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The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI.We conducted a 3-part qualitative study of international SLE experts. Facilitated small groups evaluated the construct underlying the concept of damage in SLE. A consensus meeting using nominal group technique was conducted to achieve agreement on aspects of the conceptual framework and scope of the revised damage index. The framework was finally reviewed and agreed upon by the entire group.Fifty participants from 13 countries were included. The 8 thematic clusters underlying the construct of SLE damage were purpose, items, weighting, reversibility, impact, time frame, attribution, and perspective. The revised SDI will be a discriminative index to measure morbidity in SLE, independent of activity or impact on the patient, and should be related to mortality. The SDI is primarily intended for research purposes and should take a life-course approach. Damage can occur before a diagnosis of SLE but should be attributable to SLE. Damage to an organ is irreversible, but the functional consequences on that organ may improve over time through physiological adaptation or treatment.We identified shifts in the paradigm of SLE damage and developed a unifying conceptual framework. These data form the groundwork for the next phases of SDI development.

This study was undertaken to assess the effects of a web-based program, MyLupusGuide, developed to facilitate self-management in systemic lupus erythematosus (SLE).In this randomized controlled online study, participants received either immediate access to the MyLupusGuide site or delayed access starting on month 3. The primary outcome was the patient activation measure (PAM) score. Secondary outcomes included measurements of health status, self-efficacy, coping, perceived patient-physician relationship, and medication adherence. Outcomes were measured at the baseline visit and at the 3-month and 6-month follow-up visits. We used linear mixed modeling to compare PAM scores between the 2 groups at months 3 and 6.There were 541 participants included in this study. The mean ± SE age was 50 ± 14 years; 93% were female and 74% were White. The mean ± SE disease duration was 17 ± 12 years, and 56% visited MyLupusGuide at least once. The baseline mean ± SE PAM score was 61.2 ± 13, with 36% scoring low for perceived self-management skills. After 3 months of exposure to MyLupusGuide, there were no differences in terms of PAM scores between groups. In exploratory analyses, we found significant improvement in PAM scores in those who had low PAM scores at baseline and in male individuals. We observed significant improvements in self-efficacy before and after access to MyLupusGuide and delayed improvements at month 6 compared to month 3 in terms of mental health and emotional coping.MyLupusGuide increases self-efficacy but not patient activation. A total of 56% of participants visited the MyLupusGuide site during the study period. Individuals with lupus need support to become activated toward self-management behaviors.

To assess the prevalence and potential risk factors for polypharmacy and prescribing of the potentially inappropriate medications, opioids and benzodiazepines/Z-drugs, in older adults with systemic lupus erythematosus (SLE).The study population comprised adults age ≥50 years meeting American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria followed at a tertiary care rheumatology clinic. Information on prescriptions filled in the 4 months preceding chart review was obtained from the Manitoba Drug Program Information Network. Clinical data, including age, sex, Charlson Comorbidity Index (CCI) score, Systemic Lupus Erythematosus Disease Activity Index 2000 score, prednisone use, SLE duration, and rural residence were abstracted from electronic medical records. Logistic regression analyses were performed to assess any association between polypharmacy (using 2 definitions: ≥5 and ≥10 medications), potentially inappropriate medication use, and clinical features.A total of 206 patients (mean age 62 years, 91% female, 36% rural) were included: 148 (72%) filled ≥5 medications, 71 (35%) filled ≥10 medications, 63 (31%) used benzodiazepines/Z-drugs, and 50 (24%) used opioids. Among the 77 patients age ≥65 years, 57 (74%) filled ≥5 medications, and 26 (34%) filled ≥10 medications, compared to 30% and 4%, respectively, of Manitobans age ≥65 years (National Prescription Drug Utilization Information System, 2016). The odds of polypharmacy were greater with prednisone use (adjusted odds ratio [OR] 3.70 [95% confidence interval (95% CI) 1.40-9.79] for ≥5 medications), CCI score (adjusted OR 1.62 [95% CI 1.20-2.17]), and rural residence (adjusted OR 2.05 [95% CI 1.01-4.18]). Odds of benzodiazepine/Z-drug use were increased with polypharmacy (adjusted OR 4.35 [95% CI 1.69-11.22]), and odds of opioid use were increased with polypharmacy (adjusted OR 6.75 [95% CI 1.93-23.69]) and CCI score (adjusted OR 1.29 [95% CI 1.08-1.54]).The prevalence of polypharmacy in this SLE cohort was higher than in the general Manitoban population. Polypharmacy is a strong marker for use of prescription benzodiazepines/Z-drugs and opioids.

ObjectiveTo determine predictors of change in neuropsychiatric (NP) event status in a large, prospective, international inception cohort of patients with systemic lupus erythematosus (SLE).MethodsUpon enrollment and annually thereafter, NP events attributed to SLE and non-SLE causes and physician-determined resolution were documented. Factors potentially associated with the onset and resolution of NP events were determined by time-to-event analysis using a multistate modeling structure.ResultsNP events occurred in 955 (52.3%) of 1,827 patients, and 593 (31.0%) of 1,910 unique events were attributed to SLE. For SLE-associated NP (SLE NP) events, multivariate analysis revealed a positive association with male sex (P=0.028), concurrent non-SLE NP events excluding headache (P < 0.001), active SLE (P = 0.012), and glucocorticoid use (P = 0.008). There was a negative association with Asian race (P = 0.002), postsecondary education (P = 0.001), and treatment with immunosuppressive drugs (P = 0.019) or antimalarial drugs (P = 0.056). For non-SLE NP events excluding headache, there was a positive association with concurrent SLE NP events (P < 0.001) and a negative association with African race (P = 0.012) and Asian race (P < 0.001). NP events attributed to SLE had a higher resolution rate than non-SLE NP events, with the exception of headache, which had comparable resolution rates. For SLE NP events, multivariate analysis revealed that resolution was more common in patients of Asian race (P = 0.006) and for central/focal NP events (P < 0.001). For non-SLE NP events, resolution was more common in patients of African race (P = 0.017) and less common in patients who were older at SLE diagnosis (P < 0.001).ConclusionIn a large and long-term study of the occurrence and resolution of NP events in SLE, we identified subgroups with better and worse prognosis. The course of NP events differs greatly depending on their nature and attribution.

OBJECTIVE In this study, we aimed to determine the lifetime prevalence of substance use disorder (SUD) in a Canadian rheumatoid arthritis (RA) cohort and factors associated with SUD in RA. METHODS Participants with RA (N = 154) were recruited via rheumatology clinics as part of a larger cohort study of psychiatric comorbidity in immune-mediated inflammatory diseases. SUD is defined as the uncontrolled use of a substance despite the harmful consequences of its use. To identify lifetime SUD, the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition was administered to participants. Participants' sociodemographic and RA clinical characteristics were also assessed. We examined factors associated with lifetime SUD using unadjusted and adjusted logistic regression modeling. RESULTS Twenty-three (14.9%) of 154 participants with RA met the criteria for a lifetime diagnosis of SUD. The majority of the participants were women, were White, had postsecondary education, and were on a disease-modifying antirheumatic drug. Factors associated with increased odds of SUD were male sex (adjusted odds ratio [aOR]: 3.63, 95% confidence interval [CI]: 1.03-12.73), younger age (aOR: 0.94, 95% CI: 0.90-0.98), and ever smoking (aOR: 6.44, 95% CI: 1.53-27.07). CONCLUSION We found that approximately 1 in 7 individuals with RA had a lifetime diagnosis of SUD, highlighting the importance of identifying and treating SUD in those with RA. In particular, the following factors were associated with higher odds of SUD: male sex, younger age, and smoking behaviors.

Objective Psychiatric comorbidity is frequent in rheumatoid arthritis (RA) and complicates treatment. The present study was undertaken to describe the impact of psychiatric comorbidity on health care use (utilization) in RA. Methods We accessed administrative health data (1984–2016) and identified a prevalent cohort with diagnosed RA. Cases of RA (n = 12,984) were matched for age, sex, and region of residence with 5 controls (CNT) per case (n = 64,510). Within each cohort, we identified psychiatric morbidities (depression, anxiety, bipolar disorder, and schizophrenia [PSYC]), with active PSYC defined as ≥2 visits per year. For the years 2006–2016, annual rates of ambulatory care visits (mean ± SD per person) categorized by provider (family physician [FP], rheumatologist, psychiatrist, other specialist), hospitalization (% of cohort), days of hospitalization (mean ± SD), and dispensed drug types (mean ± SD per person) were compared among 4 groups (CNT, CNT plus PSYC, RA, and RA plus PSYC) using generalized linear models adjusted for age, sex, rural versus urban residence, income quintile, and total comorbidities. Estimated rates are reported with 95% confidence intervals (95% CIs). We tested within‐person and RA‐PSYC interaction effects. Results Subjects with RA were mainly female (72%) and urban residents (59%), with a mean ± SD age of 54 ± 16 years. Compared to RA without PSYC, RA with PSYC had more than additive (synergistic) visits (standardized mean difference [SMD] 10.92 [95% CI 10.25, 11.58]), hospitalizations (SMD 13% [95% CI 0.11, 0.14]), and hospital days (SMD 3.63 [95% CI 3.06, 4.19]) and were dispensed 6.85 more medication types (95% CI 6.43, 7.27). Cases of RA plus PSYC had increased visits to FPs (an additional SMD 8.92 [95% CI 8.35, 9.46] visits). PSYC increased utilization in within‐person models. Conclusion Managing psychiatric comorbidity effectively may reduce utilization in RA.

Objective: There is a paucity of data regarding health care costs associated with damage accrual in systemic lupus erythematosus. The present study was undertaken to describe costs associated with damage states across the disease course using multistate modeling. Methods: Patients from 33 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten-year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multistate model. Results: A total of 1,687 patients participated; 88.7% were female, 49.0% were white, mean ± SD age at diagnosis was 34.6 ± 13.3 years, and mean time to follow-up was 8.9 years (range 0.6–18.5 years). Mean annual costs were higher for those with higher SDI scores as follows: $22,006 (Canadian) (95% confidence interval [95% CI] $16,662, $27,350) for SDI scores ≥5 versus $1,833 (95% CI $1,134, $2,532) for SDI scores of 0. Similarly, 10-year cumulative costs were higher for those with higher SDI scores at the beginning of the 10-year interval as follows: $189,073 (Canadian) (95% CI $142,318, $235,827) for SDI scores ≥5 versus $21,713 (95% CI $13,639, $29,788) for SDI scores of 0. Conclusion: Patients with the highest SDI scores incur 10-year cumulative costs that are ~9-fold higher than those with the lowest SDI scores. By estimating the damage trajectory and incorporating annual costs, data on damage can be used to estimate future costs, which is critical knowledge for evaluating the cost-effectiveness of novel therapies.

As the coronavirus disease 2019 (COVID-19; the disease caused by SARS-CoV-2) pandemic took hold in North America, rheumatology clinics across the continent were inundated with phone calls from patients with systemic lupus erythematosus (SLE) who were understandably fearful of COVID-19. One of the most common questions from patients was whether they should stop taking their medications. Since the beginning of the epidemic, turned pandemic, our immune-compromised patients with SLE have been overwhelmed with warnings of their higher risk of severe illness1,2. These statements are based on general knowledge of increased infection risk in patients with SLE, extrapolation from other viral illnesses, and expert opinion. However, adding to the confusion, there is no specific information on SLE per se or on any of the commonly used immunosuppressive drugs for SLE3. Even summary statements from those countries farther along the track of this pandemic broadly reference “patients with serious underlying disease” as being at high risk of poor outcomes without particulars4,5. Moreover, some very recent articles focus on the possible benefits of immunosuppressive drugs, both synthetic and biologic, to fight COVID-19, including early rumblings about the potential positive effect of chloroquine and hydroxychloroquine (HCQ)6,7. Then on Thursday, March 19, US President Donald Trump stated that antimalarials showed tremendous promise and “could be a game-changer.” Suddenly, the rumblings became a roar. The questions about stopping HCQ turned into “I can’t get HCQ, my pharmacy is out” from patients with SLE trying to access refills. All over Canada and the United States, news organizations were publishing stories of patients worried about drug supply, pharmacies documenting shortages, hospitals trying to stock up, drug companies promising to ramp up production, governments securing supply to treat patients with COVID-198,9, … Address correspondence to Dr. C.A. Peschken, University of Manitoba, RR149 Arthritis Centre, 800 Sherbrook St., Winnipeg, Manitoba R3A 1M4, Canada. E-mail: christine.peschken{at}umanitoba.ca

The Physician Global Assessment International Standardisation COnsensus in Systemic Lupus Erythematosus (PISCOS) study aimed to obtain an evidence-based and expert-based consensus standardisation of the Physician Global Assessment (PGA) scoring of disease activity in systemic lupus erythematosus (SLE). An international panel of 79 SLE experts participated in a three-round Delphi consensus process, in which 41 statements related to the PGA in SLE were rated, using a 0 (strongly disagree) to 10 (strongly agree) numerical rating scale. Statements with agreement of 75% or greater were selected and further validated by the expert panel. Consensus was reached on 27 statements, grouped in 14 recommendations, for the use of the PGA in SLE, design of the PGA scale, practical considerations for PGA scoring, and the relationship between PGA values and levels of disease activity. Among these recommendations, the expert panel agreed that the PGA should consist of a 0–3 visual analogue scale for measuring disease activity in patients with SLE in the preceding month. The PGA is intended to rate the overall disease activity, taking into account the severity of active manifestations and clinical laboratory results, but excluding organ damage, serology, and subjective findings unrelated to disease activity. The PGA scale ranges from “no disease activity” (0) to the “most severe disease activity” (3) and incorporates the values 1 and 2 as inner markers to categorise disease activity as mild (≥0·5 to 1), moderate (>1 and ≤2) and severe (>2 to 3). Only experienced physicians can rate the PGA, and it should be preferably scored by the same rater at each visit. The PISCOS results will allow for increased homogeneity and reliability of PGA ratings in routine clinical practice, definitions of remission and low disease activity, and future SLE trials.

ObjectiveThe Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in systemic lupus erythematosus (SLE), but its association with hospitalizations has not been described. Our objective was to estimate the association of baseline SLICC-FI values with future hospitalizations in the SLICC inception cohort.MethodsBaseline SLICC-FI scores were calculated. The number and duration of inpatient hospitalizations during follow-up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC-FI values and the rate of hospitalizations per patient-year of follow-up. Linear regression was used to estimate the association of baseline SLICC-FI scores with the proportion of follow-up time spent in the hospital. Multivariable models were adjusted for relevant baseline characteristics.ResultsThe 1,549 patients with SLE eligible for this analysis were mostly female (88.7%), with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9-1.5) at baseline. Mean ± SD baseline SLICC-FI was 0.17 ± 0.08. During mean ± SD follow-up of 7.2 ± 3.7 years, 614 patients (39.6%) experienced 1,570 hospitalizations. Higher baseline SLICC-FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow-up, with an incidence rate ratio of 1.21 (95% confidence interval [95% CI] 1.13-1.30) after adjustment for baseline age, sex, glucocorticoid use, immunosuppressive use, ethnicity/location, SLE Disease Activity Index 2000 score, SLICC/American College of Rheumatology Damage Index score, and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC-FI values predicted a greater proportion of follow-up time spent hospitalized (relative rate 1.09 [95% CI 1.02-1.16]).ConclusionThe SLICC-FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC-FI as a valid health measure in SLE.

ObjectiveTo test the association of early disease severity with grade 12 standards test performance in individuals with childhood-onset chronic rheumatic diseases (ChildCRDs), including juvenile arthritis and systemic autoimmune rheumatic diseases.MethodsWe used linked provincial administrative data to identify patients with ChildCRDs born between 1979 and 1998 in Manitoba, Canada. Primary outcomes were Language and Arts Achievement Index (LAI) scores and Math Achievement Index (MAI) scores from grade 12 standards test results as well as enrollment data. The secondary outcome was enrollment in grade 12 by 17 years of age. Latent class trajectory analysis identified disease severity groups using physician visits following diagnosis. Multivariable linear regression tested the association of disease severity groups with LAI and MAI scores, and logistic regression tested the association of disease severity with age-appropriate enrollment, after adjusting for sociodemographic factors and psychiatric morbidities.ResultsThe study cohort included 541 patients, 70.1% of whom were female. A 3-class trajectory model provided the best fit; it classified 9.7% of patients as having severe disease, 54.5% as having moderate disease, and 35.8% as having mild disease. After covariate adjustment, severe disease was associated with poorer LAI and MAI scores but not with age-appropriate enrollment.ConclusionAmong patients with ChildCRDs, those with severe disease performed more poorly on grade 12 standards tests, independent of sociodemographic and psychiatric risk factors. Clinicians should work with educators and policy makers to advocate for supports to improve educational outcomes of patients with ChildCRDs.

Objective: To assess cancer risk factors in incident systemic lupus erythematosus (SLE). Methods: Clinical variables and cancer outcomes were assessed annually among incident SLE patients. Multivariate hazard regression models (overall risk and most common cancers) included demographic characteristics and time-dependent medications (corticosteroids, antimalarial drugs, immunosuppressants), smoking, and the adjusted mean Systemic Lupus Erythematosus Disease Activity Index 2000 score. Results: Among 1,668 patients (average 9 years follow-up), 65 cancers occurred: 15 breast, 10 nonmelanoma skin, 7 lung, 6 hematologic, 6 prostate, 5 melanoma, 3 cervical, 3 renal, 2 each gastric, head and neck, and thyroid, and 1 each rectal, sarcoma, thymoma, and uterine cancers. Half of the cancers (including all lung cancers) occurred in past/current smokers, versus one-third of patients without cancer. Multivariate analyses indicated that overall cancer risk was related primarily to male sex and older age at SLE diagnosis. In addition, smoking was associated with lung cancer. For breast cancer risk, age was positively associated and antimalarial drugs were negatively associated. Antimalarial drugs and higher disease activity were also negatively associated with nonmelanoma skin cancer risk, whereas age and cyclophosphamide were positively associated. Disease activity was associated positively with hematologic and negatively with nonmelanoma skin cancer risk. Conclusion: Smoking is a key modifiable risk factor, especially for lung cancer, in SLE. Immunosuppressive medications were not clearly associated with higher risk except for cyclophosphamide and nonmelanoma skin cancer. Antimalarials were negatively associated with breast cancer and nonmelanoma skin cancer risk. SLE activity was associated positively with hematologic cancer and negatively with nonmelanoma skin cancer. Since the absolute number of cancers was small, additional follow-up will help consolidate these findings.

ObjectiveThe aims of this study were (1) to compare grade 12 standardized test results of patients diagnosed with childhood-onset chronic rheumatic diseases (ChildCRD) and unaffected peers; and (2) to identify factors associated with test results of patients with ChildCRD and unaffected peers.MethodsThis was a population-based retrospective cohort study. All patients with ChildCRD (juvenile arthritis and systemic autoimmune rheumatic diseases) from the only pediatric rheumatology center in Manitoba for birth cohorts January 1979 to December 1998 were linked to the provincial administrative databases containing records of healthcare use and education outcomes. Patients were matched by age, sex, and postal codes to their peers who did not have ChildCRD. The primary outcomes were the grade 12 Language Arts Achievement Index (LAI) and the Math Achievement Index (MAI) scores. ChildCRD, sociodemographic, and mental health factors were tested for their associations with LAI and MAI scores using multivariable linear regression.ResultsFive hundred and forty-one patients with ChildCRD were matched to 2713 unaffected peers. Patients with ChildCRD had lower LAI and MAI scores compared to their peers. More patients with ChildCRD failed or did not take the language arts (51% vs 41%, P < 0.001) and math (61% vs 55%, P = 0.02) tests. On multivariable analysis, ChildCRD, lower socioeconomic status, younger maternal age at first childbirth, family income assistance, involvement with child welfare services, and mental health morbidities (between ChildCRD diagnosis and standardized testing), were associated with worse LAI and MAI results.ConclusionThis population-based study showed that patients with ChildCRD performed less well than their peers on grade 12 standardized testing, independent of sociodemographic and mental health comorbidities.

Objectives Vitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in SLE. We aimed to examine the association of demographic factors, SLE phenotype, therapy and vitamin D levels with MetS and insulin resistance. Methods The Systemic Lupus International Collaborating Clinics (SLICC) enrolled patients recently diagnosed with SLE ( Results Of the 1847 patients, 1163 (63%) had vitamin D measured and 398 (34.2%) subjects were in the lowest 25(OH)D tertile. MetS was present in 286 of 860 (33%) patients whose status could be determined. Patients with lower 25(OH)D were more likely to have MetS and higher HOMA-IR. The MetS components, hypertension, hypertriglyceridemia and decreased high-density lipoprotein (HDL) were all significantly associated with lower 25(OH)D. Increased average glucocorticoid exposure was associated with higher insulin resistance. Conclusions MetS and insulin resistance are associated with lower vitamin D in patients with SLE. Further studies could determine whether vitamin D repletion confers better control of these cardiovascular risk factors and improve long-term outcomes in SLE.

Objective We assessed the information needs of persons with any of three immune-mediated inflammatory diseases (multiple sclerosis [ MS], inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]) regarding depression, as a first step toward developing patient-relevant information resources, ultimately to facilitate self-management and appropriate care. We also compared information needs across genders. Methods We surveyed participants with MS, IBD and RA regarding depression-related information needs including types of treatments, effectiveness, risks, benefits, and perceived helpfulness of treatments. We compared responses between groups using multivariate regression. Results 328 participants provided complete responses (MS: 141, IBD: 114, RA: 73). Most of the topics queried were perceived as very important, and similarly important for all groups. Women placed higher importance than men on most topics. The most popular formats for receiving information were discussion with a counselor (very preferred: 67.4%) and written information (very preferred: 65.5%); this did not differ between groups. Conclusions Persons affected by MS, IBD and RA are interested in receiving information about multiple topics related to depression treatment, from multiple sources. Women desire more information than men. Practice implications These findings can be used to design information resources to meet information needs regarding depression in MS, IBD and RA.

Objective: The spectrum of antinuclear antibodies (ANAs) is changing to include both nuclear staining as well as cytoplasmic and mitotic cell patterns (CMPs) and accordingly a change is occurring in terminology to anticellular antibodies. This study examined the prevalence of indirect immunofluorescence (IIF) anticellular antibody staining using the Systemic Lupus International Collaborating Clinics inception cohort.Methods: Anticellular antibodies were detected by IIF on HEp-2000 substrate using the baseline serum. Three serologic subsets were examined: ANA positive (presence of either nuclear or mixed nuclear/CMP staining), anticellular antibody negative (absence of any intracellular staining), and isolated CMP staining. The odds of being anticellular antibody negative versus ANA or isolated CMP positive was assessed by multivariable analysis.Results: A total of 1,137 patients were included; 1,049 (92.3%) were ANA positive, 71 (6.2%) were anticellular antibody negative, and 17 (1.5%) had an isolated CMP. The isolated CMP–positive group did not differ from the ANA-positive or anticellular antibody–negative groups in clinical, demographic, or serologic features. Patients who were older (odds ratio [OR] 1.02 [95% confidence interval (95% CI) 1.00, 1.04]), of white race/ethnicity (OR 3.53 [95% CI 1.77, 7.03]), or receiving high-dose glucocorticoids at or prior to enrollment (OR 2.39 [95% CI 1.39, 4.12]) were more likely to be anticellular antibody negative. Patients on immunosuppressants (OR 0.35 [95% CI 0.19, 0.64]) or with anti-SSA/Ro 60 (OR 0.41 [95% CI 0.23, 0.74]) or anti–U1 RNP (OR 0.43 [95% CI 0.20, 0.93]) were less likely to be anticellular antibody negative. Conclusion: In newly diagnosed systemic lupus erythematosus, 6.2% of patients were anticellular antibody negative, and 1.5% had an isolated CMP. The prevalence of anticellular antibody–negative systemic lupus erythematosus will likely decrease as emerging nomenclature guidelines recommend that non-nuclear patterns should also be reported as a positive ANA.

Objective: The Systemic Lupus International Collaborating Clinics (SLICC) 2012 systemic lupus erythematosus (SLE) classification criteria and the revised American College of Rheumatology (ACR) 1997 criteria are list based, counting each SLE manifestation equally. We derived a classification rule based on giving variable weights to the SLICC criteria and compared its performance to the revised ACR 1997, the unweighted SLICC 2012, and the newly reported European Alliance of Associations for Rheumatology (EULAR)/ACR 2019 criteria sets. Methods: The physician-rated patient scenarios used to develop the SLICC 2012 classification criteria were reemployed to devise a new weighted classification rule using multiple linear regression. The performance of the rule was evaluated on an independent set of expert-diagnosed patient scenarios and compared to the performance of the previously reported classification rules. Results: The weighted SLICC criteria and the EULAR/ACR 2019 criteria had less sensitivity but better specificity compared to the list-based revised ACR 1997 and SLICC 2012 classification criteria. There were no statistically significant differences between any pair of rules with respect to overall agreement with the physician diagnosis. Conclusion: The 2 new weighted classification rules did not perform better than the existing list-based rules in terms of overall agreement on a data set originally generated to assess the SLICC criteria. Given the added complexity of summing weights, researchers may prefer the unweighted SLICC criteria. However, the performance of a classification rule will always depend on the populations from which the cases and non-cases are derived and whether the goal is to prioritize sensitivity or specificity.

Objective.Specific risk alleles for childhood-onset systemic lupus erythematosus SLE (cSLE) vs adult-onset SLE (aSLE) patients have not been identified. The aims of this study were to determine if there is an association (1) between non-HLA–related genetic risk score (GRS) and age of SLE diagnosis, and (2) between HLA-related GRS and age of SLE diagnosis.Methods.Genomic DNA was obtained from 2001 multiethnic patients and genotyped using the Immunochip. Following quality control, genetic risk counting (GRCS), weighted (GRWS), standardized counting (GRSCS), and standardized weighted (GRSWS) scores were calculated based on independent single-nucleotide polymorphisms from validated SLE loci. Scores were analyzed in a regression model and adjusted by sex and ancestral population.Results.The analyzed cohort consisted of 1540 patients: 1351 females and 189 males (675 cSLE and 865 aSLE). There were significant negative associations between all non-HLA GRS and age of SLE diagnosis: P = 0.011 and r2 = 0.175 for GRWS; P = 0.008 and r2 = 0.178 for GRSCS; P = 0.002 and r2 = 0.176 for GRSWS (higher GRS correlated with lower age of diagnosis.) All HLA GRS showed significant positive associations with age of diagnosis: P = 0.049 and r2 = 0.176 for GRCS; P = 0.022 and r2 = 0.176 for GRWS; P = 0.022 and r2 = 0.176 for GRSCS; P = 0.011 and r2 = 0.177 for GRSWS (higher GRS correlated with higher age of diagnosis).Conclusion.Our data suggest that there is a linear relationship between genetic risk and age of SLE diagnosis and that HLA and non-HLA GRS are associated with age of diagnosis in opposite directions.

Objective Anti-beta 2 glycoprotein I IgA is a common isotype of anti-beta 2 glycoprotein I in SLE. Anti-beta 2 glycoprotein I was not included in the American College of Rheumatology (ACR) SLE classification criteria, but was included in the Systemic Lupus International Collaborating Clinics (SLICC) criteria. We aimed to evaluate the prevalence of anti-beta 2-glycoprotein I IgA in SLE versus other rheumatic diseases. In addition, we examined the association between anti-beta 2 glycoprotein I IgA and disease manifestations in SLE. Methods The dataset consisted of 1384 patients, 657 with a consensus physician diagnosis of SLE and 727 controls with other rheumatic diseases. Anti-beta 2 glycoprotein I isotypes were measured by ELISA. Patients with a consensus diagnosis of SLE were compared to controls with respect to presence of anti-beta 2 glycoprotein I. Among patients with SLE, we assessed the association between anti-beta 2 glycoprotein I IgA and clinical manifestations. Results The prevalence of anti-beta 2 glycoprotein I IgA was 14% in SLE patients and 7% in rheumatic disease controls (odds ratio, OR 2.3, 95% CI: 1.6, 3.3). It was more common in SLE patients who were younger patients and of African descent (p = 0.019). Eleven percent of SLE patients had anti-beta 2 glycoprotein I IgA alone (no anti-beta 2 glycoprotein I IgG or IgM). There was a significant association between anti-beta 2 glycoprotein I IgA and anti-dsDNA (p = 0.001) and the other antiphospholipid antibodies (p = 0.0004). There was no significant correlation of anti-beta 2 glycoprotein I IgA with any of the other ACR or SLICC clinical criteria for SLE. Those with anti-beta 2 glycoprotein I IgA tended to have a history of thrombosis (12% vs 6%, p = 0.071), but the difference was not statistically significant. Conclusion We found the anti-beta 2 glycoprotein I IgA isotype to be more common in patients with SLE and in particular, with African descent. It could occur alone without other isotypes.

Background: Depression and anxiety are common neuropsychiatric complaints in patients with systemic lupus erythematosus (SLE). Current literature examining depression and anxiety and its prevalence, impact, and associated factors have found mixed results, in part due to methodological limitations and heterogeneity of defining anxiety and depression, patient selection, and instruments used. While some tools have demonstrated acceptable psychometric properties across studies of general population and rheumatic diseases, there are a lack of studies examining their use in SLE patients. Further research will be needed to develop consensus around disease-related cutoffs and to clarify the associations of disease- and patient-related factors in SLE.

Hydroxychloroquine (HCQ) is a key systemic lupus erythematosus (SLE) drug, making concerns of drug shortages grave. Our objective was to evaluate factors associated with poor outcomes after HCQ taper or discontinuation in SLE.We studied 5 Canadian SLE cohorts between 1999 and 2019, following patients from the date of HCQ tapering (cohort 1) or discontinuation (cohort 2). A composite outcome was defined as any of the following: a need for therapy augmentation, an increase (of at least 4 points) in the Systemic Lupus Erythematosus Disease Activity Index 2000 score, or hospitalization for SLE. In each cohort, multivariable Cox regression was used to identify demographic and clinical factors associated with time to the earliest of these events. A third cohort continuing to receive HCQ was also studied, to assess whether the same factors influenced the outcome even when the HCQ dose was unchanged.The poor outcome rate, per 100 person-years, was 35.7 (95% confidence interval [95% CI] 31.6-40.3) in the HCQ taper cohort (n = 398), 29.0 (95% CI 25.5-33.0) in the discontinuation cohort (n = 395), and 16.1 (95% CI 13.2-19.6) in the maintenance cohort (n = 395). In patients tapering HCQ, baseline prednisone use was independently associated with greater risk of poor outcomes. In the discontinuation cohort, the risk of poor outcomes was greater for Black patients and those diagnosed with SLE at age ≤25 years. Among those maintaining HCQ, baseline immunosuppressive use and First Nations ethnicity were associated with poor outcomes.We identified demographic and clinical factors associated with poor outcomes after HCQ taper/discontinuation. This information is critical in the current setting of potential shortages, but over the long term, such information could inform personalized therapies.

Objective: In previous studies, atherosclerotic vascular events (AVEs) were shown to occur in ~10% of patients with systemic lupus erythematosus (SLE). We undertook this study to investigate the annual occurrence and potential risk factors for AVEs in a multinational, multiethnic inception cohort of patients with SLE. Methods: A large 33-center cohort of SLE patients was followed up yearly between 1999 and 2017. AVEs were attributed to atherosclerosis based on SLE being inactive at the time of the AVE as well as typical atherosclerotic changes observed on imaging or pathology reports and/or evidence of atherosclerosis elsewhere. Analyses included descriptive statistics, rate of AVEs per 1,000 patient-years, and univariable and multivariable relative risk regression models. Results: Of the 1,848 patients enrolled in the cohort, 1,710 had ≥1 follow-up visit after enrollment, for a total of 13,666 patient-years. Of these 1,710 patients, 3.6% had ≥1 AVEs attributed to atherosclerosis, for an event rate of 4.6 per 1,000 patient-years. In multivariable analyses, lower AVE rates were associated with antimalarial treatment (hazard ratio [HR] 0.54 [95% confidence interval (95% CI) 0.32–0.91]), while higher AVE rates were associated with any prior vascular event (HR 4.00 [95% CI 1.55–10.30]) and a body mass index of >40 kg/m2 (HR 2.74 [95% CI 1.04–7.18]). A prior AVE increased the risk of subsequent AVEs (HR 5.42 [95% CI 3.17–9.27], P < 0.001). Conclusion: The prevalence of AVEs and the rate of AVE accrual demonstrated in the present 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.

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by autoantibody production and diverse clinical manifestations. The many complex, overlapping, and closely associated factors that influence SLE susceptibility and outcomes include ethnic disparities, low adherence to medications, and poverty, and geography. Epigenetic mechanisms may provide the link between these environmental exposures and behaviors and the disproportionate burden of SLE seen in ethnic minorities. Attention to these modifiable social determinants of health would not only improve outcomes for vulnerable patients with SLE but likely reduce susceptibility to SLE as well through epigenetic changes.

Objective Systemic lupus erythematosus is a chronic autoimmune disease with varied and unpredictable levels of disease activity. The ability to self-manage lupus is important in controlling disease activity. Our objective was to determine levels of patient activation toward self-management in lupus. Methods We used baseline results from the MyLupusGuideTM study that had recruited 541 lupus patients from ten centers. We used the Patient Activation Measure (PAM), a validated self-reported tool designed to measure activation towards self-management ability, as our primary variable and examined its association with demographic, disease-related, patient-provider communication and psychosocial variables captured in our study protocol. Univariable and multivariable linear regressions were performed using linear mixed models, with a random effect for centers. Results The average age was 50±14 years, 93% were female, 74% were Caucasian and the average disease duration was 17±12 years. The mean PAM score was 61.2±13.5 with 36% of participants scoring in the two lower levels, indicating low activation. Variables associated with low activation included being single, lower physical health status, lower self-reported disease activity, lower self-efficacy, use of more emotional coping and less distraction and instrumental coping strategies, and perceived lack of clarity in patient-doctor communication. Conclusion Low patient activation was observed in more than one third of lupus patients indicating a large proportion of patients perceived that they are lacking in lupus self-management skills. These results highlight a modifiable gap in perceived self-management ability among patients with lupus.

Objective Childhood-onset SLE (cSLE) manifests differently than adult-onset SLE (aSLE). This study determined whether ethnic differences contribute to the differences in clinical presentation between the two groups. Methods This cross-sectional study used data from a multi-centred registry from eight adult and four paediatric Canadian centres gathered at study entry. We compared the frequency of clinical manifestations and autoantibodies between aSLE and cSLE. For those with a significant difference, a multivariable logistic regression was performed, adjusting for ethnicity, SLE onset (cSLE vs aSLE), disease duration and centre. Disease activity and damage between aSLE and cSLE were compared after stratifying by disease duration. Results Of 552 aSLE subjects, 502 (90.9%) were female and 381 (69.0%) were Caucasian. Mean age at diagnosis was 37.0 ± 13.6 years and disease duration 10.9 ± 9.6 years. Of 276 cSLE subjects, 231 (83.7%) were female and 101 (36.6%) were Caucasian. Mean age at diagnosis was 12.7 ± 3.3 years and disease duration 5.6 ± 8.2 years. In multivariable regression analysis, aSLE was associated with decreased odds of having a neurologic disorder (odds ratio = 0.49) and increased odds of having aCL antibodies (odds ratio = 1.85). Disease activity and damage accrual scores were higher in aSLE than cSLE within the same disease duration strata, although the differences were not clinically significant. Ethnicity was not associated with any differences in clinical manifestations or autoantibody frequency between aSLE and cSLE. Conclusion Although a crude comparison of aSLE and cSLE yielded several differences in clinical symptoms and autoantibodies, this difference was not attributable to ethnic differences between aSLE and cSLE.

BACKGROUND The aim of this study was to determine the prevalence, incidence, and onset age at rheumatoid arthritis (RA) diagnosis in First Nations (FN) and non-FN populations in Manitoba, Canada. METHODS Population-based administrative health records from April 1, 1995, to March 31, 2010, were accessed for all Manitobans. The FN population was identified using the Federal Indian Registry File. Crude and adjusted RA prevalence and incidence rates (adjusted for age, sex, health region of residence) were compared using Poisson regression and reported as relative rates (RRs) with 95% confidence intervals (CIs). Mean (CI) diagnosis age and physician visits were compared with Student t tests. RESULTS Rheumatoid arthritis crude prevalence increased between 2000 and 2010 to 0.65%; adjusted RA prevalence in females was 1.0% and in males was 0.53%. The 2009/2010 adjusted RA prevalence was higher in FN than non-FN (RR, 2.55; CI, 2.08-3.12) particularly for ages 29 to 48 years (RR, 4.52; CI, 2.71-7.56). Between 2000 and 2010, crude RA incidence decreased from 46.7/100,000 to 13.4/100,000. Adjusted RA incidence remained higher in FN than non-FN (2000-2010 RR, 2.1; CI, 1.7-2.6; p < 0.0001) particularly for ages 29 to 48 years (RR, 4.6; CI, 2.8-7.4; p < 0.0001). The FN population was younger at diagnosis than the non-FN population (mean age, 39.6 years [CI, 38.3-40.8 years] vs. 53.3 years [CI, 52.7-53.9 years]; p < 0.0001). The FN population had more physician visits but fewer rheumatology visits than the non-FN population. CONCLUSIONS Rheumatoid arthritis prevalence is increasing, and RA incidence is decreasing in Manitoba. The FN population has a greater prevalence and incidence of RA and is younger at diagnosis than the non-FN population. When combined with fewer rheumatology visits, this significant care gap highlights the need to optimize rheumatology care delivery to the FN population.

ObjectiveTo determine whether anxiety and depression are associated with cognition in multiple sclerosis (MS), and whether these associations are similar in other immune-mediated inflammatory diseases (IMID; including inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]) and in anxious/depressed individuals (ANX/DEP) without an IMID.MethodsParticipants (MS: n = 255; IBD: n = 247; RA: n = 154; ANX/DEP: n = 308) completed a structured psychiatric interview, the Hospital Anxiety and Depression Scale, and cognitive testing, including the Symbol Digit Modalities Test, the California Verbal Learning Test, and Letter Number Sequencing test. Test scores were converted to age-, sex-, and education-adjusted z scores. We evaluated associations of anxiety and depression with the cognitive z scores using multivariate linear models, adjusting for disease cohort.ResultsAll cohorts exhibited higher rates of impairment (i.e., z less than or equal to −1.5) in the domains of processing speed, verbal learning, and delayed recall memory relative to general population norms. Higher levels of anxiety symptoms were associated with slower processing speed, lower verbal learning, and lower working memory performance (all p < 0.001); higher levels of depression symptoms were associated with slower processing speed. These associations did not differ across cohorts.ConclusionAnxiety and depression are associated with lower cognitive function in MS, with a similar pattern observed in persons with other IMID, including IBD and RA, and persons without an IMID. Managing symptoms of anxiety and of depression in MS, as well as other IMIDs, is important to mitigate their effect on cognition.

Objectives To assess the prevalence of combined hormonal contraceptives (CHCs) in reproductive-age women with SLE with and without possible contraindications and to determine factors associated with their use in the presence of possible contraindications. Methods This observational cohort study included premenopausal women ages 18–45 years enrolled in the SLICC Registry ⩽15 months after SLE onset, with annual assessments spanning 2000–2017. World Health Organization Category 3 or 4 contraindications to CHCs (e.g. hypertension, aPL) were assessed at each study visit. High disease activity (SLEDAI score >12 or use of >0.5 mg/kg/day of prednisone) was considered a relative contraindication. Results A total of 927 SLE women contributed 6315 visits, of which 3811 (60%) occurred in the presence of one or more possible contraindication to CHCs. Women used CHCs during 512 (8%) visits, of which 281 (55%) took place in the setting of one or more possible contraindication. The most frequently observed contraindications were aPL (52%), hypertension (34%) and migraine with aura (22%). Women with one or more contraindication were slightly less likely to be taking CHCs [7% of visits (95% CI 7, 8)] than women with no contraindications [9% (95% CI 8, 10)]. Conclusion CHC use was low compared with general population estimates (>35%) and more than half of CHC users had at least one possible contraindication. Many yet unmeasured factors, including patient preferences, may have contributed to these observations. Further work should also aim to clarify outcomes associated with this exposure.

Objective: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC FI values with damage accrual in the SLICC inception cohort. Methods: The baseline visit was defined as the first visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short Form 36) were assessed. Baseline SLICC FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression was used to estimate the association between baseline SLICC FI values and the rate of increase in the SDI during follow-up, adjusting for relevant demographic and clinical characteristics. Results: The 1,549 systemic lupus erythematosus (SLE) patients eligible for this analysis were mostly female (88.7%) with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9–1.5 years) at baseline. The mean ± SD baseline SLICC FI was 0.17 ± 0.08. Over a mean ± SD follow-up of 7.2 ± 3.7 years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC FI values (per 0.05 increase) were associated with higher rates of increase in the SDI during follow-up (incidence rate ratio [IRR] 1.19 [95% confidence interval 1.13–1.25]), after adjusting for age, sex, ethnicity/region, education, baseline SLE Disease Activity Index 2000, baseline SDI, and baseline use of glucocorticoids, antimalarials, and immunosuppressive agents. Conclusion: Our findings indicate that the SLICC FI predicts damage accrual in incident SLE, which further supports the SLICC FI as a valid health measure in SLE.

Objective.Persistent systemic lupus erythematosus (SLE) disease activity is associated with increased morbidity and mortality. In a multicenter cohort of patients with prevalent SLE, we described persistence, patterns, and predictors of change in disease activity over time.Methods.Based on SLE Disease Activity Index (SLEDAI)-2K scores at cohort entry, patients were classified into 4 groups: low (score < 4; LOW), moderate (4 to < 6; MOD), moderately high (6 to ≤ 10; MHIGH), and very high (> 10; VHIGH). Multivariable linear and longitudinal mixed linear regression models were used to identify predictors of change over time in SLEDAI-2K.Results.There were 2019 participants, with declining followup data over 5 years (1326, 580, 274, 186, and 148 patients, respectively). At cohort entry, mean (± SD) age was 42 (± 17) years, disease duration 11 (± 10) years, and 90% were female. The 4 groups included 44% LOW (n = 891), 20% MOD (n = 400), 22% MHIGH (n = 442), and 14% VHIGH (n = 286); therefore, 36% had clinically important SLE activity. The proportion of patients in the LOW group at entry who moved to a higher activity level varied from 30% (167/557) at 1 year, to 49% (41/83) at 3 years, and 54% (30/56) at 5 years. Among 181 patients with MOD to VHIGH entry activity and 3 years of followup, 116 (64.1%) remained active. In all analyses, only higher SLEDAI-2K at cohort entry remained a significant predictor of higher SLEDAI-2K in subsequent years.Conclusion.Higher SLEDAI-2K at study entry was the single major independent predictor of higher SLEDAI-2K over time, reflecting frequent persistence of active disease, even in patients with longstanding disease. This highlights gaps in the optimal treatment of SLE.

Objective.To evaluate the diagnosis, monitoring, and treatment of systemic lupus erythematosus (SLE) in Canada.Methods.A 63-question electronic survey was developed with the Canadian Rheumatology Association and others. Descriptive analyses of responses were performed.Results.Survey respondents (n = 175) reported varying practices in the diagnosis, monitoring, and treatment of SLE. Performance of laboratory investigations for diagnosis and monitoring varied, with 78% of responders performing them at least every 6 months. Validated measures of SLE disease activity and damage were not commonly used. Most common first-line agents besides steroids for induction therapy for class III or IV lupus nephritis included intravenous cyclophosphamide and mycophenolate mofetil. Antimalarial use was common, with 96% of respondents using these in active skin disease. Over 60% of respondents indicated that 80–100% of their patients were taking antimalarials, while another 25% indicated they used these drugs in up to 80% of their patients. There were 71% of responders who reported completing frequent (6–12 mos) ophthalmology screening in patients taking antimalarials. Biologics were infrequently used. Responders were more likely to stop azathioprine and chloroquine than hydroxychloroquine in pregnant patients with SLE. Other aspects of routine care including vaccination and cardiovascular risk management varied considerably. The majority (80%) agreed that a dedicated multidisciplinary care team would improve SLE care.Conclusion.Considerable practice variation in SLE management was noted. This may help inform future recommendations for the diagnosis, monitoring, and treatment of SLE in Canada.

Background:Remission, LDA and LDAS have been proposed as treatment goals for SLE. However, the independent impact of these states on damage accrual has not been fully evaluated.Objectives:To determine the independent impact of remission (both off & on treatment), LDA, and LLDAS on damage accrual.Methods:We studied a long-term longitudinal multinational SLE cohort, including patients completing at least two annual assessments. Remission off-treatment was defined as a SLEDAI (excluding serology) =0, without prednisone and immunosuppressive (IS) drugs. Remission on-treatment was defined as a SLEDAI (excluding serology) =0, prednisone daily doseResults:There were 1,652 patients, 1464 (88.6%) were female, mean age at diagnosis was 34.6 (SD 13.4) years and mean baseline disease duration was 5.5 (SD 4.1) months. Patients had a mean follow-up of 6.5 (SD 4.3) years, 11686 visits were included. 763 patients (46.2%) had an increase in SDI score ≥1 during follow-up. 2483 (21.2%) of the visits were classified as remission off-treatment, 2276 (19.5%) as remission on-treatment, 544 (4.7%) as LDA, 657 (5.6%) as LLDAS and 5726 (49.0%) as not-optimally controlled. Being in remission off-treatment, remission on-treatment, LDA and LLDAS were predictive of a lower probability of damage accrual [remission off-treatment IRR=0.403, 95% CI 0.301-0.541); remission on-treatment IRR=0.313 (95% CI 0.218-0.451) LDA: IRR=0.469 (CI 95% CI 0.272-0.809); LLDAS IRR=0.440 (95% CI 0.241-0.803)]. The multivariable model is summarized in Table 1.Table 1.Multivariable GEE model of the impact of disease activity states on damage accrual.Incidence Rate Ratio95% CIDisease activity stateRemission off treatment0.4030.301-0.541Remission on treatment0.3130.218-0.451LDA0.4690.272-0.809LLDAS0.4400.241-0.803Gender, male1.2741.086-1.495Age at diagnosis1.0241.020-1.029EthnicityCaucasian USRef.Caucasian other1.0170.849-1.217African1.4671.211-1.776Asian0.8630.693-1.075Hispanic1.2661.034-1.550Other1.1210.759-1.656Educational level, years0.9770.957-0.996Disease duration at baseline0.9600.801-1.150Follow-up time0.9420.923-0.960Antimalarial use0.7860.681-0.908Highest prednisone dose before baseline1.0021.001-1.007SDI before1.1001.050-1.1152LLDAS: Low lupus disease activity state LDA: Low disease activity SDI: SLICC/ACR Damage IndexConclusion:Remission on- and off-treatment, LDA and LLDAS were associated with less damage accrual, even adjusting for possible confounders and effect modifiers. This highlights the importance of treating to target in SLE.Disclosure of Interests:Manuel F. Ugarte-Gil Grant/research support from: Pfizer, Janssen, John Hanly: None declared, Murray B Urowitz: None declared, Caroline Gordon Speakers bureau: UCB, Consultant of: Center for Disease Control, Astra-Zeneca, MFP, Sanofi, UCB, Sang-Cheol Bae: None declared, Juanita Romero-Diaz: None declared, Jorge Sanchez-Guerrero: None declared, Sasha Bernatsky: None declared, Ann E Clarke Consultant of: AstraZeneca, BristolMyersSquibb, GlaxoSmithKline, and Exagen Diagnostics, Daniel J Wallace Grant/research support from: Exagen, David Isenberg: None declared, Anisur Rahman: None declared, Joan T Merrill: None declared, Paul Fortin: None declared, Dafna D Gladman Consultant of: Abbvie, Janssen, Pfizer, Novartis, Amgen, Grant/research support from: Abbvie, Janssen, Pfizer, Novartis, Amgen, Ian N. Bruce: None declared, Michelle A Petri: None declared, Ellen M Ginzler Grant/research support from: Aurinia pharmaceutical, M.A. Dooley: None declared, Rosalind Ramsey-Goldman: None declared, Susan Manzi: None declared, Andreas Jonsen: None declared, Ronald van Vollenhoven Speakers bureau: AbbVie, Galapagos, GSK, Janssen, Pfizer, UCB, Consultant of: Abbvie, AstraZeneca, Biogen, Biotest, Celgen, Galapagos, Gilead, Janssen, Pfizer, Sanofie, Servier, UCB, Vielabo, Grant/research support from: BMS, GSK, Lilly, UCB, Cynthia Aranow: None declared, Meggan Mackay: None declared, Guillermo Ruiz-Irastorza: None declared, S. Sam Lim: None declared, Murat Inanc: None declared, Kenneth C Kalunian Consultant of: Roche, Biogen, Janssen, AstraZeneca, Eli Lilly, Genetech, Gilead, ILTOO, Nektar, Viela, Equillium, Bristol-Meyers Squibb, Soren Jacobsen Grant/research support from: BMS, Christine Peschken: None declared, Diane L Kamen: None declared, Anca Askanase Consultant of: Abbvie, Grant/research support from: Glaxo Smith Kline, Astra Zeneca, Janssen, Eli Lilly and Company, Mallinckrodt, Pfizer, Bernardo Pons-Estel Consultant of: GSK, Janssen, Graciela S Alarcon: None declared.

Objective.To construct a Frailty Index (FI) as a measure of vulnerability to adverse outcomes among patients with systemic lupus erythematosus (SLE), using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.Methods.The SLICC inception cohort consists of recently diagnosed patients with SLE followed annually with clinical and laboratory assessments. For this analysis, the baseline visit was defined as the first study visit at which sufficient information was available for construction of an FI. Following a standard procedure, variables from the SLICC database were evaluated as potential health deficits. Selected health deficits were then used to generate a SLICC-FI. The prevalence of frailty in the baseline dataset was evaluated using established cutpoints for FI values.Results.The 1683 patients with SLE (92.1% of the overall cohort) eligible for inclusion in the baseline dataset were mostly female (89%) with mean (SD) age 35.7 (13.4) years and mean (SD) disease duration 18.8 (15.7) months at baseline. Of 222 variables, 48 met criteria for inclusion in the SLICC-FI. Mean (SD) SLICC-FI was 0.17 (0.08) with a range from 0 to 0.51. At baseline, 27.1% (95% CI 25.0–29.2) of patients were classified as frail, based on SLICC-FI values > 0.21.Conclusion.The SLICC inception cohort permits feasible construction of an FI for use in patients with SLE. Even in a relatively young cohort of patients with SLE, frailty was common. The SLICC-FI may be a useful tool for identifying patients with SLE who are most vulnerable to adverse outcomes, but validation of this index is required prior to its use.

Objective: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients. Methods: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. Results: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy. Conclusion: PNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution. (Less)

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 Despite accumulating data on the role of type I interferons (IFN) in the pathogenesis of SLE, real-world, longitudinal clinical data on the type I IFN gene signature (IFNGS) collected from patients with SLE are limited. Objectives This initial analysis of the SLE Prospective Observational Cohort Study (SPOCS; NCT03189875) examined the prevalence of the type I IFNGS (high vs low) and its association with baseline SLE disease characteristics in patients with moderately to severely active SLE receiving standard-of-care treatment. Methods SPOCS is an international, multicenter, prospective observational cohort study of patients enrolled with moderately to severely active SLE (SLEDAI-2K ≥6 at entry) from Australia, Canada, France, Germany, Italy, Spain, the United Kingdom, and the United States; a completion date of 2022 is planned. Patients are evaluated biannually during a 3-year follow-up period. At each visit, data are collected on disease activity and damage, treatment received, type I IFNGS (stratified high or low IFNGS based on a predefined cutoff), and several patient-reported outcomes. Results As of November 15, 2018, a total of 307 patients were enrolled in SPOCS (North America, n=184; Europe, n=123), of whom 96.1% (n=295) were female, with a median age of 46 years (range: 18–88). At study entry, the prevalence of high type I IFNGS was 70.5% (n=210) vs 27.9% (n=83) for low type I IFNGS, with 1.7% (n=5) unknown (table, 9 missing data). IFNGS-high patients were younger than IFNGS-low patients (median: 42.5 years [range: 18–82] vs 50 [19–88], P Conclusion The profile of patients with a baseline high type I IFNGS differed from those with a low type I IFNGS, in that those with a high type I IFNGS comprised a group that were on average younger, had greater SLEDAI-2K scores, were more serologically active, and seemed to have fewer comorbidities. As the lupus community evolves from using a classical clinical classification of patients to one based on molecular signatures, it is important to understand the role of the type I interferon pathway on disease activity, treatment, and outcomes. SPOCS recruitment and follow-up are ongoing. Disclosure of Interests Edward R. Hammond Employee of: AstraZeneca, Martin Aringer Grant/research support from: Roche, Consultant for: AstraZeneca and Eli Lilly, Laurent Arnaud Consultant for: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugai, and UCB., Paid instructor for: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugai, and UCB., Speakers bureau: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugai, and UCB., Christine Peschken Consultant for: AstraZeneca, Jacob Knagenhjelm Consultant for: I was employed by Dfind Science & Engineering working at AstraZeneca as a contractor statistician from late May 2017 - end April 2018, Employee of: AstraZeneca, Volkan Barut Employee of: AstraZeneca, Xia Wang Shareholder of: AstraZeneca, Employee of: AstraZeneca, Barnabas Desta Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca, David Ginkel Employee of: AstraZeneca, Richard Furie Grant/research support from: Biogen, UCB Pharma, but not in the last 12 months, Consultant for: Biogen, UCB Pharma, but not in the last 12 months, Eric F. Morand Grant/research support from: AstraZeneca, Bristol Myers Squibb, Janssen, Merck Serono, and UCB, Consultant for: AstraZeneca, Eli Lilly, Janssen, and Merck Serono, Speakers bureau: AstraZeneca

Background Indirect costs (IDC) of SLE reflect lost productivity in work force (WF) and non-WF activities and can be expressed as: 1) patient self-report of lost productivity or 2) the difference between productivity of an age-and-sex matched general population and the patients stated productivity. We assess IDC calculated by both methods in a Canadian-wide cohort and compare IDC, stratified by damage, across methods. Methods Patients fulfilling the ACR or SLICC Classification Criteria from 6 centres were enrolled. Participants completed a validated questionnaire on lost productivity. Lost productivity was calculated as: 1) the difference between the time patients reported they expected they would engage in WF and non-WF activities if not ill versus the time they reported working and 2) the difference between the time worked by an age-and-sex matched general population in WF and non-WF activities versus the time patients reported working. IDC were valued using age-and-sex-specific wages from the Statistics Canada General Social Survey. IDC from non-WF activities were valued using opportunity costs (i.e., expected WF earnings, rather than expected earning of service workers). Annual IDC (2017 Canadian dollars) associated with damage measured on the SLICC/ACR Damage Index (SDI) were obtained from multiple regressions adjusting for age, race/ethnicity, and disease duration. Results 1368 patients participated, 90.4% female, 70.9% Caucasian, mean age at diagnosis 33.0 years (SD 13.5), mean SLE duration 16.8 years (SD 11.6), mean SLE Disease Activity Index (SLEDAI-2K) 2.15 (SD 3.07), and mean SDI 1.54 (SD 1.87). IDC by method #1 versus #2, stratified by SDI, are shown in table 1. Although at SDI=0, mean predicted IDC did not differ between methods, for SDI=1 through SDI 5, IDC by method #2 were greater. Conclusions IDC by method #2 were greater for SDIs 1 through 5 and the difference between methods increased significantly between lower and higher SDIs ( Funding Source(s): Canadian Initiative for Outcomes in Rheumatology cAre (CIORA)