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Background:Type I interferons and other inflammatory mediators derived from plasmacytoid dendritic cells (pDCs) are implicated in systemic lupus erythematous (SLE) pathology. BIIB059 is a humanized monoclonal antibody that targets blood dendritic cell antigen 2 (BDCA2), a pDC-specific receptor. The binding of BIIB059 to BDCA2 leads to rapid internalization of BDCA2 from the surface of pDCs and subsequent inhibition of interferon, cytokine, and chemokine production. In Part A of the 2-part, phase 2 LILAC study (NCT02847598), BIIB059 significantly reduced SLE activity, as evidenced by reduced total active joint count (primary endpoint) and higher SLE Responder Index (SRI-4)1 response (a secondary endpoint) versus placebo.2Objectives:To evaluate SRI-4 response for BIIB059 versus placebo at Week 24 in SLE participant subgroups.Methods:Enrollment in LILAC Part A was open to adults fulfilling ≥ 4 of 11 revised 1997 ACR criteria for classification of SLE, with ≥ 4 tender and ≥ 4 swollen joints, active skin disease, and positive lupus antibodies. Participants were randomized to receive either BIIB059 450 mg or placebo subcutaneously every 4 weeks for 20 weeks (with an additional dose at Week 2). SRI-4 response at Week 24 was analyzed in subgroups, though analyses were limited by small sample sizes and were not powered for statistical testing.Results:In LILAC Part A, 64 and 56 participants were dosed with BIIB059 450 mg and placebo, respectively. At week 24, SRI-4 response rate was observed in favor of BIIB059 regardless of the baseline disease activity, such as SLEDAI-2K 2Conclusion:BIIB059 treatment was associated with greater SRI-4 response rate, consistent among different subgroups of baseline disease activity as measured by SLEDAI-2K and BILAG-2004, glucocorticoid dosage, and serology. These findings provide additional evidence of the potential benefit of BIIB059 for the treatment of patients with active SLE.References:[1]Furie RA, et al. Arthritis Rheum. 2009;61(9):1143-1151. 2. Furie RA, et al. Arthritis Rheumatol. 2020;72(suppl 10). Abstract 0935.Acknowledgements:This study was sponsored by Biogen (Cambridge, MA, USA). Writing and editorial support was provided by Excel Scientific Solutions (Fairfield, CT, USA); funding was provided by Biogen.Disclosure of Interests:Ronald van Vollenhoven Consultant of: AbbVie, AstraZeneca, Biotest, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, UCB, Grant/research support from: AbbVie, Arthrogen, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, UCB, Richard Furie Consultant of: Biogen, Grant/research support from: Biogen, Kenneth Kalunian Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, Equillium, Genentech, Gilead, ILTOO, Janssen, Nektar, Roche, Viela, Grant/research support from: Lupus Research Alliance, Pfizer, Sanford Consortium, Sandra Navarra Speakers bureau: Astellas, Johnson & Johnson, Novartis, Pfizer, Consultant of: Biogen, Grant/research support from: Biogen, Juanita Romero-Diaz Consultant of: Biogen, Boehringer Ingelheim, Victoria Werth Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Gilead, GlaxoSmithKline, Janssen, Kyowa Kirin, Resolve, Viela, Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, XIAOBI HUANG Shareholder of: Biogen, Employee of: Biogen, HUA CARROLL Shareholder of: Biogen, Employee of: Biogen, Cristina Musselli Shareholder of: Biogen, Employee of: Biogen, Catherine Barbey Shareholder of: Biogen, Employee of: Biogen, NATHALIE FRANCHIMONT Shareholder of: Biogen, OMass Therapeutics, Employee of: Biogen

Background:Systemic Lupus Erythematous (SLE) is a clinically and biologically diverse disease, for which only one new therapy has been approved in the past 60 years. In a phase 2 trial on patients with mild-to-moderate SLE, ustekinumab (UST) improved clinical and laboratory measures of disease activity compared with placebo (PBO).1Objectives:We previously reported an association of IFN-γ reduction with response to UST,2suggesting an impact on the IL12/Th1 axis. To extend these findings, we performed unbiased transcriptomic analysis from baseline whole blood samples to identify genes that discriminate UST responders (UST-R) from non-responders (UST-NR) using the primary endpoint of Systemic Lupus Erythematosus Responder Index (SRI)-4 at week 24 to define response.Methods:UST was studied in a Ph2 PBO-controlled study of 102 patients with seropositive SLE and active disease despite standard therapy. Patients were randomized 3:2 to receive IV UST 6 mg/kg or placebo followed by subcutaneous injections of UST 90 mg or PBO every 8 weeks. Whole blood gene expression at baseline was measured via microarray using RNA samples from 100 patients, as samples from 2 patients failed quality control. An unbiased approach was used to identify gene signatures present at baseline that associate with UST response. Recombinant IL-12 or IL-23 was incubatedin vitrowith whole blood from 6 healthy donors for 24h and RNA-Seq was performed to determine the effect of these treatments on representative genes comprising the UST response signature.Results:A non-biased machine learning algorithm identified a 9-gene whole blood signature composed primarily of cytotoxic cell-associated transcripts (PRF1, KLRD1, GZMH, NKG7, GNLY, FGFBP2, TRGC2, TARP, TRGV2) that was enriched at baseline in UST-R vs UST-NR. By Gene Set Variation Analysis, the cytotoxic signature enrichment in UST-NR was less at baseline than both UST-R and a healthy control cohort (P=0.0087, P=0.056, respectively), whereas UST-R cytotoxic gene enrichment was similar to healthy controls (P=0.31). No significant difference in cytotoxic signature enrichment was observed at baseline between PBO responders and PBO non-responders or healthy controls (Figure). Enrichment levels of the cytotoxic gene signature remained stable over time in PBO and UST-NR groups while a trend of decreased cytotoxic signature was observed in UST-R, although never reaching levels seen in UST-NR. To begin to understand the relationship between IL-12 and IL-23, the targets of UST, and the cytotoxic signature, whole blood was stimulated with these cytokinesin vitro. Recombinant IL-12, but not IL-23, resulted in increased expression of representative members of this cytotoxic gene signature.Conclusion:We identified a novel cytotoxic signature in baseline blood samples that associated with UST response in SLE. The observation that IL-12 can increase this signaturein vitroand that IL-12 is a robust inducer of cytotoxic cell activity3as well as IFN-γ3suggests an important role of IL-12 blockade in the mechanism of action of UST in SLE.References:[1]van Vollenhoven RF. Lancet. 2018;392:1330-39[2]Jordan. ACR 2018 Abstract # 2951[3]G. Trinchieri. Nat Rev Immunol. 2003;3:133-46Figure.Disclosure of Interests:Loqmane Seridi Employee of: Janssen Research & Development, LLC, Matteo Cesaroni Employee of: Janssen Research & Development, LLC, Matthew J Loza Employee of: Janssen Research & Development, LLC, Jessica Schreiter Employee of: Janssen Research & Development, LLC, Kristen Sweet Employee of: Janssen Research & Development, LLC, Yevgeniya Orlovsky Employee of: Janssen Research & Development, LLC, Spring House, PA, United States of America, Isabelle Baribaud Employee of: Janssen Research & Development, LLC, Ashley Orillion Employee of: Janssen Research & Development, LLC, Peter Lipsky Consultant of: Horizon Therapeutics, Ronald van Vollenhoven Grant/research support from: AbbVie, Amgen, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline (GSK), Janssen Research & Development, LLC, Lilly, Pfizer, Roche, and UCB, Consultant of: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, UCB and Vertex, Speakers bureau: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, Vertex, Bevra H. Hahn Grant/research support from: Janssen Research & Development, LLC, George Tsokos Grant/research support from: Janssen Research & Development, LLC, Marc Chevrier Employee of: Janssen Research & Development, LLC, Shawn Rose Employee of: Janssen Research & Development, LLC, Frederic Baribaud Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, Jarrat Jordan Employee of: Janssen Research & Development, LLC

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease with wide clinical variability. Brazil has vast regional diversity, both from an ethnic and socio-cultural point of view.Objectives:To map the clinical profile of SLE in Brazil and explore how this distribution is associated with regional disparities.Methods:This cross-sectional study (GSK Study 207353) evaluated 300 Brazilian patients ≥18 years old with SLE (American College of Rheumatology [ACR] criteria, 1997) who had been under SLE care for ≥1 year. Five SLE reference teaching facilities were selected, one in each of the following Brazilian regions: North (NO), Northeast (NE), Midwest (CO), Southeast (SE), and South (SU). Each region included 60 patients. Clinical and demographic characteristics, and patterns of care were measured through questionnaires completed by physicians or nurses. The SLE Disease Activity Index (SLEDAI) score described disease activity and the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) described damage accrual. To assess the potential association between regional disparities and clinical outcomes, a hospitalisation profile was described. A bootstrapping approach of logistic regression was used to explore potential factors associated with hospitalisation.Results:Overall, 92.3% of patients were female, with a mean (standard deviation; SD) age of 41.8 (12.7) years and a mean (SD) disease duration of 11.8 (7.9) years. Overall, 161 (53.7%) patients were of Latino origin; in the NO this proportion was 88%. White patients predominated in the SU (58.3%); and black patients in the SE (31.7%). The mean (SD) number of years of schooling was 11.3 (4.6), and was highest in the NO (14.2 [3.6]) and lowest in the SU (9.0 [4.0]; pConclusion:This nationwide study highlights ethnic, social, and patterns-of-care disparities among Brazilian patients with SLE. The modelling shows evidence that such disparities contribute to the divergent clinical spectrum observed in Brazil.Funding:GSKFigure 1.Distribution of the A) Brazilian SLE clinical profile according to the ACR Classification Criteria and B) Brazilian prescriptive profile for SLE treatment according to the use of immunosuppressive drugs, biological agents, and corticosteroids during the study (12 months)ANA, antinuclear antibodyAcknowledgements:Medical writing assistance was provided by Helen Taylor, Fishawack Indicia Ltd., UK, part of Fishawack Health, and was funded by GSK.Disclosure of Interests:Mirhelen Abreu Grant/research support from: GSK, Amgen, Biogen, Libbs, Odirlei Monticielo Speakers bureau: GSK, AbbVie, UCB, Roche, Novartis, Consultant of: GSK, AbbVie, Janssen, Vander Fernandes Speakers bureau: Janssen, Novartis, Roche, AbbVie, Pfizer, Grant/research support from: Novartis, GSK, Pfizer, Alexandre Cristovão Maiorano: None declared, Fernando dos Santos Beserra: None declared, Flavia Lamarao Employee of: GSK, Nathalie David Shareholder of: GSK, Employee of: GSK, Bruna de Veras Employee of: GSK, Blanca Bica: None declared, Domingos Sávio Nunes de Lima Grant/research support from: GSK, Marta Maria das Chagas Medeiros: None declared

Background:Continuous monitoring of patients with Systemic lupus erythematosus (SLE) provides relevant informationObjectives:To update the analysis of clinical and immunological characteristics associated with time to severe renal involvement in patients with Systemic Lupus Erythematous in a Colombian cohort followed from January 2015 to October 2020Methods:A retrospective follow-up study based on clinical records. Patients with SLE diagnosis fulfilled either 1987 American College of Rheumatology Classification Criteria for SLE or 2011 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE. We included patients with the diagnosis of lupus nephritis according to Wallace and Dubois criteria. Patients who did not have at least two follow-up measurements or had a cause of nephritis other than lupus were excluded. The primary outcome was defined as the time from diagnosis to severe renal involvement defined as creatinine clearance ≤50ml/min, 24-hour proteinuria ≥3.5 grams o end-stage renal disease. Updated age and sex-adjusted survival functions and Hazard ratios (HR) with 95% confidence intervals and p-values were estimated using parametric Weibull models for interval-censored data. P values Results:548 patients were analyzed: 67 were left-censored as they presented renal involvement at entry, 25 were interval censored as outcome occurred between study visits (19 new events), and 456 were right-censored as involvement was not registered during follow-up. In this cohort update Age and sex-adjusted Hazard Ratios for high blood pressure were HR = 3.1 (95%CI 1.5-6.3; p-value = 0.003) and Anti-RO (per unit increase) HR = 1.003 (95%CI 1.001-1.005; p-value = 0.029). Figure 1 shows the updated age and sex-adjusted survival functionConclusion:In this cohort update, we found similar clinical and immunological characteristics associated with time to severe renal involvement in SLE patients to those reported in (1). However, continuous follow-up allows us to deepen our understanding of the progression to severe renal involvement in SLE patientsReferences:[1]Herrera S, Diaz-Coronado JC, Rojas-Gualdrón D, Betancur-Vasquez L, Gonzalez-Hurtado D, Gonzalez-Arango J, et al. SAT0210 factors associated with time to severe lupus nephritis in a cohort of colombian patients. Ann Rheum Dis. junio de 2020;79(Suppl 1):1048.2-1048Disclosure of Interests:None declared

Background:A disease model of systemic lupus erythematosus (SLE) that predicts short-term outcomes (disease activity and prednisone use) and links them to long-term outcomes (accrual of organ damage and mortality) was previously developed in a single center SLE cohort (Johns Hopkins [JH]) to support health economic analyses (Watson 2015), which has not been comprehensively replicated in other cohorts or contexts.Objectives:As part of an effort to develop and refine this existing disease model, the aim of this study was to replicate the previously estimated network of risk equations for short- and long-term outcomes in the SLICC Inception Cohort, an international cohort of patients (33 centers,11 countries).Methods:The SLICC Inception Cohort enrolled patients fulfilling ACR Classification Criteria for SLE within 15 months of diagnosis from 1999-2011 with annual follow-up through April 2020. The network of risk equations included two linear random effects models to predict (1) change in annual average Systemic Lupus Disease Activity Index (SLEDAI) score based on patient characteristics and the presence of renal, hematological, and immunological involvement in the prior year and (2) average annual prednisone dose based on SLEDAI score in the same year. These equations were then linked to parametric survival models that predicted time to the occurrence of organ damage (system-specific based on the ACR/SLICC Damage Index) and mortality. We compared model performance between the SLICC Cohort and the original analysis from the JH Cohort.Results:In comparison to the JH cohort (N=1354), the SLICC cohort (N=1697) had a smaller fraction of patients of African descent (39% vs 17%) and shorter disease duration at entry (4.8 vs 0.5 years). In the first equation predicting change in annual SLEDAI score, predictors were generally aligned with the same direction and significance, with the exception of renal involvement in the prior period, which had a positive association with change in SLEDAI in the SLICC cohort but was negatively associated in the JH cohort (Table 1). The second equation predicting prednisone dose was also consistent with the original analysis showing a significant positive association between higher disease activity and prednisone use. In all of the parametric survival analyses (individual organ damage and mortality models), coefficients were generally in the same direction and magnitude, though some were no longer significant in the SLICC cohort.Conclusion:The relationships identified in the original analysis were broadly replicated in the SLICC Inception Cohort. Observed differences may reflect differences in the patient populations, structure of the two cohorts (prevalent vs inception), and frequency of visits (quarterly visits in the JH cohort vs annual visits with the SLICC cohort may more closely capture a decrease in SLEDAI associated with treatment specifically related to renal involvement). Additional analyses relaxing the requirement to completely align with the original structure are underway to further assess the predictive accuracy of these models.References:[1]Watson P, et al. Rheumatology (Oxford). 2015;54(4):623-32.JH Cohort(N=1354)SLICC Cohort(N=1697)Female, %92.988.8African descent, %38.816.7Disease duration at entry, mean (SD), years4.8 (6.3)0.5 (0.3)SLEDAI at first visit, mean (SD)3.7 (4.1)5.4 (5.4)Change in average annual SLEDAICoefficientCoefficientConstant1.491*5.762*Annual average SLEDAI in prior period−0.460*−0.755*Male gender−0.080−0.207Log transformation of age−0.241*−1.134*Renal involvement in prior period−0.301*0.627*African descent0.383*0.126Increased DNA binding in prior period0.276*0.939*Low complement in prior period0.484*0.775*Hematological involvement in prior period0.104−0.025Anemia in prior period0.152**0.144Associated annual average prednisone dose (mg/day)Constant3.475*2.738*SLEDAI in same period0.777*0.648**pAcknowledgements:We acknowledge the support on this abstract of the following investigators of the Systemic Lupus International Collaborating Clinics:John Hanly - john.hanly@nshealth.caCaroline Gordon - p.c.gordon@bham.ac.ukSang-Cheol Bae - scbae@hanyang.ac.krJuanita Romero-Diaz - juanita.romerodiaz@gmail.comJorge Sanchez-Guerrero - jorge.sanchez-guerrero@uhn.caSasha Bernatsky - sasha.bernatsky@mcgill.caAnn Clarke - aeclarke@ucalgary.caDaniel Wallace - dwallace@ucla.edu/danielwallac@gmail.comDavid Isenberg - d.isenberg@ucl.ac.ukAnisur Rahman - anisur.rahman@ucl.ac.ukJoan Merril - JTMmail@aol.comPaul Fortin - paul.fortin@crchudequebec.ulaval.caDafna Gladman - dafna.gladman@utoronto.caMurray Urowitz - m.urowitz@utoronto.caIan Bruce - ian.bruce@manchester.ac.ukMichelle Petri - mpetri@jhmi.eduEllen Ginzler - ellen.ginzler@downstate.eduMA Dooley - Mary_Dooley@med.unc.eduRosalind Ramsey-Godman - rgramsey@northwestern.eduSusan Manzi - susan.manzi@ahn.org; Susanmanzi@gmail.comAndreas Jonsen - andreas.jonsen@med.lu.seGraciela Alarcon - galarcon@uab.eduRonald van Vollenhoven - r.vanvollenhoven@amsterdamumc.nlCynthia Aranow - CAranow@Northwell.eduMeggan Mackay – mmackay@northwell.eduGuillermo Ruiz-Irastorza - r.irastorza@outlook.esSam Lim - sslim@emory.eduMurat Inanc - drinanc@istanbul.edu.tr; minanc2008@gmail.comKenneth Kalunian - kkalunian@ucsd.eduSoren Jacobsen - sj@dadlnet.dkChristine Peschken - christine.peschken@umanitoba.caDiane Kamen - kamend@musc.eduAnca Askanase - ada20@columbia.eduDisclosure of Interests:Ann E Clarke Consultant of: BMS, AstraZeneca, GSK, and Exagen Diagnostics., Yvan St-Pierre: None declared, Victoria Paly: None declared, Ian N. Bruce Speakers bureau: GSK, UCB, Consultant of: BMS, Eli Lilly, GSK, Astra Zeneca, Merck Serono; UCB, ILTOO, Aurinia, Grant/research support from: Genzyme/Sanofi, GSK, Roche, UCB, Chiara Malmberg: None declared, Andrew Briggs Speakers bureau: Alexion, AstraZeneca, Bayer, BMS, Daiichi Sankyo, Eisai, Gilead, GSK, Kite, Merck, Novartis, Rhythm, Roche, Sanofi, Takeda, Consultant of: Alexion, AstraZeneca, Bayer, BMS, Daiichi Sankyo, Eisai, Gilead, GSK, Kite, Merck, Novartis, Rhythm, Roche, Sanofi, Takeda, Yuanhui Zhang Shareholder of: Bristol Myers Squibb., Employee of: Bristol Myers Squibb., Jiyoon Choi Shareholder of: JNJ., Employee of: BMS, Alan Brennan Consultant of: Alan Brennan is a paid consultant on advisory boards regarding cost-effectiveness modelling., Grant/research support from: Alan Brennan received research grants.

Objectives Most indices of disease activity in SLE combine physicians assessments and laboratory tests. However, there is also a need to capture patients perspectives of disease activity. Consequently, we need new, preferably quick and easy instruments to collect this information, which can be very useful for online consultations and registry purposes. We compared patients assessments of SLE disease impact/activity, as reported by a shorter version of the Quick Systemic Lupus Activity Questionnaire (Q-SLAQ), with physicians assessments using SLE Activity Measure (SLAM) and SLE Disease Activity Index (SLEDAI-2K) and with the original Systemic Lupus Activity Questionnaire (SLAQ). Methods Patients with SLE (n=115), with a disease duration of 15 years (IQR 17), completed the Q-SLAQ prior to physicians assessments by SLAM and SLEDAI-2K. A second set of patients (n=85) with similar characteristics filled out Q-SLAQ and SLAQ. Spearmans rho correlations were explored between patients total Q-SLAQ and subscales (Symptom Score, Patients Global Disease Activity) and physicians SLAM and SLEDAI-2K, with and without laboratory items (SLAM-nolab and SLEDAI-2K-nolab) and SLAQ. Corresponding items in Q-SLAQ and SLAM were compared. Results Correlations between patients and physicians assessments were higher for SLAM-nolab (total Q-SLAQ, rho=0.71; Symptom Score, rho=0.67; and Patients Global Disease Activity, rho=0.68) than for the original SLAM (total Q-SLAQ, rho=0.53; Symptom Score, rho=0.50; and Patients Global Disease Activity, rho=0.53). Regarding specific symptoms, fatigue (rho=0.72) and alopecia (rho=0.71) correlated best, while pulmonary/respiratory symptoms correlated least (rho=0.19, p=0.039). Physicians assessment with SLEDAI-2K-nolab correlated weakly with patients assessments (total Q-SLAQ, rho=0.30; Symptom Score, rho=0.30; and Patients Global Disease Activity, rho=0.36). Bivariate correlations between Q-SLAQ and SLAQ were good (rho=0.82-0.96). Conclusions Q-SLAQ and the original SLAQ performed equally well, demonstrating that the shorter Q-SLAQ can safely be used to monitor patients perception of disease impact/activity. We also noted an intriguing discrepancy between physicians and patients evaluations of pulmonary/respiratory symptoms, which requires further investigations. Funding Agencies|Swedish Rheumatism Association; King Gustaf Vs 80-year Foundation; Swedish Society of Medicine; Ingegerd Johansson Donation; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2018-02535]; Region Ostergotland (ALF); Stockholm County Council (ALF)Stockholm County Council; Selander Foundation; Gustafsson foundation Karolinska Institutet; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation

2019 antiphospholipid syndrome (APS) guideline1 has been launched and has given recommendations to the rheumatologists on how to manage APS in different situations. The guideline has been presented in detail but there are still some questions remain to be discussed. For example, we are still confused in some circumstances, in secondary APS, such as systemic lupus erythematous, glucocorticoids (GC) is widely used. But according to the guideline in primary APS, GC treatment is recommended only in first trimester of pregnancy or in catastrophic APS (CAPS). But …

The 2019 European League against rheumatism/American College of Rheumatology classification criteria (EULAR/ACR 2019 criteria) for systemic lupus erythematosus (SLE) has introduced a new scoring system to classify SLE.1 The EULAR/ACR 2019 criteria include positive antinuclear antibody at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical and three immunological domains and weighted from 2 to 10. Patients fulfilling at least one clinical criterion and accumulating ≥10 points are classified. In validation cohort, a classification threshold score of ≥10 yielded a sensitivity similar to that of the Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria (96.1% vs 96.7%) and a specificity similar to that of the ACR 1997 criteria (93.4% vs 93.4%), demonstrating both excellent sensitivity and specificity. However, we have two concerns about its additive criteria and methodology. First, some gastrointestinal injuries related to SLE, especially lupus enteritis, may be underestimated. Gastrointestinal symptoms are reported to occur in more than 50% of patients with SLE at some point in the course of their disease; …

Early scientific and public enthusiasm for hydroxychloroquine (HCQ) as a potential therapy for COVID-19 has prompted over 100 registered trials to date, although its efficacy remains to be demonstrated.1 Unfortunately, accelerated demand for HCQ has the potential to diminish supplies for patients with systemic lupus erythematosus (SLE), which is worrisome due to the known risks of SLE flare after HCQ withdrawal.2 We previously reported that rheumatologists in most Canadian provinces observed HCQ shortages early in the COVID-19 pandemic.3 However, data are lacking on the global experience with HCQ access during the pandemic, specifically in SLE. On 4 May 2020, we distributed an electronic survey to the 42 Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) members affiliated with SLE referral centres (https://sliccgroup.org), with reminders after 1 and 3 weeks. Physicians were asked about experiences with HCQ shortages during the COVID-19 pandemic, and whether they had been contacted by patients and/or pharmacists regarding difficulties accessing HCQ. Physicians who answered ‘yes’ to the latter question were asked to estimate how many and what proportion …

Background:The Systemic Lupus International Collaborating Clinics (SLICC) Frailty Index (SLICC-FI) has been developed as a predictor of outcomes in SLE patients1-3. However, it needs to be validated in several populations.Objectives:To evaluate the SLICC-FI as a predictor of future damage accrual in systemic lupus erythematosus (SLE) patients.Methods:Patients from a single-center prevalent cohort were included. Damage accrual was defined as the increase in SLICC/American College of Rheumatology (ACR) damage index (SDI) scores between the baseline and last visits. The SLICC-FI was measured at baseline. Univariable and multivariable negative binomial regression were performed to determine the association between the baseline SLICC-FI (per 0.05 increase) and damage accrual during follow-up, adjusted for sex, age at diagnosis, socioeconomic status, disease duration, SLE Disease Activity Index 2000 (SLEDAI-2K), SDI, prednisone daily dose, antimalarial and immunosuppressive drug use at baseline, and duration of follow-up.Results:Of the 265 patients included, 248 (93.6%) were female with mean (SD) age 35.1 (13.6) years at diagnosis. At baseline, mean (SD) SLE disease duration was 7.3 (6.5) years, SDI was 1.1 (1.3) and SLEDAI-2K was 5.3 (4.6). The mean (SD) baseline SLICC-FI was 0.22 (0.05). After a mean (SD) of 5.2 (2.2) years of follow-up, the SDI increased in 126 (47.5%) patients, and the final mean (SD) SDI score was 1.7 (1.7). Higher SLICC-FI scores at baseline predicted greater damage accrual in the univariable analysis [Incidence Rate Ratio (IRR)=1.283, (CI95% 1.072-1.536); p=0.007]. The SLICC-FI remained associated with damage accrual in the multivariable model, after adjustment for possible confounders [IRR= 1.224 (CI95% 1.007-1.488); p=0.042].Conclusion:The SLICC-FI predicts damage accrual in prevalent SLE, supporting the relevance of this index in the evaluation of SLE patients. This is the first study validating the SLICC-FI in South American populationReferences:[1]Legge A, Kirkland S, Rockwood K, et al. Construction of a Frailty Index as a Novel Health Measure in Systemic Lupus Erythematosus. J Rheumatol. 2020; 47: 72-81[2]Legge A, Kirkland S, Rockwood K, et al. Evaluating the Properties of a Frailty Index and Its Association With Mortality Risk Among Patients With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019; 71: 1297-107[3]Legge A, Kirkland S, Rockwood K, et al. Prediction of Damage Accrual in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC-FI). Arthitis Rheumatol. Epub ahead of print 2019 Oct 21.Disclosure of Interests:Manuel F. Ugarte-Gil Grant/research support from: Jannsen, Pfizer, Rocío Violeta Gamboa Cárdenas Grant/research support from: Pfizer, Cristina Reategui Sokolova: None declared, Victor Pimentel-Quiroz: None declared, Mariela Medina Chinchon: None declared, Claudia Elera-Fitzcarrald Consultant of: Tecnofarma, Jose Alfaro Lozano Speakers bureau: Lilly, Zoila Rodriguez Bellido: None declared, Cesar Pastor Asurza: None declared, Risto Perich Campos Consultant of: Pfizer, Speakers bureau: Pfizer, Graciela S Alarcon: None declared

Background:Systemic lupus erythematosus is an autoimmune disease with a major impact on patient’s quality of life.Objectives:To evaluate patient’s attitude toward early disease and factors that influence it.Methods:Performed case-control study included SLE patients that fulfilled SLICC, 2012 classification criteria. The research included two groups of patients: early SLE – 1stgroup (disease duration ≤24 months) and non-early SLE – 2ndgroup control (disease duration >24 months). The pattern of the disease activity was assessed by patient global assessment (PGA), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus Activity Measure (SLAM), for SLE activity, SLICC/ACR Damage Index (DI) for disease irreversible changes and SF-8 for the Quality of Life (QoL).Results:A total of 101 SLE patients with 34 in the 1stgroup (early SLE) and 67 in the 2ndgroup (non-early SLE) was analyzed. The disease activity showed high disease activity in both groups by SLEDAI (7,02±4,16 and 6,26±4,43 points, p>0,05) and SLAM (7,47±4,40 and 7,31±4,10 points, p>0,05) such as (46,97±19,39 vs 47,98±22,41 points). The QoL was appreciated as low, by both components (mental and physical), in groups. The damage index was higher in the 2nd group (0,23±0,43 and 1,07±1,29, pThe PGA in early SLE was influenced by subjective symptoms contained in SLAM index (r=0,48, p2 years), was influenced by the presence of organ damage by SLICC/ACR DI (0,23, pConclusion:The disease recognition in patients with early SLE was determined by subjective and psycho-emotional signs, while in patients with longer disease duration it was influenced by organ damage and complications.References:no referencesDisclosure of Interests:None declared

Background:Based on the characteristics of systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH), Sunet alhas put forward a scoring system to distinguish two clinical phenotypes as vasculitic and vasculopathic subtypes[1]. A weighted score ≥2 suggested a vasculitic subtype by combining two factors: The time interval between SLE and PAH diagnosis 9, 5-9 and Objectives:To find out the prognosis of two distinct clinical phenotypes of SLE-PAH.Methods:Between 2008 and 2019, a SLE-PAH cohort confirmed by right heart catheterization (RHC) from Guangdong Provincial People’s Hospital was included. Other groups of pulmonary hypertension were excluded. Based on the scoring system, patients were divided into vasculitic (weighted score≥2) and vasculopathic subtypes (weighted scoreResults:A total of 53 SLE-PAH patients were enrolled. The cases of vasculitic and vasculopathic subtype were 14 and 39, respectively. Ten endpoint events occurred. Eight attributed to PAH and the cause could not be traced in two which were still included in study. The pooled 1-, 3-, 5-year survival rates were 85.7%, 78.6%, 65.5% in vasculitic subtype, and 93.9%, 87.5%, 87.5% in vasculopathic subtype, respectively. Kaplan-Meier analysis showed vasculitic subtype tended to have a poorer prognosis than vasculopathic subtype (p=0.16, HR 2.4, 95%CI 0.5-13.8, figure 1).Figure 1.Survival curves for patients with systemic lupus erythematosus-pulmonary arterial hypertension (SLE-PAH) in two distinct subtypes. RHC, Right Heart Catheterization.Conclusion:The prognosis of the two phenotypes of SLE-PAH was statistically indifferent while the vasculitic subtype showed a trend of worse prognosis. Further studies are needed.References:[1]F. Sun, Y. Lei, W. Wu, L. Guo, K. Wang, Z. Chen, W. Xu, X. Wang, T. Li, X. Zhang, S. Ye, Two distinct clinical phenotypes of pulmonary arterial hypertension secondary to systemic lupus erythematosus, Ann Rheum Dis 78(1) (2019) 148-150.[2]J. Qian, M. Li, J. Zhao, Q. Wang, Z. Tian, X. Zeng, Inflammation in SLE-PAH: good news or not?, Ann Rheum Dis (2018).0:1–2. doi:10.1136/annrheumdis-2018-214605Disclosure of Interests:None declared

Recently, a series of letters has been published in the Annals of the Rheumatic Diseases 1–10 in response to an article by Pisetsky et al on the variability of indirect immunofluorescence (IIF) assays for testing for antinuclear antibodies (ANAs) in systemic lupus erythematodes (SLE).11 This discussion has focused on the merits and shortcomings of different assays used in the detection of ANA. Only one of the contributions briefly addresses one of the key questions: ‘What is an ANA?’.3 Because the term ANA itself has been judged anachronistic and misleading by many,12 with efforts to replace it under way,13 14 this is not a trivial question to answer. Since the terminology around ANA has developed historically, it is useful to explore the contexts in which these terms originated in order to understand their original definition and the changes therein over time. From the late 1940s onwards research into the serology of SLE gradually led to the discovery that autoantibodies against components of the cells’ nucleus could be found in sera of SLE patients.13–21 Because the exact target antigens remained largely unknown at first (except for dsDNA and histone) Holman et al coined the term ‘antinuclear antibody’ or ANA for them.22 23 With the advent of IIF testing on HEp-2-cells as standard method for the detection of ANA, it …

BackgroundThe AVISE Connective Tissue Disease (CTD) test uses autoantibody, erythrocyte-bound C4d (EC4d) and B-cell-bound C4d (BC4d) levels to aid in diagnoses of SLE, other CTDs and fibromyalgia. We evaluated the utility of the AVISE CTD test in predicting SLE disease development and damage progression.MethodsPatients who had undergone AVISE CTD testing were assessed for SLE diagnosis by the Systemic Lupus International Collaborating Clinics (SLICC) and American College of Rheumatology criteria and for SLE damage by the Systemic Lupus International Collaborating Clinics Damage Index (SDI) at the time of AVISE testing (t=0) and 2 years later (t=2).ResultsAmong 117 patients without a previous diagnosis of SLE, 65% of patients who tested positive developed SLE at t=2, compared with 10.3% of patients who tested non-positive (pConclusionsThe AVISE CTD test can aid in SLE evaluation by predicting SLE disease development and future damage progression.

Post hoc analyses of the phase III trials of belimumab BLISS-521 and BLISS-762 revealed superiority of belimumab over placebo in patients with systemic lupus erythematosus (SLE) with high baseline disease activity, positive anti–double-stranded (ds)DNA titres and low complement levels, as well as in patients receiving corticosteroids.3 Later, real-life observations demonstrated that established organ damage prior to treatment initiation predicted reduced belimumab efficacy.4 We aimed at validating this finding in the BLISS-52 and BLISS-76 SLE populations. Access to data was granted by GlaxoSmithKline (Uxbridge, UK). In total, 1684 patients were included in the analysis. The BLISS-52 trial comprised 865 and the BLISS-76 trial 819 patients with SLE who were randomised to receive belimumab 1 mg/kg, belimumab 10 mg/kg or placebo, along with standard-of-care treatment. Organ damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI).5 Response to treatment was defined as fulfilment of the SLE responder index 4 (SRI-4) conditions at week 52 (primary endpoint of the BLISS trials).1 2 Patients who withdrew or required changes in the background therapy other than those permitted by protocol …

The association between systemic lupus erythematosus and other comorbidities has been extensively studied.1 2 Recently, an article written by Orsolini et al published in Annals of the Rheumatic Diseases commented that osteoporosis and fractures are frequently found in patients with systemic lupus erythematosus.3 Orsolini et al ’s article is a timely one and provides the updated concepts to the readers. Some points are discussed here. A cohort study in South Korea conducted by Kim et al reported that the incidence of fractures was higher in patients with systemic lupus erythematosus than those with non-lupus (19 vs 6.5 per 1000 person-years).4 A cohort study in USA conducted by Tedeschi …

The recent publication1 2 of the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria for the classification for systemic lupus erythematosus (SLE) provides an important reason to continue the dialogue on testing for antinuclear antibodies (ANA) that has appeared in Annals of the Rheumatic Diseases ( ARD ). Following our article on the variability of immunofluorescence assays (IFA) for testing ANA in SLE,3 the journal published a series of very interesting and informative letters addressing our findings and reporting on other experience in ANA testing.4–12 These letters have been important in alerting the field to the challenges in ANA testing and the variety of assay approaches, including solid phase assays (SPA), that are currently available for determining the serological status of patients. While our focus was the clinical trial setting, our results are also relevant to the new classification criteria.1 2 These criteria differ from previous classification systems in the positioning of a positive ANA. Whereas a positive ANA represented one criterion in the ACR and Systemic Lupus International Collaborating Clinics criteria,13 14 in the new EULAR/ACR criteria, a positive ANA is necessary for classification; if this criterion is met, other manifestations receive varying numbers of points to determine classification. Such a positioning implies that SLE is always ANA positive, that a negative ANA can …

The new 2019 SLE European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) have been recently published.1 These criteria have been developed to find a better equilibrium between specificity and sensitivity compared with the previous criteria (SLE ACR-19972 and SLE Systemic Lupus International Collaborating Clinics (SLICC)3). Even if these criteria have been built for classification, they could be useful in clinical practice in patients with a suspicion of systemic autoimmune disease (AID) to differentiate patients with SLE from patients with another systemic AID, such as primary Sjogren’s syndrome (pSS), scleroderma or myositis. SLE and pSS share biological and clinical similarities. In clinical practice, it is frequently difficult to differentiate these two diseases. Moreover, SLE and Sjogren’s syndrome (SS) may overlap. The aim of this study was to explore the utility of the 2019 SLE EULAR/ACR criteria compared with the …

The correspondence on our study is very much appreciated.1 We have shown that the microvesicles (MVs) in the serum from patients with systemic lupus erythematisus *(SLE) contain higher concentration of double strand DNA (dsDNA) and have higher interferon-stimulated gene (ISG)-inducing activity than healthy controls. In the letter from Liu et al , authors addressed several concerns regarding the use of serum-derived MVs in experiments since these may not represent the physiological MVs present in the circulation of patients with SLE.2 We agree that plasma is preferable for the preparation of MVs. However, reporter activity could not be evaluated using …

AimsTo determine whether the proportion of time systemic lupus erythematosus patients achieve remission/low disease activity state (LDAS) is associated with a better quality of life (QoL).Patients and methodsPatients from a well-established multiethnic, multicentre US cohort were included: remission: Systemic Lupus Activity Measure (SLAM) score=0, prednisone≤5 mg/day and no immunosuppressants); LDAS not in remission, SLAM score≤3, prednisone≤7.5 mg/day, no immunosuppressants; the combined proportion of time patients were in these states was the independent variable. The endpoints were the Physical and Mental Components Summary measures (PCS and MCS, respectively) and the individual subscales of the Short Form (SF)-36 at the last visit. Linear regression was used to estimate the association between the proportion of follow-up time in remission/LDAS and the SF-36 measures with and without adjustment for possible confounders.ResultsFour hundred and eighty-three patients were included. The per cent of time on remission/LDAS was associated with better QoL after adjusting for potential confounders; for the PCS the parameter estimate was 9.47 (pConclusionsThe per cent of time lupus patients stay on remission/LDAS is associated with a better QoL as measured by SF-36.

Current treatment options for systemic lupus erythaematosus (SLE) are diverse and poorly defined, and aggressive therapy can be associated with serious toxicity and tolerability issues. There is, therefore, a need for new and improved treatments to be studied thoroughly in well-designed controlled trials. B Cell dysfunction has emerged as a key pathophysiological component of SLE and is a prime target for the development of new agents for a wide range of lupus severity, including advanced disease. Although many current drugs appear to modify B cell function, the advent of new, targeted therapies offers the hope of improved efficacy and a better long-term tolerability profile.

Objectives To determine factors associated with damage accrual in a prospective cohort of patients with SLE. Methods Patients with SLE who attended the Lupus Clinic at Monash Health, Australia, between 2007 and 2013 were studied. Clinical variables included disease activity (Systemic Lupus Erythematosus Disease Activity Index-2K, SLEDAI-2K), time-adjusted mean SLEDAI, cumulative glucocorticoid dose and organ damage (Systemic Lupus International Collaborating Clinics Damage Index (SDI)). Multivariate logistic regression analyses were performed to identify factors associated with damage accrual. Results A total of 162 patients were observed over a median (IQR) 3.6 (2.0–4.7) years. Seventy-five per cent (n=121) of patients received glucocorticoids. Damage accrual was significantly more frequent in glucocorticoid-exposed patients (42% vs 15%, p

Background Musculoskeletal Ultrasound Assessment (US) is increasingly used as a valid and reliable tool for guiding the management of inflammatory arthritides. However its use in Systemic Lupus Erythematosous (SLE) and Sjogren9s Syndrome (SS) in clinical practice remains limited 1 , thus potentially missing an opportunity to appreciate severity of joint involvement and optimise management 2 . Objectives To analyse a real life cohort of SLE and SS patients referred for US assessment on clinical grounds, to review their characteristics and whether US assessment led to a change in treatment. Methods Retrospective analysis of real life data from a dedicated rheumatology US clinic at a tertiary referral hospital. The OMERACT scoring system was used for the US examination of 22 hand joints in every patient (wrists, metacarpo-phalangeal and proximal interphalangeal (PIP) joints bilaterally). Results Over a 2 year period (01/2014–12/2015) a total of 604 patients were scanned including 19 with SLE and 17 with SS. Patient characteristics and differences between their US outcomes are shown in table 1. US assessment prompted treatment change in 84% of SLE patients and 82% of SS cohort. ESR showed a better association with swollen joint count in SS (r=0.29) than SLE (r=0.17), however this did not reach statistical significance. A subanalysis of the SLE cohort showed poor correlation of the MSK BILAG items scores with active joint disease defined as PD presence on US (r=0.189, p=0.5). Conclusions US assessment led to significant change in management for both cohorts. The SLE group had more active disease on US than SS, despite similar swollen joint count and increased prednisolone. There was poor correlation of US disease activity and MSK BILAG in SLE patients, suggesting that US can provide additional information in identifying active joint disease. US proves a useful and reliable tool to monitor musculoskeletal features and therapeutic outcomes in both SLE and SS patients that can be used routinely in real life clinical practice. References Zayat AS et al. The role of ultrasound in assessing musculoskeletal symptoms of systemic lupus erythematosus: a systematic literature review. Rheumatology (Oxford). 2015 Oct 7 Mosca, M et al. The role of imaging in the evaluation of joint involvement in 102 consecutive patients with systemic lupus erythematosus. Autoimmun Rev. 2015 Jan;14(1):10–5 Disclosure of Interest None declared

Background Systemic Lupus Erythematous (SLE) and Sjogren Syndrome (SS) are autoimmune diseases that may exhibit several manifestations including an ocular involvement. Ocular involvement may be underestimated or be subclinical since current treatments as hydroxycloroquine and steroid may exert both beneficial and side effects on eyes. Objectives To assess the eye involvement in patients affected by autoimmune diseases as SLE and SS. Methods 48 patients affected by autoimmune diseases (29 SLE, 19 SS) without an active eye involvement were prospectively and consecutively enrolled. Morphological and functional eye assessment included: complete ophthalmogical examination, Spectral Domain Optical Coherence Tomography examination, fundus perimetry (FP), standard automated perimetry (SAP). 25 age and sex-matched healthy controls (HC) were also evaluated. Results SS patients displayed a reduction of mean retinal thickness in the posterior pole compared with HC and SLE (p=0.0003 and p=0.03, Fig.1A). This reduction was demonstrated in superior and inferior hemifield compared with HC (p=0.001 and p=0.007) and in superior hemifield compared with SLE (p=0.01) (Fig.1B-C). The FP mean differential sensitivity in SLE and SS patients was reduced compared with HC (p Conclusions In a small cohort of patients with autoimmune diseases without an overt active eye involvement a morphological alteration of the retinal posterior pole and functional impairment was demonstrated suggesting a subclinical involvement thatmight be concealed by the treatment. Disclosure of Interest None declared

Background Corticosteroid (CS) use has been identified as a key factor associated with damage in SLE but detailed analyses of patterns of use in large international cohorts have not previously been reported. Objectives To describe oral (PO) and parenteral CS use in a large international SLE cohort. Methods The SLICC Inception Cohort recruited patients within 15 months of developing ≥4 1997 American College of Rheumatology (ACR) criteria for SLE, between 2000 and 2011. Details of PO and parenteral steroid use were captured at enrolment and each annual assessment, including type, dose and course dates. All CS data was converted to prednisolone equivalents and analysed using Stata 13. Results 1848 patients have been recruited to the Cohort. Those with follow up data (1686) are included in this analysis, providing data on 10,572 annual follow-up (FU) intervals. The mean (SD) total FU is 6.72 (3.60) years; 1072 (63.5%) patients contributed ≥5 years FU; 343 (20.3%) contributed ≥10 years FU. The proportion of time spent on PO CS can be calculated for 10,098 (95.5%) FU intervals. For the majority of FU intervals (n=9103 (90.1%)), NONE (4494 (44.5%)) or ALL (4609 (45.6%)) of the time was spent on PO CS. In 995 (9.9%) FU intervals, only a proportion of the time was spent on PO CS. In those FU intervals where PO CS have been received (n=5604) the median (IQR) “average daily PO dose” was 6.5 (4.75–10) mg. The average daily CS dose decreased in later FU intervals: median (IQR) at FU 1=10 (5–15) mg and at FU 5=5.5 (4.8–10.0) mg. 558 (34.7%) patients have been on PO CS for ALL of their time in the study, 720 (44.8%) for some of it and 330 (20.5%) have never been on PO CS. 228 patients (13.5%) received parenteral CS prior to and/or at enrolment at a median (IQR) total dose of 1.5 (0.5–3.0) g. CS pulses were given during 429 (4.37%) FU intervals at a median (IQR) total dose of 679.5 (120–2500) mg. This compares to a median (IQR) cumulative total PO dose between FUs of 2565 (1575–4462) mg. PO CS use between FUs (using various definitions - see table 1) was higher in those FU intervals in which pulsed CS have also been given. Conclusions CS are widely prescribed in this international SLE cohort. 79.5% have been on CS at some point and 1 in 3 patients have taken CS throughout their entire disease duration. PO CS tend to be given at low daily doses for long periods of time but with a higher average daily dose earlier in the disease. Parenteral steroid use is associated with higher overall PO CS use, however PO CS contribute most to the total cumulative dose that patients receive. Current management of SLE still relies on CS use as a mainstay of therapy in a high proportion of patients. Acknowledgement The Systemic Lupus International Collaborating Clinics (SLICC) acknowledge funding support of UCB Pharma for this study. Disclosure of Interest None declared

Background Corticosteroids (CS) have been identified as a key factor associated with long term damage in systemic lupus erythematosus (SLE). The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) has been extensively validated and a previous analysis (Gladman et al J Rheumatol 2003;30:1955–9) suggested that SDI items can be grouped according to their likely association with CS. Objectives To generate international expert consensus opinion on which SDI items have an association with the use of CS. Methods We performed a Delphi exercise amongst SLICC members and associates. A survey requested expert opinions on how each SDI item was influenced by CS use on a Likert scale. The scale ranged from -3 to +3 where -3 = I believe that CS have a strong protective link with this item, 0 = I believe that CS have no effect on this item, +3 = I believe that CS have a strong causal link with this item. A second Delphi round presented each participant with their previous rating and the group median for that item, providing the opportunity for revision. A preliminary univariate analysis of CS exposure against damage was performed within the SLICC Inception Cohort to assess the appropriateness of these groupings and if any other items needed reclassifying. Results Of 43 members/associates, 36 respondents returned 26 complete forms (60.5%). All 26 completed the second round (100%) after which adequate consensus was reached. Four items (cataract, osteoporosis, avascular necrosis and diabetes mellitus) were assessed to be highly likely to be related to CS (median & mode =3, Table 1). Ten other items were “probably”/“possibly” CS related by expert opinion. The remaining items were felt not to be associated with CS. The univariate analysis supported these groupings and identified a significant association between CS exposure and the muscle atrophy/weakness item (e.g. OR (95% CI) 6.81 (1.91–24.27) if on steroids for all of intervening follow up period c.f. some or none of the period). It was agreed that muscle atrophy/weakness should be reclassified into the 9definite association9 group. Conclusions A consensus exercise based on expert opinion and initial analysis in an international inception cohort has generated a preliminary classification of the 42 SDI items according to their likely association with CS. This classification system requires further validation but will facilitate studies examining the impact of CS exposure on SLE populations. Acknowledgement The Systemic Lupus International Collaborating Clinics (SLICC) acknowledge funding support of UCB Pharma for this study. Disclosure of Interest None declared

Background Serotonin receptor 1A and 2A genes polymorphisms (HTR1A and HTR2A) have been associated to increased risk of depression and suicide. Hypomethylated HTR1A has been associated to Systemic Lupus Erythematosus (SLE) patients manifestations. Preliminary results in our cohort showed an association between HTR2A polymorphisms and SLE manifestations development risk and depression risk in SLE patients. Objectives To investigate the association of 5-HTR2A polymorphisms (rs6314, rs6313) and clinical organ involvement, specific antibodies expression and damage accrual and time to damage accrual in SLE patients. Methods 75 SLE patients were evaluated for 5-HTR2A polymorphisms rs6314 and rs6313, by a Taqman assay and PCR-RFLP methodology, respectively. SLE diagnosis was based in ACR 1999 criteria, the organic involvement and specific antibodies were reviewed in the charts (Cumulative SLE manifestations for genetic studies) and damage was assessed by SDI (Systemic Lupus International Collaborating Clinics - Damage Index). Statistical analysis was made with SPSS 22.0. Results 75 SLE patients (70 female) with a mean age of diagnosis of 29.55 years old (SD 12.0) and mean follow-up time of 17,39 years (SD 7,70). Mucocutaneous involvement occurred in 88%, articular 85,3%, renal 46,7%, 30,7% neuropsychiatric. 38 patients (50,7%) had organ damage acrrual with a mean time to first damage accrual of 3,75 years (SD 6,88). 7 (9,3%) accrued renal damage and 15 (20%) neuropsychiatric. Polymorphism distribution was rs6313 (CC 22,7%, CT 54,7% e TT 14,7%) and rs 6314 (CC 86,7%, CT 13,3%). No association was found between these polymorphisms and any clinical involvement, cytopenias, antibodies, damage accrual or time to damage. Neuropsychiatric damage accrual was earlier in patients carrying CC rs6314. Conclusions Contradictory results are a very common phenomena in studies of complex diseases mainly due to the interaction fo several genes. Although poorly studied the serotonin receptor and transporter genes have been linked to SLE development and depression in SLE patients. In our study, there was no relation between any clinical or serological manifestations and the rs6313 and rs6314 HTR2A polymorphism but the earlier neuropsychiatric damage accrual opens a window of doubt of what might be the role of serotonin in SLE heterogeneity. Disclosure of Interest None declared

Background Juvenile-onset systemic lupus erythematosus (JSLE) is a severe multi-system inflammatory disease with very varied presentation and disease course. Diverse clinical manifestations means classification of JSLE can prove challenging. The Systemic Lupus International Collaborating Clinics (SLICC) group proposed revised classification criteria for systemic lupus erythematosus (SLICC-2012 criteria) 1 . Objectives This study aimed to compare the SLICC-2012 criteria with the widely used American College of Rheumatology classification criteria (ACR-1997 criteria) 2.3 in a national cohort of JSLE patients and evaluate how classification criteria that individual patients meet evolved over time. Methods Data from patients in the UK JSLE Cohort Study with a senior clinician diagnosis of probable, evolving or definite JSLE was reviewed. Patients were classified using both criteria within one year of diagnosis and at latest follow-up (following a minimum twelve month follow-up period). Sensitivity of each classification criteria was compared using McNemar9s test. Results 226 patients were included. The SLICC-2012 was more sensitive than ACR-1997 at diagnosis (92.9% vs 84.1% p Conclusions The SLICC-2012 was better able to classify patients with JSLE than the ACR-1997 and did so at an earlier stage in their disease course. SLICC-2012 should be considered for classification of JSLE patients for the purpose of observational studies and clinical trial eligibility. It may also be useful in daily practice to corroborate clinician diagnosis of JSLE. References Petri M, Orbai A, Alarcon G, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012;64:2677–86. Hochberg M. Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725. Tan E, Cohen A, Fries J, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271–7. Acknowledgement This abstract is written on behalf of the UK JSLE Study Group. We would like to thank all of the patients and their families for participating in this study, and acknowledge the support given by all of the multidisciplinary teams within each paediatric centre. In addition, special recognition is made to LUPUS UK for financially supporting the UK JSLE Study Group. Special recognition also goes to Mrs Carla Roberts for her continued support of the UK JSLE Cohort Study and Mr Duncan Appleby for database and information technology support. Disclosure of Interest None declared

Background Remission is the ultimate goal in SLE. However, after more than 50 years of research on this topic, no agreement on the definition of remission has been widely accepted. Developing definition(s) of remission was one of the primary research recommendations of the treat-to-target (T2T/SLE) international task force. Definitions of remission were agreed on by an international collaboration from the DORIS working group [1]. Objectives In this study, we applied four DORIS definitions of remission to a large cohort to determine the time to remission, duration of remission and predictors of remission. Methods The four DORIS definitions of remission are Clinical Remission, Complete Remission, Clinical ROT (remission on treatment) and Complete ROT. Any definition requires the clinical Systemic Lupus Disease Activity Index (cSLEDAI), meaning without serology, to be 0 and the Physician Global Assessment (PGA) to be Results The median time to remission is 8.7, 11, 1.8 and 3.1 years for Clinical Remission, Complete Remission, Clinical ROT and Complete ROT, respectively. High baseline treatment is the major predictor of a longer time to remission, followed by high baseline activity (Figure). The median duration of remission is just three months. Surprisingly, this is quite similar for all the definitions. African-American ethnicity, baseline low C3 and baseline hematologic activity are negative predictors for time to remission for all definitions. Baseline anti-dsDNA and baseline low C4 are negative predictors for Complete Remission and for Complete ROT. Baseline low C4 is also a negative predictor for Clinical Remission. In multivariable models, income and education were not significant after controlling for race. Furthermore, we did not find a significant association for sex, age group and the use of hydroxychloroquine. Conclusions Our results provide further insights into the frequency and duration of remission in SLE and call attention to the major role of baseline activity and baseline treatment in predicting remission. References van Vollenhoven RF, Aranow C, Bertsias G, et al., Remission in SLE: consensus findings from a large international panel on definitions of remission in SLE (DORIS). Ann Rheum Dis 2015;73:671 Disclosure of Interest None declared

Background The current use of the SLICC classification criteria for juvenile systemic lupus erythematosus (jSLE) is extrapolated from an adult-validated study.1 Efforts have been conducted to validate its applicability in the pediatric population.2,3 Objectives To validate the SLICC classification criteria among juvenile SLE patients Methods A diagnostic criteria validity study was conducted. Medical records of 50%) of the individual subspecialist assessments. The clinical diagnosis of the team of attending physicians, with at least 1 pediatric rheumatologist, was used as the gold standard. The sensitivity, specificity and number of misclassified cases were determined. Results The sensitivity of the SLICC criteria is at 94.0% (95%CI 88.9-97.2), and specificity at 96.7% (95%CI 92.4-98.9) in the cohort of Filipino jSLE patients. One-forty-one cases were correctly classified as jSLE, while 145 controls were correctly classified as non-jSLE. There were 9 false negatives, while 5 controls were false positives. Conclusions The SLICC classification criteria is a valid guide for clinical practitioners to diagnose patients afflicted with jSLE. References Petri, M et al. Arthritis & Rheumatism 2012; 64: 2677-2686. Fonesca, AR et al. Rheumatology. 2014. doi:10.1093/rheumatology/keu278. Sag, E at al. Clinical and Experimental Rheumatology. 2014 June; 32 (3): 440-444. Acknowledgements Dr. Pauline Camposano, Dr. Carien-Gulay-Carvajal, Dr. Christine Bernal, Dr. Karen Cruz, Dr. Shanida Camomot, and Dr. Maria Kristine Belen-Ciabal Disclosure of Interest None declared

Biological therapies have transformed the paradigm of treatment of several inflammatory rheumatic diseases such as rheumatoid arthritis, spondyloarthritis, vasculitis or systemic lupus, among others. Since the first TNF antagonists, numerous molecules targeting other immune pathways (IL-1, IL-6, IL-17, IL-12/IL-23, B Lymphocytes and co-stimulation) have become broadly available and the use of biologics is increasing worldwide. Nevertheless, blocking and neutralizing major pro-inflammatory pathways, depleting B-cells and interfering with T-cell function lowers the threshold for infections. In fact, patients on biologics are at higher risk of infectious complications, including serious infections and rare opportunistic infections. This risk is not the same for all biologics, nor for all patients, and it represents a real issue that clinicians should be aware of, recognize promptly and anticipate whenever appropriated. This lecture aims to provide an overview of current knowledge on the infectious risk associated with the use of biologics, in particular of viral infections. Importantly, preventive strategies will be addressed. Disclosure of Interest None declared

Background Developing definition(s) of remission in SLE is one of the primary recommendations on the research agenda of the treat-to-taget (T2T/SLE) international task force [1] as it is required to apply the important principle of T2T to SLE. Definitions of remission were agreed on by an international collaboration from the EULAR working group. Objectives We applied the definitions from the EULAR working group to a large clinical cohort to determine the distribution of time to remission, durability and predictors of remission. Methods Remission was defined as clinical Systemic Lupus Disease Activity Index (SLEDAI) =0, with Physician Global Assessment (PGA) ≤0.5, prednisone ≤5 mg per day and no immunosuppression. Remission on treatment (ROT) was defined as clinical SLEDAI =0, with PGA ≤0.5, prednisone ≤5 mg per day and allowance of immunosuppressives. Hydroxychloroquine was allowed for remission and ROT. The Kaplan-Meier approach was used to estimate the distribution of time until remission among patients who entered the cohort with disease activity. In addition, for patients on treatment, we identified variables that were predictive of remission in the next two visits. Results The median time to remission was 2.8 years in women and 5.7 years in men, whereas the median time to ROT was 1.3 years in women and 2.1 years in men. Of those who satisfied the definition of remission, 59% had a relapse manifested at a clinic visit within the next 90 days, and 15% more had a relapse from 90 to 180 days post remission. Only 11% had a remission lasting over one year. Considering patients treated with immunosuppressives or prednisone greater than 5 mg/day at one visit, 2.8% successfully tapered treatment and achieved remission over the next two visits. The table below shows rates of remission in various subgroups. Conclusions 50% of women and men with SLE achieve remission within 2.8 years and 5.7 years, respectively. However, most of them experience a relapse within the next 90 days. This reflects the relapsing-remitting nature of SLE for many patients. Remission and remisson on treatment are frequent in SLE. Durable remission, though, is rare. Only 11% will have durability of more than one year. African-American ethnicity, anti-dsDNA or low complement predict against achieving remission. Our results provide further insights into the nature of remission in SLE and contribute towards applying the treat-to-target principle to SLE. References van Vollenhoven, R.F., et al., Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis, 2014. 73(6): p. 958-67. Disclosure of Interest None declared

Background Primary Sjogren Syndrome (pSS) and Systemic Lupus Erythematosus (SLE) express a significant overlap in their clinical and immunological aspects. Moreover, SS often presents clinical and immunological manifestations included in the SLE classification criteria. A secondary SS (diagnosis according to AECG criteria) has been described in about 9-19% of SLE cases. Few data is available regarding the prevalence of a true overlap of the two disorders. Objectives To investigate the prevalence of patients with pSS who can be classified as having an overlap syndrome with SLE considering both the 1997-revised ACR criteria and the new criteria proposed in 2012 by the Systemic Lupus International Collaborating Clinics (SLICC). Methods Charts from patients with pSS (diagnosis according to AECG criteria) were retrospectively evaluated in order to collect clinical and laboratory data. Results Two-hundred seventy patients with pSS [8M, 262 F, mean age 57.8±12,5 years, mean age at diagnosis 52.6 years ±12.5, mean follow-up 5.6 years (range 0–42 years)] were considered. Taking into account the 1997-ACR criteria, 11 patients (4.1%) could be classified as having an overlap with SLE (SS-SLE). Considering the new SLICC criteria, the number of patients raise to 18 (6.7%). Both considering the old and the new criteria, the most frequent items satisfied by the SS-SLE group were: ANA, leukopenia, oral ulcer and arthritis (Table). The items responsible for the increasing number of patients fulfilling the new criteria were low complement and the presence of leukopenia, thrombocytopenia or hemolytic anemia since these are considered separately in the new criteria. Compared to the remaining patients with pSS (246 F, 8M, mean age at diagnosis 53.3±12.4 years), the SS-SLE group (18 F, mean age at pSS diagnosis 47.9±13.1 years) showed a significantly higher frequency of leukopenia (77.7% in SS-SLE vs 14.2% in pSS; p Conclusions The occurrence of a true overlap between SS and SLE is relatively infrequent and the new SLICC criteria may allow a higher sensitivity to detect such condition. The items responsible for the increased sensitivity are both the introduction of hyopocomplementemia and the separate consideration of different hematological disorders in the new classification criteria. In patients with SS-SLE, hypocomplementemia, leukopenia and arthritis appear to be the most frequent manifestations. Disclosure of Interest None declared

Background Anxiety and depression are frequent symptoms among children and adolescents with Systemic Lupus Eritematosus (SLE). Its impact and association with different factors require detailed analysis. Objectives The aim of this study was to determine the frequency of presentation of anxiety and depression symptoms in children and adolescents with SLE, as well as the association between these symptoms and their quality of life, disease activity index (SLEDAI) and immunosuppressant treatment. Methods SLE pediatric patients between 9 and 17 years of age were enrolled. They underwent an interview and had four variables evaluated: behavior abnormalities, immunosuppressant therapy, time of diagnosis, and SLEDAI. Data on depression and anxiety symptoms as well as quality of life were collected using the Children Depression Inventory (CDI), the Screen for Child Anxiety Related Disorders (SCARED) and the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q). Results 40 patients were included. Mean age was 14±2 years old. Mean time of SLE diagnosis was 22 months. In 52% of cases (n=21) signs of disease activity were found SLEDAI >5). 57% of patients (n=23) presented with anxiety and 37% (n=15) with depression. Finally, 37% (n=15) declared having suicidal ideation after SLE diagnosis. The mean PQ-LES-Q was 56,7 (SD ±7,32). Correlation analysis results showed a positive association between SCARED and CDI (p=0,009), with a weak correlation (correlation coefficient=0,4). As for SCARED and quality of life (PQ-LESQ), a weak negative correlation was found, which was not statistically significant (p=0,13). Analysis association between CDI and PQ-LES-Q evidenced a strong negative correlation (correlation coefficient= - 0,746) which was statistically significant (p 0,05). Likewise, analysis of anxiety and medications used for SLE treatment was made. It showed that use of prednisone was associated with a higher prevalence of anxiety symptoms (p=0,004). Nonetheless, when comparing mean corticosteroid dose, it was observed that prednisone dose has no association with the presence or absence of psychiatric manifestations (p>0,05). Conclusions Anxiety is more likely to be present in pediatric patients with SLE than depression. Anxiety is a vulnerability factor for developing depression symptoms and is related with the use of corticosteroids regardless of the dose. SLE has a major impact on quality of life and this impact becomes greater in the presence of depression symptoms. Disclosure of Interest None declared

Background Systemic lupus erythematosus (SLE) is still burdened by a significant morbidity and mortality. Objectives To determine the prevalence of organ damage, with related risk factors, and mortality in a cohort of SLE patients. Methods The clinical records of patients fulfilling the American College of Rheumatology (ACR) criteria for SLE, followed for at least 1 year in our center were retrospectively reviewed. Organ damage was assessed by the Systemic Lupus International Collaborating Clinics/ACR Damage Index (DI) at 1 year after diagnosis and then every 5 years, from the beginning until the end of the follow-up in our center. Disease activity was measured by the SLE Disease Activity Index (SLEDAI) 2K at the beginning of the follow-up. The comparison of characteristics between patients with and without damage at the end of their follow-up was performed by the Chi Square9s, Fisher9s exact and Student9s t test as appropriate; p Results This study included 511 SLE patients (92% females, 95% Caucasians), followed in our Unit between 1972 and 2014, with a mean age at diagnosis of 33 years (±13) and a mean disease duration at the end of the follow-up of 16 (±9) years. One year after diagnosis 40% of patients with measurable DI (n=400) had accrued some damage and its prevalence gradually increased over time (Table I). At 1 year ocular (13%), central nervous system (12%) and skin (8%) damage were the most frequent whereas ocular, skin and musculoskeletal were the most frequent sites of damage (40%) at 35 years. Different features were significantly associated to damage (Table II). The main causes of death in 35 patients (7%) were cancer (33%) and organ failure (22%) after a mean disease duration of 13 years. Conclusions The organ damage that accumulates over time in SLE is partly linked to disease activity, partly defined by clinical profiles (neuro-SLE, renal disease and Antiphospholipid Syndrome) that may require aggressive treatments. New, more effective and less toxic drugs could limit the progression of this process. Disclosure of Interest None declared

Background Systemic lupus erytematosus (SLE) is more common in women (∼90% of SLE-patients) and in ∼50% of the patients was the diagnosis set ≤30 y age. The neurological symptoms are not seenvery frequently, but these may be difficult to relate in SLE, especially in emergency (ED). Objectives The aim of this study was to analyze the proportion of neurological SLE patients in a tertiary University Hospital ED 2003-2012. Methods We used Helsinki University Central Hospital Meilahti ED electrical database retrospectively. We search all the patients with the SLE diagnosis. The ED visit was interpreted as neurological if the charge for the treatment was allocated for neurologist. We analyzed also the need for the spinal fluid examination in ED. Data was compared statistically by Students9 T test for continous parameters and by Mann-Whitney U Test for noncontinous ones. The point for statistical significance was set at p Results 44 SLE patients (male7) made 254 visits in ED 2003-2012. 33% of visits (n=84) were related to SLE. 19% of visits (n=48) were classified as neurological, and 67% of these (n=32) were SLE-related. Spinal fluid examination in ED was needed in 6 visits; 1 bacterial meningitis, 1 septicaemia, 1 tetraparesis, 1 disorientation, 1 hemiparesis and 1 SLE-associated muscle disease. Female SLE patients (mean 6.2) visited almost twice as many times in ER than male ones (mean 3.7). Moreover thirteen female visited ≥7 times in ED as compared to one male. The difference between genders was not, however, significant, p=0.570 and p=0.850, respectively. Indeed SLE-patients with neurological symptoms visited in ED significantly more often than those without (p=0.007). Conclusions SLE was not extremely common diagnosis in our ED. Female SLE patients were overrepresented. In 2/3 patients with neurological symptoms seemed these to be SLE-related. SLE-patients with neurological symptoms visited more often in ED than those without. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2234

Objectives To determine the prevalence of antibodies to cyclic citrullinated peptides (anti-CCP) in patients with juvenile-onset systemic lupus erythematosus (JSLE) and its potential clinical significance. Methods Anti-CCP was measured in sera from patients with JSLE (n=47), juvenile idiopathic arthritis (JIA, n=54) and the sera from age-matched healthy children (n-40) using the third generation of anti-CCP ELISA commercial kit. The association of anti-CCP with other laboratory parameters and clinical features, especially arthritic symptoms in JSLE was also analyzed. T-test, Mann-Whitney U test, Chi-square and Fisher9s exact test were used for statistical analysis. Results Out of the 47 JSLE patients, 6 (13%) were anti-CCP positive,which was significantly higher than that of the healthy controls (13% vs 0, P 0.05). As one of the initial symptoms, arthritis was ohserved in 25 of 47 JSLE patients and no one had developed deforming athropathy. There was no statistical difference in anti-CCP positivity between JSLE patients with and without articular involvement (16% vs 9%, P>0.05). Anti-CCP was not detected in any of the 3 patients with JSLE who had experienced ioint pain and limited activity during 3 years foIlow-up. Conclusions Anti-CCP could be detected in patients with JSLE.It is noteworthy when differentiate from juvenile idiopathic arthritis, but the presence of anti-CCP does not relate with the occurrence of arthritis at presentation and persistence of arthritis in JSLE. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5615

Background Today, systemic lupus erythematodes (SLE) is a chronic disease with high survival rates, manageable in the majority of cases with immunosuppressive therapy. Objectives The aim of the study was to evaluate whether treatment regimens have changed in the last decade and if clinical features of the disease as well as patient-reported outcomes have improved. Methods Between 1993 and 2012, on average 1,166 patients with SLE were recorded annually in the National Database of the German Collaborative Arthritis Centres. Within this sample, we analysed two cohorts of patients who were enrolled in 1994-1998 (1st cohort, n=467) or 2004-2008 (2nd cohort, n=376) and followed for at least five years each. Differences in immunosuppressive treatment, disease activity (physician assessment on a numerical rating scale 0-10), global health and pain (patient assessment 0-10) were compared between the two cohorts. Cross-sectional data of all SLE patients were analysed to verify whether the two cohorts were representative of the entire database. Results The use of immunosuppressive therapy was more frequent in the 2nd cohort (see table). In particular, treatments with antimalarials and combinations of immunosuppressive drugs have increased significantly (p 7.5mg during follow up. One third of the patients were taking pain medication continuously during follow-up in both cohorts. The percentage of patients with a moderate or high disease activity (4-10) decreased significantly in the 2nd cohort (p Conclusions Comparing the two cohorts, immunosuppressive treatment regimens were intensified in the 2000s and a higher percentage of SLE patients achieved a low disease activity as assessed by the physicians. Nevertheless, the long term use of GCs and pain medication as well as the impaired patient reported pain and global health assessments reflect the need to further focus on these aspects in treatment strategies. Disclosure of Interest K. Albrecht Grant/research support: The database was funded by the German Federal Minister of Research from 1999 to 2007 (grant #01 GI 0344/3). Since 2007, the Working Group of the regional corporate arthritis centers and a consortium of pharmaceutical companies has been funding the National Database by an unconditional grant to the German Rheumatological Society., D. Huscher: None declared, S. Bischoff: None declared, K. Thiele: None declared, M. Backhaus: None declared, J. Richter: None declared, I. Kotter: None declared, A. Zink: None declared DOI 10.1136/annrheumdis-2014-eular.2223

Objectives The aim of the study was to determine clinical and epidemiologic features of SLE patients in Eastern Croatia during eleven years period. Methods The study was made retrospectively by exploration patients charts from our department archive as the most reliable source of SLE patients’ data in the region. Initial screening has identified SLE patients in general population, with confirmed diagnosis or patients with high probability of SLE but without confirmed diagnosis, in ten years period between 1.1.1995. and 31.12.2005. Further screening has separated patients with four or more diagnostic criteria, according to American College of Rheumatology revised diagnostic criteria from 1997. Patients who had passed second screening step were thoroughly examined and further selection was made. Patients with SLE as part of mixed collagen tissue disease, patients with discoid lupus, lupus like syndrome or incomplete lupus, and patients who were not residents of Eastern Croatia region, as well as patients who were not regularly controlled were excluded from additional investigation. Demographic data were obtained from Croatian State Institute of Statistics. Results Of 10.000 reviewed patients charts 228 SLE patients were identified and diagnosis was confirmed by revised ACR diagnostic criteria. 202 were females and 26 males (8:1), with an average age 41,8 years at onset of disease (fulfilling diagnostic criteria). Prevalence of SLE patients in eleven years period for three counties of Eastern Croatia was 36,27/100.000 residents (95% CI 16,1-56,4). The incidence rate of SLE for study period was 2,7/100.000 annually (95% CI 2,08-3,31). In eleven years period only 4 patients died because of SLE and complications related to SLE. The study also included cautious analysis of manifestation for each SLE diagnostic criteria in observed population. Conclusions This study was the first epidemiological study of SLE in Croatia. Results were generally comparable to previous similar studies in other European countries. A few differences could be explained by unequal methodology used in different studies or some specific features of observed population. Our results might be the groundwork for further investigations in Croatia and Europe. 1. Lahita RG. Introduction. U: Lahita RG, ur. Systemic Lupus Erythematosus. New York: John Walley and sons; 2004. 2. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725-1734. 3. Petri MD. Epidemiology of systemic lupus eythematosus. Best Pract Res Rheumatol 2002;16(5);847-858. 4. Cervera R, Khamashta MS, Font J i sur. Morbidity and mortality in systemic lupus erythematosus during 10-year period: comparison of early and late manifestations in cohort of 1,000 patients. Medicine (Baltimore) 2003;82(5):299-308. 5. Anic B, Cerovec M, Cikes N. Epidemiologic characteristics od 328 Croatian SLE patients based on ACR classification criteria. Lupus 2005;14(3):240. 6. Carvera R, Khamashta MA, Hughes GRV. The Euro-lupus project: epidemiology of SLE in Europe. Lupus 2009;18(10): 869-74. Disclosure of Interest None Declared

Background The prevalence of systemic lupus erythematosus (SLE) reported in European studies has varied widely. It will be useful to have good regional estimates of the prevalence of SLE to inform public health plans and resource allocation. Objectives To determine if a single estimate of the prevalence of SLE in Europe can be obtained from the critical review of European based studies. If not, the sources of variation will be described. Methods A broad literature search of EMBASE and MEDLINE content up until 28/09/2011 was conducted using the terms “systemic lupus erythematosus” and “prevalence”. To be included each study must (1)be a primary research study (2) assess point or period prevalence of SLE after 1982 (when American College of Rheumatology classification criteria for SLE1were published), (3)be set within a European country or region, (4) not restrict by criteria other than age. All identified titles were screened by hand and relevant manuscripts were reviewed; citations from these were reviewed to identify further papers. Studies meeting inclusion criteria were rated for quality (“high”, “intermediate” or “low”) based on case ascertainment methods, diagnostic criteria and representativeness. Random-effects meta-analysis to assess heterogeneity and to produce a pooled prevalence estimate was performed on “high” and “intermediate” quality studies using the software StatsDirect. Results The search yielded 2,949 citations; 58 manuscripts were reviewed by hand. A final 21 studies met the inclusion criteria, from which 11 of “high” and 2 of “intermediate” quality were selected for the meta-analysis. Prevalence estimates ranged from 18 per 100,000 to 71 per 100,000. One high quality study was dropped from the meta-analysis due to lack of a denominator figure in the text. The pooled random-effects prevalence estimate from the remaining 12 studies was 40 per 100,000 (95% CI 34, 46). Heterogeneity statistics (I2)indicated a very high degree of variability among the study estimates (Cochran Q=180.1, df =12, p 15 only (44 per 100,000; Q=140.4, df=7, p Conclusions The best estimate of the European SLE prevalence is 40 per 100,000 based on the current studies, although this estimate is still associated with substantial variability. Subsetting the studies into potentially more homogeneous groups (e.g. on time period, region or age) did not decrease the variability. References Tan EM, Cohen AS, Fries JF. The 1982 revised criteria for the classification of systemic lupus erythrematosus. Arthritis Rheum 1982;25(11):1271-1277. Disclosure of Interest J. Davidson Shareholder of: GlaxoSmithKline plc, Employee of: GlaxoSmithKline R&D, N. Galwey Shareholder of: Glaxosmithkline plc, Employee of: Glaxosmithkline R&D, P. Egger Shareholder of: GlaxoSmithKline plc, Employee of: Glaxosmithkline R&D

Objectives Arthritis is frequently seen in human lupus, but rarely in lupus models. Pristane-induced lupus (PIL) can be induced in various mouse strains such as BALB/c and C57Bl/6. We herein characterize clinical and histological features of arthritis in the context of systemic lupus and provide a prudent comparison with models of rheumatoid arthritis (RA). Methods Arthritis is frequently seen in human lupus, but rarely in lupus models. Pristane-induced lupus (PIL) can be induced in various mouse strains such as BALB/c and C57Bl/6. We herein characterize clinical and histological features of arthritis in the context of systemic lupus and provide a prudent comparison with models of rheumatoid arthritis (RA). Results In BALB/c, clinical arthritis started at 3 months, occurred finally in 79% of PIL (but not in controls, p 0.7, p Conclusions PIL in BALB/c mice is characterized by severe organ involvement, typical auto-abs and by a mild-erosive arthritis with similarities, but also with distinct differences to RA. PIL may help to study arthritis along with other key features of SLE after therapeutic interventions or in knockout models based on a BALB/c, but not on a Bl/6 background. Disclosure of Interest None Declared

Background Post hoc analyses of belimumab BLISS trials identified baseline factors generally associated with high disease activity as predictors of improved response to treatment, such as SELENA-SLEDAI (SS)> 10, low complement levels, anti-dsDNA positivity and glucocorticoid therapy. Objectives We examined clinical outcomes in patients with high disease activity treated with belimumab in U.S. clinical practice settings in 2012. Methods OBSErve (BLM117295) is a multicenter retrospective medical chart review study. 92 rheumatologists from U.S. non-academic centers who treat >10 SLE patients annually and have >5 years of practice experience were randomly recruited. Physicians randomly identified adult SLE patients who had received ≥8 infusions of belimumab as part of usual-care. Index date is the first belimumab infusion date. This post-hoc analysis was conducted among patients with low complement and high anti-dsDNA, steroids ≥7.5mg/day, and SS>10 at index date. Results were reported for the 3 subgroups and the entire sample. The primary outcome was the change in overall SLE disease manifestations 6 months after index date based on physician judgement. Changes from index date in SS and oral steroid dose (when available at index date) were also analyzed. Results 501 eligible patient charts were abstracted. Key patient characteristics at index date were mean age 41.3 yrs; female 89%; Caucasian 53%, black/African American 24%, Hispanic 18%; and SLE disease duration≤5yrs 56%. 50% (n=252) had hypocomplementemia and high anti-dsDNA, 69% (n=347) had steroid dose≥7.5mg/day, and 86 (70%) out of 122 with available SS had SS>10 at index date. Physician impression of overall change in disease manifestations over 6 months was similar in the subgroups of high disease activity compared to the entire sample. Within the 3 subgroups, mean SS scores decline ranged from 6.8-7.5 (51-53%), and mean steroid reduction ranged from 11.5-15.0 mg/day (58-61%) over 6 months. Conclusions Among the SLE patients with markers of high disease activity treated with at least 6 months of belimumab in clinical practice settings, clinicians observed improvement in overall SLE clinical manifestations, reduction in SELENA-SLEDAI, and reduction in steroid dose 6 months after belimumab initiation with no control arm. Disclosure of Interest H. Kan Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, C. Collins Consultant for: GlaxoSmithKline, M. Dall’Era Consultant for: GlaxoSmithKline, M. McGuire Grant/research support from: GlaxoSmithKline, V. Koscielny Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, R. Pappu Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, C. Molta Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline

Background In general, pregnancy and delivery complications are more frequently observed in first pregnancy 1 . Most previous studies have not distinguished between first and subsequent births in analyses of pregnancy outcomes in SLE. Objectives To examine outcomes in first and subsequent births separately, in women with SLE versus references. Methods Women diagnosed with SLE according to International Classification of Diseases (ICD-10) and registered in the Medical Birth Registry of Norway (MBRN) formed the exposed group. Reference deliveries were all other deliveries 1999 – 2009 excluding mothers with any inflammatory rheumatic disease. Data for single births were stratified and analyzed in first and subsequent births. First birth was the first delivery of nulliparous women for patients and references. SGA (newborn small for gestational age) was defined as birth weight Results Mean age at first delivery in SLE patients and references was 29,4 and 27,7 years, respectively (p Conclusions We observed a higher risk of low birth weight, preterm delivery, transfer to NICU, perinatal deaths and congenital malformations among the newborn of the patients. The greatest differences between groups were observed in the first pregnancy, and an increased risk of perinatal mortality among children of patients was only observed in first pregnancy. Our observations indicate that special attention should be given to first pregnancy in SLE patients. References: Cunningham FD, MacDonaldPC et al. Williams Obstetrics. 20 ed. Stamford, Connecticut, USA:1997 Acknowledgements The Medical Birth Registry of Norway (data delivery) The Liaison Committee between the Central Norway Regional Health Authority and NTNU (financial support) Disclosure of Interest : None Declared

Objectives To investigate the prevalence of the anti-ribosomal P (anti-P) antibodies in childhood-onset systemic lupus erythematosus patients (cSLE) and to elucidate the association between anti-P and disease activity, laboratory and treatment features in cSLE patients Methods We included consecutive SLE patients with disease onset before the age of 16 (cSLE), first-degree relatives and age and healthy age and sex matched controls. cSLE patients were assessed for disease activity [SLE Disease Activity Index (SLEDAI)], damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)] and current drug exposures. Mood disorders were determined through Becks Depression and Becks Anxiety Inventory (BDI and BAI). Anti-P was measured by enzyme-linked immunosorbent assay using commercial kits. Clinical/laboratorial manifestations, disease activity, cumulative damage and drugs undertaken were assessed at time of blood withdrawal Results We included 50 cSLE patients (mean age 16.82±3.46), 35 first-degree relatives (mean age 38.73±3.89) and 20 health controls (mean age 18.3±4.97). Anti-P was present in 13 (26%) cSLE patients. No first-degree relatives or controls presented anti-P (p Conclusions Anti-P is frequently observed in cSLE patients and was associated with anxiety in this cohort. Grants FAPESP: 2008/02917-0; 2009/13046-3 Disclosure of Interest H. Aldar Grant/Research support from: FAPESP 2009/13046-3, A. Lapa Grant/Research support from: FAPESP 2010/13639-1, B. Belini Grant/Research support from: FAPESP 2009/12343-4, N. Sinicato Grant/Research support from: FAPESP 2010/13637-9, M. Postal Grant/Research support from: FAPESP 2009/10744-1, P. Fernandes: None Declared, L. Costallat: None Declared, R. Marini: None Declared, S. Appenzeller Grant/Research support from: FAPESP 2008/02917-0; Conselho Nacional Pesquisa Desenvolvimento-Brasil CNPq (300447/2009-4)

Background The presence both of antiphospholipid antibodies (aPL) and anti-dsDNA is immunological features of diagnostic criteria of SLE. The level of anti-dsDNA usually reflects renal involvement of SLE and antiphospholipid antibodies (aPL) is associated with thrombotic events. Cross-reaction between these antibodies is discussed. Objectives To assess the frequency of anti-dsDNA, increasing of CIC, hypocomplementemie in SLE and APS (in primary and secondary) and their connection with anticardiolipin antibodies (aCL) and clinical manifestations of the disease. Methods We studied 365 patients in mean age 31,9±10,9 years (from 14 to 63yrs.) and disease duration 9,1±7,5years (from6 month to 36 yrs). SLE was diagnosed in 135 (56M, 79F) patients (ACR criteria, 1997) and 230 (55M, 175F) patients had APS. Secondary APS (SLE+APS) was in 156 of 230 patients and primary – in 74. Anti-dsDNA and aCL were measured by ELISA. CH50 was evaluated by 50% hemolytic activity. C3, C4 were determined by immunonephelometric assay, CIC – by turbidimetric assay with 3,5% PEG. Results High level of anti-dsDNA was found to have 80% of SLE patients (mean level 68,5±28,6 OD from 30 to 120) and it was associated with glomerulonephritis and hipocomplementemia. Increased levels of IgG-aCL were detected in 22% of SLE patients and IgM-aCL - in17%, but nobody of them had any APS features. There was correlation between IgG-aCL and anti-dsDNA, CIC and IgG. High level of anti-dsDNA was found in 75% of SLE+APS patients and it was correlated with activity disease estimating by SLEDAI score (35.2±14.2 vs 12.3±5.7) but not with renal involvement. Fifty six percent of 156 SLE+APS patients were IgG-aCL positive and 28% - IgM-aCL positive. Thrombosis were revealed in 48% of IgG-aCL positive SLE+APS patients and thrombocytopenia in 15% of IgM-aCL positive patients. Immunological abnormalities have revealed in 25% of 74 PAPS patients: 25% had false positive test for siphylis, 61% - high level of CIC, 7% -anti-DNA and 19% - hipocomplementemia. High level of anti-dsDNA in PAPS patients was associated with microvascular complication: digital necrosis and Rayunad’s phenomen. There was correlation between IgG-aCL and CIC in APS patients. Conclusions High level of anti-dsDNA in SLE patients associated with renal damage. There was correlation between the levels of anti-dsDNA with SLEDAI score in SLE+APS patients and wasn’t associated with renal involvement. Immunological abnormalities (CIC, low C3, C4) except aCL-positivity have revealed in PAPS patients. Disclosure of Interest None Declared

Objectives To describe the clinical and immunological features, the damage accrual and mortality of late onset compared with adult onset SLE. Methods The data was obtained from a long term prospective cohort of 353 patients diagnosed with SLE in the Rheumatology Department of Gregorio Maranon Hospital in Madrid, Spain. Demographic, clinical, and laboratory data were collected at disease onset and during it’s course from 1986 to 2006. Patients were divided into 2 groups: adult onset 19-49 years (n=276) and late onset ≥50 years (n=77). Organ damage was scored using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index. Results A total of 353 patients were recruited, with a following mean time of 11 years. The female to male ratio differed significantly (p=0.005) between groups. At diagnosis, the late-onset group presented cutaneous manifestations less frequently (p Conclusions Late onset SLE is clinically different with less arthritis, fever, low serum complement, cutaneous, hematologic and renal manifestations compared with the adult onset group. The higher frequency of damage accrual, mortality and hypertension observed in the late-onset group can be affected by aging-related factors other than disease activity or duration. Disclosure of Interest None Declared

Primary antiphospholipid syndrome (PAPS) is defined as patients with anti-phospholipid antibodies and thrombotic or obstetric symptoms, without systemic lupus erythematous (SLE) or other systemic rheumatic diseases. PAPS patients can have incomplete SLE-like features and some can evolve into SLE during follow-up. However, few studies systematically examined lupus autoantibodies and their clinical significance in PAPS. The aim of our study is to characterise lupus autoantibodies in PAPS to analyse their clinical and laboratory correlations …