Unsupervised coexpression network analysis revealed 20 dysregulated gene modules and stratified the active LN population into 3 distinct subgroups. These subgroups were characterized by low, intermediate, and high interferon (IFN) signatures, with differential dysregulation of the "B cell" and "plasma cells/Ig" modules. Drugs annotated to the IFN network included CC-motif chemokine receptor 1 (CCR1) inhibitors, programmed death-ligand 1 (PD-L1) inhibitors, and irinotecan; whereas the anti-CD38 daratumumab and proteasome inhibitor bortezomib showed potential for counteracting the "plasma cells/Ig" signature. In silico analysis demonstrated the low-IFN subgroup to benefit from calcineurin inhibition and the intermediate-IFN subgroup from B-cell targeted therapies. High-IFN patients exhibited greater anticipated response to anifrolumab whereas daratumumab appeared beneficial to the intermediate-IFN and high-IFN subgroups. Conclusion: IFN upregulation and B and plasma cell gene dysregulation patterns revealed 3 subgroups of LN, which may not necessarily represent distinct disease phenotypes but rather phases of the inflammatory processes during a renal flare, providing a conceptual framework for precision medicine in LN.
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INTRODUCTION: Psoriatic arthritis (PsA) is associated with increased cardiovascular (CV) risk and mortality. Aortic stiffness measured by carotid-femoral pulse wave velocity (cfPWV) has been shown to predict CV risk in the general population. The present study aimed to examine cfPWV values of patients with PsA compared to healthy controls and to evaluate associations of cfPWV with patient- and disease-associated characteristics, as well as with an established traditional CV prediction score of the European Society of Cardiology (Systemic Coronary Risk Evaluation; SCORE), for the first time. METHODS: cfPWV and SCORE were evaluated in patients with PsA and healthy controls, along with clinical and laboratory disease parameters. Differences in cfPWV measurements between the two groups and associations of cfPWV with patient- and disease-associated characteristics were statistically evaluated. RESULTS: A total of 150 patients with PsA (PSOCARD cohort) and 88 control subjects were recruited. cfPWV was significantly higher in the PsA group compared to controls, even after adjustment for confounders (padj = 0.034). Moreover, cfPWV was independently associated with disease duration (r = 0.304, p = 0.001), age (rho = 0.688, p < 0.001), systolic arterial pressure (rho = 0.351, p < 0.001), glomerular filtration rate (inverse: rho = - 0.264, p = 0.001), and red cell distribution width, a marker of major adverse CV events (MACE) (rho = 0.190, p = 0.02). SCORE revealed an elevated CV risk in 8.73% of the patients, whereas cfPWV showed increased aortic stiffness and end-organ disease in 16.00% of the same cohort. CONCLUSIONS: In the largest cfPWV/PsA cohort examined to date, patients with PsA exhibited increased aortic stiffness compared to healthy controls. PsA duration was the most important independent disease-associated predictor of increased aortic stiffness, next to traditional CV risk factors. cfPWV measurements may help identify subclinical end-organ disease and abnormal aortic stiffness and thus assist CV risk classification in PsA.
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INTRODUCTION: Despite setbacks in clinical trials for systemic lupus erythematosus (SLE), three drugs have been approved for SLE and lupus nephritis (LN) treatment in the past decade. Several ongoing clinical trials, some viewed optimistically by the scientific community, underscore the evolving landscape. Emerging clinical data have established specific therapeutic targets in routine clinical practice for treating SLE, aiming to improve long-term outcomes. AREAS COVERED: Research related to treatment of SLE and LN is discussed, focusing on randomized clinical trials during the last 5 years and recommendations for the management of SLE published by the European Alliance of Associations for Rheumatology (EULAR), American College of Rheumatology (ACR), Asia Pacific League of Associations for Rheumatology (APLAR), and Pan-American League of Associations of Rheumatology (PANLAR). EXPERT OPINION: The landscape of SLE and LN treatments is evolving, as new drugs and combination treatment approaches redefine the traditional concepts of induction and maintenance treatment phases. As the therapeutic armamentarium in SLE continues to expand, the research focus is shifting from the imperative for new therapies to advancing our understanding of optimal treatment selection for individual patients, steering toward precision medicine strategies.
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Lupus Erythematosus, Systemic , Lupus Nephritis , Randomized Controlled Trials as Topic , Humans , Lupus Erythematosus, Systemic/drug therapy , Lupus Nephritis/drug therapy , Precision Medicine , Immunosuppressive Agents/therapeutic useABSTRACT
BACKGROUND: The pandemic presented unique challenges for individuals with autoimmune and rheumatic diseases (AIRDs) due to their underlying condition, the effects of immunosuppressive treatments, and increased vaccine hesitancy. OBJECTIVES: The COVID-19 vaccination in autoimmune diseases (COVAD) study, a series of ongoing, patient self-reported surveys were conceived with the vision of being a unique tool to gather patient perspectives on AIRDs. It involved a multinational, multicenter collaborative effort amidst a global lockdown. METHODS: Leveraging social media as a research tool, COVAD collected data using validated patient-reported outcomes (PROs). The study, comprising a core team, steering committee, and global collaborators, facilitated data collection and analysis. A pilot-tested, validated survey, featuring questions regarding COVID-19 infection, vaccination and outcomes, patient demographics, and PROs was circulated to patients with AIRDs and healthy controls (HCs). DISCUSSION: We present the challenges encountered during this international collaborative project, including coordination, data management, funding constraints, language barriers, and authorship concerns, while highlighting the measures taken to address them. CONCLUSION: Collaborative virtual models offer a dynamic new frontier in medical research and are vital to studying rare diseases. The COVAD study demonstrates the potential of online platforms for conducting large-scale, patient-focused research and underscores the importance of integrating patient perspective into clinical care. Care of patients is our central motivation, and it is essential to recognize their voices as equal stakeholders and valued partners in the study of the conditions that affect them.
Subject(s)
COVID-19 , Patient Reported Outcome Measures , Rheumatic Diseases , Humans , COVID-19/epidemiology , Rheumatic Diseases/therapy , Rheumatic Diseases/epidemiology , Social Media , SARS-CoV-2 , VaccinationABSTRACT
BACKGROUND: Despite the overall safety and efficacy of COVID-19 vaccinations, rare cases of systemic autoimmune diseases (SAIDs) have been reported post-vaccination. This study used a global survey to analyze SAIDs in susceptible individuals' post-vaccination. METHODS: A cross-sectional study was conducted among participants with self-reported new-onset SAIDs using the COVID-19 Vaccination in Autoimmune Diseases (COVAD) 2 study dataset-a validated, patient-reported e-survey-to analyze the long-term safety of COVID-19 vaccines. Baseline characteristics of patients with new-onset SAIDs and vaccinated healthy controls (HCs) were compared after propensity score matching based on age and sex in a 1:4 ratio. RESULTS: Of 16 750 individuals, 74 (median age 52 years, 79.9% females, and 76.7% Caucasians) had new-onset SAID post-vaccination, mainly idiopathic inflammatory myopathies (IIMs) (n = 23, 31.51%), arthritis (n = 15; 20.53%), and polymyalgia rheumatica (PMR) (n = 12, 16.40%). Higher odds of new-onset SAIDs were noted among Caucasians (OR = 5.3; 95% CI = 2.9-9.7; p < .001) and Moderna vaccine recipients (OR = 2.7; 95% CI = 1.3-5.3; p = .004). New-onset SAIDs were associated with AID multimorbidity (OR = 1.4; 95% CI = 1.1-1.7; p < .001), mental health disorders (OR = 1.6; 95% CI = 1.3-1.9; p < .001), and mixed race (OR = 2.2; 95% CI = 1.2-4.2; p = .010), where those aged >60 years (OR = 0.6; 95% CI = 0.4-0.8; p = .007) and from high/medium human development index (HDI) countries (compared to very high HDI) reported fewer events than HCs. CONCLUSION: This study reports a low occurrence of new-onset SAIDs following COVID-19 vaccination, primarily IIMs, PMR, and inflammatory arthritis. Identified risk factors included pre-existing AID multimorbidity, mental health diseases, and mixed race. Revaccination was well tolerated by most patients; therefore, we recommend continuing COVID-19 vaccination in the general population. However, long-term studies are needed to understand the autoimmune phenomena arising post-vaccination.
Subject(s)
Autoimmune Diseases , COVID-19 Vaccines , COVID-19 , Humans , Male , Female , Middle Aged , COVID-19 Vaccines/adverse effects , Autoimmune Diseases/epidemiology , Autoimmune Diseases/diagnosis , Cross-Sectional Studies , COVID-19/prevention & control , COVID-19/epidemiology , Aged , Adult , Vaccination/adverse effects , Risk Factors , SARS-CoV-2/immunologyABSTRACT
OBJECTIVE: This international task force aimed to provide healthcare professionals and persons living with systemic lupus erythematosus (SLE) with consensus-based recommendations for physical activity and exercise in SLE. METHODS: Based on evidence from a systematic literature review and expert opinion, 3 overarching principles and 15 recommendations were agreed on by Delphi consensus. RESULTS: The overarching principles highlight the importance of shared decision-making and the need to explain the benefits of physical activity to persons living with SLE and other healthcare providers. The 15 specific recommendations state that physical activity is generally recommended for all people with SLE, but in some instances, a medical evaluation may be needed to rule out contraindications. Pertaining to outdoor activity, photoprotection is necessary. Both aerobic and resistance training programmes are recommended, with a gradual increase in frequency and intensity, which should be adapted for each individual, and ideally supervised by qualified professionals. CONCLUSION: In summary, the consensus reached by the international task force provides a valuable framework for the integration of physical activity and exercise into the management of SLE, offering a tailored evidence-based and eminence-based approach to enhance the well-being of individuals living with this challenging autoimmune condition.
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Advisory Committees , Consensus , Exercise , Lupus Erythematosus, Systemic , Humans , Lupus Erythematosus, Systemic/therapy , Exercise Therapy/methods , Delphi TechniqueABSTRACT
INTRODUCTION: The growing recognition of holistic patient care highlights the various factors shaping the quality of life of individuals with autoimmune and rheumatic diseases (AIRDs). Beyond the traditional disease measures, there is an emerging acknowledgment of the less-explored aspects, including subjective well-being, social determinants of health, comorbidities, mental health, and medication adherence. Moreover, digital health services have empowered patients to engage actively in decision-making alongside clinicians. To explore these domains within the context of AIRDs, the "Collating the Voice of People with Autoimmune Diseases" COVAD survey was conceived, a successor of the previous two COVAD surveys. In this document, we present the study protocol in comprehensive detail. METHODS: The COVAD-3 survey is a cross-sectional patient self-reported e-survey incorporating multiple widely accepted scales/scores to assess various aspects of patients' lifestyles objectively. To ensure the survey's accuracy and usability across diverse regions, it will be translated into multiple languages and subjected to rigorous vetting and pilot testing. It will be distributed by collaborators via online platforms and data will be collected from patients with AIRDs, and healthy individuals over eight months. Data analysis will focus on outcome measures related to various social, demographic, economic, and psychological factors. CONCLUSION: With the increasing awareness to adopt a holistic treatment approach encompassing all avenues of life, the COVAD-3 survey aims to gain valuable insights into the impact of social, demographic, economic, and psychological determinants of health on the subjective well-being in patients with AIRDs, which will contribute to a better understanding of their overall health and well-being.
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Autoimmune Diseases , Quality of Life , Humans , Autoimmune Diseases/psychology , Cross-Sectional Studies , Rheumatic Diseases/psychology , Self Report , Medication Adherence , Mental Health , Social Determinants of Health , Research Design , Surveys and QuestionnairesABSTRACT
INTRODUCTION: Systemic lupus erythematosus with antiphospholipid syndrome (SLE-APS) represents a challenging SLE endotype whose molecular basis remains unknown. METHODS: We analysed whole-blood RNA-sequencing data from 299 patients with SLE (108 SLE-antiphospholipid antibodies (aPL)-positive, including 67 SLE-APS; 191 SLE-aPL-negative) and 72 matched healthy controls (HC). Pathway enrichment analysis, unsupervised weighted gene coexpression network analysis and machine learning were applied to distinguish disease endotypes. RESULTS: Patients with SLE-APS demonstrated upregulated type I and II interferon (IFN) pathways compared with HC. Using a 100-gene random forests model, we achieved a cross-validated accuracy of 75.6% in distinguishing these two states. Additionally, the comparison between SLE-APS and SLE-aPL-negative revealed 227 differentially expressed genes, indicating downregulation of IFN-α and IFN-γ signatures, coupled with dysregulation of the complement cascade, B-cell activation and neutrophil degranulation. Unsupervised analysis of SLE transcriptome identified 21 gene modules, with SLE-APS strongly linked to upregulation of the 'neutrophilic/myeloid' module. Within SLE-APS, venous thromboses positively correlated with 'neutrophilic/myeloid' and 'B cell' modules, while arterial thromboses were associated with dysregulation of 'DNA damage response (DDR)' and 'metabolism' modules. Anticardiolipin and anti-ß2GPI positivity-irrespective of APS status-were associated with the 'neutrophilic/myeloid' and 'protein-binding' module, respectively. CONCLUSIONS: There is a hierarchical upregulation and-likely-dependence on IFN in SLE with the highest IFN signature observed in SLE-aPL-negative patients. Venous thrombotic events are associated with neutrophils and B cells while arterial events with DDR and impaired metabolism. This may account for their differential requirements for anticoagulation and provide rationale for the potential use of mTOR inhibitors such as sirolimus and the direct fIIa inhibitor dabigatran in SLE-APS.
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Antiphospholipid Syndrome , Gene Expression Profiling , Lupus Erythematosus, Systemic , Transcriptome , Humans , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/blood , Antiphospholipid Syndrome/genetics , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/complications , Female , Male , Gene Expression Profiling/methods , Adult , Middle Aged , Case-Control Studies , Interferons , Venous Thrombosis/genetics , Venous Thrombosis/blood , Antibodies, Antiphospholipid/bloodABSTRACT
Background: Antimalarial agents (AMAs) are cornerstone drugs in the treatment of systemic lupus erythematosus (SLE), and their use has established benefits, such as improved prognosis and decelerated accrual of organ damage. The aim of this study was to investigate the frequency of discontinuation of AMAs and associated factors in a Swedish SLE population. Methods: We retrieved data from a regional SLE register where all patients fulfilled the 1982 ACR and/or the 2012 SLICC classification criteria. A total of 328 subjects were included in the analysis. Results: Altogether, 92.4% (303/328) had been prescribed AMAs at some point during their disease. At the last available visit, 67.7% (222/328) were currently prescribed AMAs. Among individuals who had discontinued use, 24.7% (20/81) had developed a contraindication. Side effects were also common reasons for discontinuation (n = 38); gastrointestinal symptoms (52.6%, 20/38) were most common. Patients who discontinued had accrued more organ damage at the last visit (mean SDI: 2.9; SD: 2.8) compared with those still on AMAs (mean SDI: 1.4; SD: 1.8; p = 0.001). Conclusions: Most patients had been exposed to AMAs, but 25% discontinued therapy. Among side effects leading to discontinuation, >50% were gastrointestinal, calling for adequate gastroprotection towards drug retention and prevention of organ damage progression.
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Objectives: We aimed to investigate the efficacy of lifestyle interventions for the management of SSc. Methods: We searched the MEDLINE, Embase, Web of Science and CINAHL databases in June 2021. We included studies conducted on five or more patients with SSc published between 1 January 2000 and the search date evaluating lifestyle interventions, excluding systematic reviews without meta-analyses. Critical appraisal was conducted using critical appraisal tools from the Joanna Briggs Institute. Thirty-six studies were included for full-text evaluation. Results: A total of 17 studies evaluated the effect of physical exercise alone, whereas 14 studies evaluated educational interventions for mental health management, often with physical exercise as a central component. At an aggregated level, these studies support patient education and physical exercise for the improvement of physical function, in particular hand and mouth function. Studies on diet and nutrition were few (n = 5) and pertained to gastrointestinal as well as anthropometric outcomes; these studies were insufficient to support any conclusions. Conclusion: Physical exercise and patient education should be considered for improving physical function in patients with SSc. These interventions can be provided alongside pharmacotherapy, but there is no evidence supporting that they can be a substitute. Further research should aim at assessing the effects of reductions of harmful exposures, including tobacco smoking and alcohol, improving sleep and enhancing social relations, three hitherto underexplored facets of lifestyle in the context of SSc.
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OBJECTIVES: Substantial proportions of patients with systemic lupus erythematosus (SLE) report poor health-related quality of life (HRQoL). Our objective was to investigate the impact of neuropsychiatric involvement (NP) in SLE on patient-reported outcomes. METHODS: We analysed data from four phase III trials (BLISS-52, BLISS-76, BLISS-SC, EMBRACE; N = 2968). The neuropsychiatric SLE (NPSLE) group comprised individuals with NP-British Isles Lupus Assessment group (BILAG) A/B/C/D or score in any descriptor of the NP-SLEDAI-2K at baseline (N = 350), while the non-NPSLE group consisted of patients with NP-BILAG E (N = 2618). HRQoL was assessed with the SF-36, EQ-5D-3L, and FACIT-F. Full health state (FHS) was defined as "no problems" in all EQ-5D dimensions. RESULTS: NPSLE patients reported lower scores in the SF-36 physical and mental component summary compared with the non-NPSLE population (mean±s.d.: 35.7±9.1 versus 39.6±9.6; p<0.001 and 37.3±12.1 versus 41.4±11.0; p<0.001, respectively). NPSLE patients also exhibited impaired HRQoL in all EQ-5D dimensions compared with non-NPSLE patients (p<0.05 for all). A substantially lower proportion among NPSLE patients experienced FHS in comparison with the non-NPSLE group (3.3% versus 14.5%; p<0.001). NPSLE was associated with severe fatigue (23.8±12.2 versus 31.5±11.6; p<0.001). Notably, our findings revealed no discernible distinctions between active and inactive NPSLE patients with regard to SF-36, EQ-5D, FHS, and FACIT-F scores. CONCLUSION: Neuropsychiatric involvement in patients with SLE has a detrimental effect on HRQoL experience and is associated with severe fatigue, regardless of the degree of neuropsychiatric disease activity. Early intervention is warranted in NPSLE patients to enhance long-term HRQoL experience.
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OBJECTIVES: To explore prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIM) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. METHODS: A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after 2 vaccine doses. We compared BIs characteristics and severity among IIMs, other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HC). Multivariable Cox regression models assessed the risk factors for BI, severe BI and hospitalisations among IIMs. RESULTS: Among 9449 included response, BIs occurred in 1447 (15.3%) respondents, median age 44 years (IQR 21), 77.4% female, and 182 BIs (12.9%) occurred among 1406 IIMs. Multivariable Cox regression among IIMs showed age as a protective factor for BIs [Hazard Ratio (HR)=0.98, 95%CI = 0.97-0.99], hydroxychloroquine and sulfasalazine use were risk factors (HR = 1.81, 95%CI = 1.24-2.64, and HR = 3.79, 95%CI = 1.69-8.42, respectively). Glucocorticoid use was a risk factor for severe BI (HR = 3.61, 95%CI = 1.09-11.8). Non-White ethnicity (HR = 2.61, 95%CI = 1.03-6.59) was a risk factor for hospitalisation. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIM = 6.0% vs AIRD = 1.8%, nrAID = 2.2%, and HC = 0.9%), intensive care unit admission (IIM = 2.2% vs AIRD = 0.6%, nrAID, and HC = 0%), advanced treatment with antiviral or monoclonal antibodies (IIM = 34.1% vs AIRD = 25.8%, nrAID = 14.6%, and HC = 12.8%), and had more hospitalisation (IIM = 7.7% vs AIRD = 4.6%, nrAID = 1.1%, and HC = 1.5%). CONCLUSION: Patients with IIMs are susceptible to severe COVID-19 BI. Age and immunosuppressive treatments were related to the risk of BIs.
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Objectives: To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs) and without autoimmune diseases (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database. Methods: Demographics, diagnosis, comorbidities, disease activity, treatments and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis. Results: We analysed responses from 1582 IIM, 4700 non-IIM AIRD and 545 nrAID patients and 3675 controls gathered through 23 May 2022. The median GPH scores were the lowest in IIM and non-IIM AIRD patients {13 [interquartile range (IQR) 10-15] IIMs vs 13 [11-15] non-IIM AIRDs vs 15 [13-17] nrAIDs vs 17 [15-18] controls, P < 0.001}. The median GMH scores in IIM patients were also significantly lower compared with those without autoimmune diseases [13 (IQR 10-15) IIMs vs 15 (13-17) controls, P < 0.001]. Inclusion body myositis, comorbidities, active disease and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function 10a and higher PROMIS Fatigue 4a scores were associated with lower GMH scores in IIM patients. Conclusion: Both physical and mental health are significantly impaired in IIM patients, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs.
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We performed a systematic review to explore existing evidence regarding the efficacy of lifestyle interventions for the management of systemic lupus erythematosus (SLE). The search was conducted on the 22nd of June 2021 for publications between 1st of January 2000 and the date of search. Additional articles within the aforementioned timeframe and until December 2023 were added by hand searching. Databases utilized were Medline, Embase, Web of Science, and Cinahl. Lifestyle interventions were defined as any intervention encompassing one or more of the following: physical exercise, diet and nutrition, mental health, harmful exposures, sleep, and social relations. The Joanna Briggs Institute critical appraisal tools were used for risk of bias assessment. The search yielded 11,274 unique records, we assessed the full text of 199 records, and finally included 102 studies. Overall, the quality of the evidence is limited, and there were multiple sources of heterogeneity. The two domains most extensively researched were mental health (40 records) and physical exercise (39 records). Psychological interventions had a positive effect on depressive symptoms, anxiety, and health-related quality of life (HRQoL), whereas physical exercise improved fatigue, depressive symptoms, aerobic capacity, and physical functioning. Studies on diet and nutrition (15 records) support that low fat intake and Mediterranean diet may be beneficial for reducing cardiovascular risk, but large interventional studies are lacking. Studies on harmful exposures (7 records) support photoprotection and use of sunscreen. While studies imply benefits regarding disease burden and drug efficacy in non-smokers and regarding HRQoL in normal-weight patients, more survey is needed on tobacco smoking and alcohol consumption, as well as weight control strategies. Studies on social relations (1 record) and sleep (no records) were sparse or non-existent. In conclusion, psychosocial interventions are viable for managing depressive symptoms, and exercise appears essential for reducing fatigue and improving aerobic capacity and physical function. Photoprotection should be recommended to all patients. Lifestyle interventions should be considered a complement, not a substitute, to pharmacotherapy.