Faculty Bibliography

Background Little is known about the association of healthcare costs with damage accrual in SLE. We describe the costsassociated with damage progression using multi-statemodeling.Methods Patients fulfilling the revised ACR Classification Criteria for SLE from 32 centres in 11 countries were enrolledin the Systemic Lupus International Collaborating Clinics(SLICC) inception cohort within 15 months of diagnosis.Annual data on demographics, SLE disease activity (SLEDAI-2K), damage (SLICC/ACR Damage Index [SDI] if-6 monthsfrom diagnosis), hospitalizations, medications, dialysis, and utilization of selected medical/surgical procedures were collected.Annual health resource utilization was costed using 2017Canadian prices. Annual costs associated with SDI states wereobtained from multiple regressions adjusting for age, sex, race/ethnicity, and disease duration. As there were relatively fewtransitions to SDI states 5 11, these were merged into a singleSDI state. Five and 10 year cumulative costs were estimatedby multiplying annual costs associated with each SDI state bythe expected duration in each state, which was forecastedusing a multi-state model and longitudinal SDI data from theSLICC Inception Cohort (Bruce IN et al. Ann Rheum Dis2015;74:1706 13). Future costs were discounted at a yearlyrate of 3%.Results 1676 patients participated, 88.7% female, 49.2% Caucasian, mean age at diagnosis 34.6 years (SD 13.4), mean disease duration at enrollment 0.5 years (range 0 1.3 years), andmean follow up 7.8 years (range 0.6 16.9 years). Healthresource utilization and annual costs (after adjustment usingregression) were markedly higher in those with higher SDIs(SDI=0, annual costs $1847, 95% CI $1120 to $2574;SDI-5, annual costs $26 772, 95% CI $19 631 to $33 813).At SDI<=2, hospitalizations and medications accounted for97.1% of direct costs, whereas at SDI-3, dialysis was responsible for 55.0%.Five and 10 year cumulative costs stratified by baseline SDIwere calculated by multiplying the annual costs associatedwith each SDI by the expected duration in that state. Fiveand 10 year costs were greater in those with the highest SDIsat baseline (table 1).Conclusions Patients with the highest baseline SDIs incurannual costs and 10 year cumulative costs that are at least 10-fold higher than those with the lowest baseline SDI. By estimating the expected duration in each SDI state and incorporating annual costs, disease severity at presentation can beused to predict future healthcare costs, critical knowledge forcost-effectiveness evaluations of novel therapies

OBJECTIVE:We describe disease activity, damage, and the accrual of key autoantibodies in an inception systemic lupus erythematosus (SLE) cohort. METHODS:The Systemic Lupus International Collaborating Clinics (SLICC) International Research Network, comprising 27 centers from 11 countries, has followed an inception cohort of SLE patients yearly according to a standardized protocol. Of these patients, 298 were followed for a minimum of 5 years and constitute the study population. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K) and damage was assessed using the SLICC/American College of Rheumatology Damage Index (SDI). Antinuclear antibody (ANA), anti-DNA, and anticardiolipin antibody (aCL) levels and lupus anticoagulant were assessed yearly. Descriptive statistics were generated and repeated-measures general linear models were used to evaluate SLEDAI-2K and SDI over time between whites and nonwhites. RESULTS:Of the 298 patients, 87% were women, 55% were white, 12% were African American, 14% were Asian, 16% were Hispanic, and 2% were categorized as "other." At enrollment, the mean age was 35.3 years, the mean SLEDAI-2K score was 5.9, and the mean disease duration was 5.5 months. Mean SLEDAI-2K scores decreased in the first year and then remained low. SLEDAI-2K scores were significantly lower at each year in whites compared to nonwhites. Mean SDI scores increased progressively over 5 years; there was no significant difference between whites and nonwhites. As expected, ANA positivity was high and anti-DNA positivity was relatively low at enrollment, and both increased over 5 years. Although lupus anticoagulant increased slightly over 5 years, aCL positivity did not. CONCLUSION/CONCLUSIONS:Disease activity in newly diagnosed patients decreases over their first 5 years, while damage increases. Antibody positivity ran variable courses over this period.

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/CONCLUSIONS: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.

OBJECTIVE:To examine change in health-related quality of life in association with clinical outcomes of neuropsychiatric events in systemic lupus erythematosus (SLE). METHODS:An 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. RESULTS:274 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 (p<0.0001) following adjustments for gender, ethnicity, centre and previous score. A consistent improvement in neuropsychiatric status (N=295) was associated with an increase in the mean (SD) adjusted MCS score of 3.66 (0.89) in SF-36 scores. Between paired visits when the neuropsychiatric status consistently deteriorated (N=30), the adjusted MCS score decreased by 4.00 (1.96). For the physical component summary scores the corresponding changes were +1.73 (0.71) and -0.62 (1.58) (p<0.05), respectively. Changes in SF-36 subscales were in the same direction (p<0.05; with the exception of role physical). Sensitivity analyses confirmed these findings. Adjustment for age, education, medications, SLE disease activity, organ damage, disease duration, attribution and characteristics of neuropsychiatric events did not substantially alter the results. CONCLUSION/CONCLUSIONS:Changes 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.

OBJECTIVE:To describe vascular events during an 8-year followup in a multicenter systemic lupus erythematosus (SLE) inception cohort and their attribution to atherosclerosis. METHODS:Clinical data, including comorbidities, were recorded yearly. Vascular events were recorded and attributed to atherosclerosis or not. All of the events met standard clinical criteria. Factors associated with atherosclerotic vascular events were analyzed using descriptive statistics, t-tests, and chi-square tests. Stepwise multivariate logistic regression was used to assess the association of factors with vascular events attributed to atherosclerosis. RESULTS:Since 2000, 1,249 patients have been entered into the cohort. There have been 97 vascular events in 72 patients, including: myocardial infarction (n = 13), angina (n = 15), congestive heart failure (n = 24), peripheral vascular disease (n = 8), transient ischemic attack (n = 13), stroke (n = 23), and pacemaker insertion (n = 1). Fifty of the events were attributed to active lupus, 31 events in 22 patients were attributed to atherosclerosis, and 16 events were attributed to other causes. The mean +/- SD time from diagnosis to the first atherosclerotic event was 2.0 +/- 1.5 years. Compared with patients followed for 2 years without atherosclerotic events (n = 615), at enrollment, patients with atherosclerotic vascular events were more frequently white, men, older at diagnosis of SLE, obese, smokers, hypertensive, and had a family history of coronary artery disease. On multivariate analysis, only male sex and older age at diagnosis were associated factors. CONCLUSION/CONCLUSIONS:In an inception cohort with SLE followed for up to 8 years, there were 97 vascular events, but only 31 were attributable to atherosclerosis. Patients with atherosclerotic events were more likely to be men and to be older at diagnosis of SLE.