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Background:Patients with systemic lupus erythematosus (SLE) experience a considerably impaired health-related quality of life (HRQoL) compared with the general population. Previous literature has implied an association between high body mass index (BMI) and HRQoL diminutions. However, data are scarce and further exploration in large study populations and, importantly, with regard to the clinical significance of this association is needed.Objectives:The aim of this study was to determine whether overweight and/or obesity were associated with impaired physical and/or mental HRQoL aspects in the SLE population of two large clinical trials.Methods:We utilised pooled baseline data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) clinical trials of belimumab (N=1684). Access to data was granted by GlaxoSmithKline. The patients were stratified into four groups based on their body mass index (BMI), according to WHO guidelines. We conducted comparisons between non-overweight versus overweight, and non-obese versus obese SLE patients. HRQoL was self-reported using the Medical Outcomes Study (MOS) short form 36 (SF-36) health survey, the functional assessment of chronic illness therapy (FACIT)-Fatigue scale and the three-level EuroQol- 5 Dimension (EQ-5D) questionnaire. We explored whether the differences in scores were clinically meaningful using previously determined thresholds for minimal clinically important differences (MCIDs). The non-parametric Mann-Whitney U test was used for comparisons between different BMI groups. Linear regression analysis was next applied to test independence in multivariable models, adjusting for age, sex, ethnicity, disease duration, disease activity, organ damage and standard of care treatment.Results:Forty-four per cent (44%) of the patients had a BMI score over the normal range, and 18% were obese. The overweight group performed worse than the non-overweight with regard to FACIT-Fatigue scores (mean ± standard deviation: 27.7 ± 12.1 vs 32.0 ± 11.3; PIn multivariable linear regression analysis, the overweight and obese group showed worse PCS scores (standardised coefficient: β=-0.09; PConclusion:BMI above normal was highly associated with HRQoL impairment, especially in physical aspects. Further survey to examine causality is warranted to support structured weight control strategies as an intervention towards a more favourable HRQoL.Disclosure of Interests:None declared

Recently, two different studies1 2 applied the criteria of the Lupus Low Disease Activity State (LLDAS)3 to the data sets of the BLISS-524 and BLISS-765 phase III trials of belimumab. The studies reported similar LLDAS attainment frequencies at key time points; however, not identical. We herein discuss possible explanations in order to guide future usage of the LLDAS. In the study by Parodis et al ,1 LLDAS at week 52 was achieved by 10.0% of the patients in BLISS-52 and 7.1% in BLISS-76, with a greater percentage within patients who received belimumab 10 mg/kg compared with patients who received placebo in BLISS-52 (11.9% vs 6.2%; p=0.030), but not in BLISS-76 (8.3% vs 6.4%; p=0.473). In the study by Oon et al ,2 LLDAS at week 52 was attained by 12.5% and 14.4% in the belimumab 10 mg/kg arm versus 5.8% and 7.8% in the placebo arm in BLISS-52 (p=0.02) and BLISS-76 (p=0.04), respectively. The small-scale differences …

Background:Myocardial infarction (MI) is estimated to be 2- to 3-fold elevated in systemic lupus erythematosus (SLE) as compared to gender- and age-matched controls (1-2). Even though some risk factors have been purposed, mechanisms of increased MI incidence remains to be determined.Objectives:To explore underlying mechanisms, we compared MI characteristics and risk factors between SLE patients with MI (MI-SLE), MI patients without SLE (MI-nonSLE) and SLE patients without MI (nonMI-SLE).Methods:We performed retrospective medical file review including angiography and echocardiography reports in 34 MI-SLE patients, 34 MI-nonSLE patients and 34 nonMI-SLE patients – all individually matched for gender and age in a ratio of 1:1:1.Results:Median age was 61 years and 88% were females. MI-SLE patients had more coronary arteries involved (table 1; p=0.038), and ≥50% coronary atherosclerosis/occlusion at MI was numerically more common compared to MI-nonSLE controls (88% versus 66%; p=0.065). The left anterior descending artery was most frequently involved in both MI groups (73% versus 59%; p=0.11). Decreased (Conclusion:We demonstrate that non-procedural MIs in SLE are in 88% of cases associated with significant coronary atherosclerosis. Increased prevalence of CAD prior MI and higher number of coronary arteries involved at MI, suggest accelerated coronary atherosclerosis in SLE patients. This calls for attentive surveillance of CVD and early atheroprotective treatment in this patients group.References:[1]Hak AE et al. Systemic lupus erythematosus and the risk of cardiovascular disease: Results from the nurses’ health study. Arthritis and rheumatism 2009;61:1396-402.[2]Fischer LM et. Effect of rheumatoid arthritis or systemic lupus erythematosus on the risk of first-time acute myocardial infarction. The American journal of cardiology 2004;93:198-200.Table 1.MI characteristicsMI-SLENtotalMI-nonSLENtotalP-valueECG findingsNSTEMI23 (72%)3221 (66%)321.0 STEMIPresence of atherosclerosis9 (28%)3211 (34%)32 0-VD3 (12%)2610 (35%)290.065 MI-CAD (≥1-VD)Number of involved arteries23 (88%)2619 (66%)29 0-VD3 (12%)2610 (35%)290.038 1-VD13 (50%)269 (31%)29 ≥2-VD10 (39%)2610 (35%)29Involvement of specific arteriesLMCA3 (12%)260 (0%)290.50 LAD19 (73%)2617 (59%)290.11 RCA7 (27%)269 (31%)290.75 Cx6 (23%)266 (21%)291.0Left ventricular ejection fraction 13 (45%)2912 (36%)330.79 ≥50%16 (55%)2921 (64%)330-VD = 0-Vessel disease. 1-VD = 1-Vessel disease. 2-VD = 2-Vessel disease. Cx = Circumflex artery. LAD = Left anterior descending artery. LMCA = Left main coronary artery. MI-CAD = MI with coronary artery disease. NSTEMI = Non-ST-elevation MI. RCA = Right coronary artery. STEMI = ST-elevation MI.Disclosure of Interests:Isak Samuelsson: None declared, Ioannis Parodis Grant/research support from: The author declare that he has no conflict of interest related to this work, Iva Gunnarsson Grant/research support from: The author declare that she has no conflict of interest related to this work, Agneta Zickert: None declared, Claes Hofman-Bang: None declared, Håkan Wallén Grant/research support from: The author declare that he has no conflict of interest related to this work, Elisabet Svenungsson Grant/research support from: The author declare that she has no conflict of interest related to this work

Background:Despite improvements in medical care that have contributed to prolonged life expectancy for people living with systemic lupus erythematosus (SLE) over the past decades, they still suffer from substantial diminutions of health-related quality of life (HRQoL) compared with the general population and with other chronic diseases.Some studies have demonstrated that conventional synthetic and biological disease-modifying agents contribute to improvements in SLE patients’ HRQoL, and responders to treatment have been shown to report greater improvements than non-responders. Although these observations are clinically relevant, improvement following a therapeutic intervention does not necessarily signify that the individual has achieved a satisfactory health state perception. In rheumatoid arthritis, significant pain and severe fatigue persist in a substantial proportion of patients who achieve a good clinical response to treatment or remission. This paradoxical observation has not been thoroughly explored in SLE.Objectives:To determine the prevalence of adverse HRQoL outcomes in patients with SLE who achieved an adequate clinical response after a 52-week long period on standard therapy plus belimumab or placebo, within the frame of two phase III clinical trials. We further aimed to compare frequencies of adverse HRQoL outcomes across different age categories and ethnic groups, and sought to identify contributing factors.Methods:We included patients who met the primary endpoint of the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials (N=760/1684), i.e. attainment of the SLE Responder Index 4 at week 52. Accordingly, evaluation of adverse HRQoL outcomes was based on patient reports at week 52 from treatment initiation, using the Medical Outcomes Study Short Form 36 (SF-36) health survey and the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-Fatigue) scale. Adverse HRQoL outcomes were defined as (i) SF-36 scale scores ≤ the 5th percentile derived from age- and sex-matched US population-based norms from the SF-36 health survey user manual; and (ii) FACIT-Fatigue scores Pearson’s chi-square or Fisher’s exact tests were used to investigate associations between dichotomous variables. Comparisons of continuous data between SLE patients and age- and sex-matched norms were performed using the Wilcoxon signed-rank test. Multivariable logistic regression models were created in order to assess independence and priority of potential factors associated with adverse HRQoL outcomes.Results:We found clinically important diminutions of HRQoL in SLE patients compared with matched norms and high frequencies of adverse HRQoL outcomes, the highest in SF-36 general health (29.1%), followed by FACIT-Fatigue (25.8%) and SF-36 physical functioning (25.4%). Overall, frequencies were higher with increasing age. Black/African American and White/Caucasian patients reported higher frequencies than Asians and Indigenous Americans, while Hispanics experienced adverse HRQoL less frequently than non-Hispanics. Increasing organ damage was associated with adverse physical but not mental HRQoL outcomes; disease activity showed no impact. In multivariable logistic regression analysis, addition of belimumab to standard therapy was associated with lower frequencies of adverse SF-36 physical functioning (OR: 0.59; 95% CI: 0.39–0.91; P=0.016) and FACIT-F (OR: 0.53; 95% CI: 0.34–0.81; P=0.004).Conclusion:Substantial proportions of SLE patients reported adverse HRQoL outcomes despite adequate clinical response to treatment, especially in physical aspects. Particularly high proportions were seen within Black/African American and White/Caucasian patients. Add-on belimumab may be protective against adverse physical functioning and severe fatigue. Our results corroborate that HRQoL diminutions constitute a substantial burden in patients with SLE, and highlight the limitations of current therapeutic strategies.Acknowledgements:The authors would like to thank GlaxoSmithKline (Uxbridge, UK) for sharing the data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials with the Clinical Study Data Request (CSDR) consortium, Dimitris Ladakis, Joaquin Matilla and Martin Pehr for contributing to the management of data, as well as all participating patients.Disclosure of Interests:Alvaro Gomez: None declared, Julius Lindblom: None declared, Victor Qiu: None declared, Arvid Cederlund: None declared, Alexander Borg: None declared, Sharzad Emamikia: None declared, Yvonne Enman: None declared, Jon Lampa: None declared, Ioannis Parodis Grant/research support from: Research funding and/or honoraria from Amgen, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline and Novartis.

Background:Immunogenicity related to treatment with TNF inhibitors (TNFi) is one of the causes for the decreased attainment of clinical response in patients with rheumatoid arthritis (RA)1. However, the involved mechanism is not entirely clear. The B-cell activating factor (BAFF) may play a role in the development of immunogenicity2.Objectives:To analyse the association between baseline serum BAFF concentration and the development of immunogenicity within 6 months (m) of TNFi treatment in patients with RA.Methods:A total of 121 patients with RA initiated at standard doses of TNFi (infliximab (n=64), adalimumab (n=13), golimumab (n=11), certolizumab (n=33)) were included in this observational study and followed for 6m. Eleven (9%) received TNFi monotherapy, 92 (65%) TNFi+MTX (methotrexate) and 31 (26%) TNFi+csDMARDs other than MTX. A cohort of 68 untreated patients with early-RA and 20 healthy individuals (age- and sex-matched with the patients) were included as controls. Serum samples were obtained at baseline and 6m, up to 24h prior to TNFi administration. The baseline serum BAFF concentration was measured using ELISA. Drug and anti-drug antibody (ADA) levels were measured using sandwich and drug-sensitive bridging ELISA, respectively. Patients were stratified according to ADA development. Depending on data distribution, comparisons were conducted using unpaired t, Mann-Whitney U or Fisher’s exact tests. The association between the development of ADA within 6m and clinical/serological variables was evaluated by uni- and multi-variable logistic regression. The presence of interactions with covariates (age, RF, ACPA, body mass index, baseline DAS28 and concomitant MTX dose) was tested, stratifying the results if this was significant (pResults:Mean serum BAFF concentration in healthy controls (373±59 pg/mL) was significantly lower compared to patients with early RA (921±388 pg/mL) or established RA (936±407 pg/mL), (pIn this cohort, 37 (31%) patients developed ADA within 6m of treatment. These patients showed higher frequency of seropositivity (RF, p54yr). The results showed that baseline BAFF concentration was associated with ADA development only in older patients (OR=1.0, p=0.02); (shown in the figure). In addition, a significant Spearman correlation between baseline BAFF concentration and ADA levels at 6m was found in older patients (r=0.5, pConclusion:Our results suggest that BAFF has a role in the development of immunogenicity. Nevertheless, this association depends on the age. In RA patients treated with TNFi, the development of ADA within 6m is associated with higher baseline BAFF concentration only in older patients but not in younger patients. The dose of concomitant MTX interacted on this association.References:[1]Pascual-Salcedo D, et al. Rheumatology (Oxford). 2011; 50: 1445-520.[2]Bitoun S, et al. Ann Rheum Dis. 2018; 77: 1463-70.Acknowledgments:Nordic PharmaDisclosure of Interests:Borja Hernández-Breijo: None declared, Ioannis Parodis: None declared, Johanna Gehin Speakers bureau: Roche, Chamaida Plasencia: None declared, Victoria Navarro-Compán Consultant of: Abbvie, Lilly, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Lilly, Novartis, Pfizer, UCB, ANA MARTÍNEZ-FEITO: None declared, David J Warren: None declared, Araceli Mezcua: None declared, Marta Novella-Navarro: None declared, Pilar Nozal: None declared, Alejandro Balsa Grant/research support from: BMS, Roche, Consultant of: AbbVie, Gilead, Lilly, Pfizer, UCB, Sanofi, Sandoz, Speakers bureau: AbbVie, Lilly, Sanofi, Novartis, Pfizer, UCB, Roche, Nordic, Sandoz

Background:In patients with lupus nephritis (LN), clinical response to treatment and renal histopathology have been shown to be discordant. No clinical or laboratory markers have to date been shown to reliably portend renal prognosis, in particular renal function impairment.Objectives:To investigate whether per-protocol repeat renal biopsies are predictive of LN relapses and long-term impairment of renal function.Methods:Forty-two patients with an incident biopsy-proven active proliferative (class III/IV ± V) LN from the LN database of the Université catholique de Louvain were included in the present retrospective study. Per-protocol repeat kidney biopsies were performed in all patients after a median time of 24.3 (IQR: 21.3–26.2) months. The NIH activity index (AI) and chronicity index (CI) scores were assessed in both baseline and repeat biopsies. We defined acute glomerular lesions as cellular proliferation, fibrinoid necrosis or karyorrhexis, cellular crescents, hyaline thrombi or wire loops, and leucocyte infiltration, and chronic glomerular lesions as glomerular sclerosis and fibrous crescents, in alignment with the NIH activity and chronicity indices. Similarly, we defined acute tubulointerstitial lesions as mononuclear cell infiltration and chronic tubulointerstitial lesions as interstitial fibrosis and tubular atrophy.Results:Despite a moderate correlation between urinary protein/creatinine (U-P/C) ratios and AI scores at repeat biopsy (r=0.48; P=0.001), ten patients (23.8%) with U-P/C ratios 3). High AI scores in repeat (but not baseline) kidney biopsies were associated with an increased probability and/or shorter time to renal relapse (N=11) following the repeat biopsy (HR: 1.2; 95% CI: 1.1–1.3; P=0.007), independently of proteinuria levels. This association remained significant for the NIH activity index items within the glomerular but not the tubulointerstitial compartment of the kidney biopsies. High NIH CI scores in repeat (but not baseline) kidney biopsies were associated with a sustained increase in serum creatinine levels corresponding to ≥120% of the baseline value (HR: 1.8; 95% CI: 1.1–2.9; P=0.016) through a median follow-up time of 131.5 (IQR: 73.8–178.2) months, being the case also for acute and chronic tubulointerstitial lesions in repeat but not baseline kidney biopsies.Conclusion:Our results highlight the usefulness of per-protocol repeat biopsies as an integral part of the treatment evaluation, also in patients who have shown adequate clinical response. Glomerular lesions consistent with active renal disease portend LN relapses, while tubulointerstitial lesions consistent with active disease and chronic damage portent long-term renal function impairment.Disclosure of Interests:Ioannis Parodis: None declared, Christina Adamichou: None declared, Selda Aydin: None declared, Alvaro Gomez: None declared, Nathalie Demoulin: None declared, Julia Weinmann-Menke: None declared, Frederic Houssiau Grant/research support from: UCB, Consultant of: GSK, Farah Tamirou: None declared

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 …

Background Lupus nephritis (LN) is a major organ manifestation of Systemic Lupus Erythematosus (SLE). Renal biopsy is the current gold standard for assessment of renal pathology in LN, as non-invasive reliable markers are lacking. Ferritin is found in most tissues as a cytosolic protein that stores iron. Small amounts are secreted into the serum, where ferritin functions as an iron carrier. Ferritin is considered an acute phase protein, as it increases in response to stresses. Studies have reported elevated serum concentrations in patients with active compared to patients with inactive SLE, and also associations with LN. Objectives We assessed serum ferritin levels in patients with LN, in order to clarify its role in this SLE subset. Methods Serum levels of ferritin were determined by ELISA (Raybiotech Inc.) in 64 patients with biopsy-proven active LN (52 proliferative LN, PLN; 12 membranous LN, MLN), before and after completion of induction treatment. Post-treatment renal biopsies were performed after a median time of 7.7 months. Clinical responders (CR) were defined by ≥50% reduced proteinuria, normal or ≥25% improved estimated glomerular filtration rate, and inactive urinary sediment. Histopathological responders (HR) were defined by ≥50% improvement of renal Activity Index in post-treatment biopsies. Results Serum levels of ferritin decreased following induction therapy for LN in the entire cohort (p Conclusions Our data suggest ferritin as a marker of histopathological response to induction treatment in patients with LN. In patients with MLN in particular, high baseline ferritin levels predicted unfavourable clinical response to induction treatment, and, despite being initially lower, baseline ferritin levels decreased in CR. This implies a role of ferritin in the pathogenesis of this LN subset and warrants further investigation. Disclosure of Interest None declared

Background Lupus nephritis (LN) is a severe manifestation of Systemic Lupus Erythematosus (SLE). Renal biopsy is the gold standard for evaluation of renal activity and damage in LN. Evaluation of new biomarkers for non-invasive assessment of renal pathology is warranted. Insulin-like growth factor-binding protein 2 (IGFBP2) has been found to be a robust diagnostic and prognostic biomarker in malignancies. In animal models, IGFBP2 expression was increased in anti-glomerular basement membrane (anti-GBM) glomerulonephritis and MRL/lpr lupus mice. Objectives We aimed to investigate the role of IGFBP2 in LN. Methods Serum levels of IGFBP2 were assessed by ELISA (R&D Systems) in 64 patients with biopsy-proven active LN (52 proliferative, 12 membranous), before and after completion of induction treatment. Post-treatment renal biopsies were performed after a median time of 7.7 months. Clinical responders (CR) were defined by ≥50% reduced proteinuria, normal or ≥25% improved estimated glomerular filtration rate (eGFR), and inactive urinary sediment. Histopathological responders (HR) were defined by ≥50% improvement of renal Activity Index (AI) in post-treatment biopsies. Long-term renal outcome after a median time of 11.3 years (range: 3.3–18.8) was determined by the last eGFR. Results Serum IGFBP2 levels decreased following induction therapy (p Conclusions The decreases in serum IGFBP2 levels following induction therapy in responding, but not in non-responding, patients suggest serum IGFBP2 as a marker of disease activity and response to treatment in LN. Interestingly, baseline IGFBP2 levels were associated with renal function deterioration following treatment, despite an overall improvement in eGFR. Post-treatment, but not baseline, levels mirrored both global SLE activity and histopathological findings, which together with the observed correlation with proteinuria levels suggests IGFBP2 as a marker of activity in patients with history of LN and no or low-grade proteinuria. Disclosure of Interest None declared

Background Lupus nephritis (LN) is a major manifestation of Systemic Lupus Erythematosus (SLE). The burden of antiphospholipid antibodies (APLA) in LN has not been clarified. Objectives We investigated a potential role of APLA levels as a biomarker of severity in renal lupus. Methods Serum levels of APLA (antibodies to cardiolipin (aCL) and β 2 -glycoprotein 1 (anti-β 2 -GP1); reference values Clinical responders (CR) were required to have ≥50% reduction in proteinuria, normal or improved renal function and inactive urinary sediment. Histopathological responders (HR) were required to have ≥50% improvement in Activity Index. Results Percentages of APLA positive patients in the active LN cohort at baseline (aCL: 12.5% IgG, 9.4% IgM; anti-β 2 -GP1: 20.3% IgG, 9.4% IgM) were comparable to the ones in the cross-sectional SLE cohort (entire cohort: 20.1% IgG, 7.1% IgM aCL, 21.3% IgG, 7.3% IgM anti-β 2 -GP1; patients with renal involvement, n=200: 22.5% IgG, 6% IgM aCL, 24% IgG, 6.5% IgM anti-β 2 -GP1; patients without renal involvement, n=295: 18.6% IgG, 8.1% IgM aCL, 19.7% IgG, 8.1% IgM anti-β 2 -GP1), but lower in the LN cohort following induction treatment (aCL: 9.4% IgG, 1.6% IgM; anti-β 2 -GP1: 10.9% IgG, 3.1% IgM). APLA titers showed significant decreases following treatment (p 2 -GP1; HR, n=43: p=0.001 for aCL, p=0.002 for anti-β 2 -GP1) but not in non-responders. IgG titers decreased significantly in all response groups, with the exception of IgG aCL in clinical non-responders (p=0.068). In the membranous LN subgroup, APLA levels remained unchanged regardless of treatment outcome. IgM titers decreased significantly in all treatment groups. IgG titers decreased significantly in patients given cyclophosphamide and mycophenolate mofetil, but remained unchanged in rituximab-treated patients. CKD stage at discharge correlated significantly with the duration of follow-up (p=0.15, r=0.3) but did not correlate with either APLA levels or positivity. Conclusions APLA levels were comparable in SLE patients with or without renal involvement and in patients with active LN, but decreased significantly following induction therapy given for LN. In proliferative LN, IgG and IgM titers were affected differently by immunosuppression with regard to treatment response: IgG titers decreased regardless of treatment outcome while IgM decreased only in responding patients. As expected, renal damage increased with disease duration; however, neither APLA levels nor positivity correlated with long-term renal outcome. Investigation of the association between APLA and treatment response in larger LN cohorts might give further insight. Disclosure of Interest None declared

Background Lupus nephritis (LN) affects up to 50% of patients with Systemic Lupus Erythematosus (SLE). The B-lymphocyte is pivotal in SLE and autoantibody production. B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) are important for the activation and maintenance of B-cells. Objectives The aim of this study was to investigate serum levels of BLyS and APRIL in patients with LN, in order to clarify how these levels are affected by conventional immunosuppression. Through comparison with clinical data and correlation with autoantibodies, we further aimed to evaluate BLyS and APRIL as potential biomarkers for LN in comparison to conventional serology. Methods Sixty-four patients with active biopsy-ascertained LN (52 proliferative LN, PLN; 12 membranous LN) and 64 individually matched controls were included. After induction therapy a follow-up biopsy was performed. Serum samples at baseline and follow-up were analyzed for BLyS, APRIL, autoantibodies and complement levels. The renal biopsies were assessed according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification system for LN 1 and scored for Activity Index (AI) and Chronicity Index (CI) 2 . Clinical response (CR) was defined as ≥50% reduction in proteinuria, normal or improved renal function and inactive urinary sediment. Histopathological response (HR) required ≥50% improvement in AI. Results Comparing patients to controls, baseline BLyS levels were significantly higher in patients (p No correlation was found between BLyS/APRIL and anti-dsDNA, anti-C1q, C3 or C4, at either baseline or follow-up. However, significant correlations were found between DBLyS and Danti-dsDNA in the combined patient group (r s =0.47, p s =0.49, p Conclusions Our results indicate that APRIL is of importance in PLN, and stress the need to evaluate BLyS as a candidate non-invasive prognostic biomarker of treatment response in LN. References Weening JJ, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Journal of the American Society of Nephrology: JASN. 2004 Feb;15(2):241-50. Austin HA, 3rd, et al. Prognostic factors in lupus nephritis. Contribution of renal histologic data. The American journal of medicine. 1983 Sep;75(3):382-91. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3863

Background Belimumab is a recombinant monoclonal antibody that specifically binds to soluble B-lymphocyte stimulator, thereby reducing autoantibody levels. It is the only biologic agent approved for treatment of Systemic Lupus Erythematosus (SLE). Objectives The aim of this study was to investigate the effects of belimumab given as an add-on to patients with active SLE despite standard-of-care therapy, with focus on low-active lupus nephritis (LN) patients. Methods Fourteen patients were included. Clinical data were acquired at baseline and week 12, 26 and 52. Disease activity was assessed using SLE Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus Activity Measure (SLAM). The primary organ manifestations comprised arthritis (n=9), skin involvement (n=11), serositis (n=3), involvement of the central nervous system (n=4) and cytopenias (n=3). Nine patients with former LN were included (median proteinuria at baseline 0.2 g/day, range 0.01-0.4 g/day). Results At baseline, all patients received oral prednisolone (mean dose 11, range 5-20 mg/day), 9 received antimalarials, 3 mycophenolate mofetil, 2 azathioprine, and 1 cyclosporine. The median SLEDAI and SLAM scores were 10 (range 2-24) and 12 (range 5-23), respectively. One patient withdrew due to allergic reaction. Significant decreases of SLAM and SLEDAI were seen at week 26 (p=0.001 and p=0.007, respectively) and 52 (p=0.028 and p=0.012, respectively). Prednisolone dosages were significantly decreased compared to baseline at week 26 (p=0.003) and 52 (p=0.008). Ten patients had low complement at baseline. We observed no significant increase in C3/C4 levels. In the patients with former LN, no renal flare was observed during the observation period. The grade of proteinuria remained unchanged at week 26 (median 0.14 g/day, range 0.01-0.5 g/day) and 52 (median 0.13 g/day, range 0.02-0.24 g/day). No severe adverse events were noted. Conclusions Belimumab treatment decreased SLE disease activity and reduced corticosteroid usage. Despite the limited number of patients, our observations indicate that belimumab may prevent renal flares and may be used in patients with former LN and persistent low-grade proteinuria. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3876

Background Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) affecting up to 60% of the patients. IFN-α is a central cytokine in the pathogenesis for LN, and recent studies also indicate a role for IFN-λ1/3. However little is known about these cytokines in the context of treatment response and how they are affected by immunosuppressive therapy in LN. Objectives We studied serum levels of IFN-α and IFN-λ1/3 in patients with LN, both at active disease and after induction treatment. Associations with clinical and histological response to treatment were evaluated. Methods Fifty-six patients with active LN, 45 proliferative- (PN) and 11 membranous nephritis (MN), were included. Renal biopsies were performed at baseline and after induction immunosuppressive treatment (median 7 months). Clinical and routine laboratory data were collected, and serum levels of IFN-α and IFN-λ1/3 were analysed by ELISA at both biopsy occasions and in 163 healthy controls. The cut-off for IFN-α was 0.02 pg/l and for IFN-λ1/3 0.3 pg/l. Biopsies were evaluated according to the ISN/RPS classification and scored for activity and chronicity indices. Clinical response was defined according to recent definitions [1]. Histological response (HR) was defined as Class I, II or III/IV-C on repeat biopsies. Results At baseline, serum levels of both IFN-α and IFN-λ1/3 were higher in patients vs. controls (p=0.01 and 0.03 respectively). There was no correlation between IFN-α and IFN-λ1/3. There was a trend towards higher levels of IFN-α in patients with PN vs. MN (p=0.06) and higher IFN-λ1/3 in MN vs. PN (0.09). In PN, 73% of the patients had detectable IFN-α vs.36% in MN (p=0.02). In all patients, IFN-α decreased after treatment (p=0.002) but IFN-λ1/3 remained unchanged. However in patients with HR, levels of IFN-λ1/3 decreased (p=0.01). Of histological non-responders, 31% had detectable levels of IFN-λ1/3 at follow-up, vs 10% of HR (p=0.05). IFN-α was positively correlated to anti-DNA and anti-C1q-antibodies and negatively to C3 and C4, but no correlations were seen for IFN-λ1/3. Neither IFN-α, nor IFN-λ1/3 correlated to proteinuria or creatinine and there was no clear association to clinical response. Conclusions Our results support a role for IFN-λ1/3, and also confirms previous findings of involvement of IFN-α, in LN. Interestingly, IFN-α and INF-λ1/3 did not correlate to each other and their levels were affected differently by immunosupressive treatment, and also differed between MN and PN. Persistently elevated levels of IFN-λ1/3 indicated poor histological response to treatment. The study indicates that IFN-α and IFN-λ1/3 may be differently involved in subgroups of LN and that IFN-λ1/3 may be a potential biomarker for treatment response. References Gordon C, Jayne D, Pusey C, et al. European consensus statement on the terminology used in the management of lupus glomerulonephritis. Lupus 2009;18(3):257-63 Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5505

Background and Objectives We have earlier investigated the content of specific IgG autoantibodies in SLE immune complexes (IC; Ahlin et al , Lupus 2012; 21:586). For that purpose we have developed a line blot technique for the quantification also of non-classical (IgA and IgM) SLE autoantibody isotypes. In SLE patients, IgG autoantibody levels drop after institution of Rituximab therapy. The objective was to investigate parallel changes IgG, IgA and IgM autoantibody isotypes in parallel to IC levels. Materials and Methods Nine SLE patients initially treated with two infusions of Rituximab were followed with repeated samplings at baseline and after 1, 3, 6 and 12 months. Thawed samples were investigated simultaneously concerning rheumatoid factor (RF) isotypes and C1q-binding IC with enzyme immunoassays. All samples from patients with ANA-associated autoantibodies (6/9) were investigated concerning IgG/A/M autoantibodies with line blot quantitated with densitometry and concerning IgG autoantibodies with ALBIA/Luminex technique. Significant changes were defined either as ≥33% drop or as ≥50% increase, compared to the lowest levels experienced during the follow-up period. Results ALBIA measurements showed significant initial drop in anti-dsDNA in 4/6 patients but also significant drop in levels of anti-histone, anti-SSA/Ro60, anti-Sm and anti-Sm/RNP in individual patients. Late increases in IC and antibodies against dsDNA, SSA/Ro52, SSA/Ro60, SSB, Sm, Sm/RNP ribosomal P protein and histones were associated with clinical relapse. Late increase in IgA/IgM anti-DNA, anti-histones and anti-nucleosomes was also found in one patient with persistent kidney disease treated with mycophenolate mofetil at 10 months. Non-classical autoantibody isotypes showed late increases that often were not paralleled by the corresponding IgG autoantibodies. Two patients showed late increase in RF isotypes in parallel to clinical relapse. Different autoantibodies/isotypes showed different kinetics of appearance/disappearance. All ANA autoantibody positive patients initially had increased IC levels, which dropped significantly after therapy in 4/6 patients. The autoantibody negative patients never had increased IC levels and showed no significant changes in RF. Conclusions Measurement of non-classical isotypes of RF and ANA-associated autoantibodies might yield clinically useful information when monitoring SLE patients treated with B cell depleting therapy.