Daniel Wojdyla

Antimalarial treatment may have a time‐dependent effect on lupus survival: Data from a multinational Latin American inception cohort

OBJECTIVE To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort. METHODS Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser). RESULTS Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6-98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P< 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6-11 months, 146 (12.8%) for 1-2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person-months of followup) were 3.85 (95% confidence interval [95% CI] 1.41-8.37), 2.7 (95% CI 1.41-4.76), and 0.54 (95% CI 0.37-0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18-4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39-0.99). CONCLUSION Antimalarial drugs were shown to have a protective effect, possibly in a time-dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus.

Childhood systemic lupus erythematosus in Latin America. The GLADEL experience in 230 children.

Abstract To evaluate disease characteristics of childhood onset SLE in Latin America and to compare this information with an adult population in the same cohort of GLADEL. A protocol was designed as a multicenter, multinational, inception cohort of lupus patients to evaluate demographic, clinical, laboratory and serological variables, as well as classification criteria, disease activity, organ damage and mortality. Descriptive statistics, chi square, Fishers exact test, Students t test and multiple logistic regression were used to compare childhood and adult onset SLE. 230 patients were < 18 years and 884 were adult SLE patients. Malar rash, fever, oral ulcers, thrombocytopenia and hemolytic anemia and some neurologic manifestations were more prevalent in children (p < 0.05). On the other hand, myalgias, Sjögren’s syndrome and cranial nerve involvement were more frequently seen in adults (p < 0.05). Afro-Latin-American children had a higher prevalence of fever, thrombocytopenia and hemolytic anemia. White and mestizo children had a higher prevalence of malar rash. Mestizo children had a higher prevalence of cerebrovascular disease and cranial nerve involvement. Children met SLE ACR criteria earlier with higher mean values than adults (p: 0.001). They also had higher disease activity scores (p: 0.01), whereas adults had greater disease damage (p: 0.02). In Latin America, childhood onset SLE seems to be a more severe disease than adults. Some differences can be detected among ethnic groups.

Early rheumatoid arthritis in Latin America: low socioeconomic status related to high disease activity at baseline.

To determine the influence of socioeconomic factors on disease activity in a Latin American (LA) early rheumatoid arthritis (RA) multinational inception cohort at baseline.

The American College of Rheumatology and the Systemic Lupus International Collaborating Clinics Classification criteria for systemic lupus erythematosus in two multiethnic cohorts: a commentary

The authors offer some comments on the advantages and possible drawbacks of using the SLICC criteria in longitudinal observational studies and clinical trials after applying and comparing them to the ACR criteria in two multinational, multiethnic lupus cohorts.

Anti-malarials exert a protective effect while Mestizo patients are at increased risk of developing SLE renal disease: data from a Latin-American cohort

OBJECTIVE To examine the role of ethnicity and the use of anti-malarials (protective) on lupus renal disease. METHODS A nested case-control study (1:2 proportion, n = 265 and 530) within GLADELs (Grupo Latino Americano De Estudio de Lupus) longitudinal inception cohort was carried out. The end-point was ACR renal criterion development after diagnosis. Cases and controls were matched for follow-up time (end-point or a comparable time, respectively). Renal disease predictors were examined by univariable and multivariable analyses. Additional analyses were done to determine if the protective effect of anti-malarials persisted after adjusting for intake-associated confounders. RESULTS Of the cases, 233 (87.9%) were women; their mean (s.d.) age at diagnosis was 28.0 (11.9) years and their median (Q3-Q1 interquartile range) follow-up time for cases and controls was 8.3 months (Q3-Q1: 23.5); 56.6% of the cases and 74.3% of the controls were anti-malarial users. Mestizo ethnicity [odds ratio (OR) 1.72, 95% CI 1.19, 2.48] and hypertension (OR 2.26, 95% CI 1.38, 3.70) were independently associated with a higher risk of renal disease, whereas anti-malarial use (OR 0.39, 95% CI 0.26, 0.58), older age at disease onset (OR 0.98, 95% CI 0.96, 0.99) and female gender (OR 0.56, 95% CI 0.32, 0.99) were negatively associated with such occurrence. After adjusting for variables associated with their intake, the protective effect of anti-malarials on renal disease occurrence persisted (OR 0.38, 95% CI 0.25, 0.58). CONCLUSION Mestizo patients are at increased risk of developing renal disease, whereas anti-malarial use protects patients from such an occurrence.

The number of flares patients experience impacts on damage accrual in systemic lupus erythematosus: data from a multiethnic Latin American cohort

Purpose To determine the association between the number of flares systemic lupus erythematosus (SLE) patients experience and damage accrual, independently of other known risk factors. Methods SLE patients (34 centres, nine Latin American countries) with a recent diagnosis (≤2 years) and ≥3 evaluations were studied. Disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage with the SLICC/ACR Damage Index (SDI). Flare was defined as an increase ≥4 points in the SLEDAI between two study visits. An ambidirectional case- crossover design was used to determine the association between the number of flares and damage accrual. Results 901 patients were eligible for the study; 500 of them (55.5%) experienced at least one flare, being the mean number of flares 0.9 (SD: 1.0). 574 intervals from 251 patients were included in the case-crossover design since they have case and control intervals, whereas, the remaining patients did not. Their mean age at diagnosis was 27.9 years (SD: 11.1), 213 (84.9%) were women. The mean baseline SDI and SLEDAI were 1.3 (1.3) and 13.6 (8.1), respectively. Other features were comparable to those of the entire sample. After adjusting for possible confounding variables, the number of flares, regardless of their severity, was associated with damage accrual (SDI) OR 2.05, 95% CI 1.43 to 2.94, p<0.001 (OR 2.62, 95% CI 1.31 to 5.24, p=0.006 for severe and OR 1.91, 95% CI 1.28 to 2.83, p=0.001for mild-moderate). Conclusions The number of flares patients experience, regardless of their severity, increases the risk of damage accrual, independently of other known risk factors.

Treatment of early rheumatoid arthritis in a multinational inception cohort of Latin American patients: the GLADAR experience.

Background Treatment of rheumatoid arthritis (RA) has evolved dramatically in the last decade. However, little is known about the way rheumatologists in Latin America treat their patients in clinical practice, outside the scope of clinical trials. Objective The objective of this study was to describe treatment patterns at disease onset in early RA with data from a large, multicenter, multinational inception cohort of Latin American patients. Methods Consecutive patients with early RA (<1 year of disease duration as diagnosed by a rheumatologist) from 46 centers in 14 Latin American countries were enrolled in the study. Clinical data, laboratory assessments, and a detailed registry on type of prescriptions were collected at baseline and at 3, 6, 12, 18, and 24 months of follow-up. Hands and feet x-rays were obtained at baseline and at 12 and 24 months. All data were captured in Arthros 6.1 database. Continuous variables were expressed as means and SDs, and categorical variables were expressed as percentages and 95% confidence intervals (95% CIs). Only therapeutic data at baseline are presented, corresponding to the period between disease onset and second visit (3 months). Results A total of 1093 patients were included. Eighty-five percent were female, and 76% had a positive rheumatoid factor. Mean age at diagnosis was 46.5 (SD, 14.2) years, and mean disease duration at the first visit was 5.8 (SD, 3.8) months. Between baseline and second visit (3 months), 75% of patients (95% CI, 72%–78%) received disease-modifying antirheumatic drugs. Methotrexate (MTX) alone or in combination was the most frequently used (60.5%), followed by antimalarials (chloroquine or hydroxychloroquine, 32.1%), sulfasalazine (7.1%), and leflunomide (LEF, 4%). In 474 patients (43%), initiation of disease-modifying antirheumatic drugs was within the first month after the first visit. In addition, 290 patients (26%; 95% CI, 23%–29%) received combination therapy as initial treatment. The most frequently used combinations were MTX + chloroquine (45%), MTX + hydroxychloroquine (25%), and MTX + sulfasalazine (16%). Eleven patients (1%; 95% CI, 0.5%–1.8%) received biologics. Sixty-four percent (95% CI, 60%–66%) received corticosteroids. Of those, 80% (95% CI, 77%–84%) received 10 mg of oral prednisone or less. Conclusions In this cohort of Latin American patients with early RA, most patients received MTX very early in their disease course. Combination therapy was used approximately in 1 of every 4 patients as initial therapy. Biologics were rarely used at this early stage, and low-dose prednisone was commonly used.

Lupus in Latin-American patients: lessons from the GLADEL cohort

The need for comprehensive published epidemiologic and clinical data from Latin American systemic lupus erythematosus (SLE) patients motivated the late Dr Alarcón-Segovia and other Latin American professionals taking care of these patients to spearhead the creation of the Grupo Latino Americano De Estudio del Lupus (GLADEL) cohort in 1997. This inception cohort recruited a total of 1480 multiethnic (Mestizo, African-Latin American (ALA), Caucasian and other) SLE patients diagnosed within two years from the time of enrollment from 34 Latin American centers with expertise in the diagnosis and management of this disease. In addition to the initial 2004 description of the cohort, GLADEL has contributed to improving our knowledge about the course and outcome of lupus in patients from this part of the Americas. The major findings from this cohort are highlighted in this review. They have had important clinical implications for the adequate care of SLE patients both in Latin America and worldwide where these patients may have emigrated.

Mestizos with systemic lupus erythematosus develop renal disease early while antimalarials retard its appearance: Data from a Latin American cohort

Objectives The objective of this paper is to assess the predictors of time-to-lupus renal disease in Latin American patients. Methods Systemic lupus erythematosus (SLE) patients (n = 1480) from Grupo Latino Americano De Estudio de Lupus (GLADEL’s) longitudinal inception cohort were studied. Endpoint was ACR renal criterion development after SLE diagnosis (prevalent cases excluded). Renal disease predictors were examined by univariable and multivariable Cox proportional hazards regression analyses. Antimalarials were considered time dependent in alternative analyses. Results Of the entire cohort, 265 patients (17.9%) developed renal disease after entering the cohort. Of them, 88 (33.2%) developed persistent proteinuria, 44 (16.6%) cellular casts and 133 (50.2%) both; 233 patients (87.9%) were women; mean (± SD) age at diagnosis was 28.0 (11.9) years; 12.2% were African-Latin Americans, 42.5% Mestizos, and 45.3% Caucasians (p = 0.0016). Mestizo ethnicity (HR 1.61, 95% CI 1.19–2.17), hypertension (HR 3.99, 95% CI 3.02–5.26) and SLEDAI at diagnosis (HR 1.04, 95% CI 1.01–1.06) were associated with a shorter time-to-renal disease occurrence; antimalarial use (HR 0.57, 95% CI 0.43–0.77), older age at onset (HR 0.90, 95% CI 0.85–0.95, for every five years) and photosensitivity (HR 0.74, 95% CI 0.56–0.98) were associated with a longer time. Alternative model results were consistent with the antimalarial protective effect (HR 0.70, 95% CI 0.50–0.99). Conclusions Our data strongly support the fact that Mestizo patients are at increased risk of developing renal disease early while antimalarials seem to delay the appearance of this SLE manifestation. These data have important implications for the treatment of these patients regardless of their geographic location.

Disease features and outcomes in United States lupus patients of Hispanic origin and their Mestizo counterparts in Latin America: a commentary

OBJECTIVE To evaluate disease features and outcomes in two populations with significant Amerindian ancestry. METHODS Hispanic patients (from Texas) from the Lupus in Minorities: Nature versus Nurture (LUMINA) cohort and Mestizo patients from the Grupo Latino Americano De Estudio del Lupus or Latin American Group for the Study of Lupus (GLADEL) cohort were included. Disease features and outcomes were evaluated at baseline and last visit. Admixture informative markers of Mestizo Genoma de Lupus Eritematoso Sistémico Network consortium (GENLES) patients and Hispanic LUMINA patients were compared. Univariable analyses were performed using Chi square or Students t test as appropriate. Multivariable analyses adjusting for possible confounders were carried out using Poisson, logistic or Cox regression models as appropriate. RESULTS A total of 114 LUMINA and 619 GLADEL patients were included. GLADEL patients had accrued more damage at baseline, but the opposite was the case at last visit. Being from LUMINA was a risk factor for damage accrual, even after adjusting for possible confounders [relative risk (RR) 1.33, 95% CI 1.12, 1.58]. Also, LUMINA patients have a higher risk of mortality than GLADEL patients [hazard ratio (HR) 2.37, 95% CI 1.10, 5.15], having 5-year survival of 85.6% and 94.5%, respectively. In addition, 79 LUMINA patients and 744 Mestizo GENLES patients were evaluated in order to compare genetic ancestry between the two groups; GENLES patients had a higher proportion of European ancestry (48.5% vs 43.3%, P = 0.003) and a lower proportion of Asian ancestry (3.7% vs 4.9%, P = 0.048), but the proportions of Amerindian and African ancestry were comparable in both. CONCLUSION USA Hispanic patients seemed to have a poorer prognosis than their counterparts from Latin America, despite having a comparable genetic background. Socioeconomic factors may account for these observations.