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Mycophenolate mofetil (MMF) significantly reduces proteinuria in experimental model of human membranous nephropathy (Heymann nephritis). Twenty consecutive SLE patients with persistent isolated severe proteinuria and/or proteinuric flare were studied for 18 months of MMF therapy. All of them presented stable renal function and 12 had biopsy proven membranous glomerulonephritis (WHO class V). The starting daily dose for MMF was 1.5 g to a maximum of 3 g. Patients were divided into: partial response, ≥50% decrease of baseline proteinuria; complete response, normal proteinuria levels (less than 0.3 g/24 h); flare, increase of at least 50% of the mean baseline proteinuria. All 20 SLE patients (100%) presented a 50% reduction of baseline proteinuria which was achieved in 8.2±3.3 months of MMF therapy, at a mean daily dose of 2.3±0.5 g. A significant decrease in 24-h protein excretion was observed compared to entry (3.47±1.26 vs. 1.33±0.67 g, P<0.0001) as well as a correspondent increase of serum albumin (3.2±0.4 vs. 3.7±0.4 mg/dl, P=0.02) and reduction of prednisone dose (33.7±20.0 to 18.6±14.1 mg/day, P=0.01). Complete response was observed in 11 SLE patients (55%) in 12.2±3.0 months of therapy with a significant decrease in proteinuria (P<0.0001), prednisone dose (P<0.0001) and an increase of serum albumin (P=0.003). Interestingly, initial proteinuria or serum albumin levels did not identify patients with complete response and those with partial response at the end of the study (P=0.543 and 0.657, respectively). Our pilot prospective study suggests that MMF appears to be effective in reducing severe persistent proteinuria in lupus glomerulonephritis, even in patients unresponsive to other immunosuppressive treatments. [ABSTRACT FROM AUTHOR]

The objective of this study is to assess the role of the 2019-European League Against Rheumatism/American College of Rheumatology (2019-EULAR/ACR) classification criteria at diagnosis and its domains in predicting long-term damage in systemic lupus erythematosus(SLE). We performed a retrospective analysis using an electronic chart database utilized in routine clinical care of SLE patients and established in 2000 in a tertiary hospital. Two hundred and nine consecutive SLE patients with disease onset ≥18 years old and long disease duration were included. Cumulative damage at the last visit was scored using the SLICC/ACR-Damage Index (SDI). The median age at SLE diagnosis was 28 years (18–63), disease duration was 14 years (8–25), and 88% were females. Damage (SDI≥1) was observed in 116/209 (55%). Patients with (SDI≥1, n=116) and without damage (SDI=0, n=93) had similar median disease duration [14 (8–25) vs. 12 (8–25) years, p=0.090] and age at diagnosis [23 (18–55) vs. 23 (18–56) years, p=0.998]. No correlation was observed between total 2019-EULAR/ACR score at diagnosis and SDI at last visit (r=0.007, p=0.913). Presence of renal domain at diagnosis was associated with renal damage at last visit (OR=3.6, 95%CI 1.2–10.4, p=0.017) and antiphospholipid antibodies domain predicted neuropsychiatric damage (OR=3.0, 95%CI 1.2–7.6, p=0.015). A ROC analysis identified that a cut-off >24 in 2019-EULAR/ACR score could predict a trend for renal damage (p=0.077) with a lower renal survival (Kaplan-Meier curve) for patients above this limit (p=0.029). A multivariate logistic regression analysis revealed that 2019-EULAR/ACR score >24 at diagnosis (OR 4.583, 95%CI 1.052–19.962, p=0.043) was independently associated with renal damage. Specific domains in the 2019-EULAR/ACR criteria at diagnosis were associated with long-term organ-specific damage, particularly renal and neuropsychiatric harm. A 2019-EULAR/ACR score >24 predicted worse renal survival. Key Points • Presence of renal domain of the 2019-EULAR/ACR classification criteria at diagnosis was associated with long-term renal damage. • Presence of antiphospholipid antibodies domain at diagnosis was associated with long-term neuropsychiatric damage. • A 2019-EULAR/ACR overall score >24 at diagnosis was independently associated with renal damage and predicted worse renal long-term survival. [ABSTRACT FROM AUTHOR]

Objective: To assess overall adrenal mineralocorticoid/glucocorticoid/androgen steroidogenesis in childhood-onset systemic lupus erythematosus (cSLE) patients and the possible effect of prednisone on adrenal hormones and ovarian reserve. Methods: Fifty-one adult cSLE (ACR criteria) patients and 23 healthy controls were evaluated for adrenal steroidogenesis including mineralocorticoid (progesterone, deoxycorticosterone, aldosterone), glucocorticoid (17-OHprogesterone, 11-desoxycortisol, cortisol), and androgen (dehydroepiandrosterone-sulfate, androstenedione, total testosterone, and dihydrotestosterone) hormones. Ovarian reserve assessment included follicle-stimulating hormone (FSH), estradiol, anti-Müllerian hormone, ovarian volumes, and antral follicle count. Results: The median of current age [29.11 (19–39.8) vs. 30.8 (19.6–42.1) years, p = 0.502] was similar in adult cSLE and controls. Regarding mineralocorticoid/glucocorticoid, the median of progesterone (p = 0.003), 17-OH progesterone (p < 0.001), and 11-desoxycortisol (p = 0.036) were significantly lower in patients compared to controls. All androgen steroidogenesis hormones were reduced in the former group [dehydroepiandrosterone-sulfate (p < 0.001), androstenedione (p = 0.001), total testosterone (p = 0.005), and dihydrotestosterone (p < 0.001)]. Further comparison of patients with and without current use of prednisone and controls revealed a predominant impact on adrenal glucocorticoid and androgen steroidogenesis with reduced levels of 17-OH progesterone [0.17 (0–0.5) vs. 0.27 (0.1–2.9) vs. 0.33 (0.1–0.8) ng/mL, p < 0.001], dehydroepiandrosterone-sulfate [0.155 (0–0.6) vs. 0.49 (0.1–1.6) vs. 1.11 (0.1–2.6) μg/mL, p < 0.001], androstenedione [0.56 (0.2–4.4) vs. 1.7 (0.5–4.5) vs. 2.33 (0.3–3.8) ng/mL, p < 0.001], total testosterone [12 (12–167) vs. 16 (12–28) vs. (16.5 (0–50) ng/d, p = 0.002], and dihydrotestosterone [92.68 (11.8–198.5) vs. 160.62 (37.9–842.1) vs. 188.3 (71.3–543.9) pg/ml, p < 0.001] in patients under this drug. In addition, patients with this therapy had reduced median ovarian volumes [4.14 (2–12) vs. 7.13 (2–25.7) vs. 5.18 (2.4–17.3) cm3, p = 0.028) that was not associated with cyclophosphamide cumulative dose (p > 0.05). The median prednisone dose was 15/mg/day (2.5–40). Conclusions: We provided novel evidence that cSLE patients have an overall androgen/glucocorticoid/mineralocorticoid adrenal suppression. Furthermore, low/moderate prednisone use seems to underlie these abnormalities and may also adversely affect ovarian reserve, independently of immunosuppressants. Key Points • cSLE patients have an overall androgen/glucocorticoid/mineralocorticoid adrenal suppression. • Low/moderate prednisone use may affect ovarian reserve, independently of immunosuppressants. [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]