Guillermo J. Pons-Estel

Understanding the Epidemiology and Progression of Systemic Lupus Erythematosus

OBJECTIVES This review examines the burden and patterns of disease in systemic lupus erythematosus (SLE) and the influence and interactions of gender, ethnicity, age, and psychosocial attributes with respect to disease progression, focusing on issues relevant to clinical practice and research. METHODS PubMed literature search complemented by review of bibliographies listed in identified articles. RESULTS An increased risk among reproductive age women is clearly seen in African Americans in the United States. However, in other populations, a different pattern is generally seen, with the highest age-specific incidence rates occurring in women after age 40 years. The disease is 2 to 4 times more frequent, and more severe, among nonwhite populations around the world and tends to be more severe in men and in pediatric and late-onset lupus. SLE patients now experience a higher than 90% survival rate at 5 years. The less favorable survival experience of ethnic minorities is possibly related to socioeconomic status rather than to ethnicity per se, and adequate social support has been shown to be a protective factor, in general, in SLE patients. Discordance between physician and patient ratings of disease activity may affect quality of care. CONCLUSIONS Our understanding of ways to improve outcomes in SLE patients could benefit from patient-oriented research focusing on many dimensions of disease burden. Promising research initiatives include the inclusion of community-based patients in longitudinal studies, use of self-assessment tools for rating disease damage and activity, and a focus on self-perceived disease activity and treatment compliance.

Protective effect of hydroxychloroquine on renal damage in patients with lupus nephritis: LXV, data from a multiethnic US cohort

OBJECTIVE To assess whether hydroxychloroquine can delay renal damage development in lupus nephritis patients. METHODS Lupus nephritis patients (n = 256) from the LUpus in MInorities, NAture versus nurture study (n = 635), a multiethnic cohort of African Americans, Hispanics, and Caucasians, age > or =16 years with disease duration < or =5 years at baseline (T0) were studied. Renal damage was defined using the Systemic Lupus International Collaborating Clinics Damage Index (> or =1 of the following lasting at least 6 months: estimated/measured glomerular filtration rate <50%, 24-hour proteinuria > or =3.5 gm and/or end-stage renal disease, regardless of dialysis or transplantation). Patients with renal damage before T0 were excluded (n = 53). The association between hydroxychloroquine use and renal damage (as defined, or omitting proteinuria) was estimated using Cox proportional regression analyses adjusting for potential confounders. Kaplan-Meier survival curves based on hydroxychloroquine intake or the World Health Organization (WHO) class glomerulonephritis were also derived. RESULTS Sixty-three (31.0%) of the 203 patients included developed renal damage over a mean +/- SD disease duration of 5.2 +/- 3.5 years. The most frequent renal damage domain item was proteinuria. Patients who received hydroxychloroquine (79.3%) exhibited a lower frequency of WHO class IV glomerulonephritis, had lower disease activity, and received lower glucocorticoid doses than those who did not take hydroxychloroquine. After adjusting for confounders, hydroxychloroquine was protective of renal damage occurrence in full (hazard ratio [HR] 0.12, 95% confidence interval [95% CI] 0.02-0.97, P = 0.0464) and reduced (HR 0.29, 95% CI 0.13-0.68, P = 0.0043) models. Omitting proteinuria provided comparable results. The cumulative probability of renal damage occurrence was higher in those who did not take hydroxychloroquine and those classified as WHO class IV glomerulonephritis (P < 0.0001). CONCLUSION After adjusting for possible confounding factors, the protective effect of hydroxychloroquine in retarding renal damage occurrence in systemic lupus erythematosus is still evident.

Estimated Frequency of Antiphospholipid Antibodies in Patients With Pregnancy Morbidity, Stroke, Myocardial Infarction, and Deep Vein Thrombosis: A Critical Review of the Literature

Antiphospholipid Syndrome Alliance For Clinical Trials and International Networking (APS ACTION) is an international research network devoted to conducting well‐designed clinical trials in persistently antiphospholipid antibody (aPL)–positive patients. One of the first needs of APS ACTION was to know the true aPL frequency in patients with pregnancy morbidity (PM), stroke (ST), myocardial infarction (MI), and deep venous thrombosis (DVT).

Renal damage is the most important predictor of mortality within the damage index: data from LUMINA LXIV, a multiethnic US cohort

OBJECTIVE Damage accrual in SLE has been previously shown to be an independent predictor of mortality. We sought to discern which SLICC Damage Index (SDI) domains are the most important predictors of survival in SLE. METHODS SLE patients (ACR criteria), age > or =16 years, disease duration < or =5 years at enrolment, of African-American, Hispanic or Caucasian ethnicity were studied. Disease activity was assessed using the SLAM-Revised (SLAM-R) at diagnosis. Damage was ascertained using the SDI at the last visit. The SDI domains associated with time to death (and interaction terms) were examined by univariable and multivariable Cox proportional hazards regression analyses; those significant in the multivariable analyses were added to the final two models (with and without poverty) that included other variables known to be associated with shorter survival. RESULTS A total of 635 SLE patients were studied of whom 97 (15.3%) have died over a mean (s.d.) total disease duration of 5.7 (3.7) years. Patients were predominantly women [570 (89.8%)]; their mean (s.d.) age was 36.5 (12.6) years; 126 (19.8%) had developed renal damage, 62 (9.3%) cardiovascular, 48 (7.8%) pulmonary and 34 (5.4%) peripheral vascular damage. When excluding poverty from the multivariable model, the renal domain of the SDI was independently associated with a shorter time to death (hazard ratio = 1.65; 95% CI 1.03, 2.66). CONCLUSIONS The renal domain of the damage index is associated with a shorter time to death when poverty, a strong predictor of this outcome, is removed from the model. Preventing renal damage in lupus patients has long-term prognostic implications.

Predictors of cardiovascular damage in patients with systemic lupus erythematosus: data from LUMINA (LXVIII), a multiethnic US cohort

OBJECTIVE To determine the features predictive of atherosclerotic cardiovascular damage in patients with SLE. METHODS SLE LUMINA (LUpus in MInorities: NAture vs nurture) patients (n = 637), aged >or=16 years, disease duration <or=5 years at baseline (T0), of African-American, Hispanic and Caucasian ethnicity were studied. Atherosclerotic cardiovascular damage was defined by the following items of the SLICC Damage Index (SDI) cardiovascular domain: angina or coronary artery by pass surgery, myocardial infarction and/or congestive heart failure; factors associated with its occurrence were examined by univariable and multivariable regression analyses. RESULTS Forty-three (6.8%) of 637 patients developed cardiovascular damage over a mean +/- S.D. total disease duration of 6.6 +/- 3.6 years. Nearly 90% of the patients were women with a mean +/- s.d. age of 36.5 (12.6) years; all ethnic groups were represented. By multivariable analyses, after adjusting for the cardiovascular manifestations present, age [odds ratio (OR) = 1.06; 95% CI 1.03, 1.09], male gender (OR = 3.57; 95% CI 1.35, 9.09) SDI at baseline (OR = 1.28; 95% CI 1.09, 1.50) and CRP levels [highest tertile (OR = 2.63; 95% CI 1.17, 5.91)] were associated with the occurrence of cardiovascular damage, whereas the number of years of education was negatively associated with such outcome (OR = 0.85; 95% CI 0.74, 0.94). CONCLUSIONS Our data suggest that atherosclerotic cardiovascular damage in SLE is multifactorial; traditional (age, gender) and disease-related factors (CRP levels, SDI at baseline) appear to be important contributors to such an occurrence. Tight control of the inflammatory process must be achieved to prevent it.

Risk factors and impact of recurrent lupus nephritis in patients with systemic lupus erythematosus undergoing renal transplantation: Data from a single US institution

OBJECTIVE To determine the risk factors for recurrent lupus nephritis, allograft loss, and survival among patients with systemic lupus erythematosus (SLE) undergoing kidney transplantation. METHODS The archival records of all kidney transplant recipients with a prior diagnosis of SLE (according to the American College of Rheumatology criteria) from June 1977 to June 2007 were reviewed. Patients who had died or lost the allograft within 90 days of engraftment were excluded. Time-to-event data were examined by univariable and multivariable Cox proportional hazards regression analyses. RESULTS Two hundred twenty of nearly 7,000 renal transplantations were performed in 202 SLE patients during the 30-year interval. Of the 177 patients who met the criteria for study entry, the majority were women (80%) and African American (65%), the mean age was 35.6 years, and the mean disease duration was 11.2 years. Recurrent lupus nephritis was noted in 20 patients (11%), allograft loss in 69 patients (39%), and death in 36 patients (20%). African American ethnicity was found to be associated with a shorter time-to-event for recurrent lupus nephritis (hazard ratio [HR] 4.63, 95% confidence interval [95% CI] 1.29-16.65) and death (HR 2.47, 95% CI 0.91-6.71), although, with the latter, the association was not statistically significant. Recurrent lupus nephritis and chronic rejection of the kidney transplant were found to be risk factors for allograft loss (HR 2.48, 95% CI 1.09-5.60 and HR 2.72, 95% CI 1.55-4.78, respectively). In patients with recurrent lupus nephritis, the lesion in the engrafted kidney was predominantly mesangial, compared with a predominance of proliferative or membranous lesions in the native kidneys. CONCLUSION African American ethnicity was independently associated with recurrent lupus nephritis. Allograft loss was associated with chronic transplant rejection and recurrence of lupus nephritis. Recurrent lupus nephritis is infrequent and relatively benign, without influence on a patients survival.

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.

US patients of Hispanic and African ancestry develop lupus nephritis early in the disease course: data from LUMINA, a multiethnic US cohort (LUMINA LXXIV)

Lupus nephritis (LN) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE).1 As previously described, LN occurs more frequently in Hispanic and African-American people in the multiethnic US LUMINA (Lupus in Minorities: Nature vs Nurture) cohort.2 With more patients (one-third) and years of observation (2949.3 patient-years from enrolment or baseline), we have now examined whether LN occurs earlier in the disease course in these patients relative to Caucasians. Four hundred and forty-nine patients (American College of Rheumatology (ACR) criteria, age ≥16 years, disease duration ≤5 years, predominantly women) were studied. Time-to-LN (ACR criterion (persistent proteinuria >0.5 g/day or ≥3 if quantitation not performed or cellular casts)) from baseline (incident cases) was examined by multivariable Cox proportional hazards regression adjusting for pertinent …

Possible protective effect of hydroxychloroquine on delaying the occurrence of integument damage in lupus: LXXI, data from a multiethnic cohort.

To determine the features predictive of time to integument damage in patients with systemic lupus erythematosus (SLE) from a multiethnic cohort (LUpus in MInorities, NAture versus nurture [LUMINA]).

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.