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Women with systemic lupus erythematosus (SLE) carry a substantially higher risk for pre-eclampsia compared with the general population.1 Aspirin reduces the risk of pre-eclampsia in high-risk pregnancies by more than half2 and thus is recommended in SLE.3–5 The European League Against Rheumatism recommends aspirin in SLE pregnancies, particularly in those with nephritis or positive antiphospholipid antibodies (aPL).5 Despite this, little is known about current practice. Therefore, we assessed the prevalence of aspirin use in SLE pregnancies within the Systemic Lupus International Collaborating Clinics inception cohort, which has been described elsewhere.6 SLE women aged 18–45 with a pregnancy documented at one or more annual study visits (spanning 2000–2017) were included. For each pregnant visit, aspirin use, traditional pre-eclampsia risk factors (hypertension, chronic kidney disease, diabetes, nulliparity, body mass index ≥35, age >40), aPL and active lupus nephritis were assessed (see variable definitions in online supplementary material). Aspirin use was compared among those with and without each/any risk factor, and over time. We identified 475 pregnancies among 300 women. Mean SLE duration at the time of pregnancy was 5.6 years (SD 3.1). Half (51%) of pregnancies had ≥1 traditional pre-eclampsia risk factor, 34/104 (33%) had positive aPL and 53/475 (11%) had …

Background The metabolic syndrome (MetS) may contribute to increased cardiovascular risk in systemic lupus erythematosus (SLE). We aimed to examine the association of demographic factors, lupus phenotype and therapy exposure with the presence of MetS. Methods The Systemic Lupus International Collaborating Clinics Registry for Atherosclerosis inception cohort enrolled recently diagnosed (

ObjectiveNeuropsychiatric 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.MethodsPatients 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-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression.ResultsDisease 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-β2 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.ConclusionIn 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.

ObjectiveTo examine change in health-related quality of life in association with clinical outcomes of neuropsychiatric events in systemic lupus erythematosus (SLE).MethodsAn international study evaluated newly diagnosed SLE patients for neuropsychiatric events attributed to SLE and non-SLE causes. The outcome of events was determined by a physician-completed seven-point scale and compared with patient-completed Short Form 36 (SF-36) health survey questionnaires. Statistical analysis used linear mixed-effects regression models with patient-specific random effects.Results274 patients (92% female; 68% Caucasian), from a cohort of 1400, had one or more neuropsychiatric event in which the interval between assessments was 12.3±2 months. The overall difference in change between visits in mental component summary (MCS) scores of the SF-36 was significant (pConclusionChanges in SF-36 summary and subscale scores, in particular those related to mental health, are strongly associated with the clinical outcome of neuropsychiatric events in SLE patients.

ObjectivesTo determine the frequency, accrual, attribution and outcome of neuropsychiatric (NP) events and impact on quality of life over 3 years in a large inception cohort of patients with systemic lupus erythematosus (SLE).MethodsThe study was conducted by the Systemic Lupus International Collaborating Clinics. Patients were enrolled within 15 months of SLE diagnosis. NP events were identified using the American College of Rheumatology case definitions, and decision rules were derived to determine the proportion of NP disease attributable to SLE. The outcome of NP events was recorded and patient-perceived impact determined by the SF-36.Results1206 patients (89.6% female) with a mean (±SD) age of 34.5±13.2 years were included in the study. The mean disease duration at enrolment was 5.4±4.2 months. Over a mean follow-up of 1.9±1.2 years, 486/1206 (40.3%) patients had ≥1 NP events, which were attributed to SLE in 13.0–23.6% of patients using two a priori decision rules. The frequency of individual NP events varied from 47.1% (headache) to 0% (myasthenia gravis). The outcome was significantly better for those NP events attributed to SLE, especially if they occurred within 1.5 years of the diagnosis of SLE. Patients with NP events, regardless of attribution, had significantly lower summary scores for both mental and physical health over the study.ConclusionsNP events in patients with SLE are of variable frequency, most commonly present early in the disease course and adversely impact patients' quality of life over time. Events attributed to non-SLE causes are more common than those due to SLE, although the latter have a more favourable outcome.

The primary objective was to assess the long-term safety of repeated courses of epratuzumab therapy in patients with moderate-to-severe systemic lupus erythematosus. Secondary objectives were to assess long-term efficacy and health-related quality of life (HRQOL).Eligible patients from the 12-week, phase IIb, randomized, placebo-controlled EMBLEM study enrolled into the open-label extension (OLE) study, SL0008. In the SL0008 study, patients received 1,200 mg epratuzumab infusions at weeks 0 and 2 of repeating 12-week cycles, plus standard of care. Safety measures included treatment-emergent adverse events (TEAEs) and serious TEAEs. Efficacy measures included combined treatment response, the British Isles Lupus Assessment Group score, the Systemic Lupus Erythematosus Disease Activity Index score, and the physician's and patient's global assessment of disease activity. Total daily corticosteroid dose and HRQOL (by the Short Form 36 health survey) were also assessed.A total of 113 of the 203 patients (55.7%) who entered the SL0008 study continued epratuzumab therapy until study closure (total cumulative exposure: 381.3 patient-years, median exposure: 845 days, and maximum exposure: 1,185 days/approximately 3.2 years). TEAEs were reported in 192 patients (94.6%); most common were infections and infestations (68.0%, 138 patients). Serious TEAEs were reported in 51 patients (25.1%), and 14 patients (6.9%) had serious infections. In patients treated for 108 weeks (n = 116), the median corticosteroid dose was reduced from 10.0 mg/day at OLE screening to 5.0 mg/day at week 108. Improvements in efficacy and HRQOL measures in EMBLEM were maintained in the OLE, while placebo patients exhibited similar improvements in disease activity upon a switch to epratuzumab.Open-label epratuzumab treatment was well tolerated for up to 3.2 years, and associated with sustained improvements in disease activity and HRQOL, while steroids were reduced.

Objective. To describe the prevalence, characteristics, attribution, and clinical significance of neuropsychiatric (NP) events in an international inception cohort of systemic lupus erythematosus (SLE) patients. Methods. The study was conducted by the Systemic Lupus International Collaborating Clinics (SLICC). Patients were enrolled within 15 months of fulfilling the American College of Rheumatology (ACR) SLE classification criteria. All NP events within a predefined enrollment window were identified using the ACR case definitions of 19 NP syndromes. Decision rules were derived to determine the proportion of NP disease attributable to SLE. Clinical significance was determined using the Short Form 36 (SF-36) Health Survey and the SLICC/ACR Damage Index (SDI). Results. A total of 572 patients (88% female) were recruited, with a mean +/- SD age of 35 +/- 14 years. The mean +/- SD disease duration was 5.2 +/- 4.2 months. Within the enrollment window, 158 of 572 patients (28%) had at least 1 NP event. In total, there were 242 NP events that encompassed 15 of 19 NP syndromes. The proportion of NP events attributed to SLE varied from 19% to 38% using alternate attribution models and occurred in 6.1-11.7% of patients. Those with NP events, regardless of attribution, had lower scores on the SF-36 and higher SDI scores compared with patients with no NP events. Conclusion. Twenty-eight percent of SLE patients experienced at least 1 NP event around the time of diagnosis of SLE, of which only a minority were attributed to SLE. Regardless of attribution, the occurrence of NP events was associated with reduced quality of life and increased organ damage. (Less)

The aim of this study was to describe the frequency, attribution, outcome and predictors of seizures in systemic lupus erythematosus (SLE).The Systemic Lupus International Collaborating Clinics, or SLICC, performed a prospective inception cohort study. Demographic variables, global SLE disease activity (SLE Disease Activity Index 2000), cumulative organ damage (SLICC/American College of Rheumatology Damage Index (SDI)) and neuropsychiatric events were recorded at enrolment and annually. Lupus anticoagulant, anticardiolipin, anti-β(2) glycoprotein-I, antiribosomal P and anti-NR2 glutamate receptor antibodies were measured at enrolment. Physician outcomes of seizures were recorded. Patient outcomes were derived from the SF-36 (36-Item Short Form Health Survey) mental component summary and physical component summary scores. Statistical analyses included Cox and linear regressions.The cohort was 89.4% female with a mean follow-up of 3.5±2.9 years. Of 1631 patients, 75 (4.6%) had ≥1 seizure, the majority around the time of SLE diagnosis. Multivariate analysis indicated a higher risk of seizures with African race/ethnicity (HR (CI): 1.97 (1.07 to 3.63); p=0.03) and lower education status (1.97 (1.21 to 3.19); p0.01). Higher damage scores (without neuropsychiatric variables) were associated with an increased risk of subsequent seizures (SDI=1:3.93 (1.46 to 10.55); SDI=2 or 3:1.57 (0.32 to 7.65); SDI≥4:7.86 (0.89 to 69.06); p=0.03). There was an association with disease activity but not with autoantibodies. Seizures attributed to SLE frequently resolved (59/78 (76%)) in the absence of antiseizure drugs. There was no significant impact on the mental component summary or physical component summary scores. Antimalarial drugs in the absence of immunosuppressive agents were associated with reduced seizure risk (0.07 (0.01 to 0.66); p=0.03).Seizures occurred close to SLE diagnosis, in patients with African race/ethnicity, lower educational status and cumulative organ damage. Most seizures resolved without a negative impact on health-related quality of life. Antimalarial drugs were associated with a protective effect.

Objective. To determine the short-term outcome of neuropsychiatric (NP) events upon enrollment into an international inception cohort of patients with systemic lupus erythematosus (SLE). Methods. The study was performed by the Systemic Lupus International Collaborating Clinics. Patients were enrolled within 15 months of SLE diagnosis and NP events were characterized using the American College of Rheumatology case definitions. Decision rules were derived to identify NP events attributable to SLE. Physician outcome scores of NP events and patient-derived mental component summary (MCS) and physical component summary (PCS) scores of the Short Form 36 were recorded. Results. There were 890 patients (88.7% female) with a mean +/- SD age of 33.8 +/- 13.4 years and mean disease duration of 5.3 +/- 4.2 months. Within the enrollment window, 271 (33.5%) of 890 patients had at least 1 NP event encompassing 15 NP syndromes. NP events attributed to SLE varied from 16.5% to 33.9% using alternate attribution models and occurred in 6.0-11.5% of patients. Outcome scores for NP events attributed to SLE were significantly better than for NP events due to non-SLE causes. Higher global disease activity was associated with worse outcomes. MCS scores were lower in patients with NP events, regardless of attribution, and were also lower in patients with diffuse and central NP events. There was a significant association between physician outcome scores and patient MCS scores only for NP events attributed to SLE. Conclusion. In SLE patients, the short-term outcome of NP events is determined by both the characteristics and attribution of the events. Conclusion. In SLE patients, the short-term outcome of NP events is determined by both the characteristics and attribution of the events. (Less)

To determine the frequencies at which either a valine or leucine occurs at position 247 in the beta2-glycoprotein I (beta2GPI) gene of normal individuals of the Caucasian, African American, and Asian ethnic groups and to compare these data with those in patients with the antiphospholipid syndrome (APS), with and without anti-beta2GPI antibodies.The DNA segment containing the position-247 polymorphism was amplified by seminested polymerase chain reaction, and the polymorphism was detected by restriction endonuclease digestion. DNA samples from 370 healthy controls of different racial backgrounds were analyzed, and the results were compared with those from 149 APS patients (66 primary; 83 secondary). Allele and genotype frequencies were compared using Fisher's exact test. When significant differences were detected, pairwise comparisons were made using Fisher's exact test with a Bonferroni adjustment.Allele and genotype expression was significantly different (P0.0001 for both) among the 3 races, with the V allele and the VV genotype occurring most often among Caucasians, less among African Americans, and least among Asians. Conversely, the V allele and the VV genotype were found more frequently among Asian APS patients than among controls (P = 0.0028 and P = 0.0023, respectively). No significant differences in allele or genotype frequencies were seen in comparisons of the Caucasian or the African American patients with appropriate controls. The differences in allele and genotype frequencies seen in the Asian APS patients were restricted to the anti-beta2GPI-positive patients (P = 0.0018 and P = 0.0005, respectively).In Asian patients with APS, expression of a V at position 247, especially in the homozygous state, is significantly associated with the presence of anti-beta2GPI antibodies and, therefore, can be viewed as a major risk factor in this ethnic group (odds ratio 9.19 and 16.33, respectively).

To determine whether antiphospholipid antibodies (aPL) are more prevalent in cardiac patients taking procainamide than in a control population of similar elderly cardiac patients and to determine whether these antibodies react in an ELISA in which the primary antigen is beta 2-glycoprotein I (beta 2-GPI).aPL and antibodies to beta 2-GPI were measured in 66 patients taking procainamide from a Veterans Administration Medical Center population and a control group of 30 similar cardiac patients not taking procainamide.21% of the patients taking procainamide and no control patients were found to have moderate to high aPL. There were similar results in an assay that measured anti-beta 2-GPI in the absence of exogenous phospholipids. aPL were associated with antinuclear antibodies and antihistone antibodies but not with diabetes or clinical manifestations of drug related lupus. There was no increase in cholesterol or past thrombotic history associated with aPL, but there was a frequent history of noncardiac thrombosis in patients taking procainamide (25.7%).The predictive significance of procainamide induced aPL remains unknown but beta 2-GPI dependent aPL may be of some concern in this elderly population already at high risk for thrombosis.