SLE Pts Research Articles

OP0193 BIIB059, A HUMANIZED MONOCLONAL ANTIBODY TARGETING BDCA2 ON PLASMACYTOID DENDRITIC CELLS (PDC), SHOWS DOSE-RELATED EFFICACY IN THE PHASE 2 LILAC STUDY IN PATIENTS (PTS) WITH ACTIVE CUTANEOUS LUPUS ERYTHEMATOSUS (CLE)

Background:CLE represents an unmet medical need with no approved therapy. BIIB059, a humanized monoclonal antibody, binds to BDCA2 and inhibits pro-inflammatory mediators production, including type I interferons. BIIB059 was evaluated in Phase 1 studiesNCT02106897andNCT03224793. LILAC is a 2-part Phase 2 study: Part A enrolled SLE pts; Part B enrolled pts with active CLE (NCT02847598).Objectives:Evaluate efficacy and safety of BIIB059 in pts enrolled in Part B at Week 16, end of treatment (EOT) period.Methods:Pts with active CLE, SCLE and/or CCLE and adjudicated Cutaneous Lupus Disease Area and Severity Index – Activity (CLASI-A) ≥8 were enrolled and randomized to receive either BIIB059 (50, 150 or 450 mg) or placebo (PBO) s.c. Q4W. Primary endpoint was dose response defined by % change in CLASI-A score from baseline (BL) to Week 16. Secondary endpoints included CLASI-50 response rate and ≥ 7-point reduction in CLASI-A score from baseline to EOT. Adverse events and serious adverse events were recorded throughout the study.Results:132 pts with active CLE were randomized. The study met its primary endpoint, demonstrating a dose response (p= 0.0005) and a statistically significant difference in % change from BL in CLASI-A score in BIIB059-treated pts vs PBO. Table 1 and Table 2 summarize efficacy and safety results, respectively.Table 1.Efficacy EndpointsBIIB059PBO50 mg150 mg450 mgLS Mean (SE)LS Mean (SE)LSMD*from PBO (95% CI)P val.LS Mean(SE)LSMD*from PBO (95% CI)P val.LS Mean(SE)LSMD*from PBO (95% CI)P val.Primary EndpointCLASI-A % change from BL-14.5 (6.4)-40.8 (7.5)-26.3 (-45.7; -7.0)0.008-47.9 (7.4)-33.5 (-52.7; -14.3)0.001-43.5 (5.5)-28.0 (-44.5; -11.5)0.001Secondary Endpointsn(%)n(%)LSMD*from PBO (95% CI)P val.n(%)LSMD*from PBO (95% CI)P val.n(%)LSMD*from PBO (95% CI)P val.Prop. of participants achieving CLASI 507/32 (21.9%)10/26 (38.5%)15.8% (-7; 39)0.13311/25 (44.0%)21 (-2.8; 45)0.05920/43 (46.5%)23 (3; 44)0.024Prop. of participants achieving a ≥7-point CLASI-A reduction from BL7/32 (21.9%)9/26 (34.6%)12.3 (-11.3; 35.8)0.22812/25 (48.0%)22.2 (-2.0; 46.3)0.05518/43 (41.8%)16.8 (-6.7; 40.4)0.048*LSMD=LS Mean DifferencePBOBIIB059OVERALLN=3350 mgN=26150 mgN=25450 mgN=48PooledN=99N=132Any Event, n(%)18 (54.5)17 (65.4)12 (48)33 (68.8)62 (62.6)80 (60.6)SeverityMild11 (33.3)11 (42.3)8 (32.0)19 (39.6)38 (38.4)49 (37.1)Moderate4 (12.1)6 (23.1)3 (12.0)12 (25.0)21 (21.2)25 (18.9)Severe3 (9.1)01 (4.0)2 (4.2)3 (3.0)6 (4.5)Related events6 (18.2)9 (34.6)4 (16.0)16 (33.3)29 (29.3)35 (26.5)Serious events2 (6.1)03 (12.0)2 (4.2)5 (5.1)7 (5.3)Related serious events1 (3.0)01 (4.0)1 (2.1)2 (2.0)3 (2.3)Events leading to drug withdrawal01 (3.8)1 (4.0)1 (2.1)3 (3.0)3 (2.3)Events leading to study withdrawal0001 (2.1)1 (1.0)1 (0.8)Fatal events000000Conclusion:BIIB059 administration to pts with active CLE resulted in statistically significant dose-related improvement in disease activity vs PBO with no untoward safety signals. Further development of BIIB059 in CLE is warranted.Disclosure of Interests:Victoria Werth Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, Consultant of: Biogen, Gilead, Janssen, Abbvie, GSK, Resolve, AstraZeneca, Amgen, Eli Lilly, EMD Serono, BMS, Viela, Kyowa Kirin, Richard Furie Grant/research support from: AstraZeneca, Biogen, Consultant of: AstraZeneca, Biogen, Juanita Romero-Diaz Consultant of: Biogen, Sandra Navarra Speakers bureau: Astellas, Novartis, Pfizer, Johnson & Johnson, Abbvie, Kenneth Kalunian Grant/research support from: Pfizer, Lupus Research Alliance, Sanford Consortium, Consultant of: Genentech, Nektar, BMS, Janssen, AstraZeneca, Biogen, Vielabio, Equillium, Eli Lilly, ILTOO, Abbvie, Amgen, Roche, Gilead, Ronald van Vollenhoven Grant/research support from: AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, and UCB, Consultant of: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB, Filippa Nyberg Consultant of: Biogen, Benjamin Kaffenberger Grant/research support from: Amgen, Biogen, InflaRx, Veloce Biopharmaceuticals, Dermatology Foundation, Saira Sheikh: None declared, Goran Radunovic: None declared, XIAOBI HUANG Shareholder of: Biogen, Employee of: Biogen, HUA CARROLL Shareholder of: Biogen, Employee of: Biogen, Francois Gaudreault Shareholder of: Biogen, Employee of: Biogen, Adam Meyers Shareholder of: Biogen, Employee of: Biogen, Catherine Barbey Shareholder of: Biogen, Employee of: Biogen, Cristina Musselli Shareholder of: Biogen, Employee of: Biogen, NATHALIE FRANCHIMONT Shareholder of: Biogen, Employee of: Biogen

FRI0382 Impact of Treatments on Major Immunologic Pathways in SLE Depends on Type I Interferon Signature: Analysis from Biomarkers of Lupus Disease (BOLD) Study

BackgroundThe BOLD study investigated biologic effects of commonly used immune suppressants (IS) on SLE patients (pts), evaluating the safety of withdrawing IS from stable pts in trials. We have reported...

AB0624 The effectiveness of different oral compounds of vitamin D3 on 25-OH vitamin D serum levels in a retrospective longitudinal study of italian SLE patients

BackgroundSystemic Lupus Erythematosus (SLE) patients (pts) are generally instructed to avoid direct sunlight, since UVB radiations may induce massive apoptosis in the skin and trigger a flare. As a consequence,...

SAT0208 Cognitive dysfunction and magnetic resonance imaging (MRI) measures in patients with neuropsychiatric systemic lupus erythematosus (NPSLE)

BackgroundSystemic lupus erythematosus is an autoimmune-mediated collagen disease that results in multiorgan failure. Cognitive dysfunction, when standardly assessed using sensitive neurocognitive instruments, is the most common NPSLE manifestation.ObjectivesStudy aimed at...

THU0037 The Effects on T-Cell Immune Phenotype in Patients with Systemic Lupus Erythematosus Treated with Two Different Regimens of Vitamin D Supplementation

BackgroundRecent studies highlight that Vitamin D (VD) may have an immunomodulatory action on T cells, inhibiting Th-1 and Th-17 response and enhancing Th-2 and Treg function. After repeated antigenic presentation,...

AB0432 Overlapping neuropsychiatric manifestations in patients with systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is a systemic disease of the connective tissue that is characterized bydamages of all organs and systems. Lesions of the nervous system in relation to the...

SAT0236 Role of serological markers at baseline and follow-up in predicting biopsy proven lupus nephritis

BackgroundStudies have shown that 30-50% of SLE patients (pts) develop lupus nephritis (LN). Patients with high affinity anti-dsDNA antibodies (abs) are more likely to develop LN. The Farr radioimmunoassay is...

THU0178 Circulating free protein S levels may be linked to cardiovascular events and venous thrombosis in SLE

BackgroundSLE patients are at risk for diverse organ systems involvement, which increases the challenges for diagnosis and predictions for the development of specific clinical features. In recent studies we have...

Sex hormones and gender influence the expression of Foxp3 and regulatory T cells in SLE patients (115.18)

Abstract Regulatory T cells have been implicated in the maintenance of immune tolerance. Whether sex hormones and gender influence the expression of FoxP3 and regulatory T cells remain obscure. We provide the first evidence in this study that numbers and percent expression of regulatory T cells are significantly reduced in healthy females compared to healthy males. We found that both CD4+CD25+hi and CD8+CD25hi+ subsets of healthy males had 3-4-fold higher Foxp3 mRNA compared to healthy females. Estrogen increases proinflammatory cytokines and plasma estradiol positively correlated with IL-21 in SLE pts. Levels of estradiol positively correlated with SLEDAI score. Testosterone level was decreased in SLE women compared to healthy women. Furthermore, testosterone significantly increased FoxP3 expression in CD4+CD25hi cells from women with SLE. Plasma concentrations of testosterone positively correlated with the expression of FoxP3 in Treg. These data demonstrate that women may be more susceptible than men to SLE and other autoimmune diseases in part because many healthy women have fewer regulatory T cells and less FoxP3 expression. In addition, women with SLE, compared to healthy women, seem to have less ability to generate CD4+ Treg in response to physiologic concentrations of 17b-estradiol, whereas testosterone metabolite increases the generation of Tregs. These data suggest that gender and sex hormones influence susceptibility to SLE via their effects on Treg and Foxp3 expression.

Modulation of active oxygen forms production by circulating phagocytes and clinical efficacy of glucocorticoid treatment in patients with systemic lupus erythematosus

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Atherogenic effect of systemic lupus erythematosus pts blood serum

Objective. To study relation of SLE pts blood serum atherogenicity to disease activity and corticosteroids (CS) administration. Methods. 40 young women with SLE were included. 20 of them did not received CS (group 1) and 20 were treated with small doses of CS (<15 mg/day) for a long time (group 2). Duration of the disease was longer in group 2 and SLEDAI indexes were higher in group 1. Control group consisted of 20 healthy women. Serum atherogenicity was examined in BALB/c mice peritoneal macrophages culture by accumulation of intracellular cholesterol (CH) induced by pts blood serum. Results. Most of pts blood serum (90%) and only 15% control blood serum possessed atherogenic potential causing 2-fold rise of intracellular cholesterol level. Frequency of serum atherogenic activity in pts having SLE for a long time was higher. Serum atherogenic activity in group 1 was higher than in group 2 (221±13% and 185±11 % respectively, p=0,044). Atherogenicity correlated with SLEDAI index (r=0,82, p=0,04). No correlation was found between atherogenicity and lipid fractions. Conclusion. Serum atherogenecity is directly dependent on disease activity what shows the significance of immunological changes in atherogenesis in SLE pts

CELEBREX IN TREATMENT OF VERTEBRAL PAIN SYNDROME IN SYSTEMICV LUPUS ERYTHEMATOSUS

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

LIPID-PROTEIN/YSTEMS OF TRANSPORTATION OF BLOOD CIOLESTEROL IN PATIENTS WITH SYSTEMIClUPUS ERYTHEMATOSUS DEPEND1N5AJN ANTIPHOSPHOLIPID SYNDROME

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Autoantibodies to the mRNA destabilizing protein hnRNP-D/AUF1 in patients with systemic autoimmune diseases

The heterogeneus nuclear ribonucleoprotein (hnRNP) D, which is also known as AU-rich element binding factor 1 (AUF1), decreases stability of many short-lived mRNAs (including mRNAs of IL-1 and TNFa) by binding to adenosine and uridine rich sequences (ARE) contained in their 3'-untranslated regions. Previous studies had indicated this protein to be recognized by sera from patients RA, SLE and MCTD. To investigate this autoimmune response in greater detail 356 sera from patients (pts) with various rheumatic disorders were tested by immunoblotting employing the recombinant 45 kDa variant of D/AUF1 (the largest of the 4 known D/AUF1 proteins). Autoantibodies (aab) were detected in 20% of RA pts (n = 105), 34% of SLE pts (n = 70), 17% of MCTD pts (n = 31) and in 25% of pts with primary Sjoegren's syndrome (n = 21), but in less than 5% of 129 pts with other rheumatic disorders and not at all in healthy controls. Importantly, anti-D/AUF1 aab were already present in 25% of 60 patients with early RA of less than 6 months duration, whereas only one of 40 non-RA patients with other forms of early arthritis showed this antibody. Epitope mapping studies showed the aab to be directed to conformational epitopes in the N-terminal part of hnRNP-D/AUF1 known to be indispensable for the protein's function. However, aab did not interfere with RNA binding as assessed by gel shift assays employing the ARE of the TNFa mRNA. Instead, they were able to supershift protein-RNA complexes indicating binding sites for RNA and aab to be distinct. Thus, these findings suggest that anti-D/AUF1 aab target the mRNA decay complex which may form another large ribonucleoprotein target structure in systemic autoimmunity. We are tempted to speculate that increased formation of such complexes (e.g. due to overexpression of instable mRNAs such as those for IL-1 and TNFa as seen in RA) may lead to pathologic autoimmune reactions against D/AUF1 and other proteins of mRNA decay complexes.