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Objective.To evaluate the efficacy/safety of belimumab plus standard therapy in patients (n = 449) with active systemic lupus erythematosus (SLE) treated up to 7 years (n = 177 currently ongoing).Methods.Patients (n = 345) who completed a double-blind, placebo-controlled, 52-week study of belimumab 1, 4, or 10 mg/kg and 24-week extension of belimumab (placebo switched to 10 mg/kg; belimumab same dose or switched to 10 mg/kg) could receive belimumab 10 mg/kg in an open-label continuation study (n = 296). Disease activity was analyzed in patients with active SLE at baseline of the initial study. Biomarker and SLE medication changes were evaluated, and adverse events (AE) were monitored throughout the study.Results.Total belimumab exposure over 7 years (double-blind and open-label periods): 1746 patient-years. SLE Responder Index (SRI) response rates at Week 52 in autoantibody-positive patients: placebo, 29%; belimumab, 46% (p < 0.05). In the continuation study, 57% of auto-antibody-positive patients had an SRI response by Year 2 and 65% by Year 7; severe flares occurred in 19% with placebo and 17% with belimumab during the first year, with the annual rate declining to 2%–9% during years 2–7. Anti-dsDNA autoantibodies in patients positive for them at baseline had a progressive decline of 40%–60% from baseline over 2–7 years with belimumab. Corticosteroid use decreased over time with ≥ 50–55% reduction in median dose during years 5–7. Serious and overall annual AE rates, including infections, were generally stable or decreased during 7-year treatment.Conclusion.Disease control and safety profile were maintained in patients with active SLE taking belimumab plus standard therapy for up to 7 years. [ClinicalTrials.govnumbers: NCT00071487 and NCT00583362]

Introduction:Women with ischemia and no obstructive coronary artery disease (INOCA) often have abnormal coronary reactivity (CR).Hypothesis:Women with abnormal CR have chronic myocardial injury. We investigated for the first time the association between coronary reactivity and ultra-high sensitivity cardiac troponin I (u-hscTnI) levels in women with INOCA.Methods:Women (N=263) with INOCA, undergoing CR testing, enrolled in the WISE-CVD study. Coronary flow reserve (CFR), in response to intracoronary (IC) adenosine, and coronary blood flow (CBF), in response to IC acetylcholine (ACH) were obtained to test microvascular function. Epicardial CR was tested by coronary dilation response to ACH and IC nitroglycerin (NTG). u-hscTnI levels were collected before CR testing and assessed using Simoa HD-1 Analyzer (Quanterix, Lexington, MA) (lower limit of quantification 0.079 pg/mL). Logistic regression models, adjusted for cardiovascular risk factors, were used to investigate the association between u-hscTnI (log transformed) and CR.Results:Compared to women with normal increase in CBF in response to ACH (?50%) and coronary dilation in response NTG (?20%), those with abnormal function had higher levels of u-hscTnI (both p=0.001) (Figure 1). U-hscTnI levels were associated with abnormal CBF in response to ACH (OR=1.38 per doubling in u-hscTnI, 95% CI 1.03-1.84; p=0.033) and abnormal epicardial coronary dilation in response NTG (OR=1.37 per doubling in u-hscTnI, 95% CI 1.04-1.81; p=0.026). There was no evidence that u-hscTnI levels and CFR and epicardial coronary artery dilation in response to ACH were associated.Conclusions:Our findings demonstrate that u-hscTnI is associated with abnormal CR in women with INOCA. This suggests that chronic ischemia may be a mechanistic pathway to the development of adverse outcomes in women with abnormal CR. Additional study to confirm and investigate these findings with regard to adverse outcome prognosis are needed.

Background:Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have coronary microvascular dysfunction (CMD) determined invasively by coronary reactivity testing (CRT). Often these women have persistent angina despite medical therapy, but it is not clear whether it is due to worsening or persistent CMD. We hypothesized that CMD can persist despite medical therapy and repeat invasive testing can help guide further management.Methods:Among 280 women undergoing clinically indicated coronary reactivity testing at a single tertiary center, we evaluated 12 (4.3%) who were testing twice. Coronary vasomotor pathways were assessed as non ? endothelial dependent microvascular function measured as coronary flow reserve (CFR) in response to intracoronary (IC) adenosine, endothelial dependent micro- and macro-vascular dysfunction as coronary blood flow change (ACH CBF ?), diameter change (ACH Dm ?) in response to IC acetylcholine and non-endothelial dependent macrovascular function as diameter change to IC nitroglycerin (NTG Dm ?). Medications initiated after diagnosis of CMD were confirmed. Angina was assessed using Seattle Angina Questionnaire (SAQ) after the initial testing. Variables were compared using paired t test.Results:At baseline CRT mean age was 52 ? 10.5 years (75% post-menopausal) and 58 ?10.7 years at follow-up. Most were treated with anti-atherosclerotic and anti-anginal therapy, with an average SAQ score of 45.87 ? 10.34 at baseline. Median time between testing was 8 years (range 2-11). At baseline 92% had abnormal CFR, with a mean of 2.27?0.55 which improved to CFR2.93?0.72 at follow-up (p= 0.02). Other pathways did not show significant improvement at follow-up (Figure).Conclusions:The results demonstrate that CMD is a persistent condition, albeit it may improve over time in the setting of medical therapy. Further prospective studies are needed to understand the impact of the antianginals on the CMD pathways.

Introduction:We have previously demonstrated that history of migraines is associated with worse cardiovascular outcomes among women being evaluated for ischemic heart disease. Vascular mechanisms may have a role in migraine pathophysiology, but the relationship between coronary vascular dysfunction and migraine history has not been studied in women with ischemia and no obstructive coronary arteries (INOCA).Methods:In the Women?s Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study, 252 women with suspected INOCA completed Seattle Angina Questionnaires (SAQ) and underwent coronary reactivity testing (CRT) to evaluate for coronary vascular dysfunction.Results:A history of migraines was reported in 126 (50%) women. Compared to women without migraines, women with migraines were younger and scored worse on SAQ angina frequency and disease perception (Table). However, there was no difference in prevalence of coronary vascular dysfunction. Linear regression models demonstrated no significant age-adjusted differences in absolute CRT variables.Conclusions:Among women with suspected INOCA, women with a history of migraines have worse angina compared to women without migraines, but coronary vascular dysfunction as diagnosed by CRT does not relate to migraine history. These findings should be further evaluated with larger populations, however may provide insight into the pathophysiology of vascular dysfunction of migraines.