Patients with neuropsychiatric involvement systemic lupus erythematosus experience poorer health-related quality of life and more fatigue than systemic lupus erythematosus patients with no neuropsychiatric involvement, irrespective of neuropsychiatric activity.

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.

Disentangling the riddle of systemic lupus erythematosus with antiphospholipid syndrome: blood transcriptome analysis reveals a less-pronounced IFN-signature and distinct molecular profiles in venous versus arterial events.

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.

Collating the voice of people with autoimmune diseases: Methodology for the Third Phase of the COVAD Studies.

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.

Lifestyle interventions in the management of systemic sclerosis: a systematic review of the literature.

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.

Recommendations for physical activity and exercise in persons living with Systemic Lupus Erythematosus (SLE): consensus by an international task force.

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.

Factors Associated with Survival and Discontinuation of Anti-Malarial Agents in Systemic Lupus Erythematosus: Results from a Tertiary Swedish Referral Centre.

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.

Characteristics and risk factors of COVID-19 breakthrough infections in Idiopathic Inflammatory Myopathies: Results from the COVAD study.

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.

Efficacy of lifestyle interventions in the management of systemic lupus erythematosus: a systematic review of the literature.

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.

Obesity and tobacco smoking are independently associated with poor patient-reported outcomes in SLE: a cross-sectional study.

We investigated associations of obesity and tobacco smoking with health-related quality of life (HRQoL), pain, fatigue, and functional impairment in systemic lupus erythematosus (SLE). Furthermore, we explored whether there was an effect modification between these two factors. We included adult SLE patients from the Linköping University Hospital (n = 325) in the present cross-sectional analysis. We further included population-based controls and performed cardinality matching to balance age and sex distributions with cases (n = 224). HRQoL was assessed with the EQ-5D index score; pain, fatigue, and overall SLE-related health state with visual analogue scales (VAS; 0 [best] to 100 [worst]); and functional impairment with the HAQ-DI. Unacceptable outcomes were defined as VAS scores corresponding to the 90th percentile derived from the matched controls. SLE patients reported worse scores than controls in all measures, and approximately 30% experienced unacceptable outcomes. When compared with normal-weight, obese SLE patients reported lower HRQoL, and greater functional impairment and risk of unacceptable pain (OR: 3.2; 95% CI 1.6-6.7) and fatigue (OR: 2.1; 95% CI 1.0-4.3). Similarly, the current smokers reported higher levels of functional impairment and a greater risk of unacceptable pain (OR: 3.8; 95% CI 1.8-8.2) and fatigue (OR: 2.8; 95% CI 1.3-5.9) than never smokers. The associations were independent of age, sex, disease duration, disease activity, and organ damage. There was no evidence of a synergistic effect between increased BMI and smoking on any outcome. In summary, obesity and smoking are risk factors for unacceptable patient-reported outcomes in SLE, regardless of clinical activity.

Factors associated with non-adherence to medications in systemic lupus erythematosus: Results from a Swedish survey.

OBJECTIVE: To identify determinants of medication non-adherence in a Swedish population of systemic lupus erythematosus (SLE). METHODS: Patients with SLE from Karolinska and Örebro University Hospitals participated in a survey-based cross-sectional study. Demographics, disease activity, organ damage, HRQoL (LupusQol, EQ-5D-5 L), medication non-adherence (<80% on CQR-19 or MASRI) and beliefs about medicines (BMQ) were registered. MASRI was used to report adherence to different drugs/drug classes, categorised into (i) antimalarial agents (AMA), (ii) glucocorticoids and (iii) other SLE medications. Multivariable logistic regression adjusted for age, sex, disease activity and organ damage. RESULTS: Among 205 respondents, the median age was 52.0 years (IQR: 34.0-70.0), 86.3% were women, 66.8% were non-adherent to their medications according to CQR-19, and 6.6% and 6.3% were non-adherent to AMA and glucocorticoids, respectively, according to MASRI. Positive beliefs about glucocorticoids (OR; 95% CI: 0.77; 0.59-0.99; p = .039) and medications overall (0.71; 0.52-0.97; p = .029) were protective against non-adherence to glucocorticoids. Anxiety/depression (3.09; 1.12-8.54; p = .029), medication concerns (1.12; 1.05-1.20; p < .001) and belief that medications are overused (1.30; 1.15-1.46; p < .001) or harmful (1.36; 1.19-1.56; p < .001) were associated with medication non-adherence (CQR-19); beliefs in the necessity of medications (0.73; 0.65-0.82; p < .001) and positive beliefs in medications were protective (0.72; 0.60-0.86; p < .001). No associations were found between other investigated factors and medication non-adherence. CONCLUSIONS: Beliefs about medications were a major determinant of medication non-adherence. Patient education may help alleviate the negative impact of misinformation/unawareness on adherence.

Impaired health-related quality of life in idiopathic inflammatory myopathies: a cross-sectional analysis from the COVAD-2 e-survey.

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.

Lessons learnt from the recent recommendations for the non-pharmacological management of systemic sclerosis.

In inflammatory rheumatic diseases, including, systemic sclerosis (SSc) there is growing evidence that treatment strategies should not only target disease control in terms of clinical features and laboratory tests but consider distinct interventions to mitigate all domains of perceived disease impact. The results of a multicentric work based on data from the Rheumatic Diseases Portuguese Registry (Reuma.pt)/Scleroderma indicated that the optimization of outcomes for patients with SSc would in all probability require assessment of the needs of individual patients and consider adjunctive interventions in clinical practice to mitigate all significantly affected domains of disease impact. Recently, in June 2023, a task force under the auspices of EULAR, comprising rheumatologists, health professionals and patient advocates published four overarching principles and twelve recommendations for the non-pharmacological management of people living with SSc and systemic lupus erythematosus (SLE).

Molecular characterisation of lupus low disease activity state (LLDAS) and DORIS remission by whole-blood transcriptome-based pathways in a pan-European systemic lupus erythematosus cohort.

OBJECTIVES: To unveil biological milieus underlying low disease activity (LDA) and remission versus active systemic lupus erythematosus (SLE). METHODS: We determined differentially expressed pathways (DEPs) in SLE patients from the PRECISESADS project (NTC02890121) stratified into patients fulfilling and not fulfilling the criteria of (1) Lupus LDA State (LLDAS), (2) Definitions of Remission in SLE remission, and (3) LLDAS exclusive of remission. RESULTS: We analysed data from 321 patients; 40.8% were in LLDAS, and 17.4% in DORIS remission. After exclusion of patients in remission, 28.3% were in LLDAS. Overall, 604 pathways differed significantly in LLDAS versus non-LLDAS patients with an false-discovery rate-corrected p (q)<0.05 and a robust effect size (dr)≥0.36. Accordingly, 288 pathways differed significantly between DORIS remitters and non-remitters (q<0.05 and dr≥0.36). DEPs yielded distinct molecular clusters characterised by differential serological, musculoskeletal, and renal activity. Analysis of partially overlapping samples showed no DEPs between LLDAS and DORIS remission. Drug repurposing potentiality for treating SLE was unveiled, as were important pathways underlying active SLE whose modulation could aid attainment of LLDAS/remission, including toll-like receptor (TLR) cascades, Bruton tyrosine kinase (BTK) activity, the cytotoxic T lymphocyte antigen 4 (CTLA-4)-related inhibitory signalling, and the nucleotide-binding oligomerization domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome pathway. CONCLUSIONS: We demonstrated for the first time molecular signalling pathways distinguishing LLDAS/remission from active SLE. LLDAS/remission was associated with reversal of biological processes related to SLE pathogenesis and specific clinical manifestations. DEP clustering by remission better grouped patients compared with LLDAS, substantiating remission as the ultimate treatment goal in SLE; however, the lack of substantial pathway differentiation between the two states justifies LLDAS as an acceptable goal from a biological perspective.

Lupus Low Disease Activity State and organ damage in relation to quality of life in systemic lupus erythematosus: a cohort study with up to 11 years of follow-up.

OBJECTIVES: Beyond prevention of organ damage, treatment goals in systemic lupus erythematosus (SLE) include optimisation of health-related quality of life (HRQoL). The Lupus Low Disease Activity State (LLDAS) has received increasing attention as a goal whenever remission cannot be achieved. How SLE disease activity, organ damage, and LLDAS attainment relate to patient-reported outcomes (PROs) is not fully explored, which formed the scope of this investigation. METHODS: We included 327 patients with SLE from a tertiary referral centre. Longitudinal registrations of disease activity using SLEDAI-2K and physician global assessment (PhGA), organ damage using the SLICC/ACR damage index (SDI), pharmacotherapies, EQ-5D-3L data, as well as visual analogue scale (VAS) scores for fatigue, pain, and overall SLE-related health state over a median follow-up time of 8.5 years were analysed. RESULTS: In the overall population, as well as subgroups of patients with recent-onset SLE and those with clinically active, autoantibody-positive disease, LLDAS attainment, lower PhGA, and lower clinical SLEDAI-2K scores were associated with favourable HRQoL by EQ-5D-3L and VAS assessments, while increasing SDI scores were associated with poor PROs yet not fatigue in the overall population. PROs were further enhanced by being in LLDAS sustainedly. In fully adjusted models of the entire study population, LLDAS attainment and lower disease activity were associated with favourable PROs, irrespective of SDI. CONCLUSION: In one of the longest to date observational studies, we demonstrated that low disease activity and being sustainedly in LLDAS were coupled with favourable HRQoL, pain, fatigue, and overall health experience, irrespective of organ damage.

Clinical trial outcomes for SLE: what we have and what we need.

The paradigm of drug approval in SLE currently relies on successful large phase III randomised controlled trials and a set of primary, secondary and additional end points. Taken together, these outcomes offer a nuanced understanding of the efficacy and safety of the investigational agent. In this review, we thoroughly examine the main outcomes used in SLE trials and highlight unmet requirements as well as potential venues for future trial design in SLE. Disease activity indices can be broadly categorised into global-specific and organ-specific indices, in particular for skin, joints and kidneys, but there is no universal consensus about their use in clinical trials. Because each of these instruments has its own intrinsic strengths and weaknesses, the assessment of treatment response has progressed from relying solely on one individual disease activity index to using composite responder definitions. Those are typically measured from the trial baseline to the end point assessment date and may be combined with the need to taper and maintain glucocorticoids (GCs) within prespecified ranges. Remission and low disease activity are two critical states in the perspective of 'Treat-to-Target' trials, but are not fully recognised by regulators. While significant progress has been made in clinical trial outcomes for SLE, there is a clear need for continued innovation. Addressing these challenges will require collaboration between researchers, clinicians, patients as well as with regulatory agencies to refine existing outcome measures, incorporate meaningful and ethnically diverse patient perspectives, foster relevant digital opportunities and explore new therapeutic avenues, including early use of investigational agents. By doing so, we can advance our ability to manage SLE effectively and safely and improve the lives of those living with this complex and impactful autoimmune disease.

OMERACT 2023 Systemic Lupus Erythematosus Special Interest Group: Winnowing and Binning Preliminary Candidate Domains for the Core Outcome Set.

BACKGROUND: The Outcome Measures in Rheumatology (OMERACT) Systemic Lupus Erythematosus (SLE) Working Group held a Special Interest Group (SIG) at the OMERACT 2023 conference in Colorado Springs where SLE collaborators reviewed domain sub-themes generated through qualitative research and literature review. OBJECTIVE: The objective of the SIG and the subsequent meetings of the SLE Working Group was to begin the winnowing and binning of candidate domain sub-themes into a preliminary list of candidate domains that will proceed to the consensus Delphi exercise for the SLE COS. METHODS: Four breakout groups at the SLE SIG in Colorado Springs winnowed and binned 132 domain sub-themes into candidate domains, which was continued with a series of virtual meetings by an advisory group of SLE patient research partners (PRPs), members of the OMERACT SLE Working Group Steering Committee, and other collaborators. RESULTS: The 132 domain sub-themes were reduced to a preliminary list of 20 candidate domains based on their clinical and research relevance for clinical trials and research studies. CONCLUSION: A meaningful and substantial winnowing and binning of candidate domains for the SLE COS was achieved resulting in a preliminary list of 20 candidate domains.

Predictors of renal flares in systemic lupus erythematosus: a post-hoc analysis of four phase III clinical trials of belimumab.

OBJECTIVES: To identify predictors of renal flares in patients with SLE treated for active extra-renal disease. METHODS: Data from four clinical trials of belimumab in SLE (BLISS-52, NCT00424476; BLISS-76, NCT00410384; BLISS-NEA, NCT01345253; BLISS-SC, NCT01484496) were used. Patients were assigned to belimumab or placebo on top of standard therapy. We investigated the performance of predictors of renal flares through 52-76 weeks using proportional hazards regression analysis. RESULTS: Of 3225 participants, 192 developed at least one renal flare during follow-up, with the first occurring after a median time of 197 days. Current/former renal involvement (HR: 15.4; 95% CI: 8.3-28.2; p< 0.001), low serum albumin levels (HR 0.9; 95% CI: 0.8-0.9; p< 0.001), proteinuria (HR: 1.6; 95% CI: 1.5-1.7; p< 0.001), and low C3 levels (HR: 2.9; 95% CI: 2.1-4.1; p< 0.001) at baseline appeared robust determinants of renal flares. Anti-dsDNA positivity yielded an increased hazard for renal flares (HR: 2.1; 95% CI: 1.4-3.2; p< 0.001), which attenuated after adjustments. Anti-Sm positivity was associated with renal flares in the placebo (HR: 3.7; 95% CI: 2.0-6.9; p< 0.001) but not in the belimumab subgroup, whereas anti-ribosomal P positivity was associated with renal flares in the belimumab subgroup only (HR: 2.8; 95% CI: 1.5-5.0; p= 0.001). CONCLUSION: A history of renal involvement, high baseline proteinuria, hypoalbuminaemia, and C3 consumption were robust determinants of impending renal flares. Beyond anti-dsDNA, anti-Sm and anti-ribosomal P protein antibody positivity may have value in surveillance of renal SLE.

Flares in IIMs and the timeline following COVID-19 vaccination: a combined analysis of the COVAD-1 and -2 surveys.

OBJECTIVES: Disease flares in the post-coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). METHODS: The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression models. RESULTS: Of 15 165 total respondents, 1278 IIMs (age 63 years, 70.3% female, 80.8% Caucasians) and 3453 AIRDs were included. Flares of IIM were seen in 9.6%, 12.7%, 8.7% and 19.6% patients by definitions (a) to (d), respectively, with a median time to flare of 71.5 (10.7-235) days, similar to AIRDs. Patients with active IIMs pre-vaccination (OR 1.2; 95% CI 1.03, 1.6, P = 0.025) were prone to flares, while those receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P = 0.010) and AZA (OR 0.3, 95% CI 0.1, 0.8, P = 0.016) were at lower risk. Female gender and comorbidities predisposed to flares requiring changes in IS. Asthma (OR 1.62; 95% CI 1.05, 2.50, P = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P < 0.001) were associated with disparity between self-reported and IS-denoted flares. CONCLUSION: A diagnosis of IIMs confers an equal risk of flares in the post-COVID-19 vaccination period to AIRDs, with active disease, female gender and comorbidities conferring a higher risk. Disparity between patient- and physician-reported outcomes represents a future avenue for exploration.

Global disparities in the treatment of idiopathic inflammatory myopathies: results from an international online survey study.

OBJECTIVES: We aimed to explore current practice and interregional differences in the treatment of idiopathic inflammatory myopathies (IIMs). We triangulated these observations considering countries' gross national income (GNI), disease subtypes, and symptoms using patient-reported information. METHODS: A cross-sectional ancillary analysis of the 'COVID-19 vaccination in auto-immune disease' (COVAD) e-survey containing demographic characteristics, IIM subtypes (DM, PM, IBM, anti-synthetase syndrome [ASSD], immune-mediated necrotizing myopathy [IMNM], overlap myopathies [OM]), current symptoms (surrogate for organ involvement) and treatments (corticosteroids [CS], immunomodulators [IM], i.e. antimalarials, immunosuppressants [IS], IVIG, biologic treatments and targeted-synthetic small molecules). Treatments were presented descriptively according to continents, GNI, IIM and organ involvement, and associated factors were analysed using multivariable binary logistic regressions. RESULTS: Of 18 851 respondents from 94 countries, 1418 with IIM were analysed (age 61 years, 62.5% females). DM (32.4%), IBM (24.5%) and OM (15.8%) were the most common subtypes. Treatment categories included IS (49.4%), CS (38.5%), IM (13.8%) and IVIG (9.4%). Notably, treatments varied across regions, GNI categories (IS mostly used in higher-middle income, IM in lower-middle income, IVIG and biologics largely limited to high-income countries), IIM subtypes (IS and CS associated with ASSD, IM with OM and DM, IVIG with IMNM, and biologic treatments with OM and ASSD) and disease manifestations (IS and CS with dyspnoea). Most inter-regional treatment disparities persisted after multivariable analysis. CONCLUSION: We identified marked regional treatment disparities in a global cohort of IIM. These observations highlight the need for international consensus-driven management guidelines considering patient-centred care and available resources.