AB0279 THE IMPACT OF HYDROXYCHLOROQUINE DAILY DOSE IN THE PREVENTION OF FLARES IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN REMISSION
Authors: S. Fasano, V. Messiniti, M. A. Coscia, E. Gaggiano, M. Iudici, F. Ciccia
Journal: Annals of the Rheumatic Diseases (2021)

Background: The EULAR recommendations for the management of systemic lupus erythematosus (SLE) suggest a hydroxychloroquine (HCQ) dose of ≤5.0 mg/kg/day instead of 6.5 mg/kg/day to reduce the risk of HCQ-induced retinopathy (1). This change in HCQ dose may potentially lead to undertreatment with blood levels below the presumed therapeutic range. Objectives: The aim of this study was to compare flare rates and HCQ blood levels between the two different oral dosages in patients with SLE in remission. Methods: Eligible patients were SLE patients in clinical remission according to the preliminary Definitions of Remission in SLE (DORIS) criteria for at least one year and treatment with stable dose of HCQ for at least six months and stable dose of glucocorticoids and/or immunosuppressants (2). Flares were defined by SELENA-SLEDAI Flare Index (3). A venous blood sample was collected on two different occasions from all patients, reflecting actual therapeutic adherence. The biosamples were analyzed in a UPLC-MS/MS system composed of a Nexera chromatograph (Shimadzu) coupled with a Q-trap 6500 spectrometer (AB Sciex). A mean [HCQ] value ([HCQm]) for each patient was then calculated. Predictors of flares were analyzed by Cox regression. Results: We selected 66 patients who were stratified according to HCQ oral dose in two groups (Table 1). We observed 23 (35%) flares that developed in mean 26,0 (±15,1) months: 8/32 (25%) patients taking HCQ 5 mg/kg/day; 15/34 (44%) in the other group. No statistically significant difference was observed between the two group in number of flares (p=0,106), mean time of occurrence (p=0,904) and median [HCQm] (p=0,983). At regression analysis, older age at baseline was protective against flare occurrence (HR 0,93), while concomitant immunosuppressive therapy showed significant positive association (HR 3,66). Conclusion: Our study suggests that low dosage of HCQ (5 mg/kg/day) may safely be prescribed in SLE patients in remission, without significant differences in terms of blood concentration and impact on the clinical course of SLE. References: [1]Fanouriakis A, et al. Ann Rheum Dis 2019;78:736-745. [2]van Vollenhoven R, et al. Ann Rheum Dis 2017;76:554-561. [3]Petri M, et al. Arthritis Rheum. 2012;64(8):2677-2686. Table 1. Demographic, clinical and therapeutic features of the cohort and follow up data. All patients (n= 66) HCQ ≤5mg/Kg/die (n=32) HCQ 6,5mg/Kg/die (n=34) P Sex, female 65 (99) 31 (97) 34 (100) 0,3026 Age, y, mean (SD) 42,00±11,27 41,80±10,25 42,10±12,30 0,9140 Disease duration, y, mean (SD) 15,70 (9,02) 17,80 (8,01) 13,67 (9,50) 0,0624 SLEDAI, median (range) 2 (0-4) 1 (0-4) 2 (0-4) 0,6480 SLICC, median (range) 0 (0-2) 0 (0-2) 0 (0-1) 0,8556 [HCQm] ng/mL, median (range) 512,60 (104,41-3105,66) 457,16 (104,41-3105,66) 538,49 (149,24-1239,15) 0,5989 [DCQ] ng/mL,median (range) 73,41 (4,16-649,84) 66,84 (4,16-649,84) 66,31 (10,75-258,41) 0,9380 Time remission, y, median (range) 2,00 (1-11) 2,96 (1-10) 2,00 (1-11) 0,6588 Previous renal involvement 31 (47) 15 (47) 16 (47) 0,9882 Time HCQ, y, median (range) 5 (0-32) 8 (0-26) 5 (1-32) 0,2391 Glucocorticoids 33 (50) 18 (56) 15 (44) 0,4700 Mycophenolate mofetil 6 (9) 2 (6) 4 (12) 0,4396 Azathioprine 7 (11) 4 (14) 3 (9) 0,6305 Methotrexate 1 (2) 0 1 (3) 0,3320 Cyclosporine 2 (3) 1 (3) 1 (3) 0,9655 Belimumab 1 (2) 0 1 (3) 0,3320 Follow up time, m, median (range) 49 (4-67) 52 (7-67) 43 (4-67) 0,1115 Number of flares 23 (35) 8 (25) 15 (44) 0,1060 Time to flare, m, mean (SD) 26,0 (±15,1) 26,6 (±16,4) 25,8 (±14,9) 0,9042 Ocular alterations 6 (9) 4 (12) 2 (6) 0,0947 Figure 1. Predictors of flares analyzed by Cox regression. *Serena Fasano and Valentina Messiniti contributed equally to this abstract Disclosure of Interests: None declared