Objective To examine the role of low-dose glucocorticoids (GCs) in major relapse, hospitalisation and damage accumulation risk during maintenance therapy in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAVs).Methods Retrospective cohort study of newly diagnosed patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) followed in three tertiary referral centres. We recorded relapses (Birmingham Vasculitis Activity Score increase >0), increases in Vasculitis Damage Index (VDI) and hospitalisations. We used time-varying and mixed-effects Cox models to examine the effect of GCs on the risk of major relapses, VDI accumulation and hospitalisations. Sensitivity analysis was also conducted to address potential confounding.Results 171 patients (GPA: 107, MPA: 64, median age: 61 years) were included with a median follow-up of 88.2 months (803.4 patient years (PY)). We recorded 65 major relapses (8.1/100 PY) in 48 patients (28%), 65 events of new damage (8.1/100 PY) and 132 hospitalisations (16.4/100 PY). By multivariable analysis, rituximab use was associated with a lower risk (HR=0.21, 95% CI 0.09 to 0.47, p=0.0001) while disease activity at diagnosis was associated with an increased risk (HR=1.17, 95% CI 1.03 to 1.33, p=0.013) of major relapses. Low-dose GCs were not associated with a reduced major relapse risk (HR=0.96, 95% CI 0.88 to 1.05, p=0.36) but they were associated with a risk of damage accumulation (HR=1.52, 95% CI 1.19 to 1.93, p=0.0007) and hospitalisations (HR=1.24, 95% CI 1.06 to 1.45, p=0.006).Conclusion Higher GC exposure during maintenance therapy was not significantly associated with a lower major relapse risk whereas it was associated with damage accrual and hospitalisation. These findings may support decision making regarding long-term GC use in patients with GPA/MPA.

EULAR recommends kidney biopsy in systemic lupus erythematosus (SLE) patients with glomerular hematuria, whereas both ACR and KDIGO require the presence of proteinuria and/or impaired kidney function. We explored the value of hematuria for the diagnosis of new-onset lupus nephritis (LN). Cross-sectional study of SLE patients who underwent diagnostic kidney biopsy in two independent centers. Clinically significant LN was defined as ISN/RPS class III, IV, V, or mixed III/IV + V. Presentation patterns were categorized by glomerular hematuria, proteinuria, and impaired kidney function. Among patients with glomerular hematuria, regression models identified factors associated with clinically significant LN, and a nomogram was constructed. Of 227 biopsies, 181 (79.7

Insufficient treatment response is common in systemic lupus erythematosus (SLE) and may be associated with progressive organ damage, yet the molecular underpinnings of treatment resistance remain elusive. RNA sequencing was performed in blood samples from 21 SLE patients who failed to achieve Lupus Low Disease Activity State after six months of treatment with cyclophosphamide (n = 9), rituximab (n = 5), or belimumab (n = 7). Molecular endotypes were identified via unsupervised clustering of Functional Analysis of Individual Microarray Expression (FAIME) scores and cluster stability was validated in an independent cohort (n = 23). Endotype-specific druggability was assessed using the L1000CDS2 platform. The pathway-based molecular stratification revealed three major endotypes among patients with inadequate treatment response: (i) a T cell-centric cluster characterized by enrichment of PD-1 signaling and DNA damage response pathways along with downregulation of CD28 co-stimulatory signaling, indicative of T cell senescence; (ii) a cytokine-driven cluster defined by elevated IL-6 and IL-17 signaling and reduced IL-2 signaling, suggesting a Th17/Treg imbalance and potential responsiveness to cytokine inhibition or low-dose IL-2 therapy; and (iii) an inflammasome-dominant cluster. A multinomial LASSO regression-derived Molecular Endotype Classification Index (MECI) - validated via 1000-fold bootstrap resampling - demonstrated potential as a surrogate marker for endotype assignment (median AUC-ROC 0.889). Transcriptome reversal analysis suggested that patients of the T cell-dominant endotype may be more responsive to CD19 CAR-T cell therapy. In summary, distinct molecular endotypes underlie insufficient response to therapy in SLE, providing a framework for personalized treatment strategies and improved clinical trial design.

A key assumption in neuropsychiatric systemic lupus erythematosus (NPSLE), is that systemic inflammation leads to a disrupted blood-brain barrier, allowing autoantibodies, immune cells and other inflammatory mediators from the peripheral blood to penetrate into the central nervous system (CNS) causing hyperexcitation, inflammation and tissue damage. Yet, the immunologically privileged nature of the CNS, suggests that early manifestations - particularly mood disorders and cognitive decline - may be due to unique brain mechanisms. Neuropsychiatric symptoms in SLE can be subtle and may start early, before overt signs of inflammation in other organs. In recent years, the integration of advanced imaging tools has provided valuable insights in early events in disease pathogenesis. Intrinsic microglial activation - in the presence of an intact BBB - is an early event and may cause cognitive impairment, anxiety and depression with both activation of microglia and complement accounting for the loss of dendrites. Since NPSLE may run independently of evidence of inflammation-linked lupus manifestations (so called type 1 SLE), common symptoms in SLE such as depression, anxiety and fatigue should not be disregarded a priori as part of the fibromyalgia and not related to SLE. From a translational standpoint, early diagnosis and intervention with molecules that inhibit early damage, could improve the prognosis of NPSLE. These molecules may include cytokine inhibitors such as IL-6 at earlier stages of disease or IFN-α later, anti-BAFF (belimumab), kinase inhibitors or oral neuroprotective agents that preserve the BBB function and/or deactivate the microglia such as captopril, or inhibitors of complement C5a or C1q.

ObjectivesTo explore pregnancy-related concerns among women with systemic lupus erythematosus (SLE) and impact of the disease on desired family size.MethodCross-sectional, single-center study, including women with SLE diagnosed before menopause. Data were collected via questionnaires and medical records. Participants were classified into three groups: (i) those who never conceived (Group 1); (ii) those who had conceived before SLE diagnosis (Group 2), and (iii) those who had conceived at least once after disease diagnosis (Group 3). Continuous variables were analyzed using Kruskal-Wallis with Mann-Whitney U post-hoc tests; categorical variables using Chi-square or Fisher's exact tests.Results152 patients were included and 75% had received information from their treating physician on reproductive health. Most common pregnancy-related concerns were the need to receive medication during pregnancy (56.6%), followed by concerns about pregnancy complications (53.9%). Women in Group 1 were younger and mainly attributed not having children to personal choice and not to SLE (56.4%). In contrast, women in Groups 2 and 3 frequently reported having fewer children than desired (35.3% and 44.6%, respectively), mostly due to SLE-related concerns (83.3% and 86.2%, respectively). In Group 3, deviation from desired family size was smaller among women who conceived in more recent periods (2015-2024, 32%), although attribution of deviations to SLE remained high.ConclusionsSLE affects women's reproductive decisions, underscoring the importance of tailored counseling.

Background: Idiopathic inflammatory myopathies (IIMs) are a heterogenous group of disorders frequently complicated by interstitial lung disease (ILD). We sought to discern phenotypic and serological differences according to the presence of ILD and initial evaluating medical specialty, i.e., rheumatology vs. pulmonology, with the goal of advancing personalized medicine. Methods: A computer-assisted search was conducted to identify patients with a diagnosis of IIM seen at Attikon University Hospital, from January 2010 to December 2025. Medical records were reviewed for clinical, laboratory and serological features. Results: We identified 140 patients with IIM; 96 (68.6%) were female with a mean age at diagnosis of 55.8 years (SD 15.7). ILD was present in 75 patients (53.6%), being more common among males (30/44, 68.2% vs. 45/96 females, 46.9%, p = 0.019). Patients in the ILD subgroup were older at diagnosis (mean age 60.2 years vs. 50.7 years, p < 0.001) and presented more often with dyspnea (41 vs. 1, p < 0.001), higher CRP (median 5.95 mg/L vs. 2.9 mg/L, p = 0.024), and lower CPK (median 103 vs. 580, p < 0.001). Patients first seen by a pulmonologist were more likely to be older (mean age 60.5 years vs. 53 years, p = 0.002) and to present with dyspnea (33 vs. 9, p < 0.001) and ILD (48 vs. 27, p < 0.001). By contrast, skin involvement (61% vs. 27%, p = 0.04), muscle weakness (53 vs. 15, p < 0.001) and elevated CPK (median 301.5 vs. 103.5, p = 0.013) were less frequent in these patients as compared to patients first evaluated by a rheumatologist. Anti-tRNA synthetase, anti-Ro52 and anti-Pm/Scl antibodies were more frequent in the ILD subgroup. Anti-tRNA antibodies were also more frequent in patients first seen by a pulmonologist. Conclusions: Patients with IIM-ILD are more likely to present without overt clinical or biochemical characteristics of muscle involvement, thereby increasing the likelihood of initial evaluation by pulmonologists.

OBJECTIVES:This study aimed to develop a set of quality indicators (QIs) based on the 2025 European Alliance of Associations for Rheumatology (EULAR) recommendations for systemic lupus erythematosus with kidney involvement and explore their association with disease outcomes. METHODS:A modified Research and Development and University of California, Los Angeles appropriateness method was used. In 2 voting rounds, 23 experts rated candidate QIs for validity and feasibility. Median ratings and agreement were calculated, leading to a core QI set. Adherence to recommended care from healthcare providers was assessed at both QI and patient levels in a single tertiary centre contemporary lupus nephritis (LN) cohort (n = 130). High adherence was defined as ≥80%. Associations between adherence to QIs, damage accrual, and renal flares were explored. RESULTS:A total of 17 QIs were developed across 4 domains: diagnosis, treatment, monitoring, and pregnancy. High adherence was observed for kidney biopsy, hydroxychloroquine use, maintenance immunosuppression, therapy switching in persistent or relapsing disease, renin-angiotensin system inhibitor use, remission before kidney transplantation, and pregnancy-related QIs. Combination immunosuppressive therapy as initial treatment had low adherence (10.7%), reflecting practice patterns preceding publication of the recommendations. High per-patient adherence was associated with lower odds of damage accrual (increase in Systemic Lupus International Collaborating Clinic Damage Index; odds ratio: 0.29, 95% CI: 0.13-0.62) and fewer renal flares, although the latter association was not statistically significant. CONCLUSIONS:These QIs may serve as a structured framework for implementing the 2025 EULAR recommendations for LN. Higher adherence was associated with reduced damage accrual in a tertiary centre cohort, but results need validation in diverse clinical settings.

The use of alkylating agents such as cyclophosphamide, has decreased in recent years because of concerns for ovarian toxicity, and is limited to patients with severe disease or disease refractory to inhibitors of nucleotide synthesis such as mycophenolate acid or azathioprine. Because of a more favorable efficacy to toxicity ratio, mycophenolate acid is the drug of first choice in moderately severe lupus and can used both as induction and maintenance therapy. Azathioprine is predominantly used as a steroid-sparing agent and as maintenance treatment. Calcineurin inhibitors like cyclosporine A and tacrolimus are used less often- predominantly as steroid sparing agents or in patients with refractory disease-because of their metabolic and renal toxicity. Patients on cytotoxic-immunosuppressive agents have increased risk for both common and opportunistic infections.

Objectives Lupus Low Disease Activity State (LLDAS) and Definition of Remission in SLE (DORIS) are associated with improved outcomes in SLE; however, their value in lupus nephritis (LN) remains unexplored. We sought to evaluate their prognostic value on organ damage accrual, renal flares and chronic kidney disease in patients with LN.Methods Multicentre retrospective cohort study of patients with biopsy-proven LN who achieved renal response. Enrolment date was the time of first renal response. Longitudinal data were analysed using Cox proportional hazards models. Modified LLDAS (mLLDAS) and DORIS (mDORIS) attainment and sustained durations were evaluated.Results 155 patients with 1703 visits were included. During a median follow-up of 3.5 years (IQR 4.5), 127 patients (81.9%) achieved mLLDAS and 92 (59.4%) achieved mDORIS. Both states demonstrated robust protective effects across all outcomes. For organ damage, mLLDAS attainment was associated with 85% risk reduction (adjusted HR (aHR 0.15, 95% CI 0.07 to 0.32), while mDORIS conferred a 79% reduction (aHR 0.21, 95% CI 0.08 to 0.55). Periods under mLLDAS were also associated with a 73% reduction in renal flare risk (aHR 0.27, 95% CI 0.14 to 0.51), with similar effects for mDORIS. Sustained achievement resulted in progressively greater protection, with the strongest effects seen for ≥24 consecutive months. Early attainment protected against damage accrual (aHR 0.31, 95% CI 0.16 to 0.61) and renal flares (aHR 0.51, 95% CI 0.29 to 1.00).Conclusions Following renal response, achievement of mLLDAS and mDORIS is strongly associated with improved outcomes in LN patients. Earlier attainment and longer duration in these states confer progressively greater protection.

Background: The introduction of rituximab (RTX) as maintenance therapy has reduced significantly relapses in patients with ANCA-associated vasculitides (AAV). Whether chronic low-dose glucocorticoid (GC) use provides an additional benefit is unclear. We examined the role of low-dose GCs in major relapse, hospitalization and damage accumulation risk during maintenance in patients with AAV. Methods: Retrospective cohort study of newly diagnosed patients with AAV (granulomatosis with polyangiitis-GPA, microscopic polyangiitis-MPA) followed in three tertiary referral centers. We recorded relapses (defined as a Birmingham Vasculitis Activity Score -BVAS increase, BVAS>0), increases in Vasculitis Damage Index (VDI), and hospitalizations. We used time-varying extended Cox and mixed effects Cox models in order to examine the effect of GCs on the risk for major flares, VDI accumulation, hospitalizations, and a composite outcome of VDI accumulation and hospitalizations. Findings: 171 patients (GPA: 107, MPA: 64, median age: 61 years) were included with a median follow-up of 88·2 months (803·4 patient-years-PY). We recorded 65 major flares (8·1/100PY) in 48 patients (28%), 65 events of new damage (8·1/100PY) and 132 hospitalizations (16·4/100PY). By multivariable analysis, RTX use was associated with a lower (HR=0·21, 95% CI: 0·09-0·47, p =0·0001) while disease activity at diagnosis, with an increased risk (HR 1·17, 95% CI: 1·03-1·33, p=0·013) for major relapses. Concomitant low-dose GC use showed no protective effect against major relapses (HR=0·96, 95% CI:0·88-1·05, p=0·36), while it was associated with an increased risk for damage accumulation (HR=1·52, 95% CI: 1·19-1·93, p=0·0007) and hospitalizations (HR=1·24, 95% CI: 1·06-1·45, p=0·0060). Interpretation: Low-dose GCs added to standard maintenance treatment, did not reduce major relapses, but increased risk for damage accumulation and hospitalizations. These findings support the earlier and more aggressive GC withdrawal following initial remission.

Interstitial lung disease (ILD) is a significant cause of morbidity and mortality in rheumatoid arthritis (RA). RNA sequencing (RNA-seq) of peripheral blood may provide an unbiased look at pathogenetic events involved. Peripheral blood was collected from RA-ILD (n = 11), RA non-ILD (n = 10), psoriatic arthritis (PsA, n = 23)patients and healthy controls (HC, n = 7) for transcriptomic analysis. All patients in the RA-ILD group were under treatment during sampling, GC and cDMARDs. The gene expression profile of RA ILD was inferred through differential gene expression analysis followed by pathway and enrichment analysis. Further transcriptomic analysis was conducted based on radiological pattern, clinical progression through Modified Medical Research Council (mMRC) Dyspnea scale, and radiological progression. Drug repurposing analysis was performed to identify perturbagens that counteract RA-ILD-specific signatures. To identify shared pathways between SSc and RA we used publicly available RNA-seq data of patients with systemic sclerosis-associated ILD (SSc-ILD). In RA-ILD patients, differential expression analysis revealed enrichment in immune response pathways, metabolism, IFNα and IFNγ response. Within the RA-ILD subgroup, differential expression analysis of clinical and/or radiological progressors versus non-progressors revealed enriched pathways related to cell cycle, DNA replication, IFNγ response, inflammasome assembly and negative regulation of immune response in progressors. Drug repurposing analysis revealed that ITK, Syk and FAK inhibitors are candidate compounds that potentially reverse the transcriptomic signature of RA-ILD progression. Comparison of RA-ILD and SSc revealed shared pathways related to metabolism, extracellular matrix, IFNγ response and response to microorganisms. In this preliminary study, RA-ILD patients exhibit enhanced immune responses, metabolism and cytokine activation. These data need to be further validated in larger studies.

OBJECTIVES:The management of neuropsychiatric systemic lupus erythematosus (NPSLE) remains challenging because of clinical heterogeneity and the complexity of pathophysiologic mechanisms involved. We sought to determine the molecular signature of NPSLE and its endotypes towards novel biomarkers and targeted therapies. METHODS:Whole-blood RNA sequencing from 308 patients with systemic lupus erythematosus (119 with NPSLE, 189 non-NPSLE) and 72-matched healthy controls (HCs) were performed. Supervised pathway enrichment analysis and unsupervised weighted gene coexpression network analysis were applied to distinguish clinically and molecularly defined NPSLE endotypes. RESULTS:Compared with HCs, patients with NPSLE demonstrated dysregulation of adaptive immune responses along with upregulation of interleukin (IL)-1, IL-6, IL-17, and IL-12/IL-23 signalling pathways. The comparison between NPSLE and non-NPSLE groups revealed a robust upregulation of complement cascade, DNA damage response, adaptive immunity, and IL-1 and IL-6 signalling. Furthermore, active NPSLE exhibited a strong autophagy signature. The B cell and complement cascade signatures exhibited a gradual upregulation across the non-NPSLE, inactive NPSLE, and active NPSLE subgroups. Within NPSLE, diffuse syndromes correlated positively with the oxidative phosphorylation module, while antiphospholipid antibody-positive NPSLE was not associated with specific signatures by unsupervised analysis. NPSLE endotypes such as cognitive dysfunction, seizures, psychosis, and optic neuritis were associated with distinct transcriptomic signatures namely IL-6 signalling and leukocyte migration, DNA damage response, inflammation, and type-I interferon, respectively. CONCLUSIONS:The clinical heterogeneity of NPSLE appears to be associated with molecular diversity, with certain endotypes or syndromes exhibiting distinct gene signatures. Upregulation of adaptive immune response and complement cascade suggests that complement inhibitors and B cell-targeted therapies could be further explored in NPSLE.

O006 / #412 Topic:AS12 - Genetics, Epigenetics, Transcriptomics SCIENTIFIC HYBRID SESSION: CLINICAL TRACK PRESENTATIONS - OUTSTANDING ABSTRACT PRESENTATIONS 23-05-2025 9:00 AM - 10:00 AM Remission, as defined by the Definition of Remission in SLE (DORIS) criteria, is the primary therapeutic target in systemic lupus erythematosus (SLE). While DORIS remission correlates with the reversal of key pathogenic processes,[1] novel approaches like CD19-targeted chimeric antigen receptor (CAR)-T cell therapy have shown potential to induce durable, drug-free remission. Yet, the molecular characteristics of CAR-T cell-induced remission compared to standard immunosuppression-induced remission remain unclear. To delineate unique molecular profiles of CD19 CAR-T cell therapy-induced remission, we performed a comparative analysis of Reactome pathways. Pseudo-bulk expression profiles were generated from single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) in 7 SLE patients post-lymphodepletion and CAR-T cell infusion. As a comparator, transcriptional profiles from 34 SLE patients in DORIS remission on standard immunosuppression from the PRECISESADS project (1) were analyzed. Functional pathway annotations were derived using the Functional Analysis of Individual Microarray Expression (FAIME) algorithm. Of 314 pathways, 22 pathways related to the immune system were significantly differentially regulated, with CAR-T cell-induced remission being associated with a greater suppression of type I interferon, complement activation, and interleukin signaling pathways. Notably, Fc gamma receptor IIIa-mediated IL-10 synthesis and lipid metabolism pathways were selectively upregulated, suggesting enhanced antiinflammatory responses and metabolic rewiring. CD19 CAR-T cell-induced remission was also marked by decreased DNA damage response activation compared to remission on standard immunosuppression. Our findings reveal a distinct immune and metabolic landscape associated with CD19 CAR-T cell-induced remission in SLE, supporting the notion of CD19 CAR-T cell-mediated immunological reset.References:[1] Parodis I. Ann Rheum Dis. 2024;83(7):889-900.

During the coronavirus disease-19 (COVID-19) pandemic, there was an unprecedented requirement for hospital bed availability. The present study aimed to examine the characteristics and outcomes of patients hospitalized in a COVID-19 unit that operated as a novel middle-step unit in Greece. The present study aimed to determine whether the middle-step unit supported the central general hospitals; thus, highlighting the potential of these models in future pandemics. During the 9-month period of operation, a total of 631 patients were admitted. In addition, 539 (85.4%) patients were discharged, 57 (9%) patients were referred to surrounding hospitals for further management and 35 (5.6%) patients succumbed. Based on the results of the present study, an algorithm for patient referral to middle-step units was outlined for future pandemics.

OBJECTIVES:There are limited real-life data regarding the efficacy and safety of rituximab (RTX) as a remission maintenance agent in microscopic polyangiitis (MPA) and granulomatosis-with-polyangiitis (GPA). We aimed to estimate the incidence and risk factors for relapses, as well for serious adverse events (SAEs) in MPA/GPA patients during RTX maintenance. METHODS:A retrospective cohort of newly diagnosed/relapsing GPA/MPA patients who received RTX maintenance (≥1 RTX cycle, ≥6 months follow-up) following complete remission (BVAS version-3 = 0 plus prednisolone ≤7.5 mg/day) with induction regimens. SAEs included serious infections, COronaVIrus-Disease 2019 (COVID-19)-associated hospitalizations, deaths, cardiovascular events, malignancies and hypogammaglobulinemia. The incidence rates (IRs) and relapse-free survival were estimated through Kaplan-Meier plots. Cox regression was conducted to investigate factors associated with the time-to-relapse. RESULTS:A total of 101 patients were included: 48% females, 69% GPA, 53% newly diagnosed, median age 63 years. During follow-up (294.5 patient-years, median: 3 RTX cycles), 30 relapses (57% major) occurred among 24 patients (24%, IR 10.2/100 patient-years). Kidney involvement (adjusted hazard ratio/aHR: 0.20; 95% CI: 0.06-0.74, P = 0.016), prior induction with RTX plus CYC (vs RTX monotherapy: aHR = 0.02; 95% CI: 0.001-0.43, P = 0.012) and shorter time interval until complete remission (aHR = 1.07; 95% CI: 1.01-1.14, P = 0.023) were associated with decreased relapse risk. We recorded 17 serious infections (IR 5.8/100 patient-years), 11 COVID-19-associated hospitalizations (IR 3.7/100 patient-years), 4 malignancies (IR 1.4/100 patient-years), 6 cardiovascular events (IR 2/100 patient-years) and 10 deaths (IR 3.4/100 patient-years). CONCLUSION:In this real-world study, relapses during RTX maintenance occurred in approximately 1 out of 4 patients. Kidney involvement, induction with RTX plus CYC, and earlier achievement of complete remission were associated with lower relapse risk. The serious infections rate was consistent with previous reports, whereas an increased rate of COVID-19-associated hospitalizations was observed.

OBJECTIVE:Organ damage is a key determinant of poor prognosis and increased mortality in systemic lupus erythematosus (SLE). However, no validated clinical tools for predicting damage accumulation currently exist. We sought to develop a machine learning-based model to predict early organ damage in patients with SLE. METHODS:Classification criteria (American College of Rheumatology (ACR)-1997, Systemic Lupus International Collaborating Clinics (SLICC)-2012, European League Against Rheumatism (EULAR)/ACR-2019) and non-criteria features of a cohort of 914 patients with SLE were analysed to predict damage (defined as SLICC/ACR Damage Index (SDI)) within 5 years since diagnosis. Feature selection and model construction were performed using the least absolute shrinkage and selection operator-logistic regression (LASSO-LR). The best model in 10-fold cross-validation was tested in an external cohort (n=50). RESULTS:A LASSO-LR model incorporating 16 criteria and non-criteria features predicted early organ damage with area under the receiver operating characteristic curve (AUC) values of 0.80 (95% CI 0.74 to 0.87) and 0.86 (95% CI 0.76 to 0.97) in the derivation and external validation cohorts, respectively, outperforming the ACR-1997 (AUC 0.70; 95% CI 0.62 to 0.78), SLICC-2012 (AUC 0.74; 95% CI 0.66 to 0.81) and EULAR/ACR-2019 (AUC 0.70; 95% CI 0.63 to 0.78) classification systems. Features most strongly associated with damage included the SLICC-2012 neurological disorder, EULAR/ACR-2019 class III/IV lupus nephritis and among non-criteria manifestations, myocarditis and interstitial lung disease. Operating the model as a binary classifier (early damage versus no damage), it demonstrated high specificity (0.90, 95% CI 0.78 to 0.95). The model can be converted to a simplified scoring system, with a threshold of ≥3 achieving an AUC of 0.86 (95% CI 0.75 to 0.96). CONCLUSION:We developed and validated a clinician-friendly model for early organ damage prediction in SLE, facilitating risk stratification.

Objectives To identify, appraise, and synthesise current evidence regarding the management of systemic lupus erythematosus (SLE) with kidney involvement towards informing the 2025 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations. Methods The Task Force formulated 11 research questions grouped into 6 distinct sections, namely indications of diagnostic kidney biopsy; treatment targets; efficacy and safety of immune treatments in lupus nephritis (LN); efficacy and safety of nonimmune treatments; treatment duration; and indications for repeat kidney biopsy. A dedicated systematic literature review (SLR) was performed for each section. SLRs were performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials from January 2019 to March 2024. Results Patients with SLE with low-grade proteinuria (<500-1000 mg/d) and/or haematuria may have histologically active disease, based on evidence of moderate quality. Observational studies of good quality have demonstrated an association between complete or partial renal response within the first 6 to 12 months and long-term kidney survival. A combination of 2 immunosuppressive agents, such as belimumab with mycophenolate mofetil (MMF)/cyclophosphamide, voclosporin with MMF, or obinutuzumab with MMF, is associated with higher response rates, based on high-quality randomised controlled trials (RCTs). Discontinuation of treatment has been linked with an increased risk of relapse, as evidenced by 3 RCTs with substantial heterogeneity. Conclusions High-quality RCTs indicate a benefit from combination treatments compared with previous standard-of-care in LN. Patients who respond within the first year of treatment tend to have better long-term outcomes. Kidney biopsy is essential for diagnosis, but the role of repeat biopsy awaits confirmation from higher-quality studies.

ObjectiveTo evaluate the long-term efficacy and safety of different doses of BI 655064 versus placebo added to standard of care during maintenance treatment for lupus nephritis (LN).Methods1293.13 was an exploratory, phase II maintenance trial. Patients were eligible for entry if they had completed 1 year of randomised treatment with BI 655064 (120, 180 or 240 mg) or placebo in the 1293.10 trial, responded to treatment at Year 1 (complete renal response [CRR], partial renal response or urinary protein/creatinine ratio ≤1) and consented to continue treatment. The primary endpoint was the proportion of patients with CRR without renal flares at Year 2. Secondary endpoints included change from baseline in Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores and safety/tolerability.Results69/121 patients (57.0%) from the 1293.10 trial entered 1293.13. The adjusted proportion of patients with CRR decreased in all groups between Year 1 (BI 655064: 53.4%-72.7%; placebo: 71.4%) and Year 2 (BI 655064: 48.2%-59.5%; placebo: 57.5%). At Year 2, mean decreases in total SELENA-SLEDAI scores were greatest with BI 655064 240 mg (-10.6 points), followed by 120 mg (-8.9 points), 180 mg (-7.2 points) and placebo (-5.3 points). SELENA-SLEDAI non-renal scores decreased at Year 1 (BI 655064: -3.0 to -3.4; placebo: -1.8); this pattern remained with BI 655064 during Year 2 (-2.4 to -4.1), whereas placebo returned to near-baseline scores (-0.4). Over 2 years of treatment, almost all patients (97.1%) experienced ≥1 adverse event (AE). Compared with the other groups, higher rates of serious AEs (42.9% vs 23.1%-33.3%)-mainly driven by serious infections (23.8% vs 7.7%-14.3%)-and severe AEs (47.6% vs 13.3%-28.6%) were reported with BI 655064 240 mg.ConclusionsThis exploratory, phase II maintenance trial failed to demonstrate the benefits of BI 655064 on renal outcomes in the treatment of LN. However, some benefits in total and non-renal SELENA-SLEDAI scores were observed.

Objective:To evaluate temporal trends in pregnancy management and outcomes in women with SLE and explore the impact of pregnancy planning on maternal and foetal complications. Methods:We conducted a retrospective study including women with SLE with one or more pregnancies after diagnosis or diagnosed during pregnancy. Data were collected through questionnaires and medical records. To assess temporal trends, the study period (1985-2024) was divided into five intervals with similar pregnancy and patient distribution. Using generalized estimating equations, we identified risk factors for adverse pregnancy outcomes and evaluated temporal trends in pregnancy characteristics. Results:We recorded 109 pregnancies from 65 women; 70.6% resulted in live births. Planned pregnancies were associated with a lower flare risk [odds ratio (OR) 0.31 (95% CI 0.11, 0.89)] and a higher likelihood of live birth [OR 3.31 (95% CI 1.41, 7.8)]. HCQ use during pregnancy was independently associated with a reduced flare risk [OR 0.26 (95% CI 0.08, 0.8)]. Pregnancies before 2005 were less often planned [OR 0.10 (95% CI 0.03, 0.4)], while HCQ use during pregnancy increased over time [OR 0.56 (95% CI 0.34, 0.95), for the period 1985-2005 vs 2021-2024], with discontinuation decreasing from 33% to <2%. The predicted probability of preventive aspirin use in patients without antiphospholipid syndrome increased from 12% before 2005 to 46% in 2021-2024, whereas continuous glucocorticoid use decreased from 58% before 2005 to 16% after 2020. The probability of foetal complications showed a decreasing trend after 2016. Conclusion:Pregnancy management and outcomes improved over time in SLE; planned pregnancy and HCQ use were associated with favourable results.