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Objective Disease activity both between and within patients with SLE is highly variable, yet factors driving this variability remain unclear. This study aimed to identify predictors of variability in SLE disease activity over time.Methods We analysed data from 2930 patients with SLE across 13 countries, collected over 38 754 clinic visits between 2013 and 2020. Clinic visit records were converted to panel data with 1-year intervals. The time-adjusted mean disease activity, termed AMS, was calculated. The yearly change in AMS, denoted as ΔAMSt, was regressed onto AMSt−1 and other potential predictors using random-effects models. Some variables were split into a person-mean component to assess between-patient differences and a demeaned component to assess within-patient variability.Results Overall, variability in SLE disease activity exhibited stabilisation over time. A significant inverse relationship emerged between a patient’s disease activity in a given year and variability in disease activity in the subsequent year: a 1-point increase in person-mean disease activity was associated with a 0.27-point decrease (95% CI −0.29 to –0.26, p

Objective To estimate the prevalence of organ damage (damage) and flare and to examine longitudinal associations between flares and subsequent damage accrual, in patients with systemic lupus erythematosus (SLE).Methods Patients enrolled in the Asia Pacific Lupus Collaboration cohort with ≥3 years of prospectively captured data were studied. Flares were assessed at routine visits, while damage ((Systemic Lupus International Collaborating Clinics/American College of Rheumatology) Damage Index) was assessed annually. Multivariable, multifailure survival analyses were carried out to quantify the association between flares and damage accrual.Results 1556 patients with SLE with a median (IQR) of 5.7 (3.9, 7.0) years of follow-up were studied. 39.5% (n=614) of patients had damage at enrolment, and 31.9% (n=496) accrued damage during the study observation period. The incidence of damage accrual during observation was ~58/1000 person-years. Overall, 74.1% (n=1153) of patients experienced a flare of any severity (mild/moderate or severe) at least once; 56.9% (n=885) experienced recurrent (≥2) flares. The risk of subsequent damage accrual in patients who experienced mild-to-moderate flare, after controlling for confounders, was 32% greater than in patients without flares (adjusted HR) (95% CI 1.32 (1.17 to 1.72)). The risk of damage accrual was greater if patients had severe flares (HR (95% CI) 1.58 (1.18 to 2.11)). For each additional flare, the risk of damage accrual increased by 7% (HR (95% CI) 1.07 (1.02 to 1.13)).Conclusions Flares independently increased the risk of damage accrual. Prevention of flares should be considered a necessary goal of SLE disease management to minimise permanent damage.

Abstract Background This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data. Methods The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes. Results Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23–82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53–0.86], p = 0.001) and methotrexate (OR 0.68 [0.47–0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64–0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual. Conclusions This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.

Objectives The lupus low disease activity state (LLDAS) allows for certain clinical and/or serological activity of SLE, provided overall disease activity does not exceed predefined cut-offs. This study aimed to evaluate the outcomes of patients who achieved LLDAS with clinical activity, serological activity only or neither clinical nor serological activity.Methods Patients with SLE enrolled in a prospective multinational cohort from March 2013 to December 2020 who were in LLDAS at least once were included. Visits that fulfilled both LLDAS and Definition of Remission in SLE (DORIS) criteria were excluded.Results 2099 patients were included, with median follow-up of 3.5 (IQR 1.3–5.8) years. At 6150 visits, patients were in LLDAS but not DORIS criteria; of these 1280 (20.8%) had some clinical activity, 3102 (50.4%) visits had serological activity only and 1768 (28.8%) visits had neither clinical nor serological activity. Multivariable regression analysis showed that compared with non-LLDAS, all three subsets of LLDAS had a protective association with flares in the ensuing 6 months and damage accrual in the ensuing 36 months. LLDAS with no clinical or serological activity had a significantly stronger protective association with severe flares in the ensuing 6 months compared with LLDAS with clinical activity (HR 0.47, 95% CI (0.27 to 0.82), p=0.007).Conclusions LLDAS without any clinical activity accounted for almost 80% of LLDAS visits. This study confirms that all subsets of LLDAS are associated with reduced flare and damage accrual. However, LLDAS without any clinical or serological activity has the strongest protective association with severe flares.

Abstract 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