Objective Recent evidence suggests that some urinary biomarkers, namely Vascular Cell Adhesion Molecule-1 (VCAM-1), Intercellular Adhesion Molecule-1 (ICAM-1), Monocyte Chemoattractant Protein 1 (MCP-1), Neutrophil Gelatinase Associated Lipocalcin and Lipocalin-type Prostaglandin D-Synthetase (L-PGDS), might discriminate SLE patients with ongoing renal activity from those with stable disease. The objective of this study was to assess the role of these markers in predicting renal flares in comparison with conventional biomarkers and to derive a biomarker panel which may improve diagnostic accuracy. Methods Eligible participants were SLE patients prospectively followed at our clinic. Urinary biomarker levels were measured in urinary sample by ELISA assay and were compared by the unpaired Student’s t test or the Mann–Whitney U test as appropriate. Receiver operating characteristic analysis was used to calculate the area under the curve. Cox regression was used to identify independent factors associated with disease flares. Results Urine was collected from 61 patients. During 8 months’ follow-up, eight patients experienced a renal flare. Urinary L-PGDS, ICAM-1 and VCAM-1 levels were significantly increased in the patients who subsequently experienced a renal flare with respect to the remaining 53. At Cox regression analysis, L-PGDS, ICAM-1, VCAM-1, hypocomplementemia and anti-dsDNA antibodies were factors associated with renal flares. Based on receiver operating characteristic analysis, a combination of novel and conventional biomarkers demonstrated an excellent ability for accurately identifying a flare. Conclusion This study might suggest the usefulness of a novel biomarker panel in predicting a renal flare in SLE.
Background A progressive tapering until withdrawal of glucocorticoids (GC) is considered one of the main goals of Systemic Lupus Erythematosus (SLE) management. However, which patient may be a candidate for safe GC withdrawal has not been determined yet. This study aimed to evaluate the rate of low-dose GC withdrawal in SLE patients in remission and to identify predictors of flares. Methods Eligible patients were SLE patients in prolonged clinical remission defined by a cSLEDAI = 0 for at least 2 years and on a stable SLE treatment (including daily 5 mg prednisone). Flares were defined by SELENA-SLEDAI Flare Index. Predictors of flares after GC withdrawal were analyzed by Cox regression. Results We selected 56 patients in whom a GC withdrawal was attempted. 98 patients were in the prednisone maintenance group. The proportion of patients experiencing a flare was not significantly lower in the maintenance group than in the withdrawal group (p = 0.81). However, among the withdrawal group, the rate of flares was significantly higher in serologically active clinically quiescent (SACQ) patients (p < 0,0001). At Cox regression analysis, duration of hydroxychloroquine (HCQ) therapy and ≥5 year remission at withdrawal were protective factors, while a SACQ disease and history of lupus nephritis increased the risk of disease flare. Conclusion GC withdrawal is an achievable target in SLE and may be attempted in patients in complete remission.However, it might underline a caution in patients with SACQ disease who may be at greater risk forflare when GCare discontinued. HCQ therapy and durable remission can significantly reduce the risk.
BackgroundRecent guidelines for SLE recommend using a hydroxychloroquine (HCQ) dose less than 5.0 mg/kg/day to reduce the risk of retinopathy. To determine if this dose reduction would have an impact on the clinical course of SLE, we compared flare incidence in a cohort of patients with SLE treated with two different oral HCQ dosages (≤5 mg/kg/day or >5 mg/kg/day). As a secondary analysis, we compared HCQ blood levels between the two different oral dosages, and evaluated the frequency of non-adherence in patients with SLE treated with HCQ.MethodsWe identified a cohort of patients with SLE taking HCQ for at least 6 months and followed for 24 months. At study entry and 6 months later, a blood venous sample was taken to measure HCQ blood levels by liquid chromatography. Incidence of new SLE flares after recruitment was put in relation to daily HCQ dose and mean HCQ blood levels. Cox regression analysis served to identify factors associated with SLE flares.Results83 patients were enrolled. We observed 11 (16%) flares that developed in mean 14.8 months of follow-up. The difference in terms of flare rate and mean HCQ blood levels between the two oral dosages was not statistically significant. There was a trend (p=0.08) for high HCQ dose being associated with a lower flare rate. At Cox analysis, higher HCQ blood levels and older age at baseline were protective against flare occurrence, while concomitant immunosuppressant therapy showed significant positive association. HCQ blood levels did not correlate with prescribed HCQ dose.ConclusionPatients with low oral HCQ dosage tend to have more flares, although the difference was not statistically significant. Higher HCQ blood levels were protective against flare occurrence. The risks and benefits must be balanced in choosing HCQ dose.
BackgroundPatients with SLE have an endothelial dysfunction (ED), which is considered the earliest marker of cardiovascular (CV) disease. Endothelial cell activation induced by proinflammatory cytokines is defined by the endothelial expression of cell-surface adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin. The aim of this study was to investigate whether serum endothelial adhesion molecule levels are influenced by blood hydroxychloroquine (HCQ) levels in SLE.MethodsConsecutive patients with SLE taking a stable dose of HCQ were investigated. At study entry and 6 months later HCQ blood levels were quantified by tandem mass spectrometry. Serum levels of P-selectin, E-selectin, ICAM-1 and VCAM-1 were also measured using a Luminex 200 instrument. Comparison of endothelial soluble adhesion molecules in groups with different HCQ blood levels was performed by t-test.Results83 patients with SLE were enrolled. Correlation were demonstrated between mean blood HCQ concentrations and endothelial soluble adhesion molecules (E-selectin, ICAM-1 and VCAM-1). Moreover, serum levels of ICAM-1 and VCAM-1 were significantly lower in the patients with SLE with HCQ blood levels >500 ng/mL (83.67±52.8 ng/mL vs 158.81±125.1 ng/mL and 8.9±2.2 ng/mL vs 10.4±2.3 ng/mL). Serum levels of E-selectin were nearly significantly lower in the patients with SLE with HCQ blood levels >500 ng/mL (64.7±30.2 ng/mL vs 71.6±42.2 ng/mL, p=0.06). No significant difference in concentration of P-selectin was detected.ConclusionsIn the present study, there was a trend towards higher adhesion molecules levels with lower HCQ blood levels in patients with SLE. Further longitudinal studies will determine whether changes in endothelial biomarkers reflect decreased clinical CV events.
Background:According to the recent recommendations for Systemic Lupus Erythematosus (SLE), a progressive tapering until withdrawal of glucocorticoids (GC) is considered one of the main goals of SLE management (1). However, which patient may be a candidate for safe GC withdrawal has not been determined yet and a proportion of patients are kept on long-term low-dose prednisone despite clinical remission.Objectives:to evaluate the rate of low-dose GC withdrawal in SLE patients in remission and to identify predictors of flares.Methods:Eligible patients were SLE patients according to the ACR criteria (2) who were in prolonged clinical remission defined by a cSLEDAI=0 for at least 2 years and on a stable SLE treatment (immunosuppressive drugs and/or hydroxychloroquine (HCQ) and daily 5 mg prednisone). A SACQ period was defined as at least 1-year period with persistent serologic activity without clinical manifestations. Flares were defined by SELENA-SLEDAI Flare Index (3). Damage was assessed by SLICC damage index (SDI). Data were compared by the unpaired student’s t test or chi-squared test as appropriate. Predictors of flares after GC withdrawal were analyzed by Cox regression.Results:Out of 246 SLE patients registered in the Naples Lupus Clinic database, 132 eligible patients were identified. Among them, we selected 57 (43%) patients in whom a GC withdrawal was attempted. 75 (57%) patients were in the prednisone maintenance group.There were no significant differences between the two treatment groups (table 1). The proportion of patients experiencing a flare was not significantly lower in the maintenance group than in the withdrawal group (15/75 vs 16/57; p=0.28). Moreover, the proportion of patients who had an increase in the SDI at the end of follow up was similar between the two groups (14/75 vs 8/57; p=0.48). However, among the withdrawal group, the rate of flares was significantly higher in SACQ patients (10/22 vs 6/35; p=0.02), while the majority of serologically inactive patients (82%) successfully stopped GCs without subsequent flares. At Cox regression analysis (Table 2), duration of HCQ therapy and >4 year remission at withdrawal were protective factors, while a SACQ disease and history of lupus nephritis (LN) increased the risk of disease flare.Table 1.Baseline characteristics of 132 patients at study entryCharacteristicsWithdrawal group (n=57)Maintenance group (n=75)p-valueFemale, no. (%)54 (94)70 (93)0.73Age, years26.7±10.128.5±11.70.37Disease duration, years8.5±2.99.1±12.90.73History of lupus nephritis, no. (%)13(22)22(29)SDI score0.40±0.70.57±0.80.26Immunosuppressive drugs, no. (%)31 (54)33(44)0.16HCQ, no. (%)52 (91)66 (88)0.06Low C3, no. (%)28 (49)41(54)0.52Increased dsDNA Ab, no. (%)11 (19)19 (25)0.41Table 2.Factors predicting lupus flares during follow-up at Cox regression analysisVariablesHR95% CIp valueSACQ2.991.08 – 8.250.03Age0.970.93 – 1.020.29Disease duration0.990.94 – 1.040.84History of LN3.381.22-9.330.01SDI score1.130.63 – 2.010.66Immunosuppressive drugs2.390.86 – 6.620.09HCQ, ever2.920.43 – 35.20.95Duration of HCQ0.840.72 – 0.980.035years remission0.120.04 – 0.390.0003Conclusion:GC withdrawal is an achievable target in SLE and may be attempted in patients in complete remission. In SACQ patients, maintenance of 5mg prednisone is superior to its withdrawal in order to prevent flares. Long-term HCQ therapy and prolonged remission can significantly reduce the risk of disease relapse after GC withdrawal.References:[1]Fanouriakis A, et al. Ann Rheum Dis. 2019;78(6):736–45.[2]Tan EM, et al. Arthritis Rheum. 1982;25(11):1271–7.[3]Petri M, et al. Lupus. 1999;8(8):685–91.Disclosure of Interests:Serena Fasano: None declared, Luciana Pierro: None declared, Melania Alessia Coscia: None declared, laura Bucci: None declared, silvia scriffignano: None declared, Antonella Riccardi: None declared, francesco ciccia Grant/research support from: pfizer, novartis, roche, Consultant of: pfizer, novartis, lilly, abbvie, Speakers bureau: pfizer, novartis, lilly, abbvie
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