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Introduction: The beneficial effect of hydroxychloroquine (HCQ) in decreasing LDL levels on Systemic Lupus Erythematosus (SLE) is well defined. The influence of this drug on HDL levels is still under debate and information about its effect on cholesterol reverse transport is lacking. Objective: To evaluate the effects of HCQ on HDL levels and the transfer of lipids to this lipoprotein in SLE. Methods: Nineteen SLE patients using only HCQ (SLE WITH HCQ), 19 SLE patients without any therapy (SLE WITHOUT THERAPY), and 19 healthy controls (CONTROL) were included. All three groups were premenopausal women age- and gender-matched. Serum lipids and apolipoproteins were determined by commercial kits. An in vitro transfer of four lipids (14C-Phospolipid, 3H-Cholesteryl ester, 3H-Triglyceride, and 14C-Unesterified cholesterol) from a radioactively labeled nanoemulsion donor to HDL was performed in all participants. Results: Groups had comparable mean age, weight, height, BMI(body mass index), and waist circumference (p >.05). Mean HDL levels were higher in SLE WITH HCQ group compared to SLE WITHOUT THERAPY(58.37 ± 14.04 vs 49.79 ± 8.0 mg/dL; p <.05) but lower than CONTROL (58.37 ± 14.04 vs 68.58 ± 9.99 mg/dL; p <.05). Total cholesterol (TC) and LDL levels were also significantly lower in SLE WITH HCQ compared SLE WITHOUT THERAPY(148.16 ± 16.43 vs 167.11 ± 30.18 mg/dL; p <.05, 75.05 ± 22.52 vs 96.05 ± 25.63 mg/dL; p <.05) and CONTROL (148.16 ± 16.43 vs 174.11 ± 23.70 mg/dL; p <.05, 75.05 ± 22.52 vs 88.53 ± 20.24 mg/dL; p <.05). The in vitro lipid transfer to HDL study revealed a significant difference among the three groups (p =.002) with a higher transfer of unesterified cholesterol(UC) in SLE WITH HCQ compared to SLE WITHOUT THERAPY(5.40 ± 1.05% vs. 4.44 ± 1.05%; p <.05). The latter was significantly decreased compared to CONTROL (5.40 ± 1.05% vs. 5.99 ± 1.71%; p <.05).The percentages of transfer of triacylglycerol (4.93 ± 0.69% vs. 4.50 ± 0.69% vs. 5.14 ± 1.01%; p =.054), esterified cholesterol (5.24 ± 0.70% vs. 4.96 ± 0.89% vs. 5.69 ± 1.27%; p =.079), and phospholipid (15.67 ± 1.03% vs. 15.34 ± 1.44% vs. 16.47 ± 1.89%; p =.066) were similar among groups. Conclusion: The present study is the first to demonstrate that HCQ promoted a higher transfer of unesterified cholesterol which may account for the increased HDL levels in lupus patients under HCQ. This desirable effect may underlie the reported reduced atherosclerosis in SLE. [ABSTRACT FROM AUTHOR]

Introduction: The American Academy of Ophthalmology (2016-AAO) recommended hydroxychloroquine (HCQ) dose not to exceed 5 mg/kg/day (real body weight). Recently, it was reported that prescribed 2016-AAO dose provided adequate HCQ levels for most lupus nephritis (LN) patients, with low flare risk. However, the minimum HCQ dose required to keep adequate levels is unknown. Objectives: To evaluate if a further reduction in 2016-AAO dose (2–3 mg/kg/day) would sustain 12-month HCQ levels in LN patients with stable inactive disease. Methods: Seventy-three stable LN patients under prescribed full HCQ 2016-AAO dose for ≥6 months and adequate baseline HCQ levels (≥613.5 ng/mL) were divided in two groups: reduced 2016-AAO dose (2–3 mg/kg/day), n = 32, and full 2016-AAO dose (5 mg/kg/day), n = 41. All patients were assessed at baseline, 3, 6, and 12 months. HCQ levels were measured by liquid chromatography-tandem mass spectrometry. Flare was defined as augment ≥ 3 in SLE Disease Activity Index-2000 and/or change in treatment. Rigorous clinical/laboratorial surveillance was performed. Results: Prospective evaluation revealed for reduced 2016-AAO dose group a decrease of HCQ levels from baseline to 3 months (1,404.9 ± 492.0 vs. 731.6 ± 385.0 ng/mL, p < 0.01), and sustained levels at 6 months (p = 0.273) and 12 months (p = 0.091) compared to 3 months. For the full 2016-AAO dose group, a decrease occurred only from baseline to 12 months (1343.5 ± 521.5 vs. 991.6 ± 576.3 ng/mL, p < 0.001). Frequencies of patients with inadequate levels at 6 months was higher in reduced 2016-AAO group than full 2016-AAO dose (59% vs. 24%, p = 0.005), as well as at 12 months (66% vs. 32%, p = 0.002). Six-month and 12-month flare frequencies were comparable for both groups (p > 0.05). Conclusions: Prescribed HCQ low-dose regimen (2–3 mg/kg/day) does not sustain, for most patients, 6- and 12-month adequate HCQ levels. Full 2016-AAO dose maintained HCQ levels way above this limit. Trail registration: ClinicalTrials.gov: NCT03122431, registered on April 20, 2017 Key Points • Reduced American Academy of Ophthalmology (2016-AAO) hydroxychloroquine (HCQ) dose (2–3 mg/kg/day, real body weight) is unable to sustain HCQ blood levels within the safe cut-off defined for flare risk. • Full 2016-AAO dose (5 mg/kg/day) maintains a safe pattern of HCQ levels up to 12 months. [ABSTRACT FROM AUTHOR]

Objectives: It is unknown if hydroxychloroquine blood level dynamics impact flare rates in lupus nephritis patients. We prospectively evaluated hydroxychloroquine levels to determine which blood-based patterns are more associated with disease activity. Methods: In total, 82 lupus nephritis patients under a prescribed hydroxychloroquine dose of 4–5.5 mg/kg actual body weight (maximum 400 mg/day) for ≥3 months were evaluated at baseline and 7 months. Hydroxychloroquine blood levels were determined by liquid chromatography-tandem mass spectrometry. Flare was defined as increase ≥3 in the Systemic Lupus Erythematosus Disease Activity Index 2000 score and/or a change or increase in therapy. Results: Overall, 9/82(11%) patients had flares during follow-up and had lower baseline hydroxychloroquine blood levels than those without flares (220.4 (53.5–1471.1) vs. 1006.3 (53.5–2137.8) ng/ml, p = 0.013). The hydroxychloroquine blood level cut-off that best predicted flares was 613.5 ng/ml (odds ratio = 8.67, 95% confidence interval: 1.66–45.18, p = 0.006). For 77 (94%) patients, the 7-month hydroxychloroquine level dynamics was evaluated and revealed: 59/77 (77%) had a persistent pattern of adequate (41/77(53%)) or fluctuating (18/77 (23%)) levels, with a low and comparable risk of flares (2/41 (5%) vs. 1/18 (5%), p = 1.000). The remaining group had persistent low levels (18/77 (23%)) and their flare frequency was significantly higher than the adequate group (5/18 (28%) vs. 2/41 (5%), p = 0.023). The frequencies of adequate/inadequate hydroxychloroquine blood levels in patients were comparable at baseline and 7 months (McNemar's test, p = 0.480). Conclusion: We provide novel evidence that hydroxychloroquine blood-level patterns (persistently low, adequate, or intermittent) have distinct impacts on flare rates in lupus nephritis patients. These findings reinforce the need of routine hydroxychloroquine measurements to maintain the appropriate blood levels. [ABSTRACT FROM AUTHOR]