Showing papers by "Christine A. Peschken published in 2011"

Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus

Abstract: Objective Neuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events. Methods Patients with a recent SLE diagnosis were assessed prospectively for up to 10 years for neuropsychiatric events using the American College of Rheumatology case definitions. Decision rules of graded stringency determined whether neuropsychiatric events were attributable to SLE. Associations between the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant (LA), anticardiolipin, anti-β 2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. Results Disease duration at enrolment was 5.4±4.2 months, follow-up was 3.6±2.6 years. Patients were 89.1% female with mean (±SD) age 35.2±13.7 years. 495/1047 (47.3%) developed one or more neuropsychiatric event (total 917 events). Neuropsychiatric events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrolment 21.9% of patients had LA, 13.4% anticardiolipin, 15.1% anti-β 2 glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. LA at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (HR 2.54, 95% CI 1.08 to 5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR 3.92, 95% CI 1.23 to 12.5, p=0.02). Other autoantibodies did not predict neuropsychiatric events. Conclusion In a prospective study of 1047 recently diagnosed SLE patients, LA and anti-ribosomal P antibodies are associated with an increased future risk of intracranial thrombosis and lupus psychosis, respectively.

A targeted association study in systemic lupus erythematosus identifies multiple susceptibility alleles

Abstract: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Multiple genetic and environmental factors contribute to the pathogenesis of this disease. Recent genome-wide association studies have added substantially to the number of genes associated with SLE. To replicate some of these susceptibility loci, single-nucleotide polymorphisms reported to be associated to SLE were evaluated in a cohort of 245 well-phenotyped Canadian SLE trios. Our results replicate previously reported associations to alleles of interferon regulatory factor 5 (IRF5), major histocompatibility complex (MHC), tumor necrosis factor (ligand) superfamily member 4 (TNFSF4), Kell blood group complex subunit-related family member 6 (XKR6), B-cell scaffold protein with ankyrin repeats 1 (BANK1), protein tyrosine phosphatase non-receptor type 22 (PTPN22), ubiquitin-conjugating enzyme E2L 3 (UBE2L3) and islet cell autoantigen 1 (ICA1). We also identify putative associations to cytotoxic T-lymphocyte-associated protein 4 (CTLA4), a gene associated with several autoimmune disorders, and ERBB3, a locus on 12q13 that was previously reported to be associated with type 1 diabetes. This study confirms the existence of multiple genetic risk factors for SLE, and supports the notion that some risk factors for SLE are shared with other inflammatory disorders.

Surveillance of systemic autoimmune rheumatic diseases using administrative data

Abstract: There is growing interest in developing tools and methods for the surveillance of chronic rheumatic diseases, using existing resources such as administrative health databases. To illustrate how this might work, we used population-based administrative data to estimate and compare the prevalence of systemic autoimmune rheumatic diseases (SARDs) across three Canadian provinces, assessing for regional differences and the effects of demographic factors. Cases of SARDs (systemic lupus erythematosus, scleroderma, primary Sjogren’s, polymyositis/dermatomyositis) were ascertained from provincial physician billing and hospitalization data. We combined information from three case definitions, using hierarchical Bayesian latent class regression models that account for the imperfect nature of each case definition. Using methods that account for the imperfect nature of both billing and hospitalization databases, we estimated the over-all prevalence of SARDs to be approximately 2–3 cases per 1,000 residents. Stratified prevalence estimates suggested similar demographic trends across provinces (i.e. greater prevalence in females-versus-males, and in persons of older age). The prevalence in older females approached or exceeded 1 in 100, which may reflect the high burden of primary Sjogren’s syndrome in this group. Adjusting for demographics, there was a greater prevalence in urban-versus-rural settings. In our work, prevalence estimates had good face validity and provided useful information about potential regional and demographic variations. Our results suggest that surveillance of some rheumatic diseases using administrative data may indeed be feasible. Our work highlights the usefulness of using multiple data sources, adjusting for the error in each.

Healthcare Cost and Loss of Productivity in a Canadian Population of Patients with and without Lupus Nephritis

Abstract: Objective To compare the healthcare cost and loss of productivity in patients with systemic lupus erythematosus (SLE) with (LN) and without lupus nephritis (lupus nephritis-negative, LNN). Methods Patients were classified into those with active (ALN and ALNN) and inactive disease (ILN and ILNN). Patients reported on visits to healthcare professionals and use of diagnostic tests, medications, assistive devices, alternative treatments, hospital emergency visits, surgical procedures, and hospitalizations as well as loss of productivity in the 4 weeks preceding enrollment. Results Enrollment was 141 patients, 79 with LN and 62 LNN. Patients with LN were more likely to visit rheumatologists and nephrologists, undergo diagnostic tests, and had higher costs for medications than patients who were LNN. The annual healthcare cost averaged $CAN 12,597 ± 9946 for patients with LN and $10,585 ± 13,149 for patients who were LNN, a difference of $2012 (95% CI –$2075, $6100). Patients with ALN had more diagnostic tests and surgical procedures, contributing to a significantly higher annual direct cost ($14,224 ± 10,265) compared to patients with ILN ($9142 ± 8419) and a difference of $5082 (95% CI $591, $9573). The healthcare cost was not different between patients with ALNN and patients with ILNN. In patients with LN and patients who were LNN, < 50% were employed and on average missed 6.5–9 days of work per month. The loss of productivity was significantly higher for caregivers of patients with LN than caregivers of patients who were LNN. Conclusion Healthcare cost and loss of productivity were similar between patients with LN and patients who were LNN; the loss of productivity for caregivers is higher for patients with LN; and the healthcare cost is greater in ALN than in ILN.

Medication use in systemic lupus erythematosus.

Abstract: Objective. To evaluate factors affecting therapeutic approaches used in clinical practice for the management of systemic lupus erythematosus (SLE), in a multicenter cohort. Methods. We combined data from 10 clinical adult SLE cohort registries in Canada. We used multivariate generalized estimating equation methods to model dichotomized outcomes, running separate regressions where the outcome was current exposure of the patient to specific medications. Potential predictors of medication use included demographic (baseline age, sex, residence, race/ethnicity) and clinical factors (disease duration, time-dependent damage index scores, and adjusted mean SLE Disease Activity Index-2K scores). The models also adjusted for clustering by center. Results. Higher disease activity and damage scores were each independent predictors of exposure to nonsteroid immunosuppressive agents, and for exposure to prednisone. This was not definitely demonstrated for antimalarial agents. Older age at diagnosis was independently and inversely associated with exposure to any of the agents studied (immunosuppressive agents, prednisone, and antimalarial agents). An additional independent predictor of prednisone exposure was black race/ethnicity (adjusted RR 1.46, 95% CI 1.18, 1.81). For immunosuppressive exposure, an additional independent predictor was race/ethnicity, with greater exposure among Asians (RR 1.39, 95% CI 1.02, 1.89) and persons identifying themselves as First Nations/Inuit (2.09, 95% CI 1.43, 3.04) than among whites. All of these findings were reproduced when adjustment for disease activity was limited to renal involvement. Conclusion. Ours is the first portrayal of determinants of clinical practice patterns in SLE, and offers interesting real-world insights. Further work, including efforts to determine how differing clinical approaches may influence outcome, is in progress.