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OBJECTIVE: In trials of systemic lupus erythematosus (SLE), the SLE Responder Index (SRI) is the most commonly used primary efficacy end point but has limited validation against long-term outcomes. We aimed to investigate associations of attainment of a modified version of the SRI (mSRI) with key clinical outcomes in SLE patients with up to 5 years of follow-up. METHODS: We used data from a large multicenter, longitudinal SLE cohort in which patients received standard of care. The first visit with active disease (defined as SLE Disease Activity Index 2000 [SLEDAI-2K] score ≥6) was designated as baseline, and mSRI attainment (defined as a reduction in SLEDAI-2K ≥4 points with no worsening in physician global assessment ≥0.3 points) was determined at annual intervals from baseline up to 5 years. Associations between mSRI attainment and outcomes including disease activity, glucocorticoid dose, flare, damage accrual, Lupus Low Disease Activity State (LLDAS), and remission were studied. RESULTS: We included 2,060 patients, with a median baseline SLEDAI-2K score of 8. An mSRI response was attained by 56% of patients at 1 year, with similar responder rates seen at subsequent annual time points. Compared to nonresponders, mSRI responders had significantly lower disease activity and prednisolone dose and higher proportions of LLDAS and remission attainment at each year, and less damage accrual at years 2 and 3. Furthermore, mSRI responder status at 1 year predicted clinical benefit at subsequent years across most outcomes, including damage accrual (odds ratio [OR] range 0.58-0.69, P < 0.05 for damage accrual ORs at all time points). CONCLUSION: In SLE patients with active disease receiving standard of care, mSRI attainment predicts favorable outcomes over long-term follow-up, supporting the clinical meaningfulness of SRI attainment as an SLE trial end point.

OBJECTIVE: Evidence for the utility of medications in settings lacking randomized trial data can come from studies of treatment persistence. The present study was undertaken to examine patterns of medication use in systemic lupus erythematosus (SLE) using data from a large multicenter longitudinal cohort. METHODS: Prospectively collected data from the Asia Pacific Lupus Collaboration cohort including disease activity (SLE Disease Activity Index 2000 [SLEDAI-2K]) and medication details, captured at every visit from 2013-2018, were used. Medications were categorized as glucocorticoids (GCs), antimalarials (AM), and immunosuppressants (IS). Cox regression analyses were performed to determine the time-to-discontinuation of medications, stratified by SLE disease activity. RESULTS: Data from 19,804 visits of 2,860 patients were analyzed. Eight medication categories were observed: no treatment; GC, AM, or IS only; GC plus AM; GC plus IS; AM plus IS; and GC plus AM plus IS (triple therapy). Triple therapy was the most frequent pattern (31.4% of visits); single agents were used in 21% of visits, and biologics in only 3%. Time-to-discontinuation analysis indicated that medication persistence varied widely, with the highest treatment persistence for AM and lowest for IS. Patients with a time-adjusted mean SLEDAI-2K score of ≥10 had lower discontinuation of GCs and higher discontinuation of IS. CONCLUSION: Most patients received combination treatment. GC persistence was high, while IS persistence was low. Patients with high disease activity received more medication combinations but had reduced IS persistence, consistent with limited utility. These data confirm unmet need for improved SLE treatments.

Background: The unmet need in systemic lupus erythematosus (SLE) with the current standard of care is widely recognised, but few studies have quantified this. The recent definition of treat-to-target endpoints and other thresholds of uncontrolled disease activity provide an opportunity to formally define unmet need in SLE. In this study, we enumerated the prevalence of these states and examined their association with adverse outcomes. Method(s): Data were collected prospectively in a 13-country longitudinal SLE cohort between 2013 and 2019. Unmet need was defined as never attaining lupus low disease activity state (LLDAS), a time-adjusted mean SLEDAI-2K (AMS) > 4, or ever experiencing high disease activity status (HDAS; SLEDAI-2K >=10). Health-related quality of life (HRQoL) was assessed using SF36 (v2) and damage accrual using the SLICC-ACR SLE Damage Index (SDI). Result(s): A total of 3384 SLE patients were followed over 30,313 visits (median [IQR] follow-up 2.4 [0.4, 4.3] years). Eight hundred thirteen patients (24%) never achieved LLDAS. Median AMS was 3.0 [1.4, 4.9]; 34% of patients had AMS > 4. Twenty-five per cent of patients had episodes of HDAS. Each of LLDAS-never, AMS>4, and HDAS-ever was strongly associated with damage accrual, higher glucocorticoid use, and worse HRQoL. Mortality was significantly increased in LLDAS-never (adjusted HR [95% CI] = 4.98 [2.07, 12.0], p<0.001) and HDAS-ever (adjusted hazard ratio (HR) [95% CI] = 5.45 [2.75, 10.8], p<0.001) patients. Conclusion(s): Failure to achieve LLDAS, high average disease activity, and episodes of HDAS were prevalent in SLE and were significantly associated with poor outcomes including organ damage, glucocorticoid exposure, poor quality of life, and mortality.Copyright © 2022, The Author(s).

Background: Healthcare quality for systemic lupus erythematosus (SLE) is a modifiable target for improving patient outcomes. We aimed to assess the quality of care processes in different clinic settings, comparing a subspecialty lupus clinic with hospital-based and private general rheumatology clinics. Method(s): Patients with SLE (n = 258) were recruited in 2016 from a subspecialty lupus clinic (n = 147), two hospital general rheumatology clinics (n = 56) and two private rheumatology clinics (n = 55). Data were collected from medical records and patient questionnaires. Quality of care was assessed using 31 validated SLE quality indicators (QI) encompassing diagnostic work-up, disease and comorbidity assessments, drug monitoring, preventative care and reproductive health. Per-QI performance was measured as a percentage of patients that met the QI relative to the number of patients eligible. Per-patient QI performance was calculated as a percentage of QIs met relative to the number of eligible QIs for each patient. Per-QI and per-patient QI performance were compared between the three clinic settings, and multiple regression performed to adjust for sociodemographic, disease and healthcare factors. Result(s): Per-QI performance was generally high across all clinic settings for diagnostic work-up, comorbidity assessment, lupus nephritis, drug monitoring, prednisolone taper, osteoporosis and pregnancy care. Median [IQR] per-patient performance on eligible QIs was higher in the subspeciality lupus clinic (66.7% [57.1-74.1]) than the hospital general rheumatology (52.7% [47.5-58.1]) and private rheumatology (50.0% [42.9-60.9]) clinics (p <0.001) and the difference remained significant after multivariable adjustment. The subspecialty lupus clinic recorded higher per-QI performance for documentation of disease activity, disease damage, cardiovascular risk factor and drug toxicity assessments, pre-immunosuppression hepatitis and tuberculosis screening, new medication counsell

BACKGROUND: The unmet need in systemic lupus erythematosus (SLE) with the current standard of care is widely recognised, but few studies have quantified this. The recent definition of treat-to-target endpoints and other thresholds of uncontrolled disease activity provide an opportunity to formally define unmet need in SLE. In this study, we enumerated the prevalence of these states and examined their association with adverse outcomes. METHODS: Data were collected prospectively in a 13-country longitudinal SLE cohort between 2013 and 2019. Unmet need was defined as never attaining lupus low disease activity state (LLDAS), a time-adjusted mean SLEDAI-2K (AMS) > 4, or ever experiencing high disease activity status (HDAS; SLEDAI-2K ≥10). Health-related quality of life (HRQoL) was assessed using SF36 (v2) and damage accrual using the SLICC-ACR SLE Damage Index (SDI). RESULTS: A total of 3384 SLE patients were followed over 30,313 visits (median [IQR] follow-up 2.4 [0.4, 4.3] years). Eight hundred thirteen patients (24%) never achieved LLDAS. Median AMS was 3.0 [1.4, 4.9]; 34% of patients had AMS > 4. Twenty-five per cent of patients had episodes of HDAS. Each of LLDAS-never, AMS>4, and HDAS-ever was strongly associated with damage accrual, higher glucocorticoid use, and worse HRQoL. Mortality was significantly increased in LLDAS-never (adjusted HR [95% CI] = 4.98 [2.07, 12.0], p<0.001) and HDAS-ever (adjusted hazard ratio (HR) [95% CI] = 5.45 [2.75, 10.8], p<0.001) patients. CONCLUSION: Failure to achieve LLDAS, high average disease activity, and episodes of HDAS were prevalent in SLE and were significantly associated with poor outcomes including organ damage, glucocorticoid exposure, poor quality of life, and mortality.

BACKGROUND: Healthcare quality for systemic lupus erythematosus (SLE) is a modifiable target for improving patient outcomes. We aimed to assess the quality of care processes in different clinic settings, comparing a subspecialty lupus clinic with hospital-based and private general rheumatology clinics. METHODS: Patients with SLE (n = 258) were recruited in 2016 from a subspecialty lupus clinic (n = 147), two hospital general rheumatology clinics (n = 56) and two private rheumatology clinics (n = 55). Data were collected from medical records and patient questionnaires. Quality of care was assessed using 31 validated SLE quality indicators (QI) encompassing diagnostic work-up, disease and comorbidity assessments, drug monitoring, preventative care and reproductive health. Per-QI performance was measured as a percentage of patients that met the QI relative to the number of patients eligible. Per-patient QI performance was calculated as a percentage of QIs met relative to the number of eligible QIs for each patient. Per-QI and per-patient QI performance were compared between the three clinic settings, and multiple regression performed to adjust for sociodemographic, disease and healthcare factors. RESULTS: Per-QI performance was generally high across all clinic settings for diagnostic work-up, comorbidity assessment, lupus nephritis, drug monitoring, prednisolone taper, osteoporosis and pregnancy care. Median [IQR] per-patient performance on eligible QIs was higher in the subspeciality lupus clinic (66.7% [57.1-74.1]) than the hospital general rheumatology (52.7% [47.5-58.1]) and private rheumatology (50.0% [42.9-60.9]) clinics (p <0.001) and the difference remained significant after multivariable adjustment. The subspecialty lupus clinic recorded higher per-QI performance for documentation of disease activity, disease damage, cardiovascular risk factor and drug toxicity assessments, pre-immunosuppression hepatitis and tuberculosis screening, new medication counselling

Systemic lupus erythematosus (SLE) remains a disease of high unmet clinical need. Because of substantial patient heterogeneity, the execution of clinical trials that successfully determine the efficacy of novel therapeutics compared with placebo is a continuous challenge. Clinician-reported outcome measures of treatment response used in SLE trials have evolved from the use of individual disease activity indices, including the SLE Disease Activity Index (SLEDAI) and British Isles Lupus Assessment Group (BILAG), to composite responder definitions such as the SLE Responder Index (SRI) and BILAG-Based Composite Lupus Assessment (BICLA), which are based on these indices. However, these approaches have notable drawbacks and defining the optimal clinical trial outcome measure for SLE remains a research goal. In this Viewpoint, we explore the strengths and limitations of existing indices and composite assessments, illustrating features which should be investigated in future analysis of trial data. Further, we provide a platform from which to advance new approaches to endpoint design, which is crucial to improve the interpretability and success of subsequent clinical trials in SLE.Copyright © 2021 Elsevier Ltd

Background/Purpose: The Lupus Low Disease Activity State (LLDAS) has recently undergone prospective longitudinal validation in a multinational cohort, demonstrating the association of attaining LLDAS with protection from damage accrual and fl are, results that have been replicated in numerous other observational cohorts. Domain 1 of the original LLDAS operational definition captured the absence of significant disease activity by requiring SLEDAI-2K <=4, the absence of SLEDAI activity in major organs, and also the absence of haemolytic anaemia (HA) and gastrointestinal (GI) activity, manifestations not accounted for in the SLEDAI-2K. The requirement for absence of these infrequent clinical features creates the potential to misclassify patients' LLDAS status, as there is no formal definition of HA and GI activity. This has in turn limited regulatory approval of LLDAS as a clinical trial endpoint. To determine the requirement for capture of HA and GI activity in the LLDAS definition we performed a sensitivity analysis. Method(s): We analysed the prospective LLDAS longitudinal validation dataset. To evaluate whether HA and GI activity were captured by the physician global assessment (PGA) criterion of LLDAS, we compared patients with and without HA and GI with respect to median PGA and the proportion of patients with PGA >1. The impact on subsequent damage accrual and fl are of time-dependent associations of criterion 1 of the LLDAS definition, with and without inclusion of HA and GI activity, were assessed using Cox regression analysis. Result(s): Data on 1,707 patients, with 12,689 visits over 2.2 years were analysed. HA and GI activity were recorded in 28 and 73 visits, respectively. The median PGA, and the proportion of patients with PGA >1, were significantly higher in patients with either HA or GI activity (Table 1). Omitting the requirement for absence of HA and GI activity from criterion 1 of the LLDAS definition had no meaningful impact on the protective associ

Background/Purpose: A key goal of treatment of SLE is the prevention of irreversible organ damage. The ability to identify patients at increased risk for damage could select patients for early intervention but is currently lacking. Conventional studies of damage outcomes in SLE utilize composite disease activity scores, and associations with damage are only modest. We evaluated whether using all available data in an unbiased fashion, including continuous laboratory data usually analysed dichotomously in disease activity scores, could give rise to superior predictive algorithms for organ damage in SLE. Method(s): Prospectively collected longitudinal data from a 13-centre multinational cohort were used. Each visit was assigned yes/no as being in a damage-transition period based on whether the nearest subsequent annual measurement of organ damage (SLICC damage index) increased. Candidate variables included demographic (3), baseline serology (4), medication classes (anti-malarial, immunosuppressant, and glucocorticoid), routine clinical laboratory parameters (14) and SLEDAI-2K. Logistic regression models were selected to predict the probability of damage transition using backward, forward, and hybrid stepwise selection methods, either including or excluding SLEDAI-2K. The primary metric evaluating performance was area under the receiver operating characteristic curve (AUC) for association with damage transition. Result(s): Data from 15,625 visits of 1,621 patients were split randomly 80:20 into training and test datasets; a separate cohort (2,178 visits, 188 patients) was used for independent validation. As there were only 1,157 damage transition visits in the training dataset, oversampling was used to create a dataset with 23,120 visits with a 'transition visit' ratio of 50%. Altogether 221 (~ 2 million) models with different combinations of predictors were analysed. After excluding models with >20 variables or training AUC < 0.62 we ranked 43,332 models excluding SLED

OBJECTIVE: Randomised controlled trials (RCTs) in systemic lupus erythematosus (SLE, lupus) typically adopt composite responder definitions as primary efficacy endpoints, however outcomes within individual organ domains are also important to understand. The aim of this scoping review was to evaluate how organ-specific disease activity and therapeutic responses have been measured and reported in lupus RCTs. METHOD(S): We searched MEDLINE, EMBASE, Cochrane registry and clinicaltrials.gov. Eligible studies were RCTs investigating efficacy of an immune-directed drug therapy in active SLE, published January 2000-March 2021, excluding studies limited to lupus nephritis. Data were extracted independently in duplicate into a template and summarised descriptively. RESULT(S): Thirty-four RCTs were included, of which 32 (94%) reported activity and/or responses in at least one organ domain. Study populations had a high, although variable, frequency of baseline musculoskeletal and mucocutaneous activity and low but also variable representation of other domains. Definitions of organ-specific responses were inconsistent, even within individual instruments. Response in most organ domains were evaluated using BILAG and SLEDAI components but meaningful comparison between treatment arms was limited by small subgroups analysed in a post hoc fashion. Specific mucocutaneous and arthritis instruments were also used, including within pre-specified organ-specific endpoints, which discriminated between treatment arms in some studies. CONCLUSION(S): Mucocutaneous and musculoskeletal manifestations predominate in SLE RCTs. Organ-specific outcome measures are commonly reported, but definitions of involvement and response are inconsistent. Research into the development of new outcome measures for key organ domains, and validation and comparison of response definitions using existing instruments, is needed.Copyright © The Author(s) 2021. Published by Oxford University Press on behalf of the Briti

OBJECTIVE: The prevalence and associations of leucopenia in SLE remain incompletely understood. We evaluated associations of disease activity and medication use with leucopenia (lymphopenia and neutropenia) in a multinational, prospectively followed SLE cohort. METHODS: Data from the Asia Pacific Lupus Collaboration cohort, in which disease activity and medications were prospectively captured from 2013 to 2018, were used. Predictors of lymphopenia (lymphocyte count <0.8 × 109/l) and neutropenia (neutrophil count <1.5 × 109/l) were examined using multiple failure, time-dependent survival analyses. RESULTS: Data from 2330 patients and 18 287 visits were analysed. One thousand and eighteen patients (43.7%) had at least one episode of leucopenia; 867 patients (37.2%) had lymphopenia, observed in 3065 (16.8%) visits, and 292 (12.5%) patients had neutropenia, in 622 (3.4%) visits. After multivariable analyses, lymphopenia was associated with overall disease activity, ESR, serology, prednisolone, AZA, MTX, tacrolimus, CYC and rituximab use. MTX and ciclosporin were negatively associated with neutropenia. Lupus low disease activity state was negatively associated with both lymphopenia and neutropenia. CONCLUSION: Both lymphopenia and neutropenia were common in SLE patients but were differentially associated with disease and treatment variables. Lymphopenia and neutropenia should be considered independently in studies in SLE.

Aims: Cognitive symptoms are commonly reported by lupus patients. Previous studies have found cognitive deficits in 30-50% of patients, but clinical associations with cognitive function are poorly understood. This study aims to examine the relationship between SLE disease parameters and cognition. It is the first Australian report on cognitive function in SLE. Method(s): Patients from the Australian Lupus Registry and Biobank (ALRB) were consecutively recruited from Monash Lupus Clinic between October 2018-December 2019. Cognitive assessment was performed using the one-hour conventional neuropsychiatric test battery recommended by the American College of Rheumatology for SLE. Seven tests were included in analysis. Clinical parameters including disease activity (SLE Disease Activity Index (SLEDAI-2 K)) and damage (SLE International Collaborating Clinics Damage Index (SDI)) are collected prospectively as per ALRB protocol; indices closest to the cognitive assessment date were used for this analysis. Univariate and multivariate linear regression were performed to look for predictors of changes in cognitive tests. Result(s): 80 patients (92.5% female) were recruited, median age 47 (range 21-64). 66% were Caucasian; the rest predominantly Asian, and all had good English proficiency. Median disease duration was 12 years (range 0.24-39 years). After adjusting for age, premorbid IQ and disease activity, damage was significantly associated with visual memory (Rey-Osterrieth Complex Figure Test) (P = 0.007) and processing speed (Coding WAIS IV Subtest) (P = 0.006). Age and premorbid IQ were significantly associated with multiple cognitive tests. There were no significant associations between cognitive test results and current disease activity or medication exposure. Conclusion(s): Cognitive function in SLE is associated with damage. In contrast, we did not see association with disease activity at the time of testing or medication exposure. Future analyses taking into account

Objective: Treat-to-target end points for systemic lupus erythematosus (SLE) have been assessed for their impact on damage accrual and flare, but whether they have an impact on the high health care utilization and costs in SLE has not been studied. The purpose of this study was to examine our hypothesis that the recently described lupus low disease activity state (LLDAS) would be associated with reduced health care cost. Method(s): Data from a single tertiary hospital longitudinal SLE cohort were assessed. Baseline demographics, disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K], physician global assessment [PhGA], and flare index), and medication use were evaluated, and direct health care utilization and cost data were obtained from hospital information systems. LLDAS was defined as previously published: briefly, SLEDAI-2K <=4 with no new activity, PhGA <=1, prednisolone <=7.5 mg/day, and optimal standard immunosuppressive agents. Analysis was performed using multivariable linear regression. Result(s): Two hundred SLE patients, contributing 357.8 person-years of observation, were included. A history of lupus nephritis was present in 42% of patients, and damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index >0) was present at study commencement in 57.3% of patients. The mean +/- SD annual direct medical cost per patient was US$7,413 +/- 13,133/year. In multivariable analysis, increased cost was associated with the presence of baseline organ damage (41.7% increase; P = 0.009) and corticosteroid use (>7.5-15 mg/day: 55.7% increase; P = 0.02; and >15 mg/day: 202% increase; P < 0.001). In contrast, spending >=50% of the observation period in LLDAS was associated with a 25.9% reduction in annual direct medical cost (P = 0.04). Conclusion(s): Greater time spent in LLDAS was associated with significantly reduced direct hospital health care costs among patients with SLE.Copyright © 2019

OBJECTIVE: Treat-to-target end points for systemic lupus erythematosus (SLE) have been assessed for their impact on damage accrual and flare, but whether they have an impact on the high health care utilization and costs in SLE has not been studied. The purpose of this study was to examine our hypothesis that the recently described lupus low disease activity state (LLDAS) would be associated with reduced health care cost. METHODS: Data from a single tertiary hospital longitudinal SLE cohort were assessed. Baseline demographics, disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K], physician global assessment [PhGA], and flare index), and medication use were evaluated, and direct health care utilization and cost data were obtained from hospital information systems. LLDAS was defined as previously published: briefly, SLEDAI-2K ≤4 with no new activity, PhGA ≤1, prednisolone ≤7.5 mg/day, and optimal standard immunosuppressive agents. Analysis was performed using multivariable linear regression. RESULTS: Two hundred SLE patients, contributing 357.8 person-years of observation, were included. A history of lupus nephritis was present in 42% of patients, and damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index >0) was present at study commencement in 57.3% of patients. The mean ± SD annual direct medical cost per patient was US$7,413 ± 13,133/year. In multivariable analysis, increased cost was associated with the presence of baseline organ damage (41.7% increase; P = 0.009) and corticosteroid use (>7.5-15 mg/day: 55.7% increase; P = 0.02; and >15 mg/day: 202% increase; P < 0.001). In contrast, spending ≥50% of the observation period in LLDAS was associated with a 25.9% reduction in annual direct medical cost (P = 0.04). CONCLUSION: Greater time spent in LLDAS was associated with significantly reduced direct hospital health care costs among patients with SLE.

Background: The objective of this study was to compare the attainability and effect of the Lupus Low Disease Activity State (LLDAS) and The Definitions of Remission in SLE (DORIS) group remissions on outcomes in a prospective multinational study. Method(s): A prospective multinational cohort study was undertaken in 13 centres between 2013-2017. Time dependent Cox proportional hazards models were used to compare LLDAS and DORIS definitions of remission in terms of impact on disease flares and damage accrual. Result(s): 1735 SLE patients were recruited, and followed for (mean +/- SD) 2.2 +/- 0.9 years, totalling 12,534 visits. LLDAS was achieved in 6922 visits (54.6%). In contrast, remission was achieved in 1.1%- 15.4% of visits. LLDAS attainment at any visit was associated with significantly reduced subsequent flare (HR 0.65, 95% CI 0.56- 0.76, P < 0.001) and damage accrual (HR 0.55, 95% CI 0.43-0.70, P < 0.001). In contrast, only the least stringent remission definition was associated with reduced damage accrual (HR 0.58, 95% CI 0.39- 0.88, P 0.01). Only remission definitions including serological remission were significantly associated with reduction in subsequent flares. Patients who spent 350% of their observed time in LLDAS had two-fold reduction in risk of damage accrual (HR 0.53, 95% CI 0.41-0.68, P < 0.001), while only the least stringent remission definition, or the related definition excluding serology, were significantly protective against damage (HR 0.59, 95% CI 0.42-0.83, P 0.003; HR 0.69, 95% CI 0.48-0.99, P 0.05, respectively). Conclusion(s): LLDAS was more attainable than any remission definition, whilst still conferring significant protection against flares and damage accrual. Among the remission definitions only the least stringent could be shown to be associated with significant reduction in damage accrual, likely reflecting a low frequency of remission attainment overall, and normal serology was required for protection from subsequent flare. LLDAS

Background: The recently validated Lupus Low Disease Activity State (LLDAS) definition has been shown to have utility as a treat to target endpoint in SLE, whereby LLDAS attainment is associated with reduction in permanent damage accrual. Robust evaluation is required to ensure this protective association is not simply reflective of milder disease phenotypes being over-represented among LLDAS attainers. Objective(s): To assess the effect of attainment of LLDAS on damage accrual in patients with active disease at baseline. SLEDAI-2K>6 was chosen as this reflects clinical trial entry criteria. Method(s): A prospective multinational cohort study was undertaken in 13 centres between 2013-2017. Patients with SLE were recruited, SLEDAI-2k, SELENA flare index, PGA, and medication data collected at every visit, and damage score (SLICC-ACR damage index (SDI)) collected annually. Subgroup analyses were performed to assess the effect of LLDAS on damage accrual in patients who had active disease at baseline (SLEDAI-2K>6). Time-dependent hazards regression models were used to assess the association of attainment of LLDAS at any time point, and proportion of time in LLDAS at the 50% observed time cut-off, with accrual of irreversible end-organ damage. Result(s): 1, 735 patients were followed for (mean +/- SD) 2.2 +/- 0.9 years, totalling 12, 717 visits. LLDAS attainment was less frequent in patients with active disease at baseline (901 of 3835 visits in LLDAS, 23.5%), compared to patients with SLE-DAI2-K<6 at baseline (5190 of 8845 visits in LLDAS, 58.7%), p<0.001. In contrast, compared to those with baseline SLEDAI-2K<6, patients with active disease at baseline demonstrated a stronger association of LLDAS attainment with reduction in risk of damage accrual, in visit by visit analysis (HR 0.49, 95% CI 0.28-0.86, p 0.01 vs HR 0.72, 95% CI 0.52-0.99, p 0.05), and in analysis of cumulative time spent in LLDAS (HR 0.52, 95% CI 0.33-0.83, p 0.01 vs HR 0.65, 95% CI 0.47-0.91, p0.01). C

Aim: The aim of this manuscript is to describe the development of the Asia Pacific Lupus Collaboration (APLC) cohort. Method(s): The APLC cohort is an ongoing, prospective longitudinal cohort. Adult patients who meet either the American College of Rheumatology (ACR) Modified Classification Criteria for systemic lupus erythematosus (SLE), or the Systemic Lupus International Collaborating Clinics (SLICC) Classification Criteria, and provide informed consent are recruited into the cohort. Patients are routinely followed up at 3- to 6-monthly intervals. Information on demographics, clinical manifestations, treatment, pathology results, outcomes, and patient-reported quality of life (Short-form 36 version 2) are collected using a standardized case report form. Each site is responsible for obtaining local ethics and governance approval, patient recruitment, data collection, and data transfer into a centralized APLC database. Result(s): The latest APLC cohort comprises 2160 patients with >12 000 visits from Australia, China, Hong Kong, Indonesia, Japan, Malaysia, Philippines, Singapore, Taiwan and Thailand. The APLC has proposed the Lupus Low Disease Activity State (LLDAS) as a treat-to-target (T2T) endpoint, and reported several retrospective and cross-sectional analyses consistent with the validity of LLDAS. Longitudinal validation of LLDAS as a T2T endpoint is currently underway. Conclusion(s): The APLC cohort is one of the largest contemporary SLE patient cohorts in the world. It is the only cohort with substantial representation of Asian patients. This cohort represents a unique resource for future clinical research including evaluation of other endpoints and quality of care.Copyright © 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd

Background/purpose: Systemic Lupus Erythematosus (SLE) patients are at increased risk of osteoporosis, due to disease-related and traditional risk factors including common use of glucocorticoids (GC). Bone mineral density (BMD) screening is important for overall fracture risk assessment; in Australia, it is reimbursed under the Medicare Benefits Schedule (MBS) for specific criteria. Objective(s): To evaluate compliance with BMD testing according to MBS reimbursement schedule. Method(s): Data on BMD testing and patient characteristics where obtained from the Australian Lupus Registry. Descriptive statistics were used to evaluate patient characteristics at the time of BMD testing. Result(s): Patients with at least 2 annual visits and seen in the last 5 years were included in the analysis (n = 263); 154 (58.6%) had at least one BMD. Most (90.3%) had taken GC at some point. The mean age at the time of undergoing the first test was 42 years. Of the patients tested, 15.6% were identified as having osteoporosis (t score <=-2.5) and 46.1% were osteopenic (t score <-1). Of 273 BMD performed, at least one of the MBS reimbursement criteria (see Table 1) was present for 59.7% of tests. In those did not fulfil criteria, 39% had at least osteopenia or osteoporosis. In 63.6% of cases, the patient had met the cumulative prednisolone exposure definition but was not on GC at the time of the test. Of the 154 patients who had BMD testing, 46.7% had repeated measurements. Compliance with testing frequency was met for 74.8% of repeat tests. Conclusion(s): The majority of patients who had BMD testing had risk factors for osteoporosis. Our audit shows that a significant proportion of patients with previous GC exposure would have been missed the strict criteria of MBS reimbursement. Since the value for repeated BMD testing is controversial, further studies should explore their utility in this population.

Background: The Definitions of Remission in SLE (DORIS) group has proposed multiple definitions of remission, but these are infrequently attained and have not been prospectively evaluated in relation to protection from damage accrual. In contrast, the Lupus Low Disease Activity State (LLDAS) is more attainable, and has been shown to be associated with improved patient outcomes. Objective(s): To compare the attainability, and association with outcomes, of LLDAS and remission in a prospective multicentre study. Method(s): A prospective multinational cohort study was undertaken in 13 centres between 2013-2017. Time dependent Cox proportional hazards models were used to compare LLDAS and DORIS definitions of remission in terms of impact on disease flares and damage accrual. Result(s): 1735 SLE patients were recruited, and followed for (mean+/-SD) 2.2+/-0.9 years, totalling 12, 717 visits. LLDAS was achieved in 47.2% of observed visits. In contrast, remission was achieved in 1.1 %-15.4% of visits depending on the stringency of remission definition. LLDAS attainment at any visit was associated with significantly reduced subsequent flare (HR 0.65, 95%CI 0.56-0.75, p<0.001) and damage accrual (HR 0.59, 95%CI 0.45-0.76, p<0.001). In contrast, only the least stringent remission definition was associated with reduced damage accrual (HR 0.58, 95%CI 0.39-0.88, p 0.01). Only remission definitions including serological remission were significantly associated with reduction in subsequent flares. Patients who spent >=50% of their observed time in LLDAS had reduction in damage accrual (HR 0.54, 95% CI 0.42-0.70, p<0.001) compared to patients with <50% of observed time in LLDAS; again, only the least stringent remission definition, or the related definition excluding serology, were associated with reduced damage (HR 0.59, 95% CI 0.42-0.83, p 0.003; HR 0.69, 95%CI 0.48-0.99, p0.05, respectively). Conclusion(s): LLDAS was more attainable than any remission definition, whilst still confe

Background/Purpose: The Definitions of Remission in SLE (DORIS) group has proposed multiple definitions of remission, but these are infrequently attained and have not previously been evaluated in relation to protection from damage accrual in a prospective study. In contrast, the Lupus Low Disease Activity State (LLDAS) is potentially more attainable, and has been shown to be associated with improved patient outcomes. The objective of this study was to compare the attainability and effect of LLDAS and remission on outcomes in a prospective multicenter study. Method(s): A prospective multinational cohort study was undertaken in 13 centres between 2013-2017. Time dependent Cox proportional hazards models were used to compare LLDAS and DORIS definitions of remission in terms of impact on disease flares and damage accrual. All eight DORIS remission definitions include a clinical SLEDAI-2K of 0, and PGA (0- 3) <0.5, whilst varying in allowing for serological activity, prednisolone and immunosuppressants. Result(s): 1735 SLE patients (meeting ACR or SLICC criteria) were recruited, and followed for (mean +/- SD) 2.2 +/- 0.9 years, totalling 12,534 visits. LLDAS was achieved in 6922 visits (54.6%). In contrast, remission was achieved in 140 (1.1%) to 1952 (15.4%) visits depending on definition. LLDAS attainment at any visit was associated with significantly reduced subsequent flare (HR 0.65, 95%CI 0.56-0.76, p<0.001) and damage accrual (HR 0.55, 95%CI 0.43-0.70, p<0.001). In contrast, considering every visit, only the least stringent remission definition (allowing serology, prednisolone <=5mg, and immunosuppression) could be demonstrated to be associated with significantly reduced subsequent damage accrual (HR 0.58, 95%CI 0.39-0.88, p 0.01). Only remission definitions including serological remission were significantly associated with reduction in subsequent flares. Using a cut off of >=50% of observed time meeting a given definition, LLDAS resulted in a two-fold reduction in

Background/Purpose: Measurement of treatment response in SLE clinical trials has been based on measurement of change from baseline; however a treat-to-target analysis has seldom been applied. The Lupus Low Disease Activity State (LLDAS), a potential response indicator for lupus clinical trials, has been found to correlate with reduced damage accrual in SLE1, indicating it may be a useful treatment target in the clinic. In a trial setting, LLDAS correlated with key outcome measures and discriminated responders from non-responders in a post-hoc analysis of the phase IIb MUSE trial of anifrolumab2. We evaluated the utility of LLDAS in this post-hoc analysis of the BLISS-523 and BLISS-764 trials of intravenous belimumab in patients with moderate-severe SLE. Method(s): LLDAS attainment was assessed at baseline and week 52. LLDAS is defined as having all of the following: a) SLEDAI-2K<=4 without major organ activity; b) no new disease activity; c) physician global assessment of activity score (PGA, 0-3)1; d) prednisolone dose <=7.5mg/day; and e) standard immunosuppressants allowed. Attainment of LLDAS, association with the primary trial endpoint (SRI-4), discrimination between belimumab and placebo-treated patients, and predictors of LLDAS attainment, were evaluated using descriptive statistics and the Chi-square test, using R (v3.4.3). Result(s): Few patients were in LLDAS at study entry (0-2.2%). At week 52, in both studies, fewer patients attained LLDAS compared to the SRI-4 (Table 1). At week 52, for belimumab 10mg/kg, 17.0% of patients in BLISS-52 and 19.3% of patients in BLISS-76 who achieved an SRI-4 also attained LLDAS. In BLISS-52, significantly more patients attained LLDAS at week 52 on belimumab 10mg/kg compared to placebo (12.5% vs 5.8%, p=0.02), with a near significant difference at the same time-point in BLISS-76 (14.4% belimumab 10mg/kg vs placebo 7.8%, p=0.06). Numerically more patients were in LLDAS at week 52 for both studies for the belimumab 1mg/kg gro

Background: The Monash Lupus Clinic, based at Monash Health in Melbourne, is Australia's first multi-disciplinary specialist lupus clinic that services a broad community and acts as a research hub, particularly as the foundation site and headquarters of the Australian Lupus Registry and Biobank (ALRB). Since its inception in 2007, the clinic has been co-run by rheumatologists and nephrologists. A carefully curated clinical dataset has been collected since clinic inception. Objective(s): We provide an overview of the characteristics and longitudinal outcomes of adult lupus patients treated at the Monash Lupus Clinic over the last ten years. Method(s): A ten-year-long dataset from the original Monash Lupus Clinic cohort, of patients subsequently enrolled in the Australian Lupus Registry and Biobank, was used for the analysis. The dataset included information on patient demographics, lupus diagnosis, serological profile, treatments, disease activity, damage accrual and other medical outcomes such as renal failure, adverse pregnancy outcomes and hospitalisations. Descriptive statistics were used to summarise the characteristics of the study population. Bivariate tests and regression analyses were used for comparisons between inception cohort patients, enrolled in the registry within 15 months of their Systemic Lupus Erythematosus (SLE) diagnosis, and existing SLE patients enrolled later in their disease course. Result(s): Of the 329 enrolled patients, the median age at enrolment was 38.0 years and 87.8% of were female. Most patients were either of Caucasian (48.6%) or Asian (36.5%) ethnicity. Patients were enrolled a median of 4.0 years after their SLE diagnosis; 31.0% of patients were inception cohort patients. Most patients (95.4%) had an abnormal titre of anti-nuclear antibodies; 65.0% of the cohort were positive for anti-dsDNA autoantibodies. Included patients were observed for a median observation period of 3.9 years. The median adjusted mean SLEDAI score over the

Background/Purpose: The adoption of treat to target approaches for Systemic Lupus Erythematosus (SLE) requires the definition of a target state validated for improved patient outcomes. The Lupus Low Disease Activity State (LLDAS) has been shown in multiple retrospective and cross-sectional studies to have face, content, construct and criterion validity and be associated with better quality of life. We report on a multinational prospective study undertaken to determine whether LLDAS attainment is associated with protection from flare and damage accrual. Method(s): A prospective multicenter cohort study was undertaken in 13 centres between 2013-2017. Patients with SLE (ACR or SLICC criteria) were recruited, SLEDAI-2k, SELENA flare index, PGA, and medication data collected at every visit, and damage (SLICC-ACR damage index (SDI)) collected annually. Time-dependent Cox proportional hazards models were used to assess the association of LLDAS at any time point, as well as the effect of the proportion of time spent in LLDAS, with disease flare and damage accrual (increase in SDI). Result(s): 1735 patients (93% female, 77.7% anti-dsDNA positive, mean baseline SLEDAI-2k 4.3 +/- 4.4) were followed for (mean +/- SD) 2.2 +/- 0.9 years, totalling 12,534 visits (mean interval 0.34 +/- 0.17y). LLDAS was achieved in 54.6% of observed visits. Attainment of LLDAS at any timepoint was highly significantly protective against subsequent flare and damage accrual (Table 1). Conclusion(s): In this large prospective multicenter study, we demonstrate that LLDAS attainment provides significant protection against disease flares and damage accrual. Our findings support the use of LLDAS as a treatment target for SLE, and as an outcome measure for clinical trials and treat-to-target strategies. (Table Presented) .

Background: Adoption of treat to target approaches for Systemic Lupus Erythematosus (SLE) requires the definition of a target state validated for improved patient outcomes. The Lupus Low Disease Activity State (LLDAS) has been shown in multiple retrospective and cross-sectional studies to have face, content, construct and criterion validity and be associated with better quality of life. We report on a multinational prospective study undertaken to determine whether LLDAS attainment is associated with protection from flare and damage accrual. Method(s): A prospective multinational cohort study was undertaken in 13 centres between 2013-2017. Patients with SLE were recruited, SLEDAI-2k, SELENA flare index, PGA, and medication data collected at every visit, and damage (SLICC-ACR damage index (SDI)) collected annually. Time-dependent Cox proportional hazards models were used to assess the association of LLDAS at any time point, as well as the effect of the proportion of time spent in LLDAS, with disease flare and damage accrual (increase in SDI). Result(s): 1735 patients were followed for (mean +/- SD) 2.2 +/- 0.9 years, totalling 12,717 visits. LLDAS was achieved in 54.6% of visits. Attainment of LLDAS at any timepoint was protective against subsequent flare (HR 0.65, 95%CI 0.56-0.76, P < 0.001) and damage accrual (HR 0.55, 95%CI 0.43-0.70, P < 0.001). Similarly, patients who spent >=50% of their observed time in LLDAS had reduction in risk of flare (RR 0.41, P < 0.001) and damage accrual (RR 0.59, P < 0.001), compared to those with < 50% of observed time in LLDAS. Increased durations of sustained LLDAS were associated with incremental reduction in risk of damage accrual. Conclusion(s): LLDAS attainment provides significant protection against disease flare and damage accrual. Our findings support the use of LLDAS as a treatment target in SLE, and as an outcome measure for clinical trials and treat-to-target strategies.

Objective: To examine longitudinal associations of active lupus nephritis with organ damage accrual in patients with systemic lupus erythematosus (SLE). Method(s): This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score >0 units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate <50%/proteinuria >3.5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual. Result(s): Patients (N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p < 0.02). Active lupus nephritis was strongly associated with damage accrual in renal but not in non-renal organ domains (hazard ratios = 13.0 (95% CI: 6.58, 25.5) p < 0.001 and 0.96 (95% CI: 0.69, 1.32) p = 0.8, respectively). There was no effect of ethnicity on renal damage accrual, but Asian ethnicity was significantly associated with reduced non-renal damage accrual. Conclusion(s): Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated w

AIM: The aim of this manuscript is to describe the development of the Asia Pacific Lupus Collaboration (APLC) cohort. METHOD: The APLC cohort is an ongoing, prospective longitudinal cohort. Adult patients who meet either the American College of Rheumatology (ACR) Modified Classification Criteria for systemic lupus erythematosus (SLE), or the Systemic Lupus International Collaborating Clinics (SLICC) Classification Criteria, and provide informed consent are recruited into the cohort. Patients are routinely followed up at 3- to 6-monthly intervals. Information on demographics, clinical manifestations, treatment, pathology results, outcomes, and patient-reported quality of life (Short-form 36 version 2) are collected using a standardized case report form. Each site is responsible for obtaining local ethics and governance approval, patient recruitment, data collection, and data transfer into a centralized APLC database. RESULTS: The latest APLC cohort comprises 2160 patients with >12 000 visits from Australia, China, Hong Kong, Indonesia, Japan, Malaysia, Philippines, Singapore, Taiwan and Thailand. The APLC has proposed the Lupus Low Disease Activity State (LLDAS) as a treat-to-target (T2T) endpoint, and reported several retrospective and cross-sectional analyses consistent with the validity of LLDAS. Longitudinal validation of LLDAS as a T2T endpoint is currently underway. CONCLUSION: The APLC cohort is one of the largest contemporary SLE patient cohorts in the world. It is the only cohort with substantial representation of Asian patients. This cohort represents a unique resource for future clinical research including evaluation of other endpoints and quality of care.

Background and Aims Systemic lupus erythematosus (SLE) is associated with significant impairment of health-related quality of life (HR-QoL). The Lupus Low Disease Activity State (LLDAS) definition has not been previously evaluated for association with patient reported outcomes. The objective of this study was to determine whether LLDAS was associated with better HR-QoL, and examine predictors of HR-QoL, in a large multiethnic, multinational cohort of SLE patients. Methods HR-QoL was measured using the Medical Outcomes Study 36-item Short Form Health Survey (SF-36v2) in a prospective study of 1422 patients. Disease status was measured using SLE disease activity index (SLEDAI-2K), physician global assessment (PGA) and LLDAS. Results Significant differences in SF-36 domain scores were found between patients stratified by ethnic group, education level, damage score, and with the presence of active musculoskeletal or cutaneous manifestations. In multiple linear regression analysis, Asian ethnicity (p<0.001), a higher level of education (p<0.001), younger age (p<0.001) and shorter disease duration (p<0.01) remained significantly associated with better physical component scores (PCS). Musculoskeletal disease activity (p<0.001) was negatively associated with PCS, and cutaneous activity (p=0.04) was negatively associated with mental component scores (MCS). Patients in LLDAS had better PCS (p<0.001) and MCS (p<0.001) scores and significantly better scores in multiple individual SF-36 domain scores. Disease damage was associated with worse PCS (p<0.001), but not MCS scores. Conclusions Ethnicity, education, disease damage, and specific organ involvement impacts on HR-QoL in SLE. Attainment of LLDAS is associated with better HR-QoL.

Objectives: To compare the health status concerns of patients with systemic lupus erythematosus (SLE) and of their physicians. Method(s): Cross-sectional questionnaire study of SLE patients and their treating physicians at a tertiary disease-specific outpatient clinic. Patients and physicians completed a questionnaire regarding their concern about specific disease manifestations and impact on quality of life. For each item, degree of concern was rated on a five-point Likert scale and summarized as median (interquartile range). Ratings between patients and physicians were compared using Mann-Whitney U tests. Result(s): A total of 84 patients and 21 physicians participated. Patients' predominant concerns centred on function and fatigue, whereas physicians' concerns focused on SLE-related organ complications. Of the 10 highest ranked patient concerns, only two were common to the 10 highest ranked physician concerns, while physicians rated seven significantly differently; all 10 highest ranked physician concerns were rated significantly lower by patients. The three highest ranked patient concerns (fatigue, pain and feeling worn out) were routinely assessed by 47.6%, 42.9% and 9.5% of physicians, respectively. Conclusion(s): There was significant discordance between SLE patient and physician health status concerns. Items which were ranked highly by patients were not assessed consistently by physicians, highlighting a significant gap in healthcare communication.Copyright © 2017, © The Author(s) 2017.

Aims. To compare the clinical characteristics of SLE patients meeting the American College of Rheumatology (ACR) classification criteria (1997) with those meeting the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria (2012) in the Asia Pacific Lupus Collaboration (APLC) cohort. Methods. All patients fulfilled either the ACR criteria (>=4 of 11 items) or SLICC criteria (>=4 of 17 items, including >=1 clinical and >=1 immunologic criteria, or biopsy-proven lupus nephritis (LN) + >=1 immunological criterion), evaluated at enrolment. Demographic and clinical data were compared using Kruskal Wallis (for medians) or chi-squared (proportions) tests. Results. 1735 patients were studied with a median ([IQR] (range)) follow up of 795 [532, 1087] (0, 1443) days. 1716 (98.9%) and 1668 (96.1%) patients met SLICC and ACR criteria respectively. 1649 (95%) patients met both criteria (ACR-SLICC group), 67 (3.9%) SLICC criteria only and 19 (1.1%) ACR criteria only. Patients in ACR-only and SLICC-only groups were significantly older than the ACR-SLICC group (median age (IQR); 50 (37, 59), 46 (34, 55), 40 (31, 50), respectively; p=0.003). At recruitment, both ACR-only and SLICC-only patients had lower SLEDAI-2k score compared to ACR-SLICC group (2 (0, 4), 2 (1, 4), 4 (2, 6) respectively (p-value=0.003), and fewer SLICC-only patients were in flare. During the observation period, SLICC-only patients had the lowest time-adjusted mean (TAM) SLEDAI-2k (P<0.01) and prednisolone dose (P<0.01), lowest proportions of flares (P<0.01) and damage accrual (P=0.4), and highest proportion of patients achieving Lupus Low Disease Activity State (LLDAS) at least once (P=0.07). In contrast, ACR-only patients had the highest proportion of patients experiencing flares and least proportion of achieving LLDAS. Conclusion. We observed a high overlap between the two classification criteria, but the use of both criteria captured a larger cohort overall. In this cohort, patients

Background and aims The Monash Lupus Clinic is Australia's first multi-disciplinary specialist lupus clinic, which runs in parallel with a clinical registry program providing healthcare quality and outcomes data for research purposes. We aim to provide an overview of the characteristics and longitudinal outcomes of lupus patients treated at the Monash Lupus Clinic over the last ten years. Methods Outcome measures included disease activity, medication use, damage accrual and other clinically-relevant events. Results Over the last 10 years, we have observed improvements in indices associated with better healthcare quality. We observed a significant reduction in the proportion of patients with a maximum SLEDAI-2K score >=10 over time (chi2 test for trend, p<0.001), and a significant trend of an increase in the proportion of patients spending >50% of their observed time meeting the criteria for LLDAS (chi2 test for trend, p=0.005). There was also a reduction in the proportion of patients experiencing at least one mild/moderate flare (p<0.001) or severe flare (p=0.006). We also observed a change in the medication use over the last 10 years, with a notable reduction in the use of higher doses of prednisolone (>7.5 mg/day; p=0.014). Conclusions Running a multi-disciplinary clinic alongside research activity is both feasible and worthwhile. Systematic collection of longitudinal data on SLE patients has shown changes that reflect better control of disease. As more targeted therapies become available for the treatment of lupus, we expect that such registry data will provide valuable real world evidence of the effectiveness of treatments and management strategies.

Background and aims To evaluate the construct validity of the Lupus Low Disease Activity State (LLDAS), a treatment target in systemic lupus erythematosus (SLE). Methods Fifty SLE case summaries based on real patients were prepared and assessed independently for meeting the operational definition of LLDAS. Fifty international rheumatologists with expertise in SLE, but with no prior involvement in the LLDAS project, responded to a survey in which they were asked to categorise the disease activity state of each case as remission, low, moderate or high. Agreement between expert opinion and LLDAS was assessed using Cohen's Kappa. Results Overall agreement between expert opinion and the operational definition of LLDAS was 77.96% (95% CI 76.34%-79.58%), with a Cohen's Kappa of 0.57 (95% CI 0.55-0.61). Of the cases (22 of 50) that fulfilled the operational definition of LLDAS, only 5.34% (59 of 22 x 50) of responses classified the cases as moderate/high activity. Of the cases that did not fulfil the operational definition of LLDAS (28 of 50), 35.14% (492 of 28 x 50) of responses classified the cases as remission/low activity. Common reasons for discordance were assignment to remission/low activity of cases with higher corticosteroid doses than defined in LLDAS (prednisolone <=7.5 mg) or with SLEDAI-2K>4 due to serological activity (high anti-dsDNA antibody and/or low complement). Conclusions LLDAS has good construct validity with high overall agreement between the operational definition of LLDAS and expert opinion. Discordance of results suggests that the operational definition of LLDAS is more stringent than expert opinion at defining a low disease activity state.

Background: Systemic lupus erythematosus (SLE) is associated with significant impairment of health-related quality of life (HR-QoL). Recently, meeting a definition of a lupus low disease activity state (LLDAS), analogous to low disease activity in rheumatoid arthritis, was preliminarily validated as associated with protection from damage accrual. The LLDAS definition has not been previously evaluated for association with patient-reported outcomes. The objective of this study was to determine whether LLDAS is associated with better HR-QoL, and examine predictors of HR-QoL, in a large multiethnic, multinational cohort of patients with SLE. Method(s): HR-QoL was measured using the Medical Outcomes Study 36-item short form health survey (SF-36v2) in a prospective study of 1422 patients. Disease status was measured using the SLE disease activity index (SLEDAI-2 K), physician global assessment (PGA) and LLDAS. Result(s): Significant differences in SF-36 domain scores were found between patients stratified by ethnic group, education level and damage score, and with the presence of active musculoskeletal or cutaneous manifestations. In multiple linear regression analysis, Asian ethnicity (p < 0.001), a higher level of education (p < 0.001), younger age (p < 0.001) and shorter disease duration (p < 0.01) remained significantly associated with better physical component scores (PCS). Musculoskeletal disease activity (p < 0.001) was negatively associated with PCS, and cutaneous activity (p = 0.04) was negatively associated with mental component scores (MCS). Patients in LLDAS had better PCS (p < 0.001) and MCS (p < 0.001) scores and significantly better scores in multiple individual SF-36 domain scores. Disease damage was associated with worse PCS (p < 0.001), but not MCS scores. Conclusion(s): Ethnicity, education, disease damage and specific organ involvement impacts HR-QoL in SLE. Attainment of LLDAS is associated with better HR-QoL.Copyright © 2017 The Author(s).