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Background 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 contrast, the Lupus Low Disease Activity State (LLDAS) is 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. 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. 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 Conclusions LLDAS was markedly more attainable than any remission definition, whilst still conferring significant protection against flares and damage accrual. Only the least stringent remission definitions 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 flare. LLDAS is a valid treatment target for SLE and is more achievable than remission. Funding Source(s): The Asia Pacific Lupus Collaboration receives project support grants from UCB, GlaxoSmithKline, Janssen, Bristo-Myers Squibb, and AstraZeneca.

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. 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 (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). Results 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 associated with reduction in subsequent flare (HR 0.65, 95% CI 0.56–0.76, p 6) or pre-existing damage (SDI>0). Conclusions LLDAS attainment provides significant protection against disease flare and damage accrual thereby supporting its use as a treatment target in SLE, and as an outcome measure for clinical trials and treat-to-target strategies. Funding Source(s): The Asia Pacific Lupus Collaboration receives project support grants from UCB, GlaxoSmithKline, Janssen, Bristo-Myers Squibb, and AstraZeneca.

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 Conclusions Ethnicity, education, disease damage, and specific organ involvement impacts on HR-QoL in SLE. Attainment of LLDAS is associated with better HR-QoL.

Background The Integrin-alpha-M (ITGAM) rs1143679 SNP has been associated with susceptibility to SLE and lupus nephritis (LN) in oriental Chinese and Thai populations. We previously found 13 ITGAM SNPs in linkage disequilibrium (LD) that were associated with susceptibility to SLE, but found no association with rs1143679. Aim To determine associations of ITGAM SNPs with SLE subphenotypes and autoantibodies. Methods We studied 248 patients fulfilling the 1997 ACR revised criteria for SLE. SLE-associated ITGAM SNP alleles were identified using custom-designed Immunochip arrays and gPLINK 1.062 software, with Bonferroni corrections for multiple comparisons. Associations of SLE-related ITGAM SNPs with SLE subphenotypes (malar or discoid rash, serositis, mouth ulcers, arthritis, haematological, renal or neurological involvement) and autoantibodies to dsDNA, Ro, RNP or Sm were determined with chi-square and Fisher’s tests and logistic regression. Results All 13 SLE susceptibility ITGAM SNPs as well as the uncommon rs1143679 SNP (n=11) were associated with LN (Table 1). The strongest association was with rs2359661 (p=0.002, uncorrected). Subjects with these SNPs were less likely to have discoid rash. There was a trend towards an association with anti-Sm. Logistic regression models for 11 SNPs retained the factors LN, discoid rash and anti-Sm, suggesting strong LD for these SNPs. Conclusions This study demonstrated novel ITGAM SNP associations with LN and confirmed the association of rs1143679 with LN. Most associated SNPs were in the regulatory region of ITGAM bearing promoter/enhancer histone marks and have been associated with expression levels in several cell types, suggesting modulation of levels of ITGAM expression to impact these subphenotypes.