BACKGROUND:Anifrolumab is a type I interferon receptor antagonist approved for the treatment of systemic lupus erythematosus (SLE). However, real-world evidence on its use, especially from large, unselected cohorts, is scarce. The ongoing REVEAL study is designed to collect real-world data on anifrolumab use. The data reported here are the pre-specified 6-month interim analysis, which aims to provide a phenotypic characterisation of a large real-world cohort of patients with SLE initiating anifrolumab, and to evaluate early treatment response in routine clinical practice. METHODS:REVEAL is a 5-year, multicentre, prospective observational study conducted in 25 tertiary rheumatology centres across Italy. A pre-specified interim analysis was planned when the first 50 patients completed the first 6 months of follow-up; this analysis includes all patients who initiated anifrolumab by the data cutoff of Feb 10, 2025. Patients with SLE were consecutively enrolled on the day of their first infusion of anifrolumab, prescribed according to clinical judgement and Italian indications for use. Eligible patients were aged 18 years or older, had a clinical diagnosis of SLE fulfilling at least one set of established classification criteria valid at the time of diagnosis (1997 American College of Rheumatology [ACR], 2012 Systemic Lupus International Collaborating Clinics, or 2019 European Alliance of Associations for Rheumatology-ACR), had active disease warranting anifrolumab treatment (including compassionate use programmes), and were naive to anifrolumab. Data were collected at baseline and at 1 month, 3 months, and 6 months. The primary outcome was the number of patients reaching remission (defined according to the Definition of Remission in SLE criteria as a clinical SLEDAI-2K score of 0, physician global assessment score of <0·5 [on a 0-3 scale], with a prednisone-equivalent dose ≤5 mg per day, and stable antimalarials or immunosuppressants), Lupus Low Disease Activity State (LLDAS; defined as a SLEDAI-2K ≤4 [with no activity in major organ systems and no new disease activity], physician global assessment ≤1·0, and a prednisone-equivalent dose ≤7·5 mg per day), and LLDAS5 (a modified version of the LLDAS with a prednisone-equivalent dose ≤5 mg per day) at 6 months. Adverse and serious adverse events were also recorded. No people with lived experience of SLE were involved in designing or conducting the study. This study is registered with ClinicalTrials.gov (NCT07215754) and with the Italian Medicines Agency (Agenzia Italiana del Farmaco; ID number 247) and recruitment is ongoing. FINDINGS:Between May 25, 2023, and Feb 10, 2025, 236 patients were recruited and included in this interim analysis. Of these, 219 (93%) were female, 17 (7%) were male, 218 (92%) were White, and the median age was 46·9 years (IQR 36·0-53·6). At baseline, the median SLEDAI-2K was 7 (IQR 6-9), and the main indications for anifrolumab were mucocutaneous (157 [67%]) and articular (116 [49%]) involvement. At 6 months, 37 (26%) of 140 patients reached remission, 80 (57%) reached LLDAS5 and 93 (66%) reached LLDAS. One patient was excluded from the outcome analysis due to missing physician global assessment data. 108 adverse events were recorded during the 6-month follow-up period; of these, 83 (77%) were infections. Five serious adverse events occurred, resulting in six hospitalisations. INTERPRETATION:This study provides the first large-scale real-world evidence of anifrolumab use in patients with SLE, supporting its clinical benefit and rapid onset of action in routine care. FUNDING:None.

BackgroundNeuropsychiatric (NP) involvement represents one of the major challenges in Systemic Lupus Erythematosus (SLE), often requiring individualized therapeutic strategies. While anifrolumab inhibits the type I interferon receptor 1 (IFNAR1) and is approved for the treatment of moderate-to-severe SLE, randomized controlled trials have not evaluated its efficacy in NPSLE.MethodsWe examined the pathophysiological rationale for inhibiting IFN-α using anifrolumab in NPSLE. To supplement this, we report an original case of NPSLE successfully treated with anifrolumab, along with similar cases identified through a systematic literature review (SLR) of Medline/PubMed and Embase, performed in accordance with PRISMA and CABARET guidelines.ResultsOverexpression of IFN-α is linked to neurological symptoms in patients with inflammatory NPSLE, such as psychosis and seizures. Blocking the IFNAR1 with anifrolumab provides a direct rationale for treating this subset of NPSLE. The SLR identified seven case reports of female patients with inflammatory NPSLE where anifrolumab was used as a rescue therapy following conventional treatment failure. NPSLE manifestations were heterogeneous, including psychosis, headache, and acute confusional state, which limits the generalizability of our findings. A 52-year-old female with SLE and seizures from our Lupus Clinic who received anifrolumab after failing multiple treatments was also reported. After an average of 11.7 months, all patients showed improvement, 87% (7 out 8) achieving complete NP symptom resolution and 62% reaching SLE remission. No emerging safety issues were reported.ConclusionPreliminary observations suggest a potential benefit of anifrolumab in NPSLE, but evidence remains insufficient to establish clinical efficacy and warrants further controlled studies.

Objective To assess the effectiveness of belimumab (BEL) in improving anaemia, thrombocytopenia, lymphopenia and leucopenia in patients with SLE.Methods The BeRLiSS (Belimumab in Real Life Setting Study) 2.0 cohort included patients with SLE from 14 Italian referral centres treated with BEL for active joint or skin involvement, based on physician judgement, between June 2013 and May 2024. Clinical and laboratory parameters were recorded at baseline and every 6 months. Patients were eligible if they had baseline haematological abnormalities defined according to British Isles Lupus Assessment Group (BILAG) (grade C or higher): haemoglobin (Hb) ≤10.9 g/dL, platelets (Plts) ≤149×109/L, lymphocytes (Lym) ≤1.0×109/L or leucocytes (Leuc) ≤3.0×109/L. Follow-up data up to month 48 were available for 33 patients with anaemia, 20 with thrombocytopenia, 44 with lymphopenia and 18 with leucopenia.Results At baseline, 76 patients had anaemia, 44 thrombocytopenia, 107 lymphopenia and 53 leucopenia. Hb levels increased significantly from 9.9±0.6 g/dL to 11.7±1.4 g/dL at month 48 (p<0.001). Platelet counts rose from 110.2±38.1×109/L to 176.6±88.7×109/L (p=0.004), Lym counts from 0.72±0.21×109/L to 1.14±0.45×109/L (p<0.001) and leucocyte counts from 2.437±0.533×109/L to 4.732±1.897×109/L at 48 months (p<0.001). Improvement in Hb (p=0.97), Plts (p=0.12), Lym (p=0.86) and Leuc (p=0.73) was similar regardless of the use of concomitant immunosuppressants. Glucocorticoid (GC) doses decreased significantly across all manifestations, except for leucopenia: anaemia (12.9±12.1 to 3.6±4.9 mg/day, p=0.003), thrombocytopenia (10.8±9.6 to 4.4±5.5 mg/day, p=0.004), lymphopenia (10.6±8.6 to 3.1±3.2 mg/day, p<0.001). Proportion of GC users declined over 48 months: anaemia 96.1–60.7%, thrombocytopenia 93.1–80%, lymphopenia 96.3–70.3% and leucopenia 95.3–80%.Conclusion In this real-world cohort, BEL treatment was associated with improvement in anaemia, thrombocytopenia, lymphopenia and leucopenia with over half of patients achieving normalisation of blood counts. Haematological responses were similar regardless of concomitant immunosuppressive therapy, supporting the role of BEL as a therapeutic option for haematological abnormalities in SLE.

To provide a useful and practical Machine Learning framework to facilitate the diagnosis of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) and Systemic Lupus Erythematosus (SLE) from Magnetic Resonance Imaging (MRI) derived features. Twenty-seven SLE patients (14 NPSLE, 13 SLE; 24 females and 3 males; average age: 43 years, age range: 21 to 62) and 20 healthy controls (17 females and 3 males; average age 41, age range: 21 to 56), were included in this cross-sectional study. VolBrain online platform was used to quantitatively assess brain structural features (regional cortical thickness) which were used as input for the Machine Learning models. Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF) and XGBoost were trained and tested, using a fivefold cross validation in the process. The Random Forest model demonstrated superior performance with an accuracy of 90

Objectives: In the perspective of an increasingly widespread application of precision medicine in rheumatoid arthritis (RA), this study aimed to compare efficacy and safety of ultrasound-guided synovial biopsy (US-SB) performed in an experienced rheumatology and community hospital setting. Methods: A post hoc analysis of R4RA, STRAP and STRAP-EU trials was performed, comparing US-SB performed in a radiology department of a community hospital without experience in RA (n = 14), versus a rheumatology academic centre with a high expertise in RA management and US-SB (n = 16). Suitability of specimens for histological and transcriptomic analysis (tissue and RNA quality) was analyzed as the main outcome. Results: Demographic and clinical features of the two patients' groups were similar, except of disease duration (p < 0.05). No differences were recorded regarding site and ultrasound of the biopsied joint. Suitability for histological (% of gradable tissue) and transcriptomic analysis (RIN >3) was similar in the two cohorts (both 85.7% vs. 87.5%, p = 0.88). Proportion of gradable biopsies in total (59.2% vs. 59.5%, p = 0.96) and for each patient (52% vs. 56.15%, p = 0.77), were similar in both cohorts. Adverse events were rare (two in community hospital cohort, one in rheumatology cohort, p = 0.54), none considered severe. Seven patients in the community hospital experienced mild or severe pain, only two referred the same in the rheumatology cohort (p = 0.04). Conclusions: US-SB can be safely and effectively performed in a community hospital without experience in RA. A larger diffusion of this technique could allow to pursuit a tailored approach also in ordinary rheumatology outpatient clinics.

Objective:To evaluate the effectiveness of belimumab in different joint and skin phenotypes of systemic lupus erythematosus (SLE). Methods:The BeRLiSS-JS 2.0 is a decade-long observational study including adult SLE patients from 14 Italian Centers treated with belimumab (intravenous/subcutaneous) stratified by articular (nondeforming nonerosive arthritis -NDNE-, Jaccoud's arthropathy, Rhupus) and cutaneous phenotypes (acute -ACLE-, subacute -SCLE-, and chronic cutaneous lupus erythematosus -CCLE-, and nonspecific manifestations). Outcome variables measured every 6 months up to 36 months included Disease Activity Score-28 joints (DAS28) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) scores, remission rates (DAS28<2.6; CLASI-A=0), and prednisone intake (mg/day). Results:Of 443 patients, 221 (49.9%) had NDNE, 30 (6.8%) Jaccoud's arthropathy, 21 (4.7%) rhupus, 112 (25.3%) had ACLE, 54 (12.2%) SCLE, and 18 (4.1%) CCLE. At 6 months a significant decrease of DAS28 was observed in NDNE (p<0.001) and by CLASI-A in ACLE and SCLE (both p<0.001). Non-specific cutaneous manifestations did not improve significantly. CLASI-D scores remained stable over 36 months. Remission rates were higher in NDNE and ACLE patients (at 6 months: NDNE 59.6%, Jaccoud's 18.8%, rhupus 30.3% - p=0.002; at 18 months: ACLE 75.9%, SCLE 56.4%, CCLE 33.3% - p=0.018). Daily prednisone dosage decreased in all organ-specific phenotypes, but more pronouncedly in patients with NDNE, ACLE, and SCLE. Higher baseline CLASI-A and DAS28 and CLASI-D were associated with lower remission rates. Conclusion:Treatment with belimumab was associated with reduced disease activity and increased remission especially in NDNE and ACLE patients. Glucocorticoid-sparing effect was also found.

PV183 / #357 Poster Topic:AS20 - Precision Medicine The TNFSF13B gene functional variant (BAFFvar) is an insertion-deletion (GCTGT→A) introducing an alternative polyadenylation motif generating a truncated/shorter gene transcript that escapes miRNA inhibition, yielding increased production of soluble BAFF.[1] The consequent overexpression of BAFF, in turn, up-regulates humoral immunity, increases the production of autoantibodies, and increases the risk of developing SLE. The present study investigates if Baffvar status influences the risk of overall and renal SLE flares and whether patients stratified according to Baffvar status might show a differential benefit from anti-BAFF treatment. This study used data from patients included in a monocentric SLE inception cohort between 1 January 2006 and 31 December 2022. Inclusion criteria were: (a) SLE classified according to the ACR/EULAR 2019 and/or SLICC 2012 and/or ACR 1997 criteria; (b) evaluation in at least 3 consecutive visits (not less than 2 visits every 12 months); (c) genotyping for BAFFvar. Demographic, clinical, serologic, and treatment variables were recorded. Flare was defined as the onset of a new SLE manifestation or worsening of a preexisting clinical manifestation resulting in a therapy change. Renal flares were nephritic (≥10 RBCs/hpf with or without a decrease in eGFR by ≥10%, irrespective of changes in proteinuria) or nephrotic (doubling of proteinuria to >1g/24h or to >2g/24h depending on the previous complete or partial response). Kaplan-Meier curves were used to analyze the association between BAFFvar and overall or renal SLE flares. Multivariate Cox regression models were built, including demographic, clinical, and serologic data and past or ongoing treatment as covariates. 194 (89.2% female) out of 256 screened patients were analyzed (Table 1). The mean age was 41.1 (± 14.8) years, the mean number of follow-up visits was 17 (± 8) and 119 (61.3%) were BAFFvar carriers. During follow-up, 119 patients (56.2%) experienced at least 1 flare, with 60 patients (30.9%) having more than 1 flare. The median number of flares was higher (p=0.038) in Baffvar carriers (1; IQR 0-2) than in BAFF-wt carriers (0; IQR 0-1). Cox regression model showed BAFFvar (HR 1.5 per copy variant; 95% CI 1.2 - 2.0; p = 0.002), disease duration <1 year (HR 0.46; 95% CI 0.30 – 0.71; p<0.001), DORIS remission (HR 0.41; 95% CI 0.24 – 0.71; p = 0.001), renal (HR 1.7; 95% CI 1.1 – 2.6; p = 0.017), and musculoskeletal (HR 5.3; 95% CI 1.3 – 21.5; 0.019) involvement as baseline factors independently associated with the risk of flare development. Out of 38 patients with biopsy-confirmed LN, 33 (86.8%) were female, 21 (55.3%) were BAFFvar carriers, and 24 (63.2%) were diagnosed with proliferative lupus nephritis class III or IV. Flares occurred in 12 (33.3%) patients, with 22 flares (5 nephritic and 17 nephrotic). The BAFFvar was independently associated with the risk of renal flare (HR 9.3; 95% CI 1.8 to 49.5; p=0.008). Out of 35 patients treated with belimumab after a flare, 9 had at least 1 flare during a median 48-month follow-up (total of 11 flares). Patients with BAFFvar had a flare rate of 13.6% (3/22), while BAFFwt carriers had a flare rate of 46.1% (6/13) (HR 0.22; 95% CI 0.05-0.90; p=0.035). Table 1. Baseline characteristics of the lupus cohort at entry into the study. Belimumab reduces the risk of overall and renal SLE flares conferred by the BAFFvar. BAFFvar identifies patients at higher risk for flare and those best responders to belimumab and may represent a potential predicting and prognostic biomarker for personalized treatment in SLE patients.References:[1.] Steri M. NEJM 2017;376:1615-26.

Background: Glucocorticoids (GCs) play a pivotal role in the treatment of active SLE, however their use is associated with the risk of organ damage which is irreversible. The lack of specific guidelines due to insufficient evidence, and the inherent heterogeneity of the disease, pose challenges for GC initiation and withdrawal. Objectives: To explore the variations in prescribing practices and attitudes toward initiating/withdrawing GC therapy in SLE, amongst physicians practicing in European and non-European countries. Methods: The LUPHPOS (LUpus PHysician’ Perspective On glucocorticoidS) study is an online cross-sectional self-reported survey on the physician’s perspective of glucocorticoids in the management of SLE, disseminated between April-December 2023. We have compared responses between practitioners practicing within Europe, and those practicing outside of Europe. Results: The survey was completed by 501 physicians, 269 (54%) from Europe and 232 (46%) from non-European countries, with the distribution of countries shown in Figure 1. The top three countries to respond were India (n=127, 25%), Italy (n=72, 14%), Spain (n=60, 12%). The majority of respondents (82%) were adult rheumatologists, and 70% reported working in a university hospital. Around half (45%) of respondents had a dedicated lupus clinic, which was more common in Europe (51% vs 39%, p=0.007).Comparing European with non-European physicians, the top three influencing factors for selecting GC dose were current disease activity (80% and 85%) and organ involvement (77% and 86%), followed by comorbidities (40%) in Europeans, and the course of the disease (34%) for non-European physicians. The most concerning GC adverse effect reported by European physicians was infection (38%), osteoporosis (21%) and cushingoid features (12%); for non-European physicians it was infection (34%), cushingoid features (20%) and avascular necrosis (16%).When initiating GCs, a weight-based regimen was used less frequently by European physicians (48% vs 70%, p<0.001). In severe flares, pulse GC was preferred in both groups (75% vs 78%). The commonest dose was 500 mg/day for European physicians (45%), and 1000 mg/day for non-European physicians (37%). In a moderate flare, in those who preferred weight-based dosing, most commonly used doses were 0.25-0.3 mg/kg/day (21% vs 25%) and 0.5mg/kg/day (15% vs 25%). In those preferring fixed-dosing, the most common dose was 15-20 mg/day (18% vs 8%). For mild flares, the majority of European and non-European respondents reported using oral GCs (77% vs 74%). The commonest doses were 0.25 mg/kg/day (46% vs 33%) or 5-10 mg/day (37% vs 41%), in Europeans compared with non-Europeans.Comparing European and non-European physicians, GC withdrawal was most commonly reported when patients had been in remission or LLDAS at least 12 months (41% vs 28%), or on achieving remission (32% vs 27%). European physicians were less likely to believe that GCs could rarely, or never be withdrawn (5% vs 11%). 51% of European and 48% of non-European physicians agreed that the most acceptable target dose for tapering steroids was ≤5 mg/day, however Europeans were less likely to find ≤10 mg/day acceptable (3% vs 7%). Both groups agreed that disease activity, organ involvement and time since latest flare were the most influential factors for withdrawing GCs. Conclusion: Physician location influences GC prescribing practices and safety considerations, impacting dosing selection, withdrawal, and tapering strategies. These geographical disparities underscore the need for a consensus on evidence-based care, and global implementation and dissemination strategies. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Sarah Dyball Novartis, UCB, Cristiana Sieiro Santos: None declared, Kunal Ashutosh Chandwar: None declared, Elisabetta Chessa: None declared, Marta Mosca Abbvie, Astra Zeneca, Gsk, Lilly, UCB, Janssen, Otsuka.Figure 1European (red) and non-European (blue) countries represented in the LUPHPOS survey

PV043 / #685 Poster Topic:AS05 - CNS Lupus Brain fog is a common symptom in systemic lupus erythematosus (SLE) patients that refers to a “clouding of mental functions.” Its prevalence is probably underestimated due to the fact that a universal definition of “lupus fog” does not exist. The aim of the study was to evaluate in a cohort of SLE patients the prevalence of subjective mental alterations, named “lupus fog” (LF) and objective mental alterations (depression, cognition, fatigue) adopting screening tools validated in SLE. The second objective was to investigate which factors are associated with LF. A cross-sectional study was conducted enrolling adult SLE patients (ACR/EULAR 2019 criteria). LF referred to the presence of mental alterations (ie, memory, concentration, attention impairment) as reported by participants. Demographic, clinical, clinimetrics, therapeutic data were collected (Table). Serum anti-ribosomal P antibodies (anti-Rib-P) were quantified using ELISA kits. Cognitive deficits were screened using the Montreal Cognitive Assessment (MoCA) test performed by certified personnel (using the standard cut-off of <26/30 and a more sensitive cut-off <28/30)[1] and assessed by a neuropsychologist exploring deficits in 8 cognitive domains with a battery of neuropsychological tests. Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale (CES-D) and adopting a more sensitive cut-off (>15) and the cut-off suggested by Kwan et al (>25).[2] Fatigue was measured using the the Functional Assessment of Chronic Illness Therapy (FACIT-F) (cut-off <30 and a more sensitive cut-off <34).[3] Chi-squared and the Mann-Whitney test were used for univariate analysis; multivariate analysis was performed building logistic regression models including variables showing p values of <0.10. Table. 114 SLE patients were enrolled (Table), 105 female (92.1%), mean age 43.7 years (+-12.2). LF was found in 54/100 patients (54%). CES-D >15 was altered in 56/105 pts (53.3%), CES-D >25 in 26 (24.7%), MoCA <26 in 45/100 pts (45%), MoCA <28 in 75 (75%), FACIT <30 in 31/69 (44.9%) and FACIT <34 in 36 (52.9%). At univariate analysis, an association emerged between the presence of LF and CES-D alterations (CES-D >15 p=0.014; CES-D >25 p=0.010, CES-D score p<0.001), FACIT (FACIT <30 p=0.039, FACIT <34 p=0.042, FACIT score p=0.012), fibromyalgia (p<0.001), the neuropsychiatric involvement (NPSLE) (p=0.015), anti-Ribonucleoprotein RNP (p=0.014), anti Rib-P (p=0.018) and disease duration (p=0.045). No association was found with MoCA test, the battery of neuropsychological test, disease activity scores or treatment. Two different models of logistic regression were built. Model 1 including fibromyalgia, showed independent association between LF and fibromyalgia (OR=34.6; 95% CI 2.3-523.1, p=0.011), CES-D score (OR=1.1 per unit, 95% CI 1.0-1.2, p=0.033) and disease duration (OR=1.1 per year, 95% CI 1.0-1.2, p=0.038). Model 2 excluding fibromyalgia showed independent association between LF and FACIT score (OR=0.93 per unit, 95% CI 0.88-0.99, p=0.013), anti-Rib-P (OR=5.2 per unit, 95% CI 1.0-1.2, p=0.033). Lupus fog is frequent. Our study also confirms the high prevalence of cognitive impairment, depressive symptoms and fatigue in SLE. A longer disease duration, depressive symptoms and the diagnosis of fibromyalgia were factors independently associated with lupus fog. Our findings suggest that SLE patients frequently have a negative perception about proper cognitive performances, without having a real impairment, supporting the multifactorial etiology of clinical issues in SLE, related to direct and indirect factors.References:[1.] Raghunath S. Lupus Sci Med 2021;8(1):e000580. [2.] Kwan A. Semin Arthritis Rheum 2019;49(2):260-6. [3.] Kawka L. RMD Open 2023;9:e003476.

OBJECTIVE:To examine whether SLE patients carrying the TNFSF13B variant (BAFF-var) differ in the risk of overall and renal flares and the benefits from belimumab. METHODS:This retrospective study analyzed data from a monocentric cohort of Sardinian SLE patients between January 2006 and December 2022. We recorded demographic, clinical, serological, and treatment variables. A flare was defined as a new SLE manifestation or worsening of an existing one that required a change in therapy. Renal flares, categorized as nephritic or nephrotic, were recorded. Soluble B-cell activating factor (sBAFF) levels were evaluated in patients naïve to any treatment. We used Kaplan-Meier curves, Cox regression, and Poisson regression to investigate the association between BAFF-var and flares. RESULTS:Among 233 screened patients, 194 (89.2 % female, 61.3 % BAFF-var carriers) were included. The mean age was 41.1 (±14.8) years, and the mean number of follow-up visits was 17 (±8). sBAFF levels increased according to BAFF-var genotype (p < 0.001). BAFF-var was significantly associated with an increased risk of flares (HR 1.5 per copy variant; 95 %CI 1.2-2.0; p = 0.002), and the frequency of flares (IRR 1.3 per copy variant; 95 %CI 1.1-1.6; p = 0.009). In 38 biopsy-confirmed lupus nephritis patients, the BAFF-var was associated with a higher risk of renal flare (HR 9.3; 95 %CI 1.7-49.5; p = 0.008). In 35 relapsing-remitting patients, belimumab reduced both the risk and frequency of flares, with higher effectiveness in patients carrying the BAFF-var (HR 0.12; 95 %CI 0.02-0.58; p = 0.009). CONCLUSIONS:Pending further validation, BAFF-var may serve as a predictive and prognostic biomarker for personalized treatment in SLE.

Objective To assess the potential role of biologic treatment for psoriasis (PsO) in reducing the likelihood of psoriatic arthritis (PsA) development, through a detailed analysis that considered the different historical phases in PsA management, the different biologic classes and the different patterns of articular involvement. Methods A monocentric cohort of 1023 PsO patients underwent a rheumatological assessment in which clinical and therapeutic data were recorded. A chi-squared test and multivariate logistic regression analysis (adjusted for the main PsA risk factors) were performed to compare the likelihood of PsA development in different treatment groups. Results The PsA prevalence in PsO patients treated at least once with biologics was significantly lower than in patients never treated with biologics (8.9% vs 26.1%, P < 0.001). In multivariate analysis, a significantly (P < 0.01) lower likelihood of PsA development in biologic-treated patients was confirmed in the whole cohort (adjusted odds ratio [adjOR] 0.228), as well as in the subgroups of patients with PsO onset after 2005 (adjOR 0.264) and after 2014 (adjOR 0.179). Separately analysing the different biologic classes, the TNF (adjOR 0.206), IL-17 (adjOR 0.051) and IL-23 or 12/23 (adjOR 0.167) inhibitors were significantly (P < 0.01) associated with a lower likelihood of PsA development. Finally, patients treated with biologics had a significantly (P < 0.04) lower prevalence of both pure peripheral PsA (adjOR 0.182) and peripheral PsA with axial involvement (adjOR 0.115). Conclusions This study provides meaningful and concordant evidence supporting the significant role of different classes of biologics in reducing the likelihood of peripheral and axial PsA development.

ObjectivesTo explore the role of newly emerging autoantibodies (AAbs) - peptidyl-arginine deiminase 4 (aPAD4), carbamylated proteins (aCarP), and anti-RA33 (aRA33) - alongside the traditionally assessed rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), in predicting the response to abatacept (ABT) and its retention rate in rheumatoid arthritis (RA) patients.MethodsData from 121 consecutive ABT-treated RA patients were recorded. The RF and ACPA status were retrospectively assessed by reviewing the patients' clinical records. Positivity for aPAD4, aCarP and aRA33 were determined by Enzyme-Linked Immunosorbent Assay (ELISA). The achievement of a moderate or good EULAR response at 6 months and the 3-years retention were analyzed as treatment outcomes. Multiple logistic regression models and Cox regression hazard analysis models were built to identify the association between such outcomes and the different AAbs, after adjustment for different confounders. The AAbs were assessed both individually and in different combinations to identify the most robust predictive model.ResultsIn the studied cohort, RF, ACPA, aPAD4, aCarP and aRA33-Ab tested positive in 74.4%, 69.4%, 43.8%, 23.9%, 14.9% patients, respectively. A moderate or good EULAR response at 6 months was achieved by 64.5% of subjects and the cumulative 3-years retention rate was 56.6%. A higher EULAR response rate was recorded in patient with positivity for RF (67% in subjects tested positive vs. 58% in negative), ACPA (68% vs. 57%), aPAD4 (68% vs. 62%), and aCarP (72% vs. 62%), although statistical significance was not reached likely due to sample size limitations. Similarly, ACPA, aPAD4, aCarP were associated with higher 3-year retention rates, though not statistically significant individually. The combined analysis revealed that positivity for ACPA and/or aPAD4 predicted a significantly higher EULAR response rate at 6 months compared with double negativity (adjusted OR 2.7, p 0.026). Furthermore, positivity for at least one of ACPA, aPAD4, or aCarP predicted a significantly higher 3-year ABT retention rate compared to triple negativity (62.1% single or double positive vs. 33.5% triple negative, adjusted HR 0.48, p 0.022).ConclusionThis study highlights the potential benefits of using a combined assessment of ACPA aPAD4 and aCarP in predicting effectiveness of ABT in RA.

Glucocorticoids play a pivotal role in the management of active SLE; however, their use is associated with the risk of irreversible organ damage. The lack of specific guidelines on steroid use, and the inherent heterogeneity of SLE, pose challenges for glucocorticoids prescribing. This study aimed to explore the variations in prescribing practices and attitudes toward initiating/withdrawing glucocorticoid therapy in SLE, between physicians practicing in European and non-European countries. The LUPHPOS (LUpus PHysician’ Perspective On glucocorticoidS) study is an online cross-sectional self-reported survey on the physician’s perspective of glucocorticoids in the management of SLE (April-December 2023). Responses were compared between practitioners practicing within Europe, and those practicing outside of Europe. A total of 501 physicians from 54 countries completed the survey; 269 (54%) from Europe and 232 (46%) from non-European countries. Most respondents (82%) were adult rheumatologists, and 70% worked within a university hospital. Around half (45%) of respondents had a dedicated lupus clinic, which was more common in Europe (51% vs 39%, p = 0.007). The primary factors influencing glucocorticoid dose selection were similar across both groups, with current disease activity (80% vs. 85%) and organ involvement (77% vs. 86%) being the most important. European physicians cited comorbidities (40%) as the third most important factor, whereas non-European physicians prioritised the disease course (34%). When initiating glucocorticoids, a weight-based regimen was used less frequently by European physicians (48% vs 70%, p < 0.001). In severe flares, pulse glucocorticoids was preferred in both groups (75% vs 78%). The commonest dose was 500 mg/day for European physicians (45%), and 1000 mg/day for non-European physicians (37%). In a moderate flare, in those who preferred weight-based dosing, most commonly used doses were 0.25-0.3 mg/kg/day (21% vs 25%) and 0.5mg/kg/day (15% vs 25%). In those preferring fixed-dosing, the most common dose was 15-20 mg/day (18% vs 8%). For mild flares, the majority of European and non-European respondents reported using oral glucocorticoids (77% vs 74%). The commonest doses were 0.25 mg/kg/day (46% vs 33%) or 5-10 mg/day (37% vs 41%), in Europeans compared with non-Europeans. Comparing European and non-European physicians, glucocorticoids withdrawal was most common when patients had been in remission for at least 12 months (41% vs 28%), or on achieving remission (32% vs 27%). European physicians were less likely to agree that glucocorticoids could rarely be withdrawn (5% vs 11%). 51% of European and 48% of non-European physicians agreed that the most acceptable target dose for tapering steroids was ≤5 mg/day; however, Europeans were less likely to find ≤10 mg/day acceptable (3% vs 7%). Physician location influences glucocorticoid prescribing practices and safety considerations, impacting dosing selection, withdrawal, and tapering strategies. These geographical disparities underscore the need for a consensus on evidence-based care, and global implementation and dissemination strategies. S. Dyball: Grants/research support; Novartis, UCB. C. Sieiro Santos: None. E. Chessa: None. K. Chandwar: None. M. Mosca: None.

Objective Patient global assessment (PtGA) is a patient-reported outcome (PRO) that reflects a patient's judgment of their health/disease activity (DA). The objective of this systematic literature review was to assess the psychometric properties of PtGA in psoriatic arthritis (PsA). Methods Research articles reporting the assessment of psychometric properties of PtGA in PsA, listed in PubMed and extracted according to the Outcome Measures in Rheumatology (OMERACT) Filter 2.1 and the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) terminology, were selected. Validity was assessed for comprehensiveness (content), correlation with other DA instruments (construct), and with quality of life measurements (criterion). A metaanalysis regarding construct validity was performed. Correlations between PtGA variations and other indices' variations (external responsiveness) and PtGA variations after treatment (internal responsiveness) were collected. Data on the formulation of PtGA and its discordance with physician global assessment (PGA) were also collected. Results Of 60 articles analyzed (comprising 17,453 patients), 44 were observational studies and 16 were trials. PtGA was assessed through 27 different formulations. In all the retrieved studies, PtGA assessed DA, and in 3 studies, PtGA was assessed as a variable of global health status. The correlation between PtGA and PROs was strong (ρ > 0.50), whereas with other DA indices and PGA, it ranged from weak to moderate (ρ 0.20-0.50). Three studies described a positive discordance (PtGA > PGA). Responsiveness, assessed in 24 studies, showed a strong correlation with joint count index variations (ρ 0.51-0.52). Conclusion PtGA is a valid and responsive tool in PsA. Correlations were higher with PROs and weaker with DA composite indices and PGA. PGA was usually scored lower than PtGA. A standardized formulation of PtGA would be useful.

Background: Cognitive deficits (CDs) are frequent and worsen the quality of life of Systemic Lupus Erythematosus (SLE) patients. The Montreal Cognitive Assessment (MoCA) is a feasible test used to screen the presence of cognitive deficits. Objectives: The aim of the study is to evaluate whether the MoCA is a valid test for identifying SLE patients who require a targeted neuropsychological evaluation for CDs and to discriminate which factors influence MoCA’s alterations (including subjective cognitive symptomatology). Methods: A cross-sectional study was conducted between April 2019 and November 2022 in which adult patients with SLE (ACR/EULAR 2019 criteria) and HC with similar demographic characteristics were recruited. Demographic, clinical, clinimetric, serological and therapeutic data were collected (Table 1). CDs were screened with the MoCA test performed by certified personnel (altered if<26/30). A neuropsychologist explored deficits in 8 cognitive domains with a battery of neuropsychological tests. Depressive symptoms were evaluated with the Center for Epidemiologic Studies Depression Scale CES-D, (altered if>15) and fatigue with FACIT-F (altered if<30). Results: Ninety-nine patients and 36 HCs were enrolled (Table 1). MoCA test was altered in 44 SLE and 7 HCs (44.4% VS 19.4%, p=0.008). MoCA values in SLE correlated significantly with the alterations found in the battery test in the domains of memory, executive functions, complex attention and problem solving (Rey Immediate Words p=0.014; Recognition p=0.043, Stroop Test p=0.010, FAB p =0.005, Digit Symbol p=0.018). High MoCA scores correlated with the absence of CDs (mean 26.86±1.86, p=0.012). At least one subjective cognitive symptom was reported by 31/57 SLE and 13/36 HC but no correlation was found with the MoCA alterations, while a correlation emerged with the CES-D values (p=0.002) and fibromyalgia (p=0.003). At multivariate analysis after correction for age, gender, level of education, disease duration, fibromyalgia, dyslipidemia, SLEDAI-2K, anti-RibP titre, the factors that influenced MoCA were male gender (β=-0.206, p=0.014), education <8 years (β=0.444, p<0.001), dyslipidemia (β=-0.205, p=0.016), and antiRib-P (β=-0.221, p=0.008). Conclusion: MoCA test is useful for screening but not for diagnosis of CDs in SLE patients. Low level of education, male gender, dyslipidemia and anti-Rib-P titer were factors independently associated with MoCA alterations. No correlation between subjective cognitive symptoms with MoCA alterations was found, while a correlation emerged with CES-D values and fibromyalgia. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Elisabetta Chessa: None declared, cristina serafini: None declared, Alberto Floris: None declared, Maria Maddalena Angioni: None declared, MATTIA CONGIA: None declared, Alessandro Mathieu: None declared, Alberto Cauli: None declared, Mauro Giovanni Carta: None declared, Matteo Piga AstraZeneca, GSK, Otsuka, Roche, AstraZeneca, GSK.Table 1Demographics, clinics, clinimetrics, serological, therapeutics characteristics of the cohortsVariablesSLE (N=99)HC (N=36)Gender, F (%)92 (92.9%)34 (94.4%)Age, mean (SD)43.6 (±12.36)40 (±14.2)Education ≤8 years, N (%)29 (29.3%)4 (11.1%)Disease duration years, median (IQR)10.3 (3.3-18.2)-Neuropsychiatric Lupus, N (%)19 (19.2%)-Dyslipidemia, N (%)22 (22.5%)9 (25%)Hypertension, N (%)33 (33.7%)4 (11.1%)Smoking, N (%)17 (17.5%)8 (23.5%)MoCA test, mean (SD)25.3 (±3.05)27 (±2.9)>=1 cognitive domain altered N (%)17 (53%)-CES-D altered (>15), N (%)46 (46.5%)14 (38.9%)CES-D, median (IQR)16 (9-21.8)13 (7-17.3)FACIT altered (<30), N (%)23 (44.2%)8 (22.2%)FACIT, median (IQR)33 (25-40)42.5 (33.8-47)Subjective cognitive symptoms N (%)31 (54.4%)13 (36.1%)Fibromyalgia, N (%)21 (21.2%)-SLEDAI-2K, median (IQR)2 (0-5.5)-PGA, median (IQR)0.2 (0-0.8)-SLICC-DI, median (IQR)0.0 (0-1)-LLDAS, N (%)58 (58.3%)-Anti-dsDNA, median (IQR)9.2 (2.2-36.8)-C3, median (IQR)89 (73-97.5)-Anti-phospholipids, N (%)29 (30.5%)-Anti Rib-P, N (%)20 (21.3%)-PDN dose mg/die, median (IQR)4.6 (2.5-7.5)-Hydroxychloroquine, N (%)78 (78.8%)-Immunosuppressors, N (%)80 (80.8%)-

Background: Anifrolumab (ANI) is a fully human monoclonal antibody against the type I interferon receptor that has recently been approved for the treatment of moderate to severe Systemic Lupus Erythematosus (SLE) as an add-on treatment to standard of care. Data from randomized controlled trials have demonstrated its efficacy and safety, but real-world data are still limited, especially regarding the impact of this new drug on patients' quality of life (QoL). Objectives: To evaluate the effect of ANI therapy on QoL and disease burden in a multicentric cohort of refractory SLE patients. Methods: Consecutive adult SLE patients (2019 EULAR/ACR criteria) were prospectively enrolled at ANI prescription. Data on demographic features, medical history, previous therapies and SLICC-DI were collected from clinical charts at enrolment. Patients' assessments were performed at the first ANI infusion and subsequently after one, three and six months of treatment. At each time-point, the clinical evaluation included SLEDAI-2K, SLE-DAS, Physician Global Assessment, number of tender and swollen joints and cutaneous activity and damage assessed using the Cutaneous LE Disease Area and Severity Index (CLASI-A for activity and -D for damage). Patients' perspective was assessed by self-administration of validated Patient Reported Outcomes (PROs): Lupus Impact Tracker (LIT) to assess the overall impact of SLE on patients' QoL, Functional Assessment of Chronic Illness Therapy – Fatigue scale (FACIT-F) to measure self-reported fatigue and its impact on daily activities and, in a subgroup of patients with mucocutaneous involvement, Skindex-16 which is a specific PRO to investigate the impact of the skin disease in symptom, emotional and functioning spheres. Results: Twenty-five patients (96% female, 92% Caucasian) with a median age of 45 years (IQR 37-58) and a median disease duration of 11 years (IQR 7.5-21.5) were enrolled. In the whole cohort, 24 patients (96%) had a history of articular involvement, 23 (92%) of mucocutaneous involvement, 16 (64%) of haematological involvement, 7 (28%) of lupus nephritis, 5 (20%) of serositis and 4 (16%) of neuropsychiatric involvement. At baseline, 23 patients (92%) were on concomitant steroid therapy (median prednisone daily dose 7.5 mg, IQR 5-10), 19 (76%) on hydroxychloroquine and 23 (92%) on immunosuppressive treatment (10 methotrexate, 9 mycophenolate mofetil, 3 azathioprine, 1 cyclosporine). Active disease manifestations at the time of ANI prescription were in most cases mucocutaneous (18/25, 72%), followed by articular (10/25, 40%) and haematological (5/25, 20%) involvement. As reported in Table 1, after ANI start, all the disease activity measures showed a progressive improvement over time. A significant correlation was observed between LIT and joint count and Skindex-16 and CLASI-A at baseline (r≥0.464, p≤0.026 for LIT; r≥0.731, p≤0.04 for Skindex-16). During follow-up, LIT and Skindex-16 exhibited progressively and significantly improved scores, while no changes were observed in FACIT-F scores. Notably, Skindex-16 was significantly improved as early as 4 weeks after the first drug infusion (symptoms p=0.028, emotions p=0.03, functioning p=0.05), while LIT reached statistical significance after 12 weeks of treatment (p=0.046), maintaining in both cases the result achieved over time (Figure 1). Conclusion: Our preliminary data show that ANI not only allows a rapid clinical improvement of SLE activity, but also of QoL as shown by the significant amelioration of PROs from the very first months of treatment. Further long-term studies on larger cohorts are needed to confirm and corroborate these results. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.