BILAG Index Research Articles

P158 Cutaneous vasculitis in systemic lupus erythematosus: trends of incidence and risk factors

Abstract Background/Aims Cutaneous vasculitis (CV) is the most common form of vasculitis observed in patients with SLE; however, the precise epidemiological trends and underlying risk factors remain uncertain. The aim of this study was to define the incidence, prevalence, and risk factors of CV in systemic lupus erythematosus (SLE) patients over a period of 20 years. Methods The Birmingham Lupus Cohort is a longitudinal observational cohort of patients with SLE. All patients fulfilled the 1997 ACR Updated Classification Criteria for SLE. Inception patients were recruited within three years of their fourth ACR criterion. Disease activity was assessed using the classic BILAG index and laboratory results recorded. The BILAG vascular domain was used to determine the incidence rate, which refers to the rate at which new cases of minor and major CV attributed to active SLE occur. Cox proportional hazards frailty models were developed to identify clinical and laboratory variables associated with development of CV. Results We analysed 392 patients, of whom 375 (92.5%) were females. There were 213 (55.0%) White, 72 (18.6%) African-Caribbean, 82 (21.1%) South Asian, 9 (2.3%) East Asian, and 11 (2.8%) other ethnicities. The median (IQR) age at enrolment was 33 (26 - 44) years and the median duration of follow up was 9.2 (5.1 - 14.7) years. The incidence rates of minor and major CV were reported in Table 1. In Cox proportional hazards models, there was a positive association between CV and discoid rash (hazard ratio [HR] 2.16 [95% CI: 1.01, 4.61]), Raynaud’s phenomenon (HR 5.67 [95% CI: 4.11, 7.81]), livedo reticularis (HR = 4.69 [95% CI: 1.83, 12.0]), arthritis (HR 3.02 [95% CI: 2.20, 4.15]), renal involvement (OR 2.40 [95% CI: 1.55, 3.71]), haematological involvement (HR = 2.46 [95% CI: 1.80, 3.36]), and Afro-Caribbean descent (HR 1.96 [95% CI: 1.03, 3.74]). In addition, CV was positively associated with anti-dsDNA (HR = 2.33 [95% CI: 1.67, 3.27]), low C3 or C4 (HR 2.29 [95% CI: 2.18, 4.10]), and history of anti-Ro or anti-La (HR = 1.92 [95% CI: 1.15, 3.21]). Conclusion The incidence rates of CV decrease over the duration of follow-up and are associated with defined clinical and serological features. Disclosure A. Saleh: Grants/research support; A.S. is a sponsored PhD student by the Egyptian ministry of higher education represented by The Egyptian Bureau for Cultural & Educational Affairs in London. C. Gordon: None. J. Reynolds: None.

Gastrointestinal Manifestations in Systemic Lupus Erythematosus: Data from an Indian Multi-institutional Inception (INSPIRE) Cohort.

To study the prevalence, correlates, and outcomes of GI manifestations in a prospectively enrolled nationwide cohort of SLE in India (INSPIRE). It is an observational cohort study with analysis of the baseline database of the INSPIRE cohort with early outcomes assessed till April 10, 2023. Cases with GI manifestations as per the BILAG index were selected, pertinent clinical and laboratory data were retrieved for analysis. Patients with GI manifestations were compared with the rest of the cohort and factors associated with death were determined. Of the 2503 patients with SLE enrolled in the INSPIRE cohort, 243(9.7%) had GI manifestations observed early in the disease course(1,0-3 months). Ascites(162,6.5%), followed by enteritis(41,1.6%), pancreatitis(35,1.4%) and hepatitis(24,0.9%) were the most prevalent manifestations.All patients received immunosuppressive therapy, and four patients required surgery. Twenty-nine patients died(11.9%), with uncontrolled disease activity(17,58.6%) and infection(6,20.7%) accounting for the majority of deaths. Low socioeconomic class[lower(Hazard Ratio (95% Confidence intervals- CI) 2.8(1.1-7.9); upper lower 7.5(2-27.7); reference as upper class] and SLEDAI 2K[1.06(1.02-1.11)] were associated with death in the GI group.GI manifestations were significantly associated with age[Odds Ratio & 95% CI 0.97(0.96-0.99)], pleural effusion[4.9(3.6-6.7)], thrombocytopenia[1.7(1.2-2.4)], myositis[1.7(1.1-2.7)], albumin[0.7(0.5-0.8)], alkaline phosphatase(ALP)[1.01(1.0-1.002)], low C3[1.9(1.3-2.5)], total bilirubin[1.2(1.03-1.3)], alopecia[0.62(0.5-0.96], elevated anti-dsDNA[0.5(0.4-0.8)], and anti-U1RNP antibody[0.8(0.5-0.7)] in model one; and age[0.97(0.96-0.99)], creatinine[1.2(1.03-1.4)], total bilirubin[1.2(1.03-1.3)], ALP[1.01(1.0-1.002)], albumin[0.6(0.5-0.7)], andanti-U1RNP antibody[0.6(0.5-0.8)] in model two in multivariate analysis compared with patients without GI features. The mortality was higher in the GI group(11.9% and 6.6%, p= 0.01) as compared with controls. GI manifestations were observed in 9.7% of the cohort and were always associated with systemic disease activity and had higher mortality.

Predictors of British Isles Lupus Assessment Group-based outcomes in patients with systemic lupus erythematosus: Analysis from the Systemic Lupus International Collaborating Clinics Inception Cohort.

We aimed to identify factors associated with a significant reduction in SLE disease activity over 12months assessed by the BILAG Index. In an international SLE cohort, we studied patients from their 'inception enrolment' visit. We also defined an 'active disease' cohort of patients who had active disease similar to that needed for enrolment into clinical trials. Outcomes at 12months were; Major Clinical Response (MCR: reduction to classic BILAG C in all domains, steroid dose of ≤7.5mg and SLEDAI ≤ 4) and 'Improvement' (reduction to ≤1B score in previously active organs; no new BILAG A/B; stable or reduced steroid dose; no increase in SLEDAI). Univariate and multivariate logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) and cross-validation in randomly split samples were used to build prediction models. 'Inception enrolment' (n = 1492) and 'active disease' (n = 924) patients were studied. Models for MCR performed well (ROC AUC = .777 and .732 in the inception enrolment and active disease cohorts, respectively). Models for Improvement performed poorly (ROC AUC = .574 in the active disease cohort). MCR in both cohorts was associated with anti-malarial use and inversely associated with active disease at baseline (BILAG or SLEDAI) scores, BILAG haematological A/B scores, higher steroid dose and immunosuppressive use. Baseline predictors of response in SLE can help identify patients in clinic who are less likely to respond to standard therapy. They are also important as stratification factors when designing clinical trials in order to better standardize overall usual care response rates.

LB0004 EFFICACY AND SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE, ALLOSTERIC TYK2 INHIBITOR, IN PATIENTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

LB0004 EFFICACY AND SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE, ALLOSTERIC TYK2 INHIBITOR, IN PATIENTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

P246 Revision to musculoskeletal domain of BILAG-2004 index to incorporate ultrasound findings

Abstract Background/Aims The BILAG-2004 index grades musculoskeletal (MSK) inflammation as mild (C), moderate (B) and severe (A), based on clinical features. In a recent study, 27% of SLE patients with MSK pain have ultrasound (US) synovitis without swelling, and respond better to therapy than those with normal ultrasound. We aimed to revise the MSK domain of the BILAG-2004 index to improve its utility in modern practice. Methods An MSK sub-committee reviewed the existing BILAG-2004 MSK definitions and glossary, then re-analysed data from recent studies to propose revised definitions. Results The new definitions/changes are: (i) BILAG-C arthralgia (if US is not performed) is defined as a classical inflammatory symmetrical small-joint distribution of symptomatic joints on clinical assessment, based on the features most associated with US inflammation in a previous study. If US is performed, all previous BILAG-C patients are reclassified: (ii) BILAG-B now includes patients without swelling if they have significant synovitis/tenosynovitis on US in symptomatic joints/tendons; (iii) patients with arthralgia without swelling are scored as BILAG-D instead of C, if US of the symptomatic joints has been performed and is normal; (iv) a more detailed definition of functional impairment is provided for BILAG-A. Data from 221 symptomatic SLE patients (BILAG-A-C) in two recent studies were re-analysed in the light of the above changes. 121/221 (54.8%) were graded clinically as having arthralgia / myalgia (BILAG-C) on BILAG-2004 . Of these, 53/121 (43.8%) had evidence of synovitis (GS > 1 or PD > 0) or tenosynovitis (GS > 0 or PD > 0) on US. The effect on grading if US were performed on all BILAG C cases is shown in table 1. Conclusion Future versions of the BILAG index will allow the use of US to classify patients who are graded as mild inflammatory arthritis (BILAG-C) to moderate (BILAG-B) or non-inflammatory pain (BILAG-D/E). Although US is not required for all assessments it may be used when there is diagnostic uncertainty. This is in keeping with clinical practice in inflammatory arthritis care, and similar to use of other investigations (e.g. renal biopsy) that contribute to BILAG assessments of other systems. Disclosure R.D. Sandler: None. E.M. Vital: None. A. Prabu: None. C. Riddell: None. K.I. Mahmoud: None. L. Teh: None. C.J. Edwards: None. C. Yee: None.

High-Mobility Group Box 1 Protein (HMGBl): Role in Lupus Nephritis

Abstract Background: According to recent studies, in renal disease High Mobility Group Box 1 protien (HMGB1) levels in blood and urine, its expression in renal tissue, and its levels in the cytoplasm and extracellular medium are all elevated. Aim of Study: Was to assess serum and urinary levels of HMGB1 in correlation to renal histopathology, disease activity and organ damage in systemic lupus patients (SLE). Patients and Methods: Serum and urine levels of HMGB1 were measured in 25 SLE patients with active nephritis by ELISA at baseline (I) and after 6 months follow-up (II). Renal biopsies were performed at baseline. Results: There was high statistical significant difference between serum and urine HMGB 1 at baseline (I) and after follow-up (II) and between total BILAG score (I) and (II). There was statistically significant difference between SLE nephritis patients (responders and non responders) as regard total BILAG index, p 0.05. After follow-up, there was significant difference between patients with BILAG category A and C in serum (but not urinary) high mobility box protein 1 (II). There was significant positive correlation between total BILAG score after follow-up and serum level of High Mobility Box protein 1 (II) and SLICC score, p < 0.05. There was a significant positive correlation between renal BILAG score after follow-up and serum High Mobility Box protein 1 (II) after follow-up. There was a significant positive correlation between 24hrs urinary proteins and urinary level of High Mobility Box protein 1 (II) after follow-up p < 0.05. Conclusion: HMGB 1 levels (serum and/or urinary) are high in SLE patients with nephritis compared to reference range. There is an association/correlation not only between HMGB1 and general disease activity in SLE patients but also between it and renal disease activity, severity and class. It could be a useful marker of lupus nephritis activity and class that may influence therapeutic strategies replacing rebiopsy.

FRI0599 USEFUL II: DERIVATION OF THE LUPUS ARTHRITIS AND MUSCULOSKELETAL DISEASE ACTIVITY SCORE (LAMDA) USING DATA FROM A MULTICENTRE LONGITUDINAL STUDY

Background:Musculoskeletal (MSK) disease is the commonest manifestation of SLE. We showed that the MSK components of the BILAG index and SLEDAI have limited sensitivity, specificity and responsiveness compared to ultrasound (US) synovitis. The USEFUL study evaluated response to glucocorticoids in SLE patients with inflammatory pain.Objectives:To develop a disease activity tool for lupus MSK manifestations that is continuous, responsive, sensitive, and correlates with US-synovitisMethods:133 patients who received depomedrone 120mg IM were assessed at 0, 2 and 6 weeks for 66/68 swollen and tender joint counts, BILAG2004 index, SLEDAI-2K, physician global and MSK-VAS, inflammatory markers, patient pain and disease activity-VAS. Total US score (OMERACT-EULAR) in the hands and wrists was calculated blinded to patient and clinical assessor. Patients reported overall response using a Likert scale.The LAMDA was developed by modelling a core set of clinical variables against total US score using penalized (Lasso) regression. Responsiveness was compared between LAMDA and other variables at week 6 using effect sizes. Minimum clinically important difference (MCID) was explored using the SEM and minimal disease activity threshold using ROC.Results:The variables selected for the LAMDA score were swollen joint count, patient MSK pain VAS, physician MSK disease activity VAS and ESR. A continuous score was derived. This had a theoretical range from 0 to 26.5 based on maximum ESR of 100. The highest value observed in USEFUL was 15. LAMDA was significantly higher in patients with active US (mean (SD) 5.71 (2.67), n=78) compared to patients with normal US (3.27 (1.77), n=55; difference (95% CI) -2.45 (-3.26, -1.63), t=-5.93, p&lt;0.001). This difference remained significant in patients with no swollen joints (difference (95% CI) -0.71 (-1.40, -0.02), t=-2.06, p=0.044).Effect size was greater for the LAMDA (0.37) than the BILAG-MSK (0.31), SLEDAI-MSK (0.27) and total US score (0.33). In patients with active US at baseline, LAMDA’s effect size was 0.42.The MCID was 0.71 and correlated with patient-reported change in pain. A threshold for minimal disease activity of 3.23 optimized sensitivity (0.77 (0.65, 0.89)) and specificity (0.80 (0.68, 0.92)) against US score &gt;0.Conclusion:The LAMDA score is a novel continuous disease activity instrument for MSK manifestations of SLE derived from variables familiar to rheumatologists. The LAMDA score is sensitive to imaging detected synovitis without swelling and more responsive than other instruments. . LAMDA may improve the ability of clinicians to accurately determine therapeutic efficacy in clinical trials and practice. Future work will validate the LAMDA score in independent cohorts and randomized trials.Acknowledgements:This project was funded by Lupus UKDisclosure of Interests:Khaled Mahmoud: None declared, Ahmed Zayat: None declared, Md Yuzaiful Md Yusof: None declared, Coziana Ciurtin Grant/research support from: Pfizer, Consultant of: Roche, Modern Biosciences, Chee-Seng Yee: None declared, David Isenberg Consultant of: Study Investigator and Consultant to Genentech, Lee-Suan Teh: None declared, Katherine Dutton: None declared, David d’cruz Grant/research support from: GlaxoSmithKline, Nora Ng: None declared, Philip G Conaghan Consultant of: AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GSK, Novartis, Pfizer, Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp &amp; Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp &amp; Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Christopher Edwards Grant/research support from: Abbvie, Biogen, Roche, Consultant of: Abbvie, Samsung, Speakers bureau: Abbvie, BMS, Biogen, Celgene, Fresenius, Gilead, Janssen, Lilly, Mundipharma, Pfizer, MSD, Novartis, Roche, Samsung, Sanofi, UCB, Elizabeth Hensor: None declared, Edward Vital Grant/research support from: AstraZeneca, Roche/Genentech, and Sandoz, Consultant of: AstraZeneca, GSK, Roche/Genentech, and Sandoz, Speakers bureau: Becton Dickinson and GSK

ALCAM and VCAM-1 as urine biomarkers of activity and long-term renal outcome in systemic lupus erythematosus.

ObjectivesWe investigated the cell adhesion molecules (CAMs) Vascular CAM 1 (VCAM-1) and Activated Leucocyte CAM (ALCAM) as urinary biomarkers in SLE patients with and without renal involvement.MethodsFemale SLE patients (n = 111) and non-SLE population-based controls (n = 99) were enrolled. We measured renal activity using the renal domain of the BILAG index and urine (U) and plasma (P) concentrations of soluble (s)VCAM 1 and U-sALCAM using ELISA. U-sCAM levels were next corrected by U-creatinine.ResultsU-sVCAM-1/creatinine and U-sALCAM/creatinine ratios were higher in SLE patients vs non-SLE controls (P < 0.001 for both), as well as in patients with active/low-active (BILAG A–C; n = 11) vs quiescent (BILAG D; n = 19) LN (P = 0.023 and P = 0.001, respectively). U-sALCAM/creatinine but not U-sVCAM-1/creatinine ratios were higher in patients with nephritis history (BILAG A–D; n = 30) vs non-renal SLE (BILAG E; n = 79) (P = 0.014). Patients with baseline U-sVCAM-1/creatinine ratios ≥75th percentile showed a 23-fold increased risk of a deterioration in estimated glomerular filtration rate by ≥25% during a 10-year follow-up (odds ratio: 22.9; 95% CI: 2.8, 189.2; P = 0.004); this association remained significant after adjustments for age, disease duration and organ damage. Traditional markers including anti-dsDNA antibodies did not predict this outcome.ConclusionWhile high U-sVCAM-1 levels appear to reflect SLE disease activity, sALCAM might have particular importance in renal SLE. Both U-sVCAM-1 and U-sALCAM showed ability to distinguish SLE patients with active renal involvement from patients with quiescent or no prior nephritis. High U-sVCAM-1 levels may indicate patients at increased risk for long-term renal function loss.

THE EFFICIENCY OF BIOLOGICAL THERAPY AND THE FEATURES OF HUMORAL IMMUNITY IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Objective: to investigate the effect of various biological agents (BAs), including combined treatment with rituximab (RTM) and belimumab (BLM), on the activity of systemic lupus erythematosus (SLE) and to evaluate their efficacy and impact on some parameters of humoral immunity.Subjects and methods. BAs were prescribed to 54 patients with a reliable diagnosis of SLE with high and medium activity according to SLEDAI-2K; 40 of them received RTM, 7 – BLM; 7 – combined therapy with RTM and BLM. Clinical and laboratory examinations were made in all the patients at the time of their inclusion and then every 3 months during a year. The results were assessed using SLEDAI-2K, BILAG index, Lupus Erythematosus National Assessment (SELENA)-SLEDAI Flare index (SFI) (a moderate, severe exacerbation), and SLE Responder Index (SRI).Results and discussion. At 3, 6, and 12 months after start of therapy, the use of BAs in all the patients resulted in a disease activity reduction. It was statistically significant (p &lt; 0.00001) in the RTM group; and no statistical analysis was carried out in the BLM and RTM+BLM groups due to the small numbers of patients. At the same time, there was a progressive decrease in the levels of anti-double-stranded DNA (ds-DNA) antibodies (Abs) and an increase in the concentration of the complement fractions C3 and C4 in the RTM and RTM+BLM groups (p &lt; 0.05) at one-year follow-up. After 12 months of therapy with BAs, there was a decrease in IgG (p &lt; 0.02) and IgM (p &lt; 0.03) levels; but overall it remained within the reference ranges. Prior to therapy, irreversible organ damages were recorded in 23 (42.6%) of the 54 patients. The increased damage index at 12 month was observed only in patients receiving RTM, which is probably due to the use of higher-dose glucocorticoids.Conclusion. All three methods of therapy with BAs in SLE patients demonstrated good efficiency shown as a significant decrease in clinical and laboratory activity measures that were assessed by SLEDAI-2K and the levels of anti-ds-DNA and complement components C3 and C4. The decrease in immunoglobulin levels did not go beyond the reference values. Therapy with BLM and RTM+BLM allowed for managing patients with the low and average doses of oral glucocorticoids, which contributed to the reduction of not only the activity, but also risk of irreversible organ damages.

From BILAG to BILAG-based combined lupus assessment-30 years on.

Disease activity in SLE can be difficult to measure and there is no biomarker that uniformly reflects disease activity. There are various disease activity scores, but there is no gold standard assessment tool. This is a review of the development of the BILAG index from the classic BILAG disease activity index to the BILAG-2004 disease activity index and composite response criteria. The original classic BILAG index was revised and distinguished nine organs/systems. Features that indicated damage, such as avascular necrosis, were excluded. There was improvement in the glossary, scoring system and software. The BILAG-2004 index has been shown to be reliable, valid and sensitive to change. The BILAG-2004 index has been modified for pregnancy and has also been used in paediatrics. The SLE Responder Index (SRI) and the BILAG-based combined lupus assessment (BICLA) are composite responder indices incorporating the BILAG index. Since the initial development of the BILAG index in 1984, major improvements have been made in the measurement of disease activity in lupus. However, the BILAG-2004 index is the only transitional index that grades clinical features as being new, the same, worse or improving and incorporates severity in the scoring.

Interferon-α-induced B-lymphocyte stimulator expression and mobilization in healthy and systemic lupus erthymatosus monocytes.

The aim of this study was to investigate the cellular populations and regulatory factors responsible for B-lymphocyte stimulator (BLyS) overexpression in SLE patients. Surface and intracellular BLyS levels were quantified by flow cytometry in healthy and SLE monocytes cultured in the presence of TNF-α, IFN-α, IFN-γ, GM-CSF and SLE immune complexes (SLE-ICs), while soluble BLyS was measured by ELISA. Also, both surface and intracellular BLyS expression by different cell subsets was determined in 23 SLE patients and 16 healthy controls. Disease activity was assessed using classic BILAG index. In vitro experiments using healthy monocytes showed that IFN-α and SLE-ICs induced a progressive increase in surface-bound BLyS with respect to the intracellular stores. IFN-α-treated SLE monocytes, especially from patients with high anti-dsDNA levels or disease activity, exhibited higher intracellular levels of BLyS that was mobilized to the membrane more rapidly and subsequently released. Furthermore, ex vivo analysis of SLE patients revealed up-regulated BLyS expression in B cells, myeloid and plasmacytoid dendritic cells (DCs), whereas active patients had an increased surface:intracellular BLyS ratio in monocytes and myeloid DCs. Monocyte BLyS induction and mobilization from intra- to extracellular compartments seems to be influenced by IFN-α and disease activity or anti-dsDNA levels. Accordingly, monocytes and myeloid DCs from active patients presented the highest membrane-bound:intracellular BLyS ratio. In addition, expression levels in several blood cells support the existence of generalized immune stimulation in SLE patients.

FRI0384 Background Treatment and Disease Variables Affecting High Placebo Responses in Systemic Lupus Erythematosus (SLE) Trials: Update from the Soccit Program

BackgroundMost clinical trials for SLE allow various background immune suppressants to which investigational agents are added (1). The impact of these standard-of-care (SOC) treatments or clinical variables on placebo group...

Why and how should we measure disease activity and damage in lupus?

The assessment of disease activity and flare and differentiating them from permanent damage in patients with SLE is challenging. The SLEDAI, SLEDAI-2K and SELENA-SLEDAI measure global disease activity. The BILAG measures organ-specific activity. The BILAG better captures the change in the different organs at the expense of complexity. The SRI is a composite index incorporating both BILAG and SLEDAI indices and a physician's global assessment. It has been used in the most recent clinical trials. Damage correlates with prognosis; it is assessed by the SLICC/SDI index. This index scores damage whatever the cause, disease or treatment related, or the consequence of concomitant disease. The disease activity and damage indices do not correlate well with the patient's health related quality of life (HRQoL), the degree of disability or the impact of disease. The impact of the patients' joint disease on their HRQoL is assessed via the HAQ questionnaire and the global health status via the SF-36 index, or one of the more recently described lupus specific quality of life indices [Lupus QoL]. The global assessment instruments and the BILAG index can also be used in children and adolescents with SLE. However, a modified paediatric version of the SLICC/SDI damage index is advised. Many advances have been achieved in disease activity and damage measurement in the past 20 years but the problem of how best to capture flare accurately remains.

Vitamin D levels in Jamaican patients with systemic lupus erythematosus

Vitamin D has important effects on the immune system as it has been shown to exert antiproliferative and relative immunosuppressant effects. Low levels of this hormone may contribute to the immune activation in systemic lupus erythematosus (SLE) and other autoimmune diseases. Serum levels of 25-OH vitamin D were measured in 75 patients with SLE in Jamaica, using an enzyme-linked immunoassay. Correlations with clinical data and disease activity as determined by the BILAG index were determined. Of a total of 75 patients, 33 (44%) had vitamin D sufficiency with mean vitamin D level of 39.45 ng/ml (range, 30.35-58.16). Forty-two (56%) patients had either vitamin D deficiency or insufficiency, 30 (40%) had vitamin D insufficiency, mean 26.36 ng/ml (range, 20.26-29.88), and 12 (16%) had vitamin D deficiency, mean 16.07 ng/ml (range, 7.78-19.90). There was an overall negative relationship between the total disease activity score using the BILAG index and vitamin D levels, and this was influenced primarily by the relationship seen among the vitamin D-deficient subgroup. This was also impacted on by a patient population that was significantly skewed toward low disease activity. The negative association trended toward statistical significance. Vitamin D deficiency is prevalent among patients with SLE in Jamaica. A relationship between low serum levels of vitamin D and SLE activity may occur.

Pentraxin 3 is associated with disease activity but not atherosclerosis in patients with systemic lupus erythematosus

Objectives Pentraxin 3 (PTX3) plays an important role in inflammation, immunity, and atherosclerosis. Plasma PTX3 level has drawn attention as a marker that responds to local inflammation. Systemic lupus erythematosus (SLE), a chronic inflammatory disorder which can affect multiple organs, develops atherosclerosis prematurely. We examined the hypotheses that the concentration of plasma PTX3 increases in patients with SLE and that PTX3 is associated with the disease activity and premature atherosclerosis.Methods Plasma PTX3 concentrations were measured in 65 patients with SLE and 53 control subjects. The patients were also evaluated with respect to their clinical characteristics, disease activity indices, and corticosteroid therapy. We performed carotid ultrasonography to measure subclinical atherosclerosis in patients with SLE.Results Plasma PTX3 concentration of the SLE patients was significantly higher than that of the healthy controls (median 3.9 vs. 2.0 ng/mL, p < 0.001). In patients with SLE, PTX3 concentrations were correlated with SLEDAI (p = 0.011), BILAG index (p < 0.001), C-reactive protein (p < 0.001), anemia (p = 0.020), hypoalbuminemia (p = 0.022), and daily dose of prednisolone (p = 0.008) after adjustment for age and sex. PTX3 was not associated with disease duration, anti-ds DNA antibody, CH50, or carotid atherosclerosis.Conclusions Patients with SLE have increased concentrations of PTX3 compared with control subjects. PTX3 was significantly associated with disease activity but not with carotid atherosclerosis.

FRI0293 Validation of the revised selena flare index in systemic lupus erythematosus

BackgroundThe SELENA flare index (SFI) has functioned well in clinical and clinical trial settings (1), but has the limitation that it classifies only severe versus combined mild/moderate flares.ObjectivesSince mild flares...

AB0617 Characterization of SLE patients experiencing flares in epratuzumab clinical trials

BackgroundEpratuzumab is a humanized anti-CD22 monoclonal antibody in development for the treatment of moderate-to-severe systemic lupus erythematosus (SLE). Its efficacy in SLE has been demonstrated in three double-blind, placebo-controlled studies:...

AB0696 Measurement of arterial stiffness in a cross-section of SLE patients and relationship to treatment with intravenous methlyprednisolone – a pilot study

BackgroundSLE is associated with high cardiovascular (CV) morbidity and mortality. Patients have increased exposure to traditional and lupus specific risk factors, which accelerate plaque formation. Recurrent disease flares may facilitate...

Pentraxin 3 is associated with disease activity but not atherosclerosis in patients with systemic lupus erythematosus

Pentraxin 3 (PTX3) plays an important role in inflammation, immunity, and atherosclerosis. Plasma PTX3 level has drawn attention as a marker that responds to local inflammation. Systemic lupus erythematosus (SLE), a chronic inflammatory disorder which can affect multiple organs, develops atherosclerosis prematurely. We examined the hypotheses that the concentration of plasma PTX3 increases in patients with SLE and that PTX3 is associated with the disease activity and premature atherosclerosis. Plasma PTX3 concentrations were measured in 65 patients with SLE and 53 control subjects. The patients were also evaluated with respect to their clinical characteristics, disease activity indices, and corticosteroid therapy. We performed carotid ultrasonography to measure subclinical atherosclerosis in patients with SLE. Plasma PTX3 concentration of the SLE patients was significantly higher than that of the healthy controls (median 3.9 vs. 2.0 ng/mL, p < 0.001). In patients with SLE, PTX3 concentrations were correlated with SLEDAI (p = 0.011), BILAG index (p < 0.001), C-reactive protein (p < 0.001), anemia (p = 0.020), hypoalbuminemia (p = 0.022), and daily dose of prednisolone (p = 0.008) after adjustment for age and sex. PTX3 was not associated with disease duration, anti-ds DNA antibody, CH50, or carotid atherosclerosis. Patients with SLE have increased concentrations of PTX3 compared with control subjects. PTX3 was significantly associated with disease activity but not with carotid atherosclerosis.

Long-term follow-up in lupus nephritis patients treated with rituximab--clinical and histopathological response

To investigate the long-term clinical, histological and serological affects of B-cell-depleting therapy (BCDT) in patients with LN refractory to conventional treatment. Twenty-five patients, followed for a mean time of 36 months (9-95 months), were included. Renal disease activity was evaluated with the BILAG index and renal response was determined according to the LN European consensus statement. Renal biopsies were performed for histological evaluation at baseline and follow-up. Partial response (PR) or complete renal response (CR) was observed in 22 of 25 after a median of 12 months. Sixteen patients achieved CR after a median of 24 months. Six patients experienced a renal relapse. Proteinuria decreased significantly (P = 0.0002) from baseline to 36 months. A noteworthy histological improvement was seen in nearly all patients with a significant reduction in activity index (P = 0.01). Longer depletion time and low baseline values of IgM were indicative of achieving clinical remission during the first year after treatment (P = 0.03 and P = 0.04, respectively). In therapy-resistant LN, BCDT induced clinical and histological improvements in the majority of patients. Transition from PR to CR was mainly seen during the second year of follow-up. Patients with longer depletion time and low baseline levels of IgM were more likely to gain a faster remission, suggesting that the clinical benefit may be linked to suppression of autoreactive plasmablasts. Although formal evidence of BCDT in LN is lacking, our data may provide guidance to clinicians considering therapeutic options in patients with refractory LN.