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REMISSION AND LOW DISEASE ACTIVITY ARE ASSOCIATED WITH LOWER HEALTH CARE COSTS IN AN INTERNATIONAL INCEPTION COHORT OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS [Meeting Abstract]

Clarke, A E; Ugarte-Gil, M F; Barber, M R W; Hanly, J G; Urowitz, M B; St, Pierre Y; Gordon, C; Bae, S -C; Romero-Diaz, J; Sanchez-Guerrero, J; Bernatsky, S; Wallace, D J; Isenberg, D A; Rahman, A; Merrill, J T; Fortin, P R; Gladman, D D; Bruce, I N; Petri, M; Ginzler, E M; Dooley, M A; Ramsey-Goldman, R; Manzi, S; Jonsen, A; Van, Vollenhoven R F; Aranow, C; Mackay, M; Ruiz-Irastorza, G; Lim, S S; Inanc, M; Kalunian, K C; Jacobsen, S; Peschken, C A; Kamen, D L; Askanase, A; Pons-Estel, B A; Alarcon, G S
Background/Purpose Remission and low disease activity (LDA) are associated with decreased flares, damage, and mortality. However, little is known about the impact of disease activity states (DAS) on health care costs. We determined the independent impact of different definitions of remission and LDA on direct and indirect costs (DC, IC) in a multicentre, multiethnic inception cohort. Methods Patients fulfilling revised ACR classification criteria for SLE from 33 centres in 11 countries were enrolled within 15 months of diagnosis and assessed annually. Patients with >=2 annual assessments were included. Five mutually independent DAS were defined: 1) Remission off-treatment: clinical (c) SLEDAI-2K=0, without prednisone or immunosuppressants 2) Remission on-treatment: cSLEDAI-2K=0, prednisone <=5mg/d and/or maintenance immunosuppressants 3) LDA-Toronto Cohort (TC): cSLEDAI-2K<=2, without prednisone or immunosuppressants 4) Modified Lupus LDA State (mLLDAS): SLEDAI-2K<=4, no activity in major organs/systems, no new disease activity, prednisone <=7.5mg/d and/or maintenance immunosuppressants 5) Active: all remaining assessments Antimalarials were permitted in all DAS. At each assessment, patients were stratified into 1 DAS; if >1 definition was fulfilled per assessment, the patient was stratified into the most stringent. The proportion of time patients were in a specific DAS at each assessment since cohort entry was determined. At each assessment, annual DC and IC were based on health resource use and lost workforce/non-workforce productivity over the preceding year. Resource use was costed using 2021 Canadian prices and lost productivity using Statistics Canada age-and-sex-matched wages. To examine the association between the proportion of time in a specific DAS at each assessment since cohort entry and annual DC and IC, multivariable random-effects linear regression modelling was used. Potential covariates included age at diagnosis, disease duration, sex, race/ethnicity, education, region, smoking, and alcohol use. Results 1631 patients (88.7% female, 48.9% White, mean age at diagnosis 34.5) were followed for a mean of 7.7 (SD 4.7) years (table 1, Panel A). Across 12,281 assessments, 49.3% were classified as active (table 1, Panel B). Patients spending <25% vs 75-100% of their time since cohort entry in an active DAS had lower annual DC and IC (DC $4042 vs $9101, difference -$5060, 95%CI -$5983, -$4136; IC $21,922 vs $32,049, difference -$10,127, 95% -$16,754, -$3499) (table 2, Panel B&C). In multivariable models, remission and LDA (per 25% increase in time spent in specified DAS vs active) were associated with lower annual DC and IC: remission off-treatment (DC -$1296, 95%CI -$1800, -$792; IC -$3353, 95%CI -$5382, -$1323), remission on-treatment (DC -$987, 95%CI -$1550, -$424; IC -$3508, 95%CI -$5761, -$1256), LDA-TC (DC -$1037, 95%CI -$1853, -$222; IC -$3229, 95%CI -$5681, -$778) and mLLDAS (DC -$1307, 95%CI -$2194, -$420; IC -$3822, 95%CI -$6309, $-1334) (table 3, Model B). There were no differences in costs between remission and LDA. Conclusions Remission and LDA are associated with lower costs, likely mediated through the known association of these DAS with more favourable clinical outcomes
EMBASE:640016238
ISSN: 2053-8790
CID: 5513532

M-PHASE PHOSPHOPROTEIN 1 (MPP-1) AUTOANTIBODIES AS A POTENTIAL BIOMARKER FOR CRANIAL NEUROPATHIES IN AN INTERNATIONAL SLE INCEPTION COHORT [Meeting Abstract]

Krustev, E; Hanly, J G; Chin, R; Buhler, K; Cardwell, F; Urowitz, M B; Gordon, C; Bae, S -C; Romero-Diaz, J; Sanchez-Guerrero, J; Bernatsky, S; Wallace, D J; Isenberg, D A; Rahman, A; Merrill, J T; Fortin, P R; Gladman, D D; Bruce, I N; Petri, M; Ginzler, E M; Dooley, M A; Ramsey-Goldman, R; Manzi, S; Jonsen, A; Alarcon, G S; Van, Vollenhoven R F; Aranow, C; Mackay, M; Ruiz-Irastorza, G; Lim, S; Inanc, M; Kalunian, K C; Jacobsen, S; Peschken, C A; Kamen, D L; Askanase, A; Buyon, J; Fritzler, M J; Clarke, A E; Choi, M Y
Objectives We previously reported in a single centre prevalent SLE cohort that antibodies against the cytokinesis-associated protein M-Phase Phosphoprotein 1 (anti-MPP-1) were associated with SLE-related cranial neuropathy (CN), a rare manifestation of neuropsychiatric SLE (NPSLE). The purpose of this study was to assess whether anti-MPP-1 is a biomarker for CN or other NPSLE manifestations using an international SLE inception cohort. Methods SLE patients fulfilling the updated 1997 ACR classification criteria for SLE were included. Anti-MPP-1 antibody testing was performed on baseline samples (within 15 months of diagnosis) or first annual assessment using an addressable laser bead immunoassay (ALBIA) with purified recombinant human protein with results expressed as median florescence units (MFU). Based on healthy controls, a dilution of >=1:500 MFU was considered positive. NPSLE manifestations occurring over the first 5 years of follow up were documented annually based on ACR case definitions using published NPSLE attribution rules1). The frequency of anti-MPP-1 positivity between patients with versus without each of the 19 NPSLE manifestations was compared using univariate logistic regression. For any NPSLE manifestations where anti-MPP-1 positivity differed between patients with versus without the manifestation, baseline demographic and clinical characteristics were compared using t-tests and twosample tests of proportions. For NPSLE manifestations associated with anti-MPP-1 positivity in the univariate analysis, multivariable logistic regression analysis using penalized maximum likelihood estimates was then performed to assess the relationship between anti-MPP-1 and the NPSLE manifestation, adjusting for age at anti-MPP-1 testing, female, White race/ethnicity, and significantly different baseline clinical characteristics. Results Seven hundred and ninety-five SLE patients were assessed; 29.8% were anti-MPP-1 positive, 88.7% female, and 52.1% White. The frequency of anti-MPP-1 positivity differed only for those with versus without CN (70.0% vs. 29.3%; odds ratio [OR] 5.16, 95%CI 1.44, 18.54) (table 1). Compared to patients without CN (n=785), patients with CN (n=10) were more likely to fulfill the ACR hematologic (difference: 23.9%, 95%CI 5.0%, 42.8%) and antinuclear antibody criteria (difference: 4.3%, 95%CI 2.9%, 5.8%) (table 2). (Table Presanted)In the multivariate analysis, anti-MPP-1 remained associated with CN (OR 5.24, 95%CI 1.44, 19.09) after adjusting for age at anti-MPP-1 testing, female, White race/ethnicity, hematologic disorder, and antinuclear antibody (table 3). Conclusion Anti-MPP-1 is a potential biomarker for CN. Although anti-MPP-1 is differentially expressed in a variety of neurological cells and tissues, the link to a pathogenic role requires further study
EMBASE:640015976
ISSN: 2053-8790
CID: 5513552

EXPLORATORY SEGREGATION OF PATIENTS UPON THEIR LEVELS OF ANTI-MITOCHONDRIAL ANTIBODIES (AMAS) REVEALS ASSOCIATIONS BETWEEN AMAS AND DISEASE MANIFESTATIONS [Meeting Abstract]

Becker, Y L C; Boilard, E; Rollet-Labelle, E; Lood, C; Julien, A -S; Leclerc, J; Levesque, T; Urowitz, M; Hanly, J; Gordon, C; Bae, S -C; Romero-Diaz, J; Sanchez-Guerrero, J; Clarke, A E; Bernatsky, S; Wallace, D; Isenberg, D; Rahman, A; Merrill, J; Gladman, D; Bruce, I N; Petri, M; Ginzler, E; Dooley, M A; Ramsey-Goldman, R; Manzi, S; Jonsen, A; Alarcon, G; Van, Vollenhoven R; Aranow, C; Ruiz-Irastorza, G; Lim, S; Inanc, M; Kalunian, K; Jacobsen, S; Peschken, C; Kamen, D; Askanase, A; Buyon, J; Fortin, P R
Background Mitochondria are intracellular organelles derived from the endosymbiosis between an a-proteobacterium and a primitive eukaryotic cell. Mitochondria thus display proinflammatory and antigenic properties, when released into the extracellular milieu. Several cross-sectional studies reported increased levels of anti-mitochondrial antibodies (AMAs) in patients with systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). These autoantibodies also displayed correlations with the SLE disease activity index 2000 (SLEDAI-2K) and associations with various clinical manifestations (e.g. lupus nephritis, thromboses, carotid plaque). In the present study, we aim to detect AMAs against either whole organelles (AwMA), mitochondrial DNA (mtDNA) or RNA (mtRNA) through time in samples from patients included in the SLICC cohort. Methods Clinically relevant variables (e.g., sociodemographic variables, disease-specific outcomes including death and arterial vascular events (AVE)) were documented and biosamples were harvested upon patient enrolment in the SLICC cohort, as well as at each follow-up visit. AMA levels were measured by in-house direct ELISAs whereas SLE autoantibodies were detected by clinical laboratories. Healthy individuals, defined as having no known illnesses and infectious symptoms at the time of the blood draw, were recruited. 90% confidence intervals were calculated for both limits of the 95% nonparametric two-sided reference intervals for values measured in healthy donors. AMA values were segregated into 3 categories: Normal values were determined as within the inner limits of the range while values outside this range were characterized as abnormal, either lower or higher than the reference interval. (figure 1). Marginal Cox models with AMAs in 3 categories were adjusted for covariables and are presented as [hazard ratio (95% CI)]. Interactions with sex were tested in models with the AMAs as continuous variables. Results Sera from healthy individuals (n=126) or SLE patients included in the SLICC cohort, from their inclusion, up to 7 years of follow-up (n=1114 patients at baseline, 3577 samples in total). AwMA displayed lower correlations with antibodies to mitochondrial nucleic acids (versus AmtDNA: rs=0.37, and vs AmtRNA: rs=0.38), while antibodies to mitochondrial DNA or RNA shown higher correlations (rs=0.59). During our preliminary analyses on the distribution of the variables, We made intriguing observations regarding patients with AMA levels that were either lower or higher than those of healthy individuals. This information led us to categorize SLE patients as described in the methods and in figure 1. For each of the three antibodies assessed, SLE patients displayed more abnormal AMA levels at baseline than controls. The percentage of patients with higher levels of AwMA and AmtRNA increased at subsequent follow-up visits, while a slight decrease was observed for AmtDNA (figure 2). SLE patients with higher levels of AwMA showed higher risks of death [2.12 (1.18-3.83)]. It is of interest that an inverse relationship was found between AmtRNA and AVEs, with a small subset of patients with low levels of AmtRNA (n = 4), this autoantibody was associated with increased risks of this manifestation [4.46 (1.71-11.66)]. Additionally, patients with higher levels of AmtDNA and AmtRNA displayed increased risks of lupus nephritis [respectively: 3.05(2.05-4.54), and 1.56(1.12-2.18)]. Interestingly, there was an interaction with sex for AmtRNA levels effect on AVEs [males: 0.32 (0.11-0.99). Females: 1.56 (1.11-2.19)], and AmtDNA association with nephritis was only significant in female patients [4.00 (2.51-6.36)] (table 1). Conclusion These results show that AMAs display different associations with disease manifestations in various clusters of patients. These results prompt for further analyses by machine-learning in order to delineate clusters of clinical interests by adding AMAs in the routine serological assessment of SLE autoantibodies. Acknowledgements We acknowledge the contribution of the study participants, individual center support staff as well as investigators of the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort project who for the past 20 years have made this study possible. LAY ABSTRACT The mitochondrion is a part of the cell that controls various biological mechanisms (e.g., energy supply, whether the cell should live or die, control, or produce various cellular components). They are derived, through evolution, from a microbe. Mitochondria may sometimes be jettisoned out of their host cell and subsequently elicit immune reactions - including the production of antibodies. Previous studies indicated that patients with autoimmune conditions such as systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS) have antibodies against mitochondria in their blood stream. Presence of these antibodies was associated with increased disease activity and clinical manifestations of these diseases (e.g. kidney disease, arterial vessel disease). In this study, we studied blood samples harvested by an international group dedicated to the study of SLE [i.e., the SLE International Collaborating Clinics (SLICC) cohort] and observed that patients may be clustered into groups, upon their levels of antibodies and/or sex, allowing to have a better appreciation of their risks of death, vascular events, and kidney disease. These results might lead to improved diagnosis and/or prognosis in SLE and thus, in improved care and quality of life for the people living with lupus
EMBASE:640016011
ISSN: 2053-8790
CID: 5513992

LLDAS (LOW LUPUS DISEASE ACTIVITY STATE), LOW DISEASE ACTIVITY (LDA) AND REMISSION (ON- OR OFF-TREATMENT) PREVENT DAMAGE ACCRUAL IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) PATIENTS IN A MULTINATIONAL MULTICENTER COHORT [Meeting Abstract]

Ugarte-Gil, M. F.; Hanly, J.; Urowitz, M. B.; Gordon, C.; Bae, S. C.; Romero-Diaz, J.; Sanchez-Guerrero, J.; Bernatsky, S.; Clarke, A. E.; Wallace, D. J.; Isenberg, D.; Rahman, A.; Merrill, J. T.; Fortin, P.; Gladman, D. D.; Bruce, I. N.; Petri, M. A.; Ginzler, E. M.; Dooley, M. A.; Ramsey-Goldman, R.; Manzi, S.; Jonsen, A.; Van Vollenhoven, R.; Aranow, C.; Mackay, M.; Ruiz-Irastorza, G.; Lim, S. S.; Inanc, M.; Kalunian, K. C.; Jacobsen, S.; Peschken, C.; Kamen, D. L.; Askanase, A.; Pons-Estel, B.; Alarcon, G. S.
ISI:000692629300286
ISSN: 0003-4967
CID: 5017572

ECONOMIC EVALUATION OF HYDROXYCHLOROQUINE USE IN AN INTERNATIONAL INCEPTION COHORT [Meeting Abstract]

Barber, M R W; St, Pierre Y; Hanly, J G; Urowitz, M B; Gordon, C; Bae, S -C; Romero-Diaz, J; Sanchez-Guerrero, J; Bernatsky, S; Wallace, D J; Isenberg, D A; Rahman, A; Merrill, J T; Fortin, P R; Gladman, D D; Bruce, I N; Petri, M; Ginzler, E M; Dooley, M A; Ramsey-Goldman, R; Manzi, S; Jonsen, A; Alarcon, G S; Van, Vollenhoven R F; Aranow, C; Mackay, M; Ruiz-Irastorza, G; Sam, Lim S; Inanc, M; Kalunian, K C; Jacobsen, S; Peschken, C A; Kamen, D L; Askanase, A; Clarke, A E
Background While there is overwhelming evidence for the beneficial role of hydroxychloroquine (HCQ) in SLE, little is known about its economic impact. We estimated annual direct, indirect, and total costs (DC, IC, TC) associated with HCQ use. Methods A subset of patients from the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) inception cohort were assessed annually between 2014 and 2019 for health resource use, lost work-force/non-work-force productivity and concurrent HCQ use. Resource use was costed using 2021 Canadian prices and lost productivity using Statistics Canada age-and-sex specific wages. At each assessment, HCQ dose over the past year and weight were documented and patients were stratified into 1 of 3 HCQ dosage groups: nonusers (0 mg/kg/day), low-intensity users (<= 5 mg/kg/day), or high-intensity users (>5 mg/kg/day). Costs associated with HCQ dose were calculated by averaging all observations within each dosage group. Multiple random effects linear regressions adjusted for the possible confounding of age at diagnosis, sex, race/ethnicity, disease duration, geographic region, education, alcohol use, and smoking on the association between annual DC and IC and HCQ dose. A possible mediating effect of disease damage (SLICC/ACR DI) on these associations was also investigated. Results 661 patients (89.4% female, 59.3% non-Caucasian race/ethnicity, mean age and mean disease duration at the start of economic assessments was 42.1 years and 9.5 years, respectively) were followed over a mean of 2.8 years. Across 1536 annual assessments, 36.1% of observations were provided by HCQ non-users, 43.1% by low-intensity users (mean dosage 3.4 mg/kg/day), and 20.8% by high-intensity users (mean dosage 5.9 mg/kg/day). Annual adjusted DC were higher in nonusers ($9599) versus low-intensity users ($6344) and highintensity users ($6333) (table 1). When disease damage was included in the regression, there were no significant differences in DC between dosage groups. While unadjusted IC were higher in non-users ($37,610) versus low-intensity users ($32,480) and high-intensity users ($31,418), adjusted IC did not differ. Adjusted TC were higher in non-users ($46,157) versus low-intensity users ($39,257) and high-intensity users ($37,634). Conclusion SLE patients reported higher adjusted annual DC and TC during periods of HCQ non-use versus periods of use, regardless of the intensity of use. There was no additional cost savings in those using high intensity dosages. The cost-savings effect of HCQ could potentially be partially mediated through reduced damage. In addition to its well-established therapeutic potential, there may be an economic imperative for HCQ use in SLE patients
EMBASE:638287701
ISSN: 2053-8790
CID: 5292882

IDENTIFYING CLUSTERS OF LONGITUDINAL AUTOANTIBODY PROFILES ASSOCIATED WITH SYSTEMIC LUPUS ERYTHEMATOSUS DISEASEOUTCOMES [Meeting Abstract]

Choi, M Y; Chen, I; Clarke, A; Fritzler, M J; Buhler, K A; Urowitz, M; Hanly, J G; Gordon, C; St, Pierre Y; Bae, S -C; Romero, Diaz J; Sanchez-Guerrero, J; Bernatsky, S; Wallace, D; Isenberg, D; Rahman, A; Merrill, J T; Fortin, P R; Gladman, D D; Bruce, I; Petri, M A; Ginzler, E; Dooley, M A; Ramsey-Goldman, R; Manzi, S; Jonsen, A; Alarcon, G S; FVan, Vollenhoven R; Aranow, C; Mackay, M; Ruiz-Irastorza, G; Lim, S; Inanc, M; Kalunian, K C; Jacobsen, S; Peschken, C; Kamen, D; Askanase, A; Sontag, D; Buyon, J; Costenbader, K H
Background Prior studies of SLE clusters based on autoantibodies have utilized cross-sectional data from single centers. We applied clustering techniques to longitudinal and comprehensive autoantibody data from a large multinational, multiethnic inception cohort of well characterized SLE patients to identify clusters associated with disease outcomes. Methods We used demographic, clinical, and serological data at enrolment and follow-up visits years 3 and 5 from 805 patients who fulfilled the 1997 Updated ACR SLE criteria and were enrolled within 15 months of diagnosis. For each visit, ANA, dsDNA, Sm, U1-RNP, SSA/Ro60, SSB/La, Ro52/ TRIM21, histones, ribosomal P, Jo-1, centromere B, PCNA, anti-DFS70, lupus anticoagulant (LAC), IgG and IgM for anticardiolipin, anti-b2GP1, and aPS/PT, and IgG anti-b2GP1 D1 were performed at a single lab (except LAC). K-means clustering algorithm on principal component analysis (10 dimensions) transformed longitudinal ANA/autoantibody profiles was used. We compared cluster demographic/clinical outcomes, including longitudinal disease activity (total and adjusted mean SLEDAI- 2K), SLICC/ACR damage index and organ-specific domains, SLE therapies, and survival, using one-way ANOVA test and a Benjamini-Hochberg correction with false discovery rate alpha=0.05. Results were visualized using t-distributed stochastic neighbor embedding. Results Four unique patient clusters were identified (table 1). Cluster 1, characterized by high frequency of anti-Sm and anti-RNP over time, was the youngest group at disease onset with a high proportion of subjects of Asian and African ancestry. At year 5, they had the highest disease activity, were more likely to have active hematologic and mucocutaneous involvement, and to be on/exposed to immunosuppressants/ biologics. Cluster 2, the largest cluster, had low frequency of anti-dsDNA, were oldest at disease onset, and at year 5, had the lowest disease activity, and were least likely to have nephritis and be on/exposed to immunosuppressants/biologics. Cluster 3 had the highest frequency of antiphospholipid antibodies over time, were more likely to be of European ancestry, have an elevated BMI, be former smokers, and by year 5, to have nephritis, neuropsychiatric involvement, including strokes and seizures (SLICC/ACR damage index). Cluster 4 was characterized by anti-SSA/Ro60, SSB/La, Ro52/TRIM21, histone antibodies, and low complements at year 5. Overall, survival of the 805 subjects was 94% at 5 years, and none of the clusters predicted survival. Conclusions Four SLE patient clusters associated with disease activity, organ involvement, and treatment were identified in this analysis of longitudinal ANA/autoantibody profiles in relation to SLE outcomes, suggesting these subsets might be identifiable based on extended autoantibody profiles early in disease and carry prognostic information
EMBASE:638287699
ISSN: 2053-8790
CID: 5292892

ECONOMIC EVALUATION OF NEUROPSYCHIATRIC (NP) LUPUS IN AN INTERNATIONAL INCEPTION COHORT USING A MULTISTATE MODEL APPROACH [Meeting Abstract]

Clarke, A E; Hanly, J G; St, Pierre Y; Gordon, C; Bae, S -C; Romero-Diaz, J; Sanchez-Guerrero, J; Bernatsky, S; Wallace, D J; Isenberg, D A; Rahman, A; Merrill, J T; Fortin, P R; Gladman, D D; Urowitz, M B; Bruce, I N; Petri, M; Ginzler, E M; Dooley, M A; Ramsey-Goldman, R; Manzi, S; Jonsen, A; Alarcon, G S; Van, Vollenhoven R F; Aranow, C; Mackay, M; Ruiz-Irastorza, G; Sam, Lim S; Inanc, M; Kalunian, K C; Jacobsen, S; Peschken, C A; Kamen, D L; Askanase, A; Farewell, V
Background Little is known about the economic burden of NP lupus. We estimated direct and indirect costs (DC, IC) associated with NP events attributed to SLE and non-SLE causes using multistate modelling. Methods Patients fulfilling ACR classification criteria for SLE from 31 centres in 11 countries were enrolled within 15 months of diagnosis. NP events were documented annually using ACR NP definitions and attributed to SLE or non-SLE causes. At each assessment and for SLE and non-SLE events, patients were stratified into 1 of 3 NP states (no, resolved, or new/ongoing NP event). The change in NP status characterized by transition rates between states was analyzed using multistate modelling (doi:10.1002/art.41876). At each assessment, annual DC and IC were based on health resource use and lost work-force/non-work-force productivity over the preceding year. Resource use was costed using 2021 Canadian prices and lost productivity using Statistics Canada age-and-sex specific wages. Costs associated with SLE and non-SLE NP states were calculated by averaging all observations in each NP state. Multiple regressions adjusted for possible confounding of age at diagnosis, sex, race/ethnicity, disease duration, geographic region, education, and smoking on the association of annual DC and IC and NP state. 5 and 10-year cumulative costs for NP states were predicted by multiplying adjusted annual costs for each state by the expected state duration, forecasted using multistate modelling. Results 1697 patients (89% female, 51% non-Caucasian race/ ethnicity, mean age at enrolment 35.1 years) were followed a mean of 8.8 years. 1971 NP events occurred in 956 patients, 32% attributed to SLE. For SLE NP events, annual DC were higher in those with new/ongoing vs no events ($10,809 vs $6715) (table 1). Annual and 5-yr IC were higher in new/ ongoing vs no events and new/ongoing vs resolved events (5- yr: new/ongoing vs no: $172,674 vs $136,970). For non-SLE NP events, annual IC were higher in new/ongoing vs no events, new/ongoing vs resolved events, and resolved vs no events and 5 and 10-yr IC were higher in new/ongoing vs no events (10-yr: new/ongoing vs no: $342,434 vs $279,874). For all NP states, IC exceeded DC 2.8 to 4-fold. Conclusion IC are 1.3-fold higher in patients with new/ ongoing vs no NP events. While DC trended higher in new/ ongoing events, they were not significantly higher across all NP states and times. Impaired productivity associated with ongoing and resolved NP lupus is substantial, contributing to the previously documented reduced quality of life
EMBASE:638287636
ISSN: 2053-8790
CID: 5292922

Accrual of atherosclerotic vascular events in a multicentre inception SLE cohort

Urowitz, M B; Gladman, D D; Farewell, V; Su, J; Romero-Diaz, J; Bae, S C; Fortin, P R; Sanchez-Guerrero, J; Clarke, A E; Bernatsky, S; Gordon, C; Hanly, J G; Wallace, D J; Isenberg, D; Rahman, A; Merrill, J; Ginzler, E; Alarcón, G S; Chatham, W W; Petri, M; Bruce, I N; Khamashta, M; Aranow, C; Dooley, M; Manzi, S; Ramsey-Goldman, R; Nived, O; Jönsen, A; Steinsson, K; Zoma, A; Ruiz-Irastorza, G; Lim, S; Kalunian, K C; Ỉnanç, M; van Vollenhoven, R; Ramos-Casals, M; Kamen, D L; Jacobsen, S; Peschken, C; Askanase, A; Stoll, T
BACKGROUND/PURPOSE/OBJECTIVE:In previously published work, atherosclerotic vascular events (AVE) occurred in approximately 10% of patients with SLE. We aimed to investigate the annual occurrence and potential risk factors for AVE in a multinational, multiethnic inception cohort of patients with SLE. METHODS:A large 33-centre cohort of SLE patients was followed yearly between 1999-2017. AVEs were attributed to atherosclerosis on the basis of SLE being inactive at the time of the AVE, and typical atherosclerotic changes on imaging or pathology, and/or evidence of atherosclerosis elsewhere. Analysis included descriptive statistics, rate of AVE's per 1000 patient-years, and univariable and multivariable relative risk regression models. RESULTS:Of the 1848 patients enrolled in the cohort, 1710 had at least one follow up visit after enrolment, for a total of 13,666 patient-years. Of 1710, 3.6% had one or more AVEs attributed to atherosclerosis, for an event rate of 4.6 per 1000 patient-years. In multivariable analyses, lower AVE rates were associated with antimalarials (HR: 0.54[95% CI 0.32, 0.91]) while higher AVE rates were associated with any prior vascular event (VE) (HR: 4.00[1.55,10.30]) and body mass index (BMI) >40 (HR: 2.74[1.04,7.18]) A prior AVE increased the risk for subsequent AVE (HR 5.42[3.17,9.27], p<0.001). CONCLUSION/CONCLUSIONS:The prevalence of AVE and rate of AVE accrual in this study is much lower than that seen in previously published data. This may be related to better control of both the disease activity and classic risk factors.
PMID: 32515554
ISSN: 2326-5205
CID: 4491642

Glucocorticosteroid usage and major organ damage in patients with systemic lupus erythematosus-meta-analyses of observational studies published between 1979 and 2018 [Meeting Abstract]

Mak, A; Cheung, M W L; Leong, W Y J; Dharmadhikari, B; Kow, N Y; Petri, M; Manzi, S; Clarke, A; Aranow, C; Arnaud, L; Askanase, A; Bae, S -C; Bernatsky, S; Bruce, I; Buyon, J; Chatham, W W; Costedoat-Chalumeau, N; Dooley, M A; Fortin, P; Ginzler, E M; Gladman, D; Gordon, C; Hanly, J G; Inanc, M; Isenberg, D A; Jacobsen, S; James, J; Jonsen, A; Kalunian, K C; Kamen, D; Lim, S S; Morand, E; Peschken, C; Pons-Estel, B A; Rahman, A; Ramsey-Goldman, R; Romero-Diaz, J; Ruiz-Irastorza, G; Sanchez-Guerrero, J; Steinsson, K; Svenungsson, E; Urowitz, M; Van, Vollenhoven R; Vinet, E; Voskuyl, A; Wallace, D J; Alarcon, G
Background/Purpose : The impact of glucocorticoid (GC) use on major organ damage in SLE patients has not been formally studied by amalgamating the relevant data published in the literature over the past 40 years. We aimed to study the association between GC use and the occurrence of major organ damage in SLE patients by performing meta-analyses of observational studies published between 1970 and December 2018. Methods : Literature search on PubMed (from 1966 to December 2018) for prevalence and longitudinal studies which reported GC exposure (proportion of GC users in the cohort [%GC use] and/or GC use in defined doses) and the occurrence (prevalence/incidence) of major organ damage in SLE patients using the keywords cataract, cerebrovascular (CVA), stroke, cardiovascular (CVS), angina, myocardial infarction (MI), coronary artery bypass, osteoporosis, avascular necrosis (AVN) and osteonecrosis in respective combinations with lupus was conducted. Studies with sample size < 50 and observation duration < 12 months were excluded. The logit of the proportion of patients with disease damage was modelled as a random effect in the meta-analysis, which was employed to study the association between the proportion of patients with organ damage and variables of GC use (mean daily [mg/day] and cumulative [gm] prednisone [PDN] doses and %GC use). A 2-stage estimation of the random-effects logistic regression models was used with restricted maximum likelihood estimation. Univariate associations between organ damage and moderators were examined for statistical significance, and variables related to GC use were adjusted for SLE disease duration in multivariate models if their univariate P values were < 0.2. Results : Out of 8,882 publications screened, 212 articles involving 205,619 SLE patients were eligible for the metaanalyses (Figure 1), of which 97 were prevalence and 115 were longitudinal studies. Univariate analyses of prevalence studies revealed that mean daily PDN dose (odds ratio [OR]=1.10, p=0.007) and lower proportion of female in the cohort (OR=0.002, p=0.002) were associated with the prevalence of overall CVS events. Mean daily PDN dose (OR=1.52, p< 0.001) and %GC use (OR=2,255.2, p< 0.001) were associated with the prevalence of AVN. A significant association between cumulative PDN dose and prevalence of CVA was found after multivariate adjustment for SLE disease duration (OR=1.07, p=0.017). In longitudinal studies, a significant association was identified between cumulative PDN dose and incidence of cataracts after adjustment for SLE disease duration (OR=1.04, p=0.013). While the incidence of MI in SLE patients has dropped over the past 40 years (OR=0.94, p=0.002), it was associated with % GC use after adjustment for SLE disease duration (OR=8.18, p=0.012). Interestingly, significant univariate associations were found between antimalarial use and lower prevalence of MI (OR=0.05, p=0.002) and lower incidence of CVA (OR=0.20, p=0.032). Conclusion : Independent of SLE disease duration, cumulative PDN dose was associated with higher prevalence of CVA and incidence of cataracts, and higher incidence of MI was associated with overall GC use
EMBASE:633059985
ISSN: 2326-5205
CID: 4633432

Cancer risk in a large inception SLE cohort: Effects of age, smoking, and medications [Meeting Abstract]

Bernatsky, S; Ramsey-Goldman, R; Urowitz, M; Hanly, J; Gordon, C; Petri, M; Ginzler, E M; Wallace, D J; Bae, S -C; Romero-Diaz, J; Dooley, M A; Peschken, C; Isenberg, D A; Rahman, A; Manzi, S; Jacobsen, S; Lim, S S; Van, Vollenhoven R F; Nived, O; Kamen, D; Aranow, C; Buyon, J; Ruiz-Irastorza, G; Bruce, I; Gladman, D; Fortin, P; Merrill, J T; Sanchez-Guerrero, J; Kalunian, K C; Steinsson, K; Ramos, M; Zoma, A; Stoll, T; Khamashta, M A; Inanc, M; Clarke, A E
Background/Purpose : Many studies of cancer risk in SLE are limited by small sample size or use of administrative data, which rely on billing code diagnoses instead of clinical data. No studies to date focused on incident SLE. We studied cancer risk in the largest-ever cohort of clinically confirmed incident SLE patients. Methods : Patients meeting ACR criteria for new-onset SLE (within 15 months of diagnosis) were enrolled into the SLICC Inception Cohort, across 32 centres. Patients are followed yearly using a standard protocol, with detailed data collection including SLE Disease Activity Index-2000 (SLEDAI-2K) and damage, and drugs in the past year. New cancer diagnoses are recorded by the examining physician at the annual study visit, and confirmed with chart review including pathology reports. Multivariate proportional hazard regression was performed, using baseline variables for demographics (age at SLE onset, sex, race/ethnicity), and time-dependent variables for drugs (corticosteroids, anti-malarial drugs, immunosup-pressive drugs), smoking, and SLEDAI-2K. As well as cancer over-all, we evaluated risk factors for the most common cancer types. Results : Of 1848 new-onset SLE patients enrolled between 1999-2011, 1668 had at least one follow-up; these were the sample for the current analysis. End date was the first of death, last visit, or end of study interval for this analysis (Aug. 2015). Baseline demographics are shown in Table 1. Over 14,215 years (mean 8.5 years) there were 60 cancers (incidence 4. 2 events per 1,000 patient-years). This included 12 breast cancers, 9 non-melanoma skin, 7 lung, 6 hematological, 5 melanoma, 5 prostate, 3 cervical, 3 renal, 2 gastric, 2 head and neck, 2 thyroid, and one each rectal, sarcoma, thymoma, and uterine. Almost half of the cancer cases (including all of the lung cancers) were associated with baseline smoking, versus only one-third of those patients who did not develop cancer. Univariate analyses of all cancer types suggested a higher risk of cancer among patients of white race/ethnicity and among those with the highest quartile of disease activity at cohort entry. However, the multivariate proportional hazard regression indicated that among SLE patients, the over-all cancer risk was related primarily to male sex and older age at SLE diagnosis. In those analyses, the effect of race/ethnicity was not clearly evident, and the point estimate for highest quartile of disease activity actually reversed to suggest a nonsignificant trend towards lower cancer risk. In the multivariate analyses specifically for breast cancer, age at SLE diagnoses remained a risk factor, and antimalarials were associated with a decreased risk. This effect of anti-malarials was not clearly seen for any other cancer type. For non-melanoma skin cancer, both age at SLE diagnosis and cyclophosphamide were strongly linked with risk. Conclusion : This is the first large, multicentre cohort study to clearly show how different cancer types in SLE are associated with specific risk factors. Additional follow-up may allow additional determination of the possible effects of disease activity and drugs on cancer subtypes
EMBASE:633058049
ISSN: 2326-5205
CID: 4633802