POS0105 PREDICTORS OF FLARE IN SLE PATIENTS ATTAINING LUPUS LOW DISEASE ACTIVITY STATE: A REAL-LIFE COHORT STUDY OF 292 PATIENTS WITH 36-MONTH FOLLOW-UP
Authors: A. R. Cunha, L. Saraiva, J. A. P. Da Silva, L. Inês
Journal: Annals of the Rheumatic Diseases (2021)

Background: Lupus Low Disease Activity State (LLDAS) is a target for management of patients with SLE, that should be maintained in the long-term by preventing flares. Stratification of flare risk would be useful to optimize management. Objectives: To identify predictors of flare in SLE patients attaining LLDAS. Methods: Patients with SLE fulfilling classification criteria [ACR (1997) and/or SLICC and/or EULAR/ACR], followed at an academic lupus clinic from January 2017 to March 2020 were eligible. Baseline for each patient was the first visit with LLDAS within the study period. Patients never fulfilling LLDAS were excluded. Flares were identified as change from baseline by 3 instruments: revised SELENA flare index (r-SFI); SLEDAI-2K; Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS). Time to first flare up to 36 months was identified separately for each instrument. Predictors of flare were sought through survival analysis, with distinct models for each of the three definitions of flare. Univariate analysis was performed using Kaplan-Meir curves and Log-Rank tests. Tested variables at baseline were: gender; age at time of SLE diagnosis; disease duration; cumulative SLE organ involvement (arthritis; mucocutaneous; renal; neurologic; haematological; anti-phospholipid syndrome); cumulative immunological features (anti-dsDNA; anti-Sm; anti-RNP, anti-phospholipid antibodies; hypocomplementemia); ongoing treatment (hydroxychloroquine; prednisone; immunosuppressants). Variables with p&lt;0.1 were further tested in multivariate Cox regression models. Hazard ratios (HR) were determined with 95% confidence intervals (95%CI). Results: From 322 patients in this SLE cohort, 292 (90.7%) fulfilled LLDAS and were included in the analyses (female: 87.3%; mean age: 46.2±14.5 years; previous lupus nephritis: 36.0%; receiving ongoing antimalarials, immunosuppressants, glucocorticoids: 92.8%, 34.6% and 29.8%, respectively. Over follow-up, the proportion of patients with flares according to each definition were: 28.4% (r-SFI), 24.7% (SLE-DAS) and 13.4% (SLEDAI-2K). The r-SFI flares were moderate in 28.9% and severe in 9.6% of the cases. From all patients, 54.1% maintained stable glucocorticoid-free control of the disease, without flares during follow-up. In the multivariate models, the following parameters were independent predictors of flare, as defined by any of the definitions (Table 1): anti-RNP+; oral glucocorticoids; immunosuppressants. Conclusion: Patients attaining LLDAS but requiring ongoing treatment with immunosuppressants and/or glucocorticoids present a higher risk of flare and thus might need a tighter clinical monitoring. Anti-RNP+ was newly identified as a potential biomarker for higher risk of flares. Glucocorticoid-free, stable low disease activity is an achievable target. References: [1]Mathian A, Pha M, Haroche J, Cohen-Aubart F, Hié M, Pineton de Chambrun M, et al. Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: a randomised clinical trial. Ann Rheum Dis. 2020;79(3):339-46. [2]Inês L, Duarte C, Silva RS, Teixeira AS, Fonseca FP, da Silva JA. Identification of clinical predictors of flare in systemic lupus erythematosus patients: a 24-month prospective cohort study. Rheumatology (Oxford). 2014;53(1):85-9. Table 1. Predictors of flare in multivariate Cox regression according to each of the flare definitions (r-SFI; SLE-DAS; SLEDAI-2K) r-SFI SLE-DAS SLEDAI-2K Anti-RNP+ 2.11 (1.30-3.42) 2.39 (1.44-3.95) 2.22 (1.11-4.42) Immunosuppressants 1.96 (1.22-3.15) 2.32 (1.38-3.88) 2.26 (1.12-4.54) Prednisone* 1.93 (1.19-3.14) 1.99 (1.18-3.35) 2.17 (1.07-4.38) Blood cytopenias § 2.08 (1.03-4.17) n.s. n.s. Arthritis § n.s. n.s. 2.23 (1.12-4.44) * Prednisone ≤7.5 mg/day as required by LLDAS. § Blood cytopenias; arthritis: cumulative SLE features up to baseline. Risk for each predictor reported as Hazard Ratio (95% Confidence Interval); n.s.: non-significant Disclosure of Interests: None declared