Eduardo Ferreira Borba

Objectives: To compare the treatments used for the first episode of lupus nephritis (LN) in two Latin American cohorts (historical and contemporary) over a 25-year period, and their associations with clinical outcomes. Methods: Patients with biopsy-confirmed first LN episode were classified as non-proliferative (class V) or proliferative (classes III/IV). Sociodemographic, clinical, and treatment variables were described. Propensity score matching was used to examine the associations with four outcomes: mortality, damage accrual (SDI), hospitalization, and end-stage renal disease (ESRD). Results: A total of 532 SLE patients were included: 362 from GLADEL 1.0 (historical cohort) and 170 from GLADEL 2.0. (contemporary). Compared to GLADEL 1.0, patients in GLADEL 2.0 received lower doses of oral glucocorticoids (GC), more frequently GC pulses and antimalarials but less frequently cyclophosphamide. An increase in the use of mycophenolate mofetil and other immunosuppressants was also observed. In the logistic regression models, SDI was associated with baseline SDI and GC pulses, whereas belonging to the GLADEL 2.0 was a protective factor. Mortality was associated with Mestizo ethnicity and partial health coverage; antimalarial was identified as a protective factor. Hospitalizations were associated with baseline SLEDAI and SDI, follow-up time, and lower educational level. Belonging to the GLADEL 2.0 cohort was protective against the occurrence of ESRD. Conclusions: Patients in the contemporary cohort benefited from advances in treatment strategies, with less cumulative damage and progression to ESRD, although mortality remained unchanged. These improvements likely reflect the increased use of newer therapies, more targeted approaches, in line with current treatment guidelines, and better access to specialized care.

Objective: To assess the effect of antimalarials (AMs) on overall damage and on its most frequently affected domains, as measured by the Systemic Lupus International Collaborating Clinics Damage Index (SDI) in patients from the GLADEL cohort. Methods: New damage was defined as a ≥1 point increase in SDI since cohort entry. AMs users were those who received AMs for at least 6 months after entering the cohort. AMs users and non-users were matched for age, sex, ethnicity, and baseline SDI using stratified random sampling. Two comparisons were carried out: patients with and without new damage, and AM users versus non-users. Propensity score matching was used to determine the effect of AM use on the most frequently affected damage domains. Results: A total of 850 patients were included; 419 (49.3%) were AM users and 431 (50.7%) non-users. During a median follow-up of 48.5 (IQR 19.3, 69.0) months, 472 (55.5%) developed damage. The most affected domains were skin (18.4%), renal (14.6%), neuropsychiatric (10.8%), musculoskeletal (6.9%), and cardiovascular (4.5%). AMs use was associated with a lower proportion of patients accruing damage at follow-up (170 [40.6%] vs 208 [48.3%]; p = .028). AMs were protective against overall damage (HR 0.7, 95% CI [0.5–0.9]; p = .002), renal (HR 0.4, 95% CI [0.3–0.6]; p < .001), and neuropsychiatric damage (HR 0.5, 95% CI [0.3–0.9]; p = .022). Conclusion: AM use is independently associated with a lower probability of overall, renal, and neuropsychiatric damage accrual. These findings support early and sustained AM treatment in lupus patients, unless contraindicated.

Objective: To describe baseline characteristics of a multinational, multiethnic Latin American cohort of SLE patients with and without lupus nephritis (LN) from Latin American Group for the Study of Lupus (GLADEL) 2.0. Methods: GLADEL 2.0 is an observational prevalent and incident cohort. Adult patients (≥18 years) with SLE who fulfilled the 1982/1997 American College of Rheumatology (ACR) and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria from 43 centres in 10 Latin American countries were categorised into four groups: (1) without LN, (2) prevalent inactive LN, (3) prevalent active LN and (4) incident LN. Baseline demographics, clinical manifestations, treatments, disease activity and damage were recorded. A cross-sectional analysis and logistic regression was conducted to identify factors associated with LN and cumulative damage (SLICC/ACR Damage Index (SDI)). Results: Among 1083 patients, 89.6% were female, median age at diagnosis was 27 years, median disease duration was 66.2 months and 65.0% were Mestizo. Patients with LN (n=653) were younger and had shorter disease duration than patients without LN. LN was negatively associated with older age at diagnosis (OR, 0.98) and discoid rash (OR, 0.53) and positively associated with male gender (OR, 1.91), Mestizo ethnicity (OR, 1.46), comorbidities (OR, 3.2), thrombocytopenia (OR, 3.44), anti–double-stranded DNA (anti-dsDNA) positivity (OR, 3.23) and low complement (OR, 1.54). SDI ≥1 was associated with older age at diagnosis, longer disease duration, cumulative prednisone dose and cyclophosphamide use. Conclusions: Male sex, Mestizo ethnicity, comorbidities, thrombocytopenia, anti-dsDNA positivity and low complement levels were associated with LN occurrence. Cumulative damage was associated with older age at diagnosis, longer disease duration, higher cumulative dose of prednisone and the use of cyclophosphamide. Trial registration number: NCT04534647 .

Objective: The aim of this study was to assess the epidemiological and clinical characteristics of herpes zoster (HZ) and to identify the factors associated with its first episode in Latin American SLE patients. Methods: GLADEL 2.0 (Grupo Latino Americano De Estudio del Lupus) is a multiethnic, Latin American observational cohort of SLE patients. Demographic, clinical, laboratory, treatment and disease activity/damage data were compared between patients with and without HZ; its prevalence was assessed at cohort entry, incidence rates of first and recurrent HZ infections were calculated based on person-years of follow-up. Logistic regression was used to identify factors associated with HZ events, while Cox regression was used to determine the variables associated with time to first event. Results: Among 1083 SLE patients, the HZ cumulative incidence after its diagnosis was 11.5%, with a prevalence of 8.6% at cohort entry. During 5-year of follow-up, the incidence of HZ was 2.9% and 16.8% patients had recurrent episodes. Patients with HZ showed higher frequencies of alopecia, psychosis and seizures, along with higher disease activity, damage accrual, proteinuria and higher daily prednisone doses prior to the event. Multivariate analyses identified female sex, higher SLE Disease Activity Index 2000 (SLEDAI-2K) and higher daily prednisone dose as independent predictors of HZ occurrence. Older age at diagnosis, psychosis, disease activity and a higher daily prednisone dose were associated with a shorter time to HZ onset. Conclusion: In the GLADEL 2.0 cohort, the high burden of HZ in SLE, together with its association with active disease, corticosteroid exposure and neuropsychiatric manifestations, underscores the need for proactive risk stratification in clinical practice.

Objective: To evaluate whether hydroxychloroquine (HCQ) dose reduction (2–3 mg/kg/day) sustain lipoprotein levels achieved with higher doses of 2016-American Academy of Ophthalmology (2016-AAO) in stable lupus nephritis (LN) patients. Methods: Forty-seven consecutive stable LN patients using HCQ 2016-AAO recommended dose for ≥6 months were enrolled and assigned to one of two groups: Reduced HCQ group (n = 21):LN patients who, upon inclusion, reduced 2016-AAO dose (2–3 mg/kg/day); and Maintenance HCQ group ( n = 26):LN patients who continued on the standard 2016-AAO recommended HCQ dose (4.0–5.5 mg/kg actual body weight, maximum 400 mg/day) throughout 12-month study period. Blood HCQ levels, lipid profile and SLE parameters (including SLEDAI-2K) were assessed at baseline, 3 and 12-month. Results: Baseline demographics, comorbidities and disease parameters were similar among groups ( p > .05). Initial blood levels of Reduced HCQ group were 1219.4 (1041.7–1926.6)ng/mL and a progressive significant decrease were identified after 3 and 12 months [651.2 (538.4–832.6)vs.468.8 (228.4–925.6)ng/mL, p < .001]. Maintenance HCQ group had no changes in HCQ levels during the study [1179.7 (905.5–1607.3)vs.1026.2 (710.5-1345.8)vs.907.9 (663.9-1304.2)ng/mL, p = .158]. No changes were observed on the longitudinal total cholesterol levels of Reduced HCQ [166 (113–198)vs.153 (85–192)vs.150 (90–231)mg/dL, p = .964] and Maintenance HCQ [155 (114–244)vs.154 (122–210)vs.155 (112–213)mg/dL, p = .395]. LDL cholesterol levels of Reduced HCQ [91 (52–163)vs.83 (41–136vs.87 (47–165)mg/dL, p = .917] and Maintenance HCQ [79 (36–114)vs.76.5 (33–111)vs.75.5 (63–131)mg/dL, p = .412] remained similar. Other lipoprotein levels remained stable during 1 year of study. Conclusion: This is the first study to show that reducing HCQ to 2-3 mg/kg/day preserves lipid stability over 12 months in stable lupus nephritis patients.

Objective: To identify factors associated with individual Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) accrual items in 1385 patients from the Latin American SLE incident cohort (GLADEL (Grupo Latino Americano Del Estudio de Lupus)). Methods: Longitudinal cohort study. SDI assessed yearly, and damage accrual defined as a SDI change in any individual item during follow-up. Sociodemographic and clinical characteristics at entry, along with regular medication use up to the month prior to each damage item accrued, were analysed using multivariate Cox proportional hazard models with time-varying hazard risk effect performed. Models for overall damage and 10 items with at least 28 patients per item are reported. Results: New damage was accrued by 658 patients with SLE (48%) over a median of 54 months (p25–75: 29–71) of follow-up. Mestizo ethnicity, recent SLE Disease Activity Index (SLEDAI) and immunosuppressants were predictors of overall damage accrual, while antimalarials and rural residence were protectors; mixed effects were observed for SDI >0 and glucocorticoids (GCs) use. Protectors for scarring chronic alopecia (23.7% at 7 years follow-up) included older age, longer disease duration, diagnostic delay, SDI >0 and cytotoxic use. Proteinuria >3.5 g/24 hours (11.5% at 7 years follow-up) was associated with protective factors like older age, longer disease duration and higher GCs dose, while risk factors were Mestizo ethnicity, low medical coverage, higher SLEDAI scores and cytotoxic use. In addition, Mestizo ethnicity was a risk factor for estimated glomerular filtration rate 3.5 g/24 hours. Recent disease activity and cytotoxic use were significant risk factors for additional items. Conclusions: Factors associated with damage accrual differ substantially by individual SDI items. Mestizo ethnicity and recent disease activity increased renal risks, while antimalarials were protective. GCs showed mixed effects. Item-specific strategies are crucial to mitigate long-term damage.

The study aimed to: (i) characterize dietary intake and identify disorders eating attitudes in women with SLE, (ii) evaluate possible differences in both dietary intake and disorders eating attitudes in patients with SLE according to nutritional status, (iii) investigate possible associations between eating disorders attitudes, anthropometric characteristics and food consumption. Methods: This cross-sectional study included 46 premenopausal female patients (18-40 years), with inactive disease, using prednisone 25 kg/m ² ). Food consumption was assessed according to the processing level and energy and macronutrient content. The Disordered Eating Attitude Scale (DEAS) was applied. Results: Patients with excess weight had a higher DEAS score when compared to those with normal weight (34 ± 8.7 vs 25 ± 5.9, p = .001). A higher percentage of patients with excess weight demonstrated disturbance in their relationship with food and concerns about food and weight gain versus those with normal weight. DEAS score was positively associated with BMI, abdominal circumference, and fat mass percentage and negatively associated with lipid intake. Conclusion: Disordered eating attitudes differ in SLE patients according to nutritional status, and those with excess weight show higher DEAS scores, which may be related to food and weight gain.

Background: Patients with autoimmune rheumatic diseases (ARDs) are at an increased risk for herpes zoster (HZ). Vaccination is recommended for this population. Objective: The aim of this study was to evaluate the safety of vaccination with the recombinant zoster vaccine (Shingrix) in ARD patients, humoral immunogenicity (HI), cellular immunogenicity (CI), and the incidence of HZ. Methods: This randomized, double-blind, placebo-controlled phase 4 study involves 1180 ARD patients and a control group (CG) of 393 balanced healthy individuals, aged ≥50 years. ARD patients will be randomly assigned in a blinded manner (1:1 ratio) to 2 groups: vaccine or placebo (on days 0 and 42), administered intramuscularly. Outcomes will be assessed at baseline, 6 weeks, and 12 weeks after vaccination, including disease activity (using specific disease activity scores), HI, and CI. Adverse events will be assessed using a standardized questionnaire after each vaccine dose. Incident HZ cases will be monitored throughout the study. One year following the second dose, the persistence of HI and CI will be evaluated in both ARD patients and CG. HI and CI will be assessed using serum concentrations of anti-gE antibodies and the frequencies of gE-specific CD4+ T cells, respectively. Comparisons of anti-gE titers between ARD patients and CG at different time points will be analyzed using 2-way repeated-measures analysis of variance. Multiple regression analysis will be conducted, with a positive immune response as the dependent variable, and variables with p < 0.2 from univariate analysis as independent variables. Conclusions: This large trial addresses a critical gap by examining disease safety, efficacy, adverse effects, and immunogenicity, considering the impact of diverse therapies following recombinant zoster vaccine administration in ARD patients.