Evelyne Vinet

Biologic therapy and pregnancy outcomes in women with rheumatic diseases

Most of the autoimmune rheumatic diseases are more common in women than in men. Because many of these conditions (e.g., rheumatoid arthritis [RA]) affect women of childbearing potential, reproductive issues related to disease management often emerge. Although some autoimmune rheumatic diseases tend to improve during pregnancy, treatment is sometimes required throughout the pregnancy and/or during the postpartum period. Unfortunately, some important therapeutic agents (e.g., methotrexate [MTX] in RA and cyclophosphamide in vasculitis) are teratogenic; therefore, treatment options during pregnancy are limited, and newer treatment options would be welcome. However, none of the newer biologic therapies (anti–tumor necrosis factor [anti-TNF] agents, anakinra, rituximab, or abatacept) are classified by the US Food and Drug Administration (FDA) as safe to use during pregnancy (1). This lack of safety classification is mainly attributable to the lack of adequate and well-controlled studies. Still, in the last decade, numerous case series and case reports of pregnant patients exposed to biologic therapy have accumulated in the literature. Because biologic agents may constitute an important therapeutic alternative in pregnant women experiencing persistent or increased disease activity, we present a comprehensive review of the relevant data. Search strategy. We performed a systematic literature review to identify all studies with original human data on fetal and/or child outcomes following exposure to biologic agents during pregnancy and/or lactation. We searched the following electronic databases for primary studies: PubMed (1950 to October 2008), EMBase (1996 to October 2008), and Web of Science (1991 to October 2008). Our search strategy was restricted to articles published in English, French, or Spanish and included the following medical subject headings (MeSH)

Associations between Ambient Fine Particulate Levels and Disease Activity in Patients with Systemic Lupus Erythematosus (SLE)

Background Systemic lupus erythematosus (SLE) is a chronic disease of unclear etiology, characterized by an overactive immune system and the production of antibodies that may target normal tissues of many organ systems, including the kidneys. It can arise at any age and occurs mainly in women. Objective Our aim was to evaluate the potential influence of particulate matter (PM) air pollution on clinical aspects of SLE. Methods We studied a clinic cohort of SLE patients living on the island of Montreal, followed annually with a structured clinical assessment. We assessed the association between ambient levels of fine PM [median aerodynamic diameter ≤ 2.5 μm (PM2.5)] measured at fixed-site monitoring stations and SLE disease activity measured with the SLE Disease Activity Index, version 2000 (SLEDAI-2K), which includes anti–double-stranded DNA (anti-dsDNA) serum-specific autoantibodies and renal tubule cellular casts in urine, which reflects serious renal inflammation. We used mixed effects regression models that we adjusted for daily ambient temperatures and ozone levels. Results We assessed 237 patients (223 women) who together had 1,083 clinic visits from 2000 through 2007 (mean age at time of first visit, 41.2 years). PM2.5 levels were associated with anti-dsDNA and cellular casts. The crude and adjusted odds ratios (reflecting a 10-μg/m3 increase in PM2.5 averaged over the 48 hr prior to clinical assessment) were 1.26 [95% confidence interval (CI), 0.96–1.65] and 1.34 (95% CI, 1.02–1.77) for anti-dsDNA antibodies and 1.43 (95% CI, 1.05–1.95) and 1.28 (0.92–1.80) for cellular casts. The total SLEDAI-2K scores were not associated with PM2.5 levels. Conclusions We provide novel data that suggest that short-term variations in air pollution may influence disease activity in established autoimmune rheumatic disease in humans. Our results add weight to concerns that pollution may be an important trigger of inflammation and autoimmunity.

Decreased live births in women with systemic lupus erythematosus

Multiple disease‐related factors may limit the number of children born to women with systemic lupus erythematosus (SLE). We calculated live births in women with SLE and compared this with general population rates.

Systemic Lupus and Risk of Restless Legs Syndrome

Objective. To determine the prevalence of restless legs syndrome (RLS) in women with systemic lupus erthythematosus (SLE), and to compare this to a rheumatic disease sample without SLE. Methods. Unselected consecutive female patients were SLE were recruited from a lupus clinic. A RLS questionnaire based on 4 criteria, validated by the International Restless Legs Syndrome Study Group, was administered during a face-to-face interview. Smoking history and height and weight data were collected. Similar methods were used to determine RLS prevalence in a comparator group of women with rheumatic diseases other than SLE. Controls were frequency-matched by age group (in 5-year age bands) to SLE subjects. Controls were otherwise unselected. Results. We recruited 33 women with SLE and 32 controls. Twelve of 33 female SLE subjects scored positively for RLS (37.5%; 95% CI 22.9, 54.7) compared to 4 of 32 controls (12.5%; 95% CI 5.0, 28.1). Multivariate logistic regression showed that adjusted for age, obesity, and smoking, women with SLE were more likely to have RLS than the female controls (adjusted odds ratio 6.61, 95% CI 1.52, 28.77). In our multivariate analyses of all rheumatic patients, including SLE, the adjusted OR for obesity and RLS was 5.14 (95% CI 1.07, 24.6). Conclusion. These novel data indicate that RLS is more prevalent in women with SLE than in controls. Although obesity was a significant risk factor for RLS in our sample, the predictive covariates examined were limited.

Increased risk of autism spectrum disorders in children born to women with systemic lupus erythematosus: Results from a large population-based cohort

In utero exposure to maternal antibodies and cytokines are potential risk factors for autism spectrum disorders (ASDs). The aim of this study was to determine whether children born to mothers with systemic lupus erythematosus (SLE) have an increased risk of ASD compared to children born to mothers without SLE.

A population-based assessment of live births in women with systemic lupus erythematosus

Objectives The authors aim to calculate the number of live births, before and after systemic lupus erythematosus (SLE) diagnosis, in women diagnosed during their reproductive years and to compare this with general population rates. Methods The authors identified women with SLE using Quebec administrative databases (1 January 1994 to 31 December 2003). The authors determined the number of live births, and calculated the standardised incidence ratio (SIR) of observed to expected live births. Results 1334 women with SLE were identified. Overall, the number of live births over the interval (559) was below that which would be expected (708) (SIR 0.79; 95% CI 0.73 to 0.86). Compared with the general population, live births were substantially lower after SLE diagnosis (SIR 0.62; 95% CI 0.55 to 0.70) than before diagnosis (SIR 1.01; 95% CI 0.90 to 1.13). Conclusion After diagnosis, women with SLE have substantially fewer live births than the general population.

Rheumatoid arthritis disease severity indices in administrative databases: a systematic review.

Objective. We aimed to systematically review rheumatoid arthritis (RA) disease severity indices for use in administrative healthcare databases. We also provide an overview of alternative methods to control for RA disease severity in administrative database research. Methods. We conducted a systematic review of studies that developed/validated an index for RA disease severity using variables in administrative databases, and compared the convergent validity/reliability of the index with a standard measure of RA severity. Results. After reviewing 539 articles, 2 studies were included. The claims-based index for RA severity (CIRAS) was developed in one study. Components of the CIRAS included tests for inflammatory markers, number of chemistry panels/platelet counts ordered, rheumatoid factor test, number of rehabilitation and rheumatology visits, and Felty’s syndrome. The CIRAS correlated moderately well with a previously validated RA medical records-based index of severity. The second study assessed whether current and lifetime treatment with disease-modifying antirheumatic drugs and/or biologics accurately predicted RA severity, as measured by the patient-reported Patient Activity Scale (PAS). Treatment variables did not fully distinguish patients in the highest and lowest quartiles of PAS scores (67.2% correctly classified). Conclusion. Two claims-based indices of RA severity were identified but have some limitations for routine use. A concerted effort from experts in the field is needed to define, develop, and validate a widely applicable measure of RA disease severity for administrative database research.

Rheumatic autoimmune diseases in women and midlife health

Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (scleroderma) preferentially affect women, and are characterized by systemic inflammation leading to target organ dysfunction. The public health burden of autoimmune diseases, which collectively represent a leading cause of morbidity and mortality among women throughout adulthood, is substantial. While some features of these diseases have been observed to improve over the menopausal transition, such as disease flare rate in SLE and skin softening and thinning in scleroderma, others, such as swollen and tender joints and radiographically confirmed damage in RA may worsen. The general trends, however, are not consistent or conclusive for all disease-related manifestations. Of great importance is the recognition that comorbid diseases, including osteoporosis and accelerated cardiovascular disease, contribute excess morbidity and mortality that becomes increasingly apparent as women with autoimmune diseases undergo the menopausal transition.

Increased Risk of Autism Spectrum Disorders in Children Born to Women with Systemic Lupus Erythematosus: Results from the OSLER Cohort

In utero exposure to maternal antibodies and cytokines are potential risk factors for autism spectrum disorders (ASDs). The aim of this study was to determine whether children born to mothers with systemic lupus erythematosus (SLE) have an increased risk of ASD compared to children born to mothers without SLE.

Increased Congenital Heart Defects in Children Born to Women With Systemic Lupus Erythematosus Results From the Offspring of Systemic Lupus Erythematosus Mothers Registry Study

Background— In a large population-based study, we aimed to determine whether children born to women with systemic lupus erythematosus (SLE) have an increased risk of congenital heart defects (CHDs) in comparison with children born to women without SLE. Methods and Results— The Offspring of SLE Mothers Registry (OSLER) includes all women who had ≥1 hospitalization for delivery after SLE diagnosis, identified through Quebec’s healthcare databases (1989–2009), and a randomly selected control group of women, matched ≥4:1 for age and year of delivery. We identified children born live to SLE mothers and their matched controls, and ascertained CHD based on ≥1 hospitalization or physician visit with relevant diagnostic codes, within the first 12 months of life. We performed multivariable logistic regression analyses, using the generalized estimating equation method, to adjust for relevant covariates. Five hundred nine women with SLE had 719 children, whereas 5824 matched controls had 8493 children. In comparison with controls, children born to women with SLE experienced more CHD (5.2% [95% confidence interval (CI), 3.7–7.1] versus 1.9% [95% CI, 1.6–2.2], difference 3.3% [95% CI, 1.9–5.2]). In multivariable analyses, children born to women with SLE had a substantially increased risk of CHD (odds ratio, 2.62; 95% CI, 1.77–3.88) in comparison with controls. In addition, in comparison with controls, offspring of SLE mothers had a substantially increased risk of having a CHD repair procedure (odds ratio, 5.82; 95% CI, 1.77–19.09). Conclusions— In comparison with children from the general population, children born to women with SLE have an increased risk of CHD, and an increased risk of having a CHD repair procedure, as well.