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The Physician Global Assessment International Standardisation COnsensus in Systemic Lupus Erythematosus (PISCOS) study aimed to obtain an evidence-based and expert-based consensus standardisation of the Physician Global Assessment (PGA) scoring of disease activity in systemic lupus erythematosus (SLE). An international panel of 79 SLE experts participated in a three-round Delphi consensus process, in which 41 statements related to the PGA in SLE were rated, using a 0 (strongly disagree) to 10 (strongly agree) numerical rating scale. Statements with agreement of 75% or greater were selected and further validated by the expert panel. Consensus was reached on 27 statements, grouped in 14 recommendations, for the use of the PGA in SLE, design of the PGA scale, practical considerations for PGA scoring, and the relationship between PGA values and levels of disease activity. Among these recommendations, the expert panel agreed that the PGA should consist of a 0–3 visual analogue scale for measuring disease activity in patients with SLE in the preceding month. The PGA is intended to rate the overall disease activity, taking into account the severity of active manifestations and clinical laboratory results, but excluding organ damage, serology, and subjective findings unrelated to disease activity. The PGA scale ranges from “no disease activity” (0) to the “most severe disease activity” (3) and incorporates the values 1 and 2 as inner markers to categorise disease activity as mild (≥0·5 to 1), moderate (>1 and ≤2) and severe (>2 to 3). Only experienced physicians can rate the PGA, and it should be preferably scored by the same rater at each visit. The PISCOS results will allow for increased homogeneity and reliability of PGA ratings in routine clinical practice, definitions of remission and low disease activity, and future SLE trials. © 2022 Elsevier Ltd

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: 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.

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.

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: 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: 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) .

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.

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