Background: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) positive dermatomyositis is a distinct subset of idiopathic inflammatory myopathies (IIMs), often associated with unique cutaneous features and interstitial lung disease (ILD). While East Asian cohorts frequently report high mortality due to rapidly progressive ILD (RP-ILD), data regarding Central and Eastern European populations remain scarce. Methods: We conducted a retrospective multicenter study of anti-MDA5 positive Caucasian patients managed at four Hungarian rheumatology centers between 2020 and 2025. Demographic, clinical, serological, and radiological data were analyzed. Antibody profiling was performed using a standardized 16-antigen immunoblot assay. Results: Anti-MDA5 positivity was confirmed in 24 out of 742 patients (3.23%) treated in the four centers. The median age at diagnosis was 49.5 years (range: 24-81). Classic dermatomyositis was the predominant clinical phenotype (75%), followed by clinically amyopathic dermatomyositis (CADM) (12.5%) and polymyositis (12.5%). ILD was identified in 58.3% of patients, presenting with organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP), and usual interstitial pneumonia (UIP) patterns. At diagnosis, median creatine kinase (CK) (193.5 U/L) and C-reactive protein (CRP) (4.24 mg/L) levels remained low even in the ILD group, whereas lactate dehydrogenase (LDH) was elevated in 91.7% of the cohort. Anti-Ro52 positivity (45.8% overall) emerged as a notable predictor of ILD (odds ratio [OR]: 22.5, 95% confidence interval [CI]: 2.10-240.48; p = 0.0045), being present in 71.4% of affected patients. RP-ILD occurred in two patients (8.3%). Therapeutic management followed an early, aggressive strategy, frequently utilizing cyclophosphamide (45.8%) and methotrexate (37.5%), with Janus kinase (JAK) inhibitors or rituximab employed in refractory cases. Overall disease-specific survival was 100% during the study period (median follow-up: 72.0 months); no mortality was directly attributable to IIM-related complications. Conclusions: Our study demonstrates that anti-MDA5 positive dermatomyositis in a Hungarian cohort is characterized by heterogeneous manifestations and a significant association between anti-Ro52 and ILD. The observed dissociation between low CK/CRP and elevated LDH underscores the necessity for a high index of suspicion, with LDH serving as a superior marker for disease activity. While ILD presents a significant risk, early and intensive multi-modal intervention may yield superior survival outcomes in European patients compared to the historical mortality rates reported in Asian cohorts.

Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies are critical biomarkers in myositis, associated with distinct clinical features and prognosis. This study aimed to evaluate the proportion of anti-MDA5 positivity and compare the diagnostic performance of local immunoblotting (IB) with gold-standard immunoprecipitation (IP). We performed a retrospective analysis of 3272 physician-requested anti-MDA5 IB determinations over a five-year period (2019-2023). A subsequent exploratory pilot study of ten Hungarian patients with myositis was conducted to compare IB results with radiolabeled protein IP. Confirmatory in-house enzyme-linked immunosorbent assay (ELISA) was used to distinguish between 140 kDa bands (anti-MDA5 vs. anti-NXP2). Indirect immunofluorescence (IIF) on HEp-2 cells was also evaluated. In the retrospective cohort, 3.7% (n = 121) of samples were non-negative. Among 64 borderline patients, only one (1.6%) had a definitive diagnosis of dermatomyositis (DM). Conversely, the proportion of confirmed myositis cases was notably higher among patients with strong positive IB results. In our exploratory cross-sectional pilot study, complete concordance between the two assays was observed for negative and strong positive results. Discrepancies were noted in borderline and weak positivity ranges, where anti-MDA5 was not detected by IP; instead, alternative autoantibodies were identified. The three IP-confirmed MDA5 positive samples were all validated by ELISA. The characteristic IIF cytoplasmic staining was identifiable in 2 out of 10 cases (20%). In our cohort, borderline IB cases were frequently potential false positives, highlighting the need for careful clinical evaluation. Borderline and weak results require clinical correlation or confirmatory testing to avoid misdiagnosis.

Background/Objectives: Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). Chronic kidney disease (CKD) and its progression into end-stage renal disease (ESRD) are serious complications in LN and the main cause of death in SLE. We aimed to investigate the prognostic factors of the progression of CKD and the development of ESRD in SLE patients. Methods: In our retrospective cohort study, we assessed the clinical and laboratory data of 127 patients who were diagnosed with LN between 1990 and 2022 and received regular follow-up care at our autoimmune centre. We compared class IV (diffuse) LN patients with non-class IV LN patients and assessed the differences in clinical and laboratory data of the patients, subdivided into complete, partial, and non-responders to therapy. Results: The prevalence of class IV LN is significantly higher in patients with CKD stage 3–5. Age above 42, class IV LN, Coombs positivity, and high chronicity index are prognostic factors for the development of CKD stage 3–5. On the other hand, anti-RNP and anti-SS-B antibody positivity and a high chronicity index are prognostic factors for the development of ESRD. The chronicity index, as well as the SLICC/ACR Damage Index (SDI) score, was significantly higher in non-responders compared to patients with complete remission. Conclusions: Based on our results, the progression of CKD into stage 3–5 or the development of ESRD should be expected at a chronicity index above 3.5 points. An early diagnosis, as well as aggressive, timely, and adequate treatment, is fundamental to prevent unfavourable outcomes of LN.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with premature atherosclerosis and vascular impairment. However, the role of endocan, a biomarker of glycocalyx injury, is not completely clarified in the detection of vascular damage. Therefore, our aim was to investigate serum endocan in comparison with conventional inflammatory markers, arterial stiffness parameters, and carotid ultrasound findings in a cohort of young patients with SLE. Methods: We enrolled 47 clinically active young SLE patients (40 females and 7 males) in the study. Arterial stiffness indicated by augmentation index and pulse wave velocity (PWV) was measured by arteriography. Brachial artery flow-mediated dilatation and common carotid intima-media thickness were detected by ultrasonography. The serum concentrations of endocan, IL-6, MPO, MCP-1, MMP-3, -7, and -9, as well as TNFα, were measured by an enzyme-linked immunosorbent assay (ELISA). Results: We found significant negative correlations between serum endocan and both CH50 and C3. Serum endocan was higher in active SLE patients compared to inactive patients, however, the difference was not statistically significant (241.4 (183–295) vs. 200.3 (167–278) pg/mL; p = 0.313). Serum TNFα and hsCRP significantly correlated with PWV. However, we did not detect significant correlations between vascular diagnostic tests and serum endocan levels. Conclusions: Based on our results, serum endocan is associated with disease activity; however, further studies are needed to clarify the value of serum endocan in the cardiovascular risk estimation of SLE patients. Measurement of serum endocan, as well as the routine assessment of arterial stiffness parameters, should be integrated into the comprehensive management plans of young patients with SLE.

Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by autoantibody production and multi-organ involvement. Anifrolumab, a monoclonal antibody targeting the type I interferon (IFN) receptor, has been approved for the treatment of SLE. Our aim was to investigate the long-term effects of inhibited type I IFN signaling on circulating follicular helper T subsets (TFH), follicular regulatory T cells (TFR), and B lymphocyte subpopulations, reflecting the ongoing germinal center reactions in SLE patients. Peripheral blood samples were obtained from ten SLE patients before the initiation of anifrolumab treatment, and at months 6 and 12 of the intervention period. Flow cytometry analysis was performed to assess the frequencies of circulating TFH cell subsets, TFR cells, and certain B cell subpopulations. Serological parameters, including autoantibody levels and complement components, were determined as part of the routine diagnostic evaluation. We observed a significant and sustained reduction in the percentage of activated circulating TFH cells. Notably, the frequency of CXCR3−CCR6+ TFH17 cells decreased, whereas the proportion of CXCR3+CCR6− TFH1 cells increased significantly. Furthermore, the proportion of the IgD−CD27− double-negative B lymphocytes was also significantly reduced. These findings suggest that anifrolumab therapy attenuates TFH cell activation, which may contribute to its clinical efficacy by modulating germinal center responses in SLE.

OBJECTIVES:B cell depletion or B cell activating factor (BAFF) blockade has shown benefits in systemic lupus erythematosus (SLE). We compared ianalumab, a monoclonal antibody targeting BAFF receptor (BAFF-R)-expressing B cells to lyse B cells and block BAFF-R, with placebo for SLE treatment combined with standard therapies. METHODS:Patients with active SLE were randomised (1:1) to monthly subcutaneous ianalumab 300 mg or placebo. The primary outcome was a composite of SLE Responder Index (SRI)-4 at week 28 in patients successfully achieving corticosteroid (CS) tapering criteria. Patients subsequently received open-label (OL) ianalumab until week 48, followed by exploratory assessments at week 52 and off-treatment to week 68. Safety monitoring continued until B cell recovery. This report describes interim analyses conducted on the week 68 dataset. RESULTS:Sixty-seven patients were randomised and received blinded treatments until week 28. The primary composite endpoint was more frequently achieved with ianalumab vs placebo: 15/34 (44.1%) vs 3/33 (9.1%), with responses sustained to week 52 and replicated by placebo transitioned to OL ianalumab: 15/33 (45.5%) and 13/32 (40.6%). Positive treatment effects were consistently observed across other lupus disease activity outcomes (SRI-6, Definition of Remission in SLE, Lupus Low Disease Activity State, flare reduction, and CS use) at week 28, with clinical benefits until weeks 52 and 68. Ianalumab was not associated with increased serious adverse events or serious infections. Nonserious local injection site reactions occurred more frequently with ianalumab. CONCLUSIONS:At week 28, reduced disease activity was observed in patients with SLE receiving ianalumab plus standard therapies compared with those receiving standard therapies alone, with sustained benefits with further treatment until 1 year, which was well tolerated.

Central nervous system (CNS) involvement is an extremely rare manifestation in eosinophilic granulomatosis with polyangiitis (EGPA), associated with a poor prognosis. Here we present a case of 50-year-old female patient with long-term asthma treatment who presented initially with extreme eosinophilia (56%) and severe progressive ascending paresis, similar to Guillain–Barré syndrome, leading to tetraplegia. After navigating through diagnostic mazes, the diagnosis of EGPA was established based on eosinophilia, myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) positivity, asthma, eosinophil granulomatosis in the gastrointestinal tract, and severe peripheral nervous system involvement, complicated with rare central nervous granulomas and ischemia. With combined immunosuppressive and immunomodulatory treatment including high-dose corticosteroids, rituximab and intravenous immunoglobulin along with symptomatic treatment and planned rehabilitation over 6 months, our patient recovered gradually from tetraplegia and adverse events such as severe infections and osteoporotic fractures. Now, from a 2-year perspective, we can conclude a successful treatment leading to decrease in all of her symptoms. Due to persistent eosinophilia after steroid tapering, she was switched to mepolizumab maintenance treatment and demonstrated continuous improvement of motor and sensory functions. Thanks to periodically repeated rehabilitation, she became self-sufficient and returned to her previous job. Our case highlights that EGPA patients should be treated in a center of expertise due to the rarity of the disease and complexity of diagnosis and treatment. Careful multidisciplinary cooperation, the huge effort of the patient, and a supportive environment can show a way back from immune-mediated tetraplegia.

Objective Lupus nephritis (LN) is one of the most severe organ manifestations in SLE. The aim of our study was to determine the incidence of LN and to compare the clinical characteristics, survival rate and outcome of SLE patients with and without LN. We also compared the data of patients diagnosed with LN before and after 2005. Methods The patients were followed up between 1990 and 2020 at the Dept. of Clinical Immunology, Faculty of Medicine, University of Debrecen. We recorded the clinical and laboratory findings of the patients, as well as their immunosuppressive treatments. Results Of 384 SLE patients, 127 had LN (33.07%). The age at the onset of SLE was significantly lower in patients with LN (p<0.001). Discoid lupus erythematosus (p<0.001) and subacute cutan lupus erythematosus (p=0.01) occurred more often in SLE patients without LN. Rheumatoid arthritis (p=0.009), antiphospholipid(p=0.044) and Sjögren's syndrome (p=0.017) were also more common in patients without LN. Anaemia (p<0.001) and anti-RNP positivity (p=0.049) were more common in patients with LN. Antimalarials (p=0.004) and methotrexate (p=0.001) were used more often in patients without LN, while rituximab (p<0.001), cyclophosphamide (p<0.001) and MMF (p<0.001) were more commonly used in LN group. LN did not significantly worsen the survival in SLE patients. Male gender was a negative prognostic factor in patients without LN. Remission status was a positive prognostic factor in patients with and without LN, but low disease activity significantly improved survival only in patients with LN. Sepsis-related mortality was higher in the LN group (p=0.031). The prevalence of serositis (p=0.007) and neurological manifestations of SLE (p=0.001) were decreased in patients with LN diagnosed after 2005. After 2005, the use of mycophenolate mofetil therapy increased (p<0.001). The use of cyclophsophamide and the cumulative steroid doses also decreased after 2005. The SLICC damage index score decreased after 2005 as well (p=0.001). Conclusion Lupus nephritis did not influence disease outcome in our SLE patients. Low disease activity status significantly improves survival in LN but not in SLE patients without LN. The main therapeutic goal is to achieve remission in SLE patients with or without LN.

Background: Ianalumab (VAY736) is a novel defucosylated, human immunoglobulin (Ig) G1 monoclonal antibody targeting the B cell activating factor receptor (BAFF-R) of the tumour necrosis factor family, providing both enhanced (afucosylated) antibody-dependent cellular cytotoxicity–mediated depletion of B cells and blockade of BAFF:BAFF-R signaling driving B-cell activation. Objectives: To expand upon previously published 28-week (wk) results from the phase 2 study CVAY736X2208 with longer-term results reported from additional 24-wk open-label ianalumab treatment. Methods: Multi-centre, randomised, parallel-group trial consisting of treatment: 1) 28wk blinded, placebo-controlled, 2) 24-wk open-label, and 3) post-treatment follow up. Herein, we report interim analysis results for the ianalumab treatment cohort completing 68 weeks. Randomisation (1:1) to treatment with either ianalumab 300 mg subcutaneous or placebo every 4 wks (qwk) until switch at wk 28 of all patients to open-label ianalumab to wk 48. Patients with anti-nuclear antibodies ≥ 1:80, ≥4 of 11 ACR 1997 systemic lupus erythematosus (SLE) classification criteria, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) -2K score ≥6 and British Isles Lupus Assessment Group (BILAG) -2004 ≥1 A or ≥2 B were included. Outcomes were measured at baseline, q4w to wk 52, wk 60 and wk 68. The primary w28 outcome was composite endpoint of patients who both achieved SLE Responder Index (SRI-4) and met corticosteroid (CS) responder criteria (tapering prednisone ≤5 mg/d or ≤ baseline dose, whichever was lower, by wk 16 and kept within that range to wk 28). Wk 52 composite responders met CS responder criteria from wk 40 to wk 52. Other outcomes included SRI-4, SRI-6, SRI-8, incidence BILAG-2004 flares* (BILAG-2004 ≥1 A or ≥2 B scores), proportion of patients achieving Lupus Low Disease Activity State (LLDAS) and Definition of Remission in SLE (DORIS), safety/tolerability, and laboratory markers for B cell counts and immune activation. Results: 67 patients enrolled from 19 Dec 2018 to 31 Jan 2022 with median age 42 y and 39 y for ianalumab and placebo arms, respectively, with 8 males (ianalumab: 2, placebo: 6). Baseline median (range) values for ianalumab and placebo arms, respectively, were: SLEDAI-2K scores 10 (6-32) and 10 (4-18), and prednisone 10.0 mg (0-30.0) and 10.0 mg (0-27.5). The proportion of patients treated with ianalumab or placebo achieving composite endpoint criteria for SRI-4 + CS responder at wk 28 was 44.1% (n/N=15/34) vs. 9.1% (n/N=3/33), respectively, and at wk 52 for patients switching from active treatment to open-label ianalumab or switching from placebo to ianalumab was 45.5% (n/N=15/33) vs. 40.6% (n/N=13/32; Figure 1). Longer duration of q4w ianalumab exposure at wk 52 vs wk 28, or for placebo+24 wks, resulted in further improvements in outcomes (Table 1) for incidence BILAG flare, status of SRI-6, SRI-8, DORIS and LLDAS, and serum levels of complement and autoantibodies. IgG reductions from baseline (geo-mean, 95% CI) at wk 52 were (0.78, 0.73-0.84). Of patients randomised to ianalumab from start of study, reported serious adverse events (AE) were: blinded treatment (n=1), open-label period (n=2), and safety follow up period (n=3); none considered study drug related. Two non-serious AE-related dropouts occurred during open-label treatment (ianalumab arm, morphoea; placebo/ianalumab arm, worsening of SLE). Five other patients discontinuing open-label treatment included 2 (patient’s decision), 1 (pandemic related), and 2 (lack of efficacy). Conclusion: Treatment of SLE with ianalumab up to 1 year was well tolerated, and data suggest longer exposure provides further clinical and laboratory benefits. These positive results support ongoing lupus phase 3 evaluations for ianalumab.Table 1. Clinical and laboratory outcomes at week 28 and week 52 REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Nancy Agmon-Levin: None declared, Stanislav Ignatenko: None declared, Alexander Gordienko: None declared, Josefina Cortés-Hernández: None declared, Pongthorn Narongroeknawin: None declared, Katarzyna Romanowska -Prochnicka: None declared, Nan Shen: None declared, Hana Ciferská: None declared, Masanari Kodera: None declared, James Cheng-Chung Wei Speakers bureau for Abbvie, AstraZeneca, BMS, Chugai, Eisai, Eli Lilly, Janssen, and Pfizer, Consultation fee from Abbvie, BMS, Celgene, Chugai, Eisai, Eli Lilly, GSK, Janssen, Novartis, Pfizer, Sanofi-Aventis, TSH Taiwan, and UCB pharma, Research grants from Abbvie, Amgen, BMS, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, SUN pharma, UCB, Piotr Leszczynski Speaker fees from Novartis, AbbVie, AstraZeneca, MSD, and UCB, Received a grant for this study from Novartis, Joung Liang Lan: None declared, Eduardo Mysler Speaker: Pfizer, Abbvie, Novartis, GSK, Sanofi, Janssen, Astra Zeneca, Amgen, Roche, Hi Bio, Alpine Immunology, Sandoz, Advisor: Pfizer, Abbvie, Novartis, GSK, Sanofi, Janssen, Astra Zeneca, Amgen, Roche, Hi Bio, Alpine Immunology, Sandoz., Grants: Pfizer, Abbvie, Novartis, GSK, Sanofi, Janssen, Astra Zeneca, Amgen, Roche, Hi Bio, Alpine Immunology, Sandoz., Rafał Wojciechowski: None declared, Tunde Tarr: None declared, Elena Vishneva: None declared, Yi-Hsing Chen: None declared, Yuko Kaneko: None declared, Stephanie Finzel Sponsored talks/courses: Abbvie, Chugai, Galapagos, Novartis, UCB, Consultant of: AstraZeneca, Novartis. Participated in Data Safety Monitoring Board or advisory board of AstraZeneca, Novartis, Received support for attending meetings and/or travel from Janssen, Alberta Hoi Sponsorship: AstraZeneca (Sponsorship of the Australian Lupus Registry and Biobank and Asia Pacific Lupus Collaboration, and also contract research on unmet needs in Australian lupus patients), BMS, Merck Serono, GSK, Eli Lilly, UCB (Sponsored Asia Pacific Lupus Collaboration, for which I contribute data towards), Janssen (Contracted the Asia Pacific Lupus Collaboration to conduct a research study on medication use), Novartis, Janssen, Recordati Honoraria, Grant recipient: Arthritis Australia, Perpetual IMPACT fund, Masato Okada consulting fees and/or honoraria from AbbVie, Amgen, Asahi Kasei Pharma, Astellas, Astra Zeneca, Ayumi Pharma, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, GSK, Janssen, Novartis, Ono Pharma, Pfizer, Mitsubishi Tanabe Pharma, and UCB Pharma, Ajchara Koolvisoot: None declared, Shin-Seok Lee: None declared, Lie Dai: None declared, Hiroshi Kaneko: None declared, Bernadette Rojkovich: None declared, Lingyun Sun: None declared, Eugeny Zotkin: None declared, Jean-François Viallard: None declared, Masao Katayama: None declared, Berta Paula Magallares: None declared, Tirtha Sengupta Shareholder of Novartis, Employee of Novartis, Carole Sips Shareholder of Novartis, Employee of Novartis, Carol Lau Shareholder of Novartis, Employee of Novartis, Alexandre Avrameas Shareholder of Novartis, Employee of Novartis, Stephen Oliver Shareholder of Novartis, Employee of Novartis.Figure 1SRI-4 Responders over time and composite SRI-4+CS Responders (bar graphs)

Introduction Ianalumab est un nouvel Ac monoclonal IgG1 humain défucosylé ciblant le BAFF-R, induisant à la fois une déplétion augmentée (afucosylée) des cellules B et un blocage de la voie de signalisation BAFF :BAFR. Nous rapportons ici les résultats jusqu’à 52 semaines (S) de l’étude de phase 2 CVAY736X22028, multicentrique, randomisée en groupe parallèle contrôlée vs placebo (PLB) évaluant le ianalumab chez les patients (pts) atteints de LES. Patients et méthodes Les pts ont été randomisés 1 :1 sous ianalumab 300mg sc toutes les 4 semaines ou PLB. De S28 à S48 tous les pts ont reçu ianalumab en ouvert puis ont été suivis après l’arrêt du traitement pendant au moins 12 semaines. Nous rapportons ici l’analyse intermédiaire des patients ayant complétés les 68 semaines de l’étude. Ont été inclus des patients répondant aux critères de de classification ACR SLE de 1997, avec ANA≥1 :80, SLEDAI-2K≥6, BILAG-2004≥1A ou ≥2B. Le critère principal composite à S28 était la réponse SRI-4 et une réduction des corticoïdes (CO) [décroissance maintenue des CO ≤5mg/d ou ≤ à la dose à l’inclusion (la dose la plus faible prévalent) de S16 à S28]. À S52, pour ce critère composite était pris en compte une réduction des CO maintenue entre S40 et S52. Les autres critères d’évaluation comprenaient : la réponse SRI-4, -6, -8, l’incidence des poussées BILAG-2004 (score BILAG-2004≥1A ou ≥2B), le LLDAS, la DORIS, l’innocuité/tolérabilité, et les marqueurs biologiques du nombre de lymphocytes B et de l’activation immunitaire. Résultats Entre le 19/12/2018 et le 31/12/2022, ont été inclus 67 patients, dont 8 hommes (ianalumab : 2, PLB : 6), avec pour les groupes ianalumab et PLB un âge médian de 42 ans et 39 ans, un SLEDAI-2K médian de 10 (6–32) et 10 (4–18) et une dose médiane de prednisone de 10,0mg (0–30,0) et 10,0mg (0–27,5). La proportion de pts atteignant le critère composite SRI-4+CO à S28 était de 44,1 % (n/N=15/34) sous ianalumab vs 9,1 % (n/N=3/33) sous PLB. À S52, le taux de réponse composite était de 45,5 % (n/N=15/33) chez les pts ayant poursuivi le ianalumab et de 40,6 % (n/N=13/32) pour ceux ayant switchés du PLB au ianalumab en ouvert. Une amélioration des autres critères d’évaluation et des concentrations sériques du complément et des auto-anticorps a été observée entre S28 et S52 pour les 2 groupes (Tab1). Parmi les pts randomisés initialement sous ianalumab, le nombre d’EIG rapportés était : traitement en aveugle (n=1), période ouverte (n=2) et période de suivi de l’innocuité (n=3), aucun n’a été considéré comme lié au traitement à l’étude. Deux arrêts liés à des EI non graves sont survenus au cours de la période en ouvert (ianalumab, sclérodermie en plaque, placebo/ianalumab, aggravation du LES). Les autres causes d’arrêt en ouvert étaient décision du patient (n=2), pandémie (n=1) et manque d’efficacité (n=2) (Tableau 1). Conclusion Le traitement par l’ianalumab jusqu’à 1 an a été bien toléré et a permis la poursuite de l’amélioration des paramètres cliniques et biologiques déjà observés à S28 dans le LES. Ces données soutiennent le développement du ianalumab en phase 3 dans le LES.

In systemic lupus erythematosus (SLE), cardiovascular complications are among the leading causes of death. Cardiovascular risk in SLE is even higher in the presence of antiphospholipid antibodies or secondary antiphospholipid syndrome (APS). The aim of this retrospective, single-center study was to investigate the occurrence of antiphospholipid antibodies and non-thrombotic cardiac manifestations in 369 SLE patients. We also assessed the clinical and laboratory characteristics of the patients to reveal the risk factors for cardiac manifestations. Patients were divided into two groups based on the presence of antiphospholipid antibodies (APA); 258 (69.9%) patients were APA positive, and 111 (30.1%) patients were APA negative. Mitral and tricuspid insufficiency, aortic stenosis and pulmonary arterial hypertension were more common in APA-positive patients. Anticardiolipin IgG showed the strongest correlation with any non-thrombotic cardiac manifestations. Based on our results, the adjusted global antiphospholipid syndrome score (aGAPSS) above 8.5 is predictive of valvulopathies and ischemic heart disease, while aGAPSS above 9.5 is predictive of cardiomyopathies. The presence of antiphospholipid antibodies may affect the development of cardiac manifestations in SLE. Periodic cardiological and echocardiographic screening of patients without cardiac complaints, as well as regular monitoring of antiphospholipid antibodies, have great importance during the treatment of SLE patients.

Background/Objectives: Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). The aim of our retrospective cohort study was to compare the clinical characteristics, therapy, survival, causes of death, and prognostic factors of LN and non-LN lupus patients. Moreover, we compared a wide spectrum of clinical data of LN patients diagnosed before and since 2005 to determine any changes in disease course and outcomes. Methods: We assessed the clinical and laboratory data of 384 SLE patients, out of whom, 127 patients were diagnosed with LN between 1990 and 2020. Results: Based on our observations, discoid LE, subacute cutaneous LE, antiphospholipid syndrome, Sjögren’s syndrome, and rheumatoid arthritis were more common in non-LN patients, while anemia and anti-RNP positivity were more frequent in LN patients. Development of LN did not affect survival rates; male sex and presence of APS were negative prognostic parameters in the non-LN group while achieving remission was a positive prognostic factor in both groups. Death caused by sepsis was more prevalent in the LN group. Serositis and neurological manifestations occurred less frequently in LN patients diagnosed after 2005. The use of mycophenolate mofetil became more common, and the cumulative corticosteroid dose decreased. The SLICC Damage Index score also decreased. Conclusions: Our study demonstrated that the disease course has changed in recent years, and the main therapeutic goal in both SLE and lupus nephritis should be to achieve remission because this significantly improves long-term prognosis and patient survival.

Background Ianalumab (VAY736) is a novel defucosylated, human IgG1 mAb targeting the receptor for B cell Activating Factor of TNF Family (BAFF-R), providing both enhanced antibody-dependent cellular cytotoxicity-mediated depletion of B cells and blockade of BAFF:BAFF-R signaling that drives B cell differentiation, proliferation and survival. Objectives Evaluate safety and efficacy of ianalumab in patients with active SLE. Methods Multi-center, randomised, parallel group, double-blind trial consisting of 2 separate, placebo-controlled treatment cohorts for ianalumab and for iscalimab (CFZ533; anti-CD40 mAb) randomised 1:1 between active:placebo. Patients (ianalumab cohort n= 67, iscalimab cohort n= 40) with ANA ≥1:80 and meeting ≥4/11 ACR 1997 SLE classification criteria, with SLEDAI-2K score ≥6 and BILAG-2004 ≥1 ‘A’ or two ‘B’ scores that included activity in either mucocutaneous and/or musculoskeletal domains were enrolled from 19 Dec 2018 through 31 Jan 2022. Here we report interim analysis results for ianalumab treatment cohort (active n=34, placebo n=33) completing the 28-week blinded treatment period, which comprised of monthly s.c. injection of ianalumab 300 mg or placebo. Outcomes were measured at baseline (BL) and weeks (w) 4, 8, 12, 16, 24 and 28. The primary w28 outcome was proportion of patients meeting composite endpoint requirements consisting of patients who both achieved SRI-4 and also tapered predniso(lo)ne ≤5 mg/d or ≤ BL dose, whichever was lower, by w16 and kept within that range to w28. Other outcomes included safety and tolerability, incidence of BILAG-2004 moderate or severe flares, proportion of patients achieving Lupus Low Disease Activity State (LLDAS), change from BL in SLEDAI-2K and BILAG-2004, physician/patient global visual analog scale (VAS) assessments and laboratory markers of inflammation and immune activation. Post-w28 patients received open-label ianalumab for 20w, then safety follow up off treatment up to 2 years (y). Results Median age was 42y and 39y for ianalumab and placebo arms, respectively, with 8 males (ianalumab: 2, placebo: 6). BL median (range) values for ianalumab and placebo arms, respectively, were: SLEDAI-2K scores 10 (6-32) and 10 (4-18), and predniso(lo)ne 10.0 mg (0-30.0) and 10.0 mg (2.5-27.5). Proportion of patients treated with ianalumab or placebo, respectively, achieving SRI-4 at w28 (Figure 1) was 70.6% (n=24) vs. 24.2% (n=8), and also meeting composite endpoint (Figure 1 insert): 44.1% (n=15) vs. 9.1% (n=3). Ianalumab showed benefit vs placebo in other outcomes (Table 1) for incidence moderate or severe flare, time to moderate or severe flare, achieving w28 LLDAS, and serum levels of complement and autoantibodies. No drug-related SAEs were reported with ianalumab during blinded or subsequent 20w open-label treatment. There were 2 AE-related dropouts occurring during open-label treatment, one in ianalumab arm (morphoea) and one with placebo (worsening of SLE). Pandemic-related discontinuations included one from each arm during the blinded treatment period, and 2 occurring post-w28 in the ianalumab arm: one each in open label and during safety follow up. Conclusion Treatment of SLE with ianalumab was well tolerated and met the composite primary endpoint of SRI-4 response with sustained steroid reduction, with additional benefits seen across other study endpoints. These positive results support further evaluation of ianalumab in SLE. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Josefina Cortés-Hernández: None declared, Stanislav Ignatenko: None declared, Alexander Gordienko: None declared, Nancy Agmon-Levin: None declared, Pongthorn Narongroeknawin Speakers bureau: Novartis (Speaker/Honoraria (includes speakers bureau, symposia, and expert witness)), Grant/research support from: AstraZeneca, Galapagos, Glaxo-Smith Kline, Novartis (Researcher), Katarzyna Romanowska -Prochnicka: None declared, Nan Shen: None declared, Hana Ciferská: None declared, Masanari Kodera: None declared, James Cheng-Chung Wei: None declared, Piotr Leszczynski Speakers bureau: AbbVie/Abbott, AstraZeneca, Novartis, Roche, UCB ((includes speakers bureau, symposia, and expert witness)), Grant/research support from: AbbVie/Abbott, Novartis, Roche, UCB, Joung Liang Lan: None declared, Rafal Wojciechowski Speakers bureau: Eli Lilly, Novartis (Speaker/Honoraria (includes speakers bureau, symposia, and expert witness)), Tunde Tarr: None declared, Elena Vishneva: None declared, Yi-Hsing Chen: None declared, Yuko Kaneko Speakers bureau: Speaker/Honoraria (includes speakers bureau, symposia, and expert witness: AbbVie/Abbott, Asahi Kasei Pharma, Astellas Pharma, AstraZeneca, AYUMI Pharmaceutical K. K., Bristol-Myers Squibb(BMS), Chug- Pharm, Chug-Pharm, Eisai, Eli Lilly, Gilead, GlaxoSmithKlein(GSK), Janssen, Novartis, Pfizer, Tanabe Mitsubishi Pharma, UCB Japan, Consultant of: Advisor or Review Panel Member: AbbVie/Abbott, Asahi Kasei Pharma, Astellas Pharma, AstraZeneca, AYUMI Pharmaceutical K. K., Bristol-Myers Squibb(BMS), Chug- Pharm, Chug-Pharm, Eisai, Eli Lilly, Gilead, GlaxoSmithKlein (GSK), Janssen, Novartis, Pfizer, Tanabe Mitsubishi Pharma, UCB Japan, Stephanie Finzel Speakers bureau: AbbVie/Abbott, Amgen, Galapagos, Novartis, UCB (Speaker/Honoraria (includes speakers bureau, symposia, and expert witness)), Consultant of: Amgen, Novartis, Novonordisk (Advisor or Review Panel Member), Alberta Hoi Speakers bureau: Sandoz, UCB, Janssen (Speaker/Honoraria (includes speakers bureau, symposia, and expert witness)), Consultant of: AbbVie/Abbott (Consultant, Professional service), AstraZeneca, Pfizer (Consultant), Janssen (Consultant, Sponsor of Australian Lupus Registry & Biobank), Grant/research support from: AstraZeneca, Merck Serono (Grant/Research Support), Masato Okada: None declared, Ajchara Koolvisoot: None declared, Shin-Seok Lee: None declared, Lie Dai: None declared, Hiroshi Kaneko: None declared, Bernadette Rojkovich: None declared, Lingyun Sun: None declared, Evgeniy Zotkin: None declared, Berta Magallares: None declared, Tirtha Sengupta Employee of: Novartis, Carole Sips Shareholder of: Novartis (Stock options or bond holdings in a for-profit corporation or self-directed pension plan), Employee of: Novartis, Stephen Oliver Shareholder of: Novartis (Stock options or bond holdings in a for-profit corporation or self-directed pension plan), Employee of: Novartis.Table 1Selected secondary and exploratory outcomesOutcomesIanalumab (n=34)Placebo (n=33)Incidence of flare*n (%)15 (44)21 (64)Time to first flare* (Days)Mean (SD)108 (73)87 (39)Median (range)87 (29-276)84 (30-170)Week 28 LLDASn (%)9 (27)3 (9)Ratio BL at Week 28Serum C3Geo-mean(95% CI)1.13 (1.05, 1.22)0.95 (0.88, 1.03)Serum C41.44 (1.24, 1.67)1.01 (0.90, 1.13)Anti-dsDNA0.52 (0.39, 0.70)0.88 (0.73, 1.06)Anti-CXCL130.50 (0.37, 0.67)0.83 (0.68, 1.02)Anti-C1q0.70 (0.56, 0.87)0.85 (0.71, 1.02)*Moderate or severe: post-BL BILAG 2004 domain activity ≥1 ‘A’ or ≥2 ‘B‘

Limited data are available on the predisposing factors to fractures and falls of patients with psoriatic arthritis (PsA). Our study intended to explore the differences between PsA patients and controls, concerning bone mineral density (BMD), the 10-year fracture risk, the number of prevalent fractures, the frequency of falls and to investigate the association of the same factors with PsA disease characteristics within the PsA group. Medical reports of 61 PsA patients and 69 consecutive, age-matched controls were analyzed, physical examination and bone mineral density (BMD, and T-score) were performed, and the 10-year fracture risk was calculated. The results were subjected to statistical analysis. Femoral neck BMD, as well as vertebral and femoral neck T-scores were lower, the odds ratio (OR) for low BMD and the 10-year risk of hip fracture was higher (p = 0.0029; 0.0002, p < 0.0001, OR = 21,9, p = 0.014) in the PsA group. The PsA patients were more predisposed to prevalent fractures, including peripheral fractures, and vertebral fractures as well as falls (OR 3.42; 2.26; 13.33; 3.95, respectively), compared to controls. Within the PsA group (beyond the age) scalp psoriasis and late-onset psoriasis, were significantly associated with a greater number of prevalent fractures (p = 0.0049; 0.029), while the number of falls per year correlated with late-onset psoriasis and the flexural psoriasis (p = 0.007; 0.023). Our results suggest that PsA is an independent risk factor for reduced bone density and falls hence to related bone fractures. Patients with late-onset psoriasis are more likely to suffer falls and related fractures, especially if their disease is characterized by the involvement of the hairy scalp and body folds.

Systemic lupus erythematosus (SLE) is often associated with antiphospholipid syndrome (APS), which potentially results in a more severe disease course and reduced life expectancy. Since the therapeutic guidelines have been refined in the last 15 years, we assumed that the diseases course has become more favorable. In order to shed light on these achievements, we compared the data of SLE patients diagnosed before and since 2004. In our retrospective study, we assessed a wide spectrum of clinical and laboratory data of 554 SLE patients who received regular follow-up care and therapy at our autoimmune center. Among these patients, 247 had antiphospholipid antibodies (APAs) without clinical signs of APS, and 113 had definitive APS. In the APS group, among patients diagnosed since 2004, deep vein thrombosis (p = 0.049) and lupus anticoagulant positivity (p = 0.045) were more frequent, while acute myocardial infarction was less frequent (p = 0.021) compared with patients diagnosed before 2004. Among the APA positive patients without definitive APS, anti-cardiolipin antibody positivity (p = 0.024) and development of chronic renal failure (p = 0.005) decreased in patients diagnosed since 2004. Our study demonstrates that the disease course has changed in recent years; however, in the presence of APS, we have to expect repeated thrombotic events despite adequate anticoagulant therapy.