Prevalence of Flare and Influence of Demographic and Serologic Factors on Flare Risk in Systemic Lupus Erythematosus: A Prospective Study
ABSTRACT We determined the prevalence of and risk factors for British Isles Lupus Activity Group (BILAG) flare in patients with systemic lupus erythematosus (SLE).
We followed 299 patients for 1 year with the BILAG scores calculated using British Lupus Integrated Prospective System software and confirmed with manual calculation.
"A" flares occurred at a rate of 0.254/year, "B" flares 1.637/year, and A or B flares 1.765/year. The most common A flares were renal and mucocutaneous. The most common B flares were hematologic, renal, mucocutaneous, and musculoskeletal. Risk factors for a later A or B flare in the hematological system included: low C3 (p < 0.0001), low C4 (p = 0.0004), and positive anti-double-stranded (ds)DNA (p = 0.003); in the mucocutaneous system: low C3 (p = 0.02) and low C4 (p = 0.0004); and in the renal system: low C3 (p = 0.02) and low C4 (p = 0.02). In a stepwise regression model, only ethnicity (p = 0.02) and low C4 (p = 0.0002) remained as independent predictors of later A or 2B flares.
The organ system distribution of A and B flares is very different, with A flares more common in renal and mucocutaneous, and B flares more common in hematologic and renal systems. A or 2B flares are significantly more common in African Americans and in patients with abnormal serologies (low C3, low C4, or high anti-dsDNA). If flare is an outcome in an SLE clinical trial, these factors must be balanced by taking them into account at baseline in terms of randomization, or by statistical adjustment in final analyses.
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ABSTRACT: Objective Correlates of systemic lupus erythematosus (SLE) Responder Index (SRI) response with clinical trial end points were examined using pooled data from the Study of Belimumab in Subjects with SLE (BLISS) trials (N=1684). Methods Changes in clinical, laboratory and health-related quality of life measures from baseline at 52 weeks were compared between SRI responders (n=761) and non-responders (n=923). Results More SRI responders than non-responders had ≥4-point (100% vs 3.8%) and ≥7-point (40.3% vs 1.3%) Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index reductions, no new British Isles Lupus Assessment Group (BILAG) A and ≤1 new B scores (91.9% vs 35.9%), and a 25% reduction in corticosteroid dose decrease of 25% from >7.5 mg/d to ≤7.5 mg/d (25.5% vs 13.9%), and fewer had a corticosteroid increase from ≤7.5 mg/d to >7.5 mg/d (4.1% vs 21.3%; all p<0.001). More responders than non-responders had improved organ domains: Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (mean 1.45 vs 0.40), BILAG (2.00 vs 0.39), and greater improvement in Physician's Global Assessment (all p<0.001). Risks for developing any SLE flare or severe flare were reduced in responders by 42% and 87%, respectively (p<0.001). Responders reported greater improvements in Medical Outcomes Survey Short Form version 2 Physical and Mental Components and all domain scores, and Functional Assessment of Chronic Illness Therapy-Fatigue score compared with non-responders (all p<0.001). Conclusion Overall, SRI response in patients with active, autoantibody-positive SLE was associated with improvements in clinical, laboratory and patient-reported outcome measures, indicating that SRI response was associated with a global benefit. Trial registration number NCT00424476; NCT00410384.06/2014; 1(1):e000031. DOI:10.1136/lupus-2014-000031
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ABSTRACT: Introduction Environmental effectors, such as ultraviolet radiation exposure, infection and stress, have been established as having a role in exacerbating lupus symptoms. However, unpredictable patterns of flare events still remain a mystery. Occupational effectors have also been suggested as having a contributing role; however, they are not widely researched. In this paper we report a pilot study designed to generate focus areas for future research regarding occupational exposures and systemic lupus erythematosus (SLE). Methods The study explored potential links between exposures and the occurrence of patient-reported flare events in 80 Australian women with SLE (American College of Rheumatology (ACR) criteria classified). Specifically, the study assessed the hypothesis that occupational exposure is associated with significant changes in the likelihood of lupus flares. Lifetime employment history was analysed with the Finnish Job Exposure Matrix (FINJEM), 40 different semiquantified exposure class estimates for a wide number of occupations based on probability of exposure (p≥5%=exposed) were analysed with the construction of negative binomial regression models to test relationships between occupational agents and flare days. A backward stepwise elimination was used to generate a parsimonious model. Results Significant associations were noted for exposure classes of manual handling burden, (p=0.02, incidence rate ratio (IRR) 1.01), Iron (p=0.00, IRR 1.37), wood dust (p=0.00, IRR 3.34) and asbestos (p=0.03, IRR 2.48). Conclusion Exposure assessment results indicated that occupations, such as nursing, with a high manual handling burden, posed increased risk to patients with SLE, however, the greatest risk was associated with wood dust and iron exposure with teachers and specialist labourers.Science & medicine 04/2014; 1(e000023). DOI:10.1136/lupus-2014-000023
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ABSTRACT: Objective. Identify predictors of moderate-severe systemic lupus erythematosus (SLE) flare in 562 patients treated with standard therapy alone in phase 3 belimumab trials and evaluate impact of standard therapies on preventing flares. Methods. Post-hoc analysis assessed baseline demographics, disease activity, and biomarkers in patients with and without flare at treatment weeks 24/52. Severe flare: modified SLE Flare Index (SFI) and 1 new British Isles Lupus Assessment Group (BILAG) A. Severe and moderate flare: any new BILAG A/2 new B scores. Baseline characteristics associated with ≥10% absolute difference/≥50% increase in flare rates were considered predictive. Results. Frequencies of SFI, BILAG 1A, and BILAG 1A/2B flares over 52 weeks were 24%, 23%, and 32%, respectively. Flare predictors by univariate analysis on all 3 indices at weeks 24/52: Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) ≥12, anti-dsDNA positivity and proteinuria (≥0.5 g/24h); BILAG renal, vasculitic, and hematologic scores; elevated C-reactive protein, and B-lymphocyte stimulator (BLyS) ≥2 ng/mL. Independent predictors by multivariate analysis at week 52: SELENA-SLEDAI/BILAG renal involvement and anti-dsDNA ≥200 IU/mL (all 3 indices); SELENA-SLEDAI/BILAG neurologic and vasculitic involvement (BILAG A/2 B or 1A scores); BLyS ≥2 ng/mL (SFI and BILAG 1A/2B scores); and low complement 3 (C3; SFI). Baseline medications did not significantly decrease or increase moderate-severe SLE flare risk. Conclusion. Patients on standard SLE therapy with renal, neurologic, or vasculitic involvement, elevated anti-dsDNA or BLyS, or low C3 had increased risk for clinically meaningful flare over 1 year. Hydroxychloroquine use was not predictive. © 2013 by the American College of Rheumatology.Arthritis & Rheumatology 08/2013; 65(8). DOI:10.1002/art.37995 · 7.87 Impact Factor