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Objective. Double contour sign (DCS) is considered part of the new gout classification. This study aims to determine the agreement of blinded musculoskeletal sonologists in identifying the double contour sign among asymptomatic hyperuricemic patients. Methods. Participants with asymptomatic hyperuricemia (n=65) underwent a gray-scale ultrasound assessment of both of their 1st metatarsophalangeal joints (MTPJs) done on 3 positions (dorsal, medial, plantar) in longitudinal view. The static images were read by 2 independent blinded sonologists for presence of double contour sign. Results. Among the 130 1st MTPJs, the sonologists were able to positively identify DCS on 48R and 52L, negative in 10R and 10L, with discordant readings in 7R, 3L. The overall kappa agreement was statistically significant at 0.674 (substantial agreement) and 0.842 (almost perfect agreement) on the right and left respectively, (both p

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.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.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.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.

Summary Systemic lupus erythematosus (SLE) is prevalent in Asia and carries a variable prognosis among patients across the Asia-Pacific region, which could relate to access to health care, tolerability of medications, and adherence to therapies. Because many aspects of SLE are unique among patients from this region, the Asia-Pacific League of Associations for Rheumatology developed the first set of consensus recommendations on the management of SLE. A core panel of 13 rheumatologists drafted a set of statements through face-to-face meeting and teleconferences. A literature review was done for each statement to grade the quality of evidence and strength of recommendation. 29 independent specialists and three patients with SLE were then recruited for a modified Delphi process to establish consensus on the statements through an online voting platform. A total of 34 consensus recommendations were developed. Panellists agreed that patients with SLE should be referred to a specialist for the formulation of a treatment plan through shared decision making between patients and physicians. Remission was agreed to be the goal of therapy, but when it cannot be achieved, a low disease activity state should be aimed for. Patients should be screened for renal disease, and hydroxychloroquine is recommended for all Asian people with SLE. Major organ manifestations of SLE should be treated with induction immunosuppression and subsequently maintenance; options include cyclophosphamide, mycophenolate mofetil, azathioprine, and calcineurin inhibitors, in combination with glucocorticoids. Biologics, combination regimens, plasma exchange, and intravenous immunoglobulins should be reserved for cases of refractory or life-threatening disease. Anticoagulation therapy with warfarin is preferred to the direct oral anticoagulants for thromboembolic SLE manifestations associated with a high-risk antiphospholipid antibody profile.

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.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.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).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 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 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.

Summary Background Evaluating the contribution of glucocorticoid use to organ damage in systemic lupus erythematosus is confounded by glucocorticoid use in active disease. We sought to determine the independence of the contribution of glucocorticoid use to damage accrual from associations with disease activity by analysing patients without measurable disease activity. Methods Patients (age >18 years) who met the criteria for systemic lupus erythematosus were recruited from 13 centres in Australia, Indonesia, Japan, Malaysia, the Philippines, Singapore, Taiwan, and Thailand, and followed longitudinally. Disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] and Physician Global Assessment [PGA] scores) and treatment details were recorded at each visit (at least once every 6 months), and organ damage measured annually according to the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Glucocorticoid use during the study period was recorded as any exposure to prednisolone, cumulative prednisolone exposure, and time-adjusted mean daily prednisolone dose. Multivariate survival analyses were used to examine time-dependent associations of glucocorticoid use with damage accrual (defined as an increase of ≥1 on SDI). A SLEDAI-2K score of 0 was taken to indicate the absence of clinical and serological disease activity; a subset of patients without disease activity during the study were defined by a time-adjusted mean SLEDAI-2K (AMS) score of 0. Findings Between May 1, 2013, and Dec 31, 2016, 1707 patients were recruited. Over a median observation period of 2·2 years (IQR 1·5–3·0), damage accrual events were observed in 255 (14·9%) patients. 1405 (82·3%) of patients were exposed to prednisolone, with a median time-adjusted mean prednisolone dose of 5·0 mg/day (IQR 1·9–8·8). As SLEDAI-2K and PGA scores were highly correlated, two multivariable models were set, each including one of these two variables. In the model including AMS score, baseline SDI damage (SDI >0) was independently associated with damage accrual (HR 1·32 [95% CI 1·01–1·73], p=0·0427). In the other model, time-adjusted mean PGA score was independently associated with damage accrual (1·05 [1·02–1·08], p=0·0012). In both models, factors independently associated with damage accrual included time-adjusted mean prednisolone dose, age at enrolment, and ethnicity (Asian vs non-Asians). 157 (9·2%) patients had an AMS score of 0 (no disease activity), among whom 103 (65·6%) had glucocorticoid exposure and the median time-adjusted mean prednisolone dose was 2·0 mg/day (IQR 0·0–5·0). Accrual of irreversible organ damage occurred in 21 (13·4%) of these patients and was independently associated with time-adjusted mean prednisolone dose (HR 1·14 [95% CI 1·03–1·26], p=0·0117), time-adjusted mean PGA score (1·13 [1·03–1·23], p=0·0144), and age at enrolment (1·04 [1·01–1·07], p=0·0061), but not baseline SDI damage (0·94 [0·43–2·06], p=0·8675). Interpretation Glucocorticoid use contributes to damage accrual in systemic lupus erythematosus independently of the presence of clinical or serological disease activity. Funding UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca (to the Asia-Pacific Lupus Collaboration).

Objective To examine longitudinal associations of active lupus nephritis with organ damage accrual in patients with systemic lupus erythematosus (SLE). Methods 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 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. Results 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 Conclusion Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated with renal, but not non-renal, damage accrual in SLE.

Summary Background Treat-to-target strategies have improved outcomes in single-organ diseases with simple clinical or laboratory endpoints. A lack of validated endpoints has prevented adoption of treat to target for complex multiorgan conditions, such as systemic lupus erythematosus (SLE). We report the first prospective study undertaken to specifically validate a treat-to-target endpoint for SLE. Methods In this prospective cohort study, patients aged 18 years or older with SLE were recruited from 13 centres in eight countries and followed prospectively. Patients with at least two visits over the study period no more than 6 months apart were included in the longitudinal analysis. Patients with no visits in the final year of the study were censored from their last visit. Attainment of the lupus low disease activity state (LLDAS) was assessed at each visit. The primary outcome measure was accrual of irreversible end-organ damage, defined as at least a 1-point increase in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. We used time-dependent hazard regression models and generalised linear models to measure the association between LLDAS (attainment at any timepoint, cumulative time in LLDAS, and sustained LLDAS) with accrual of irreversible end-organ damage or flare (key secondary outcome). This study is registered with ClinicalTrials.gov , NCT03138941 . Findings Between May 1, 2013, and Dec 31, 2016, 1707 patients were recruited and followed for a mean of 2·2 years (SD 0·9), totalling 12 689 visits. Attainment of LLDAS at any timepoint was associated with reduction in damage accrual (hazard ratio 0·59, 0·45–0·76; p Interpretation LLDAS attainment is associated with significant protection against flare and damage accrual in SLE. These findings validate LLDAS as an endpoint for clinical studies in SLE. Funding The Asia Pacific Lupus Collaboration received project support grants from UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca.

Summary Background Validated outcome measures are needed from which to derive treatment strategies for systemic lupus erythematosus (SLE). However, no definition of remission for SLE has been widely adopted. The Definitions of Remission in Systemic Lupus Erythematosus (DORIS) group has proposed a framework with multiple potential definitions of remission. In this study, we aimed to assess the attainability and effect on disease outcomes of the DORIS definitions of remission, compared with the lupus low disease activity state (LLDAS), in patients with SLE. Methods In this prospective cohort study, we enrolled patients with SLE from 13 international centres that are part of the Asia Pacific Lupus Collaboration. Eligible patients were older than 18 years and fulfilled one of two classification criteria for SLE (1997 American College of Rheumatology criteria or the 2012 Systemic Lupus International Collaborating Clinics criteria). Visits were according to clinical need, with a minimum frequency of one visit per 6 months. We assessed attainment of remission on the basis of the eight DORIS definitions of remission, which varied in terms of serological activity, glucocorticoid use, and use of immunosuppresive agents; attainment of LLDAS; and disease flares at each visit. Irreversible organ damage accrual was recorded annually. Our primary aim was to assess exposure of patients to each of the remission definitions or LLDAS, and the respective association of these states with accrual of irreversible organ damage as the primary outcome measure. Occurrence of disease flares was the key secondary outcome. We used time-dependent Cox proportional hazards models and generalised linear models to assess DORIS definitions of remission and LLDAS in terms of their association with damage accrual and disease flares. Findings Between May 1, 2013, and Dec 31, 2016, 1707 patients with SLE were recruited and followed for a mean of 2·2 years (SD 0·9), totalling 12 689 visits. Remission, depending on DORIS definition, was achieved in 581 (4·6%) to 4546 (35·8%) of 12 689 visits. Spending 50% or more of observed time in any remission state was associated with a significant reduction in damage accrual, except for the two most stringent remission definitions, for which the frequency of attainment was lowest. Remission definitions disallowing serological activity were associated with the greatest reductions in disease flares. LLDAS was more attainable than any remission definition and was associated with a similar magnitude of protection from damage accrual and disease flares. Sustained remission and LLDAS were associated with a wider spread of effect sizes for reduction in risk of damage. By analysing patients who met the definition for LLDAS but not remission, we found that LLDAS was significantly associated with reduction in damage accrual, independent of all definitions of remission, except the least stringent. Interpretation Attainment of remission was associated with significant reductions in damage accrual and disease flares. LLDAS was more achievable than remission based on the DORIS criteria, but was similarly protective. Remission definitions with less stringency might be insufficiently distinct from LLDAS to substantially affect outcome measures, and further studies are needed to distinguish the protective effects of the various remission definitions. Funding UCB, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca.

Introduction Serotonin syndrome is a potentially life-threatening condition characterized by the triad of mental status changes, autonomic instability, and neuromuscular changes. We report a case of serotonin syndrome masquerading as disease flare in a lupus nephritis patient with end-stage renal disease receiving linezolid for the treatment of infected pseudoaneurysm. Case report A 36-year-old female lupus nephritis patient on maintenance hemodialysis for end-stage renal disease had been on multiple antibiotics, including anti-tuberculosis medications, over the past month for infected pseudoaneurysm complicating her arteriovenous fistula. Due to minimal response, she underwent pseudoaneurysmal ligation and given linezolid. Two days later, she developed chest pain, tachycardia, hypertension, tremors, later accompanied by high-grade fever, diarrhea, insomnia, and body weakness. Although fully awake and oriented, she was markedly agitated, mildly icteric, had hyperreflexia and asthenia with proximal muscle strength graded 3/5 in all extremities. Blood counts revealed anemia and thrombocytopenia; ancillary tests showed aspartate aminotransferase markedly higher than alanine aminotransferase, elevated serum lactate dehydrogenase and creatine kinase, and low C3 levels. Intravenous hydrocortisone was started for a suspected lupus flare. On the background of linezolid, isoniazid, and tramadol administration, serotonin syndrome with rhabdomyolysis was strongly considered. Offending drugs were discontinued, resulting in the dramatic improvement of symptoms and improved strength and well-being. The steroid was successfully tapered to 5 mg/day and a week later, she remained afebrile without recurrence of symptoms. Conclusion Serotonin syndrome should be considered in patients on multiple serotonergic agents on the background of end-stage renal disease. Prompt recognition and distinction from lupus activity can significantly impact management decisions.

Background:The recent prospectively validated definition of the lupus low disease activity state (LLDAS) allows characterisation of patients not achieving a treatment goal, providing impetus for an analysis of unmet needs in SLE using formal definitions. Other recently described definitions of high disease burden include disease activity over time, high disease activity status (HDAS) episodes, and the combination of high disease activity, serological activity and glucocorticoid (GC) use (HDAS+SA+GC).Objectives:To determine the prevalence of formal categories of unmet need, and the association of these with adverse outcomes, in SLE.Methods:Data from a 13-country longitudinal SLE cohort (ACR/SLICC criteria) were collected between 2013 and 19 using standard templates. Unmet need was defined as (i) patients never attaining LLDAS defined as in Golder et al., 2019 [1], (ii) having persistently active disease (time adjusted mean SLEDAI-2K (AMS) > 4), (iii) ever exhibiting high disease activity status (HDAS; SLEDAI-2K ≥10[2]), or (iv) ever exhibiting all of SLEDAI≥10, serological activity, and glucocorticoid use (HDAS+SA+GC)[3]. Health-related quality of life (HRQoL) was assessed using SF36 (v2) surveys and damage accrual using SLE Damage Index (SDI).Results:3,384 SLE patients were followed for 30,313 visits over median [IQR] 2.4 [0.4, 4.3] years. 53% of all visits were not in LLDAS; 813 patients (24%) never achieved LLDAS during observation. Median AMS was 3.0 [1.4, 4.9] and 34% of patients had AMS > 4 throughout the study. 25% of patients had at least one episode of HDAS, representing 8% of visits. 702 patients (21%) had at least one episode of HDAS+SA+GC, representing 8% of visits. Each of never-LLDAS, AMS>4, ever-HDAS, and ever-HDAS+SA+GC were associated with significantly greater number of physician visits, higher mean glucocorticoid dose, lower HRQoL and higher mortality. 31%, 58% and 83% of never-LLDAS, AMS>4, and ever-HDAS patients respectively were also HDAS+SA+GC on at least one occasion.Conclusion:Data from a multinational longitudinal SLE cohort indicate that unmet need, defined by LLDAS-never, AMS>4, HDAS, or HDAS+SA+GC, is prevalent in SLE, and that these definitions are associated with poor outcomes.References:[1]Golder, V., et al., Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. The Lancet Rheumatology, 2019. 1(2): p. e95-e102.[2]Koelmeyer, R., et al., High disease activity status suggests more severe disease and damage accrual in systemic lupus erythematosus. Lupus Sci Med, 2020. 7(1).[3]van Vollenhoven, R.F., et al., Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Annals of the Rheumatic Diseases, 2012. 71(8): p. 1343-1349.Acknowledgements:The APLC acknowledges all the Data Collectors and Patients for their valuable contributions to research.Disclosure of Interests:Rangi Kandane-Rathnayake: None declared, Worawit Louthrenoo: None declared, Alberta Hoi Consultant of: Abbvie and GSK, Grant/research support from: AstraZeneca, GSK, BMS, Janssen, and Merck Serono, Vera Golder: None declared, Yi-Hsing Chen Speakers bureau: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, AstraZeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Consultant of: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, AstraZeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Gilead, Grant/research support from: Pfizer, Norvatis, BMS, Abbevie, Johnson & Johnson, Roche, Sanofi, Guigai, Roche, Boehringer Ingelheim, UCB, MSD, Astra-Zeneca, Astellas, Gilead, Shue Fen Luo: None declared, Yeong-Jian Jan Wu Speakers bureau: Pfizer, Lilly, Novartis, Abbvie, Aisha Lateef: None declared, Jiacai Cho: None declared, Laniyati Hamijoyo Speakers bureau: Pfizer, Novartis, Abbot, Chak Sing Lau Shareholder of: Pfizer, Sanofi, and Janssen, Sandra Navarra Speakers bureau: Pfizer, Johnson & Johnson, Novartis, Astellas, Grant/research support from: Astellas, Johnson & Johnson, Leonid Zamora: None declared, Zhanguo Li Speakers bureau: Eli, Lilly, Novartis, GSK, AbbVie, Paid instructor for: Pfizer, Roche, Johnson., Consultant of: Lilly, Pfizer, Grant/research support from: Pfizer, Yuan An: None declared, Sargunan Sockalingam Speakers bureau: Pfizer, Roche, Novartis, Grant/research support from: Roche and Novartis, Yasuhiro Katsumata Speakers bureau: Chugai Pharmaceutical Co., Ltd., Glaxo-Smithkline K.K., and Sanofi K.K., masayoshi harigai Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Consultant of: AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma., Grant/research support from: AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Yanjie Hao: None declared, Zhuoli Zhang Speakers bureau: Norvatis, GSK, Pfizer, Jun Kikuchi: None declared, Tsutomu Takeuchi Speakers bureau: AbbVie AYUMI Pharmaceutical Corp. Bristol-Myers Squibb Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan, Gilead Sciences, Inc. Mitsubishi-Tanabe Pharma Corp. Pfizer Japan Inc. Sanofi K.K., Consultant of: Astellas Pharma, Inc. Chugai Pharmaceutical Co, Ltd. Eli Lilly Japan, Mitsubishi-Tanabe Pharma Corp., Grant/research support from: AbbVie, Asahikasei Pharma Corp. Chugai Pharmaceutical Co, Ltd. Mitsubishi-Tanabe Pharma Corp. Sanofi K.K., BMDB Basnayake: None declared, Fiona Goldblatt: None declared, Madelynn Chan Speakers bureau: AbbVie, Novartis, Consultant of: Pfizer, Eli-Lilly, Kristine Ng Speakers bureau: Abbvie, Novartis, Janssen, Sang-Cheol Bae: None declared, Shereen Oon: None declared, Sean O’Neill Consultant of: GSK, Kathryn Gibson Speakers bureau: UCB, Consultant of: Novartis, Janssen, Grant/research support from: Novartis, Sunil Kumar: None declared, Nicola Tugnet: None declared, Yoshiya Tanaka Speakers bureau: Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers, Eisai, Chugai, Abbvie, Astellas, Pfizer, Sanofi, Asahi-kasei, GSK, Mitsubishi-Tanabe, Gilead, Janssen, Grant/research support from: Abbvie, Mitsubishi-Tanabe, Chugai, Asahi-Kasei, Eisai, Takeda, Daiichi-Sankyo, Mandana Nikpour Speakers bureau: Actelion, GSK, Janssen, Pfizer, UCB, Paid instructor for: UCB, Consultant of: Actelion, Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB, Grant/research support from: Actelion, Astra Zeneca, BMS, GSK, Janssen, UCB, Eric F. Morand Speakers bureau: AstraZeneca, Paid instructor for: Eli Lilly, Consultant of: AstraZeneca, Amgen, Biogen, BristolMyersSquibb, Eli Lilly, EMD Serono, Genentech, Janssen, Grant/research support from: AstraZeneca, BristolMyersSquibb, Eli Lilly, EMD Serono, Janssen.

Background:In the absence of evidence-based treatment guidelines, medication use in SLE is highly variable. Low rates of remission and lupus low disease activity state (LLDAS) suggest that suboptimal responses to standard medications, which include glucocorticoids (GC), anti-malarial (AM) drugs and immunosuppressive (IS) agents, are common. Understanding the utility of current medications will facilitate the selection of patients for advanced therapies as they emerge.Objectives:To examine medication use patterns in a large multicentre SLE cohort.Methods:We used 2013-18 data from the Asia Pacific Lupus Collaboration (APLC) cohort in which disease activity (SLEDAI-2K) and medication details were captured at every visit. LLDAS was defined as in Golderet al., 2019 (1). We examined the use of medication (med) categories (GC &/or AM &/or IS) by SLE disease activity and LLDAS at the visit level. Additionally, we performed Cox regression analyses to determine the time-to-discontinuation of meds stratified by SLE disease activity, ranked by time-adjusted mean SLEDAI-2K, and by percent-time spent in LLDAS.Results:We analysed data from 19,804 visits of 2,860 patients. We observed 8 med categories: no meds; GC, AM or IS only; GC+AM; GC+IS; AM+IS and GC+AM+IS (triple therapy). Triple therapy was the most frequent med pattern (32%); single agents were used in 21% of visits and biologicals in only 3%. Among visits where SLEDAI-2K was ≥10, triple therapy was used in 46%, with median [IQR] GC dose 10 [6, 24] mg/day; in contrast, among visits with SLEDAI-2K≤4 triple therapy was used in 28% (pMed persistence (survival analysis) varied widely, with lowest survivals for IS. Patients with time-adjusted mean SLEDAI-2K ≥10 had lower discontinuation of GC and higher discontinuation of IS including azathioprine, leflunomide and cyclosporine (Table 1). In contrast, increased time in LLDAS was associated with reduced discontinuation of AM and azathioprine.GCAMISMPhMPhAAZAMTXCyALEFOverall med survival, days to 25% discontinuation (95%CI)1048(938, 1197)1267(1113, 1428)175(175, 182)387(252, 756)409(350, 476)525(219, 686)268(182, 350)329(190, 524)Univariable associations,HR (95% CI) p-valueDisease activity≤41.001.001.001.001.001.001.001.00>4 & 0.69 (0.56,0.84)p1.15 (0.92,1.44)0.20.92 (0.80,1.05)0.21.37 (0.78,2.42)0.31.16 (0.97,1.39)0.111.11 (0.72,1.71)0.61.26 (0.90,1.77) 0.181.88 (1.07,3.30) 0.03≥100.65 (0.35,1.21) 0.181.56 (0.94,2.59) 0.080.84 (0.45,1.57)0.61.92 (0.80,4.63)0.142.69 (1.86,3.91) p1.85 (0.92,3.71) 0.082.66 (1.36,5.21) 0.0041.62 (1.13,2.32)0.009LLDAS1.001.001.001.001.001.001.001.00≥50%1.30 (1.09, 1.55)0.0030.67 (0.54, 0.84)1.22 (1.08, 1.40)0.0020.83 (0.44,1.57)0.60.83 (0.69, 1.00)0.0540.70 (0.46, 1.07)0.101.29 (0.92, 1.83)0.140.43 (1.5, 1.25)0.12Conclusion:In a large multicentre SLE cohort, most patients were receiving combination treatment. AM treatment survival was high and associated with low disease activity, GC survival was high and associated with high disease activity, while IS survival was low. Patients with high disease activity received more medication combinations but had reduced IS survival. These data suggest ongoing unmet need for improved medications for treatment of SLE.Reference:Golder, V., et al Lancet Rheum. 2019 1(2):e95-102Disclosure of Interests:Rangi Kandane-Rathnayake Grant/research support from: The APLC has received financial (non-restricted educational) grants from AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Janssen, EMD Serono, Eli Lilly and UCB for the LLDAS Validation Study., Worawit Louthrenoo: None declared, Shue Fen Luo: None declared, Yeong-Jian Wu Consultant of: Pfizer, Lilly, Novartis, Abbvie, Roche, Speakers bureau: Lilly, Novartis, Yi-Hsing Chen Grant/research support from: Taiwan Ministry of Science and Technology, Taiwan Department of Health, Taichung Veterans General Hospital, National Yang-Ming University, GSK, Pfizer, BMS., Consultant of: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, GSK, Astra& Zeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Gilead., Paid instructor for: Pfizer, Novartis, Johnson & Johnson, Roche, Lilly, Astra& Zeneca, Sanofi, Astellas, Agnitio Science Technology, United Biopharma., Speakers bureau: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, GSK, Astra& Zeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Gilead., Vera Golder: None declared, Aisha Lateef: None declared, Jiacai Cho: None declared, Sandra Navarra Speakers bureau: Astellas, Novartis, Pfizer, Johnson & Johnson, Abbvie, Leonid Zamora: None declared, Laniyati Hamijoyo Speakers bureau: Pfizer, Novartis, Tanabe, Abbot, Dexa Medica, Roche, Sargunan Sockalingam: None declared, Yuan An: None declared, Zhanguo Li: None declared, Yasuhiro Katsumata: None declared, masayoshi harigai Grant/research support from: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., and Teijin Pharma Ltd. MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Oxford Immuotec, Pfizer Japan Inc., and Teijin Pharma Ltd. MH is a consultant for AbbVie, Boehringer-ingelheim, Kissei Pharmaceutical Co., Ltd. and Teijin Pharma., Yanjie Hao: None declared, Zhuoli Zhang: None declared, Madelynn Chan: None declared, Jun Kikuchi: None declared, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd., Fiona Goldblatt: None declared, Sean O’Neill: None declared, Chetan Karyekar Shareholder of: Johnson & Johnson, Consultant of: Janssen, Employee of: Janssen Global Services, LLC. Previously, Novartis, Bristol-Myers Squibb, and Abbott Labs., Jennifer H. Lofland Employee of: Janssen, Sang-Cheol Bae: None declared, Chak Sing Lau: None declared, Alberta Hoi: None declared, Mandana Nikpour: None declared, Eric F. Morand Grant/research support from: AstraZeneca, Consultant of: AstraZeneca, Speakers bureau: AstraZeneca

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. Objectives To compare the attainability, and association with outcomes, of LLDAS and remission in a prospective multicentre study. Methods 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. Results 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 Conclusion LLDAS was more attainable than any remission definition, whilst still conferring significant reduction in flares and damage accrual. Only the least stringent remission definitions could be shown to be associated with significantly lower damage accrual, likely reflecting a low frequency of remission attainment overall. LLDAS is a valid treatment target for SLE and is more achievable than remission. Disclosure of Interests Vera Golder: None declared, Eric F. Morand Grant/research support from: AstraZeneca, Bristol Myers Squibb, Janssen, Merck Serono, and UCB, Consultant for: AstraZeneca, Eli Lilly, Janssen, and Merck Serono, Speakers bureau: AstraZeneca, Rangi Kandane-Rathnayake: None declared, Molla Huq: None declared, Worawit Louthrenoo: None declared, Shue Fen Luo: None declared, Yeong-Jian Wu: None declared, Aisha Lateef : None declared, Sargunan Sockalingam: None declared, Sandra Navarra: None declared, Leonid Zamora: None declared, Laniyati Hamijoyo: None declared, Yasuhiro Katsumata: None declared, masayoshi harigai Grant/research support from: Tokyo Women’s Medical University (TWMU) has received unrestricted research grants for Division of Epidemiology and Pharmacoepidemiology of Rheumatic Diseases from Ayumi Pharmaceutical Co. Ltd., Bristol Meyers Squib, Chugai Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Taisho Toyama Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp., and with which TWMU paid the salary of MH. MH has also received research grants from AbbVie Japan GK, Eisai Co. Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Madelynn Chan: None declared, Sean O’Neill: None declared, Fiona Goldblatt: None declared, Chak Sing Lau: None declared, Zhanguo Li: None declared, Alberta Hoi Grant/research support from: GSK, AstraZeneca, UCB and Merck Serono, Consultant for: Janssen Steering Committee, Speakers bureau: Novartis, Mandana Nikpour: None declared

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. Objectives 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. Methods 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. Results 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 SLEDAI2-K Conclusion Despite lower attainment of LLDAS in patients with higher disease activity at baseline, the magnitude of association of LLDAS attainment with lower damage accrual was greater in this subgroup of patients compared to those less active baseline disease. This supports the validity of LLDAS as an outcome measure, in a population similar to that typically selected into clinical trials, and further highlights the potential impact of achieving a target outcome in SLE patients with active disease. Disclosure of Interests Vera Golder: None declared, Eric F. Morand Grant/research support from: AstraZeneca, Bristol Myers Squibb, Janssen, Merck Serono, and UCB, Consultant for: AstraZeneca, Eli Lilly, Janssen, and Merck Serono, Speakers bureau: AstraZeneca, Rangi Kandane-Rathnayake: None declared, Molla Huq: None declared, Hieu Nim: None declared, Worawit Louthrenoo: None declared, Shue Fen Luo: None declared, Yeong-Jian Wu: None declared, Aisha Lateef : None declared, Sargunan Sockalingam: None declared, Sandra Navarra: None declared, Leonid Zamora: None declared, Laniyati Hamijoyo: None declared, Yasuhiro Katsumata: None declared, masayoshi harigai Grant/research support from: Tokyo Women’s Medical University (TWMU) has received unrestricted research grants for Division of Epidemiology and Pharmacoepidemiology of Rheumatic Diseases from Ayumi Pharmaceutical Co. Ltd., Bristol Meyers Squib, Chugai Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Taisho Toyama Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp., and with which TWMU paid the salary of MH. MH has also received research grants from AbbVie Japan GK, Eisai Co. Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Madelynn Chan: None declared, Sean O’Neill: None declared, Fiona Goldblatt: None declared, Chak Sing Lau: None declared, Zhanguo Li: None declared, Alberta Hoi Grant/research support from: GSK, AstraZeneca, UCB and Merck Serono, Consultant for: Janssen Steering Committee, Speakers bureau: Novartis, Mandana Nikpour: None declared

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of manifestations and potential to affect several organ systems. Complications arise from both disease and medications especially glucocorticoids, significantly contributing to overall morbidity and mortality. SLE predominantly affects patients during their prime productive years resulting in substantial economic burden on the patient, caregivers, and society due to direct, indirect, and intangible costs. This illness burden is compounded in developing countries with limited resources due to various disparities in healthcare delivery. Physician education and practical referral and endorsement guidelines adapted to the local setting reinforce continuity and coordinated care. Likewise, patient education, self-help programs, and shared decision-making are essential best practice in the clinics. Both physician education and patient education improve overall outcomes in chronic diseases like SLE. As a developing country with very few rheumatologists and/or lupus specialists, efficient healthcare delivery for most Filipino lupus patients remains elusive. We describe our experience in confronting these challenges through development of strategies which focus on physician and patient education. KEY POINTS: • Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a highly variable course, requiring specialized, individualized, and coordinated care by a healthcare team. • Health disparities and limited resources significantly contribute to illness burden on the patient, family, and society. • Physician education on SLE must commence at undergraduate medical school, be integrated in Internal Medicine and Pediatrics, and reinforced through specialized training in Rheumatology and related specialties. • Patient education and empowerment are integral to improving healthcare outcomes especially in a resource-limited setting.

Background Lupus nephritis (LN) is a common feature of systemic lupus erythematosus (SLE). While LN is considered a contributor to irreversible organ damage in SLE, the magnitude of impact of active renal disease relative to other contributors to damage accrual is unknown. Objectives To determine the time-dependent association of active lupus nephritis (LN) with organ damage accrual in SLE. Methods This study was performed on patients from the Asia Pacific Lupus Collaboration (APLC) cohort. SLE Disease Activity Index-2000 (SLEDAI-2k) is collected per-visit and SLICC-ACR Damage Index (SDI) annually. Analysis was restricted to patients with ≥2 SDI scores. Active LN was defined if patients had urinary casts, proteinuria, haematuria or pyuria as indicated in the SLEDAI-2k descriptor. Organ damage accrual was defined as a change of SDI (ΔSDI>0) between baseline and final visit. Glucocorticoid (GC) categories were defined according to cumulative GC exposure at each visit as either no GC (cum.GC=0); low GC (cum.GC ≤median) or high GC (cum.GC >median). Cox regression analyses were performed. Results 1735 patients and 5593 visits were included in the analysis. 93% of patients was female with a median ([inter-quartile range (IQR), (range)] age of 40 years.31, 51 18, 77 Median study observation period was 853 days [621, 1094].98, 1443 36% were Chinese; 20% Thai and 10% Caucasian ethnicity. 82% of patients were exposed to glucocorticoids. 40% had active renal disease at least once during the study period, and active renal disease was observed in 22% of visits (n=1238 visits). 41% of patients had organ damage at baseline and 14% accrued organ damage (272 damage accrual episodes in 250 patients). Active renal disease was significantly associated with damage accrual; after adjusting for confounders, patients with active renal disease were 66% more likely to accrue organ damage compared to those without active renal disease (adjusted hazard ratio=1.66 (95% CI: 1.26, 2.19), p-value Conclusions Active LN is an independent risk factor for damage accrual in SLE. The concomitant independent association of GC exposure with damage accrual suggests non-GC treatments to reduce active LN are needed to reduce damage burden in SLE. Disclosure of Interest None declared

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.

Significant progress has been made in the development of therapies for systemic lupus erythematosus (SLE). These include agents which target interferons, cytokines, T lymphocytes and co-stimulatory molecules, B-lymphocytes and B stimulatory molecules. The latter are of special interest having the most robust efficacy data to date, ranging from clinical experience to clinical trials, with belimumab as the first Food and Drug Administration-approved biologic for the treatment of SLE. Given the wide disease heterogeneity, certain issues like clinical trial design and pharmacogenomics will continue to challenge drug development in SLE, there will always be a growing and compelling need for more of these drugs in order to alleviate the burden of illness in lupus patients.

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. 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 the SLE disease activity index (SLEDAI-2 K), physician global assessment (PGA) and LLDAS. Results 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

Background Systemic lupus erythematosus (SLE) is a chronic heterogeneous disease with considerable burden from disease activity and damage. A novel clinical treatment target in the form of the lupus low disease activity state (LLDAS) has been recently reported, with retrospective validation showing that time spent in LLDAS translates to reduced damage accrual. The objectives of this study were to describe the frequency and identify the predictors of attaining LLDAS in a large multinational cohort of patients with SLE. Methods Data were collected at the recruitment visit in patients with SLE enrolled in a longitudinal study in nine countries. Data were analysed cross-sectionally against the recently published definition of LLDAS, and the frequency and characteristics associated with presence of LLDAS were determined. Stepwise multivariable logistic regression was used to determine predictors of LLDAS. Results Of the 1846 patients assessed, criteria for LLDAS were met by 44 %. Patients with shorter disease duration were less likely to be in LLDAS (OR 0.31, 95 % CI 0.19–0.49, p

Background Systemic lupus erythematosus (SLE) is a heterogeneous disease characterised by fluctuating disease activity. A low disease activity endpoint, the Lupus Low Disease Activity State (LLDAS), was recently reported and retrospective validation showed that time spent in LLDAS translated into reduced damage accrual (Franklyn, Ann Rheum Dis, 2015). A large prospective study to validate LLDAS in a multiethnic cohort of lupus patients from the Asia Pacific Region is underway. Objectives To describe the frequency and identify the predictors of fulfilling criteria for LLDAS in baseline visit data from a large multinational multiethnic cohort of patients with SLE in nine Asia Pacific countries. Methods Prospectively collected baseline visit data from 1846 SLE patients enrolled in a longitudinal study were analysed cross sectionally against the recently published definition of LLDAS, and patient characteristics associated with LLDAS attainment determined. Results LLDAS criteria were met by 44% of patients at a single baseline visit. Stepwise multivariable logistic regression revealed that patients with shorter disease duration were less likely to be in LLDAS (OR 0.31, 95% CI 0.19–0.49, p Conclusions Low disease activity was observed in less than half of SLE patients at a single point in time. Disease duration and phenotype, as well as national social wealth, were predictive of LLDAS attainment. Disclosure of Interest None declared