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ObjectivesTo evaluate systemic lupus erythematosus (SLE) flares following hydroxychloroquine (HCQ) reduction or discontinuation versus HCQ maintenance.MethodsWe analysed prospective data from the Systemic Lupus International Collaborating Clinics (SLICC) cohort, enrolled from 33 sites within 15 months of SLE diagnosis and followed annually (1999–2019). We evaluated person-time contributed while on the initial HCQ dose (‘maintenance’), comparing this with person-time contributed after a first dose reduction, and after a first HCQ discontinuation. We estimated time to first flare, defined as either subsequent need for therapy augmentation, increase of ≥4 points in the SLE Disease Activity Index-2000, or hospitalisation for SLE. We estimated adjusted HRs (aHRs) with 95% CIs associated with reducing/discontinuing HCQ (vs maintenance). We also conducted separate multivariable hazard regressions in each HCQ subcohort to identify factors associated with flare.ResultsWe studied 1460 (90% female) patients initiating HCQ. aHRs for first SLE flare were 1.20 (95% CI 1.04 to 1.38) and 1.56 (95% CI 1.31 to 1.86) for the HCQ reduction and discontinuation groups, respectively, versus HCQ maintenance. Patients with low educational level were at particular risk of flaring after HCQ discontinuation (aHR 1.43, 95% CI 1.09 to 1.87). Prednisone use at time-zero was associated with over 1.5-fold increase in flare risk in all HCQ subcohorts.ConclusionsSLE flare risk was higher after HCQ taper/discontinuation versus HCQ maintenance. Decisions to maintain, reduce or stop HCQ may affect specific subgroups differently, including those on prednisone and/or with low education. Further study of special groups (eg, seniors) may be helpful.

ObjectiveTo evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.MethodsData were collected at annual study visits between 1999 and 2019. We followed patients with incident SLE from first visit on HCQ (time zero) up to time of retinal toxicity (outcome), death, loss-to-follow-up or end of study. Potential retinal toxicity was identified from SLICC Damage Index scores; cases were confirmed with chart review. Using cumulative HCQ duration as the time axis, we constructed univariate Cox regression models to assess if covariates (ie, HCQ daily dose/kg, sex, race/ethnicity, age at SLE onset, education, body mass index, renal damage, chloroquine use) were associated with HCQ-related retinal toxicity.ResultsWe studied 1460 patients (89% female, 52% white). Retinal toxicity was confirmed in 11 patients (incidence 1.0 per 1000 person-years, 0.8% overall). Average cumulative time on HCQ in those with retinal toxicity was 7.4 (SD 3.2) years; the first case was detected 4 years after HCQ initiation. Risk of retinal toxicity was numerically higher in older patients at SLE diagnosis (univariate HR 1.05, 95% CI 1.01 to 1.09).ConclusionsThis is the first assessment of HCQ and retinal disease in incident SLE. We did not see any cases of retinopathy within the first 4 years of HCQ. Cumulative HCQ may be associated with increased risk. Ophthalmology monitoring (and formal assessment of cases of potential toxicity, by a retinal specialist) remains important, especially in patients on HCQ for 10+ years, those needing higher doses and those of older age at SLE diagnosis.

ObjectiveWe conducted an international survey of patients with SLE to assess their access, preference and trust in various health information sources pre-COVID-19 and during the COVID-19 pandemic.MethodsPatients with SLE were recruited from 18 observational cohorts, and patients self-reporting SLE were recruited through five advocacy organisations. Respondents completed an online survey from June 2020 to December 2021 regarding the sources of health information they accessed in the 12 months preceding (pre-11 March 2020) and during (post-11 March 2020) the pandemic. Multivariable logistic regressions assessed factors associated with accessing news and social media post-11 March 2020, and self-reporting negative impacts from health information accessed through these sources.ResultsSurveys were completed by 2111 respondents; 92.8% were female, 76.6% had postsecondary education, mean (SD) age was 48.8 (14.0) years. Lupus specialists and family physicians were the most preferred sources pre-11 March 2020 and post-11 March 2020, yet were accessed less frequently (specialists: 78.5% pre vs 70.2% post, difference −8.3%, 95% CI −10.2% to −6.5%; family physicians: 57.1% pre vs 50.0% post, difference −7.1%, 95% CI −9.2% to −5.0%), while news (53.2% pre vs 62.1% post, difference 8.9%, 95% CI 6.7% to 11.0%) and social media (38.2% pre vs 40.6% post, difference 2.4%, 95% CI 0.7% to 4.2%) were accessed more frequently post-11 March 2020 vs pre-11 March 2020. 17.2% of respondents reported negative impacts from information accessed through news/social media. Those outside Canada, older respondents or with postsecondary education were more likely to access news media. Those in Asia, Latin America or younger respondents were more likely to access social media. Those in Asia, older respondents, males or with postsecondary education in Canada, Asia or the USA were less likely to be negatively impacted.ConclusionsPhysicians, the most preferred and trusted sources, were accessed less frequently, while news and social media, less trusted sources, were accessed more frequently post-11 March 2020 vs pre-11 March 2020. Increasing accessibility to physicians, in person and virtually, may help reduce the consequences of accessing misinformation/disinformation.

ObjectiveCognitive impairment is common in patients with SLE but the cause is unknown. The current cross-sectional study examined the association between select SLE-related autoantibodies, other serological biomarkers and extensive blood–brain barrier (BBB) leakage in patients with SLE with and without cognitive impairment. In addition, we determined whether the relationship between SLE autoantibodies, other biomarkers and cognitive impairment differed depending on the presence or absence of concurrent extensive BBB leakage.MethodsConsecutive patients with SLE, recruited from a single academic medical centre, underwent formal neuropsychological testing for assessment of cognitive function. On the same day, BBB permeability was determined using dynamic contrast-enhanced MRI scanning. SLE autoantibodies and other serological biomarkers were measured. Regression modelling was used to determine the association between cognitive impairment, extensive BBB leakage and autoantibodies/biomarkers.ResultsThere were 102 patients with SLE; 90% were female and 88% were Caucasian, with a mean±SD age of 48.9±13.8 years. The mean±SD SLE disease duration was 14.8±11.0 years. Impairment in one or more cognitive tests was present in 47 of 101 (47%) patients and included deficits in information processing speed (9%), attention span (21%), new learning (8%), delayed recall (15%) and executive abilities (21%). Extensive BBB leakage was present in 20 of 79 (25%) patients and was associated with cognitive impairment (15 of 20 (75%) vs 24 of 59 (41%); p=0.01) and shorter disease duration (median (IQR): 7 (8–24 years) vs 15 (2–16 years); p=0.02). No serological parameters were associated with extensive BBB leakage and there was no statistically significant association between cognitive impairment and circulating autoantibodies even after adjusting for BBB leakage.ConclusionsExtensive BBB leakage alone was associated with cognitive impairment. These findings suggest that BBB leakage is an important contributor to cognitive impairment, regardless of circulating SLE-related autoantibodies.

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.

We thank Dr Pamuk et al 1 for their interest in our work,2 and for providing insights regarding mechanisms that may help explain our findings. Their correspondence highlights the importance of further understanding the processes underlying our main finding: extensive blood-brain barrier (BBB) leakage affects ~25% of patients with systemic lupus erythematosus (SLE) and is linked to smaller grey matter volume and cognitive impairment. We agree that the mechanisms resulting in BBB leakage in SLE remain poorly understood, and that …

Early scientific and public enthusiasm for hydroxychloroquine (HCQ) as a potential therapy for COVID-19 has prompted over 100 registered trials to date, although its efficacy remains to be demonstrated.1 Unfortunately, accelerated demand for HCQ has the potential to diminish supplies for patients with systemic lupus erythematosus (SLE), which is worrisome due to the known risks of SLE flare after HCQ withdrawal.2 We previously reported that rheumatologists in most Canadian provinces observed HCQ shortages early in the COVID-19 pandemic.3 However, data are lacking on the global experience with HCQ access during the pandemic, specifically in SLE. On 4 May 2020, we distributed an electronic survey to the 42 Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) members affiliated with SLE referral centres (https://sliccgroup.org), with reminders after 1 and 3 weeks. Physicians were asked about experiences with HCQ shortages during the COVID-19 pandemic, and whether they had been contacted by patients and/or pharmacists regarding difficulties accessing HCQ. Physicians who answered ‘yes’ to the latter question were asked to estimate how many and what proportion …

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

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

Aims To compare the British Isles Lupus Assessment Group (BILAG) 2004, the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) flare index (SFI) and physician9s global assessment (PGA) in assessing flares of disease activity in patients with systemic lupus erythematosus (SLE). Methods Sixteen patients with active SLE were assessed by a panel of 16 rheumatologists. The order in which the patients were seen was randomised using a 4×4 Latin square design. Each patient9s flare status was determined at each assessment using the BILAG 2004 activity index; the SFI and a PGA. A group of five specialists designated each patient into severe, moderate, mild or no flare categories. Results The rate of complete agreement (95% CI) of the four individual examining physicians for any flare versus no flare was 81% (55% to 94%), 75% (49% to 90%) and 75% (49% to 90%) for the BILAG 2004 index, SELENA flare instrument and PGA, respectively. The overall agreement between flare defined by BILAG 2004 and the SFI was 81% and when type of flare was considered was 52%. Intraclass correlation coefficients (95% CI), as a measure of internal reliability, were 0.54 (0.32 to 0.78) for BILAG 2004 flare compared with 0.21 (0.08 to 0.48) for SELENA flare and 0.18 (0.06 to 0.45) for PGA. Severe flare was associated with good agreement between the indices but mild/moderate flare was much less consistent. Conclusions The assessment of flare in patients with SLE is challenging. No flare and severe flare are identifiable but further work is needed to optimise the accurate ‘capture’ of mild and moderate flares.

ObjectivesTo develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations.MethodsThe authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design.ResultsSystemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence >5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1–5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD.ConclusionsNeuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.

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

Background Disease-modifying anti-rheumatic drugs (DMARDs) generally have the greatest impact if they are initiated early in the course of the disease. We hypothesized that greater cumulative exposure to DMARDs soon after RA diagnosis is associated with longer time to joint surgeries. Objectives To evaluate early exposure to DMARDs and time to joint surgery, comparing incident rheumatoid arthritis (RA) populations from Ontario (ON) and Quebec (QC). Methods Using a standard protocol, we performed population-based cohort analyses on new-onset RA patients in ON and QC from 2000-2013. Incident RA patients were followed from cohort entry until their first joint surgery, or were censored at death date, or the end of study period, whichever came first. We studied all recipients of public drug coverage, aged 66 years and older. Analyses were confined to “new users” for the drug of interest. We used Cox proportional hazards regression with time-dependent variables measuring duration of drug use (daily exposures in the first year of follow-up), separately for methotrexate and other DMARDs, adjusting for baseline age, sex, urban vs. rural residence, socioeconomic status, co-existing osteoarthritis (OA), comorbidities, prior joint surgeries, extra-articular RA manifestations, time-varying number of physician visits, and drug exposures (anti-TNF inhibitors, COXIBs, NSAIDs, systemic steroids). Adjusted hazard ratios (HRs) along with 95% confidence intervals (CIs), were estimated. Results Among 20,918 ON and 6,740 QC RA patients, 68% were female and the mean (SD) age was 75 (6) years in each setting. During follow-up, 2,201 (11%) in ON and 494 (7%) patients in QC underwent joint surgery, for a rate of 2 events per 100 person-years in both settings. In the multivariable analyses, greater exposure to methotrexate (HR 0.97 95%CI 0.95-0.98), and other DMARDs (HR 0.98 95%CI 0.97-0.99) within the first year was associated with longer time to surgery in both settings. The strongest independent associations with shorter time to surgery in ON and QC, respectively, included previous joint surgeries [HR=1.9 vs. 2.8], co-existing OA [HR=1.5 vs. 1.8], and greater exposure to NSAIDs [HR=1.2 vs. 1.3], and COXIBs [HR=1.1 vs. 1.3]. Conclusions Greater cumulative exposures to methotrexate and other DMARDs, within 1 year after RA diagnosis, were associated with longer time to joint surgeries in both ON and QC. Our coordinated approach across provincial data sources identified highly comparable and consistent findings. Disclosure of Interest None declared

Background Neuropsychiatric (NP) events in patients with SLE include mood disorders. Objectives To determine the frequency, characteristics, clinical and autoantibody associations of mood disorders in a large, multi-ethnic/racial, inception cohort of SLE patients. Methods A prospective study of new onset SLE patients was performed by an international network of 32 academic centers in 11 countries. Patients were evaluated at enrollment and annually for up to 14 years. Data were collected at each assessment on demographic and clinical manifestations, medications, SLE disease activity index-2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage index (SDI). Nervous system events were recorded using the ACR case definitions for 19 NP syndromes. These include mood disorders, determined by clinical judgment (based on Diagnostic and Statistical Manual, DSM-IV, criteria) and consisting of: (i) major depressive-like episode, (ii) mood disorder with depressive features, (iii) mood disorder with manic features and (iv) mood disorder with mixed features. Lupus anticoagulant, IgG autoantibodies to cardiolipin, β 2 -glycoprotein I, ribosomal P and NMDA glutamate receptor 2 were measured at enrollment. Pre-defined rules determined the attribution of NP events to SLE and non-SLE causes. Cox regression was used to examine the associations of various factors with the occurrence of first mood disorder and first SLE-attributed mood disorder. Results Of 1,827 SLE patients, 88.9% were female, 48.9% Caucasian with mean ± SD age 35.1±13.3 years. At enrollment, mean SLE duration was 5.6±4.8 months, SLEDAI-2K was 5.3±5.4, SDI was 0.31±0.74. The mean follow-up was 4.73±3.45 years. Over the study 863 (47.2%) patients had 1,627 NP events of which 503 (30.9%) were attributed to SLE. Mood disorders were the second most frequent NP event: 232 patients experienced 256 mood disorders of which 98/256 (38.3%) were attributed to SLE. The predominant mood disorders were major depressive-like episodes [134/256 (52.3%)], followed by mood disorder with depressive features [114/256 (44.5%)] and the remaining two mood disorders accounted for only 8/256 (0.03%) events. The estimated cumulative incidence of any mood disorder and any SLE-attributed mood disorder after 10 years was 17.7% (95%CI=[15.1%,20.2%]) and 7.9% (95%CI=[6.0%,9.9%]), respectively. A total of 110/256 (43.0%) mood disorders occurred in isolation without other concurrent NP events. Multivariate regression revealed a greater risk of mood disorder in patients with other concurrent NP events (p≤0.01) and a lower risk with Asian race/ethnicity (p=0.01) and immunosuppressive drugs taken in the absence of antidepressants (p=0.003). No association was found between mood disorders and SLEDAI-2K, SDI scores or lupus autoantibodies, whether or not the analysis was confined to mood disorders attributed to SLE. Conclusions Mood disorders are the second most frequent NP event in SLE patients and about one third are attributable to lupus. The lack of association of most mood disorders with global SLE disease activity, cumulative organ damage and lupus autoantibodies emphasize their multifactorial etiology and a role for non-lupus specific therapies. Disclosure of Interest None declared

Background Health Related Quality of Life (HRQoL) is important in systemic lupus erythematosus (SLE) for both global and organ specific disease. Objectives To examine the association between lupus nephritis at inception and patient self-report HRQoL in a large, multi-ethnic/racial, cohort of SLE patients. Methods An observational cohort study of new onset SLE (ACR classification criteria 60 ml/min); state 2 (eGFR: 30 – 60 mL/min); and state 3 (eGFR: 3.0 gr/day). HRQoL was determined by patient self-report SF-36 subscale scores, mental (MCS) and physical (PCS) component summary scores. Statistical analyses were based on analysis of variance or equivalent t-tests. Results There were 1,827 patients, 89% females, predominantly Caucasian (49.2%) with a mean ± SD age of 35.1±13.3 years. The mean ± SD disease duration was 0.5±0.3 years and the mean duration of follow-up was 4.6±3.4 years. The cumulative occurrence of lupus nephritis was 38.4% and the majority of patients (71.2%) were diagnosed at enrollment. SF-36 subscale and summary scores were not significantly lower in patients with lupus nephritis compared to those without nephritis at enrollment. However, for patients with lupus nephritis at enrollment or follow-up, those in state 3 GFR had clinically and statistically significant lower scores in three subscales (Physical function, Physical role and Bodily pain) and in the Physical component summary score of the SF-36 (p Conclusions The presence of lupus nephritis in a large multi-ethnic cohort was not associated with a reduction in HRQoL. However, severe impairment in renal function and to a lesser extent heavy proteinuria, were associated with lower subscale and physical component summary scores of the SF-36. Patient self-report HRQoL is reduced in severe lupus nephritis and may be an important outcome variable in clinical trials of renal disease in SLE. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1114

Background The outcome of lupus nephritis has evolved over the past decade due to improved immunosuppressive therapies and close attention to co-morbidities. Objectives To study a large, prospective, multi-ethnic/racial, inception cohort of patients with systemic lupus erythematosus (SLE) to determine the outcome of lupus nephritis with current standard of care. Methods An international research network of 37 investigators in 32 academic centers from 11 countries participated in this study. Patients who fulfilled the American College of Rheumatology (ACR) classification criteria for SLE were evaluated within 15 months of diagnosis of SLE and annually thereafter, using a standardized protocol. Data collection included patient demographics, ACR classification criteria, medications, International Society of Nephrology (ISN) classification of chronic kidney disease (CKD) and of renal biopsies (when performed), estimated glomerular filtration rate (eGFR) and proteinuria (ePrU), end stage renal disease (ESRD), SLE disease activity index-2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage index (SDI). Chi-squared test and t-tests were used for group comparisons and Kaplan-Meier curves were produced for time to event analyses. Results There were 1,827 SLE patients, 89% females with a mean ±SD age of 35.1±13.3 years. The ethnic/racial distribution was 49.2% Caucasian, 16.6% African, 15.4% Hispanic, 14.9% Asian and 3.9% other. At enrollment, SLE duration was 0.5±0.3 years, SLEDAI-2K was 5.4±5.4, SDI was 0.31±0.74. The duration of follow-up was 4.6±3.4 years. Lupus nephritis, as defined in the ACR classification criteria, occurred in 499 (27.3%) patients at enrollment and in an additional 202 (11.1%) during follow-up for a cumulative prevalence of 38.4%. The frequency of nephritis was more common in Africans (46%), Hispanics (55%) and Asians (44%) compared to Caucasians (26%) (p Conclusions Lupus nephritis occurred in 38% of SLE patients in a large multi-ethnic/racial inception cohort. Nephritis presented most frequently around the time of diagnosis of SLE and was associated with individual patient9s racial/ethnic background. Although the outcome with standard of care was generally favourable, the results indicate the need for further therapeutic advances in the care of patients with lupus nephritis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1113

Background Early DMARD use in RA may prevent damage and possibly, need for joint replacement. Objectives To assess joint replacements within incident RA patients in Quebec, Canada, and potential associations with early DMARD use. Methods A cohort of incident RA patients was identified from Quebec9s physician billing and hospitalization databases from 2002-2008; all patients covered by the provincial drug insurance for the duration of the study were included in analyses. We used Cox regression with time-dependent variables for: 1) methotrexate (MTX) use, 2) other non-biologic DMARDs and 3) anti-tumor necrosis factor (TNF) agents. Models were adjusted for baseline sociodemographic characteristics, co-morbidity including pre-existing osteoarthritis, and prior health service use, and for time-dependent variables reflecting cumulative use of other drugs (COXIBs, NSAIDs, and systemic steroids) and time-dependent indicators of disease severity (extra-articular RA features and number of rheumatology visits). The outcome (any joint replacement) was defined using procedure codes. Results During follow-up, 321 joint replacements occurred among 5,199 incident RA patients observed for a total of 19,693 years (1.6 events/100 person-years). The best-fitting models relied on cumulative duration of MTX and cumulative duration of non-MTX traditional DMARD use in the first year after RA diagnosis. Controlling for anti-TNF exposure, joint replacement rates throughout follow-up appeared to be significantly lower with greater cumulative MTX and with greater cumulative non-MTX traditional DMARD use in the first year of RA (Hazard ratio, HR=0.95 per month of MTX use, 95% Confidence Interval, CI 0.91-0.98; HR=0.93 per month of use of non-MTX traditional DMARDs, 95% CI 0.90-0.97). However, patients receiving both MTX and non-MTX traditional DMARDs, concurrently or sequentially, within the first year after RA onset, had a significantly higher risk of joint replacement than those who used only one of the two drug classes within the first year. We could not establish independent effects for anti-TNF agents. Conclusions Higher cumulative use of MTX and higher cumulative use of non-MTX traditional DMARDs within the first year after RA diagnosis appeared to be associated with fewer joint replacements. This may be consistent with joint-sparing effects of aggressive, early use of these drugs, though a causal link cannot be established with these observational data. The increased joint replacement risk in patients taking both MTX and other DMARDS, concurrently or sequentially, in the first year, suggests potential confounding by indication, as patients taking multiple drugs may have more severe disease, and greater risk for joint damage. References Gramling A, O9Dell JR (2012). Initial management of rheumatoid arthritis. Rheum. Dis. Clin. North Am. 38 (2): 311–25. Acknowledgements Canadian Institutes for Health Research/Drug Safety and Effectiveness Network (CIHR/DSEN) Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3061

Background The spectrum of autoantibody-associated vasculitis includes a newly recognized syndrome induced by levamisole-adulterated cocaine (L/CS). Emerging data has incriminated levamisole as the culprit. The syndrome is characterized clinically by purpuric skin changes, arthralgia or arthritis and systemic symptoms in a cocaine-user, combined with the presence of autoantibodies and occasionally neutropenia. The spectrum of autoantibodies in this setting has been variable. Of interest, antibodies to human neutrophil elastase (HNE), an uncommon subset of anti-neutrophil cytoplasmic antibodies (ANCA), have been linked with cocaine-related inflammatory conditions and because there can be concomitant low reactivity with the common ANCA specificities (proteinase 3 [PR3] and myeloperoxidase [MPO]) confusing results can be generated in clinical laboratory assays. Objectives We aimed to examine the autoantibody specificities, particularly for anti-nuclear antibodies (ANAs) and ANCAs, in 4 patients with the L/CS to determine (i) if a consistent profile can be identified, (ii) to compare results for ANCA obtained in a clinical laboratory and in a research immunology laboratory and (iii) to establish whether the presence of the antibodies corresponds with concurrent cocaine use and/or active disease. Methods In the clinical laboratory ANA (dsDNA, Chromatin, Riposomal P, Ro, La, Centromere, Sm, Sm/RNP, Scl-70, and Jo-1) and ANCA (PR3 and MPO) were evaluated by multiplex flow immunoassay (Bio Plex 2200). In the research immunology laboratory a broad panel of ANCA target antigens (azurocidin, BPI, catalase K, cathepsin G, defensins, elastase, lactoferrin, lysozyme, MPO and PR3) was evaluated by ELISA. Results Nineteen serum samples from 4 female users of crack cocaine with the L/CS were examined. Urine toxicology for levamisole was positive in each case. The mean age was 41 years (range: 32-49). All 4 patients had purpuric skin changes of varying severity, arthralgia or arthritis, malaise and positive autoimmune serology. Two had a remitting and relapsing course and the mean follow-up period was 8 months (range 0-12). Serological tests in the clinical laboratory indicated that all 4 patients were ANA+ with specificity for chromatin in 4 and Ro in 1. In the same laboratory, evaluation of sequential samples for ANCA showed inconsistent dual positivity for MPO and PR3 in 3 cases. Determination of ANCA target antigen specificities in the research immunology laboratory revealed borderline dual positivity for PR3 and MPO in 2 patients. Anti-HNE antibodies were found in 3 cases and anti-lactoferrin in 4. A temporal association between the presence of any of the antibodies and use of cocaine or active disease was not demonstrated. Conclusions Data from this small but well characterized population suggests that, in an appropriate clinical setting, a positive ANA with specificity for chromatin and a positive ANCA with specificity for HNE and/or lactoferrin support a diagnosis of the L/CS. Despite their potential diagnostic utility these serological tests are not reliable biomarkers of concurrent cocaine use or active disease. Disclosure of Interest None Declared

Background Seizures are a manifestation of neuropsychiatric (NP) SLE and occur in 6% to 51% of adult and pediatric patients. Objectives To describe the frequency, attribution and outcome of seizure disorders and to identify clinical and laboratory predictors of their occurrence. Methods An international, research network enrolled patients within 15 months of SLE diagnosis and performed annual assessments for up to 10 years. Seizures were recorded per ACR case definitions and decision rules determined their attribution. Additional information included clinical and demographic variables, global SLE disease activity (SLEDAI-2K), cumulative organ damage (SLICC/ACR Damage Index (SDI)), physician outcome (7 point Likert scale) and patient outcome using the mental (MCS) and physical (PCS) component summary scores of the SF-36. At enrollment lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor antibodies were measured. Statistical analyses included univariate and multivariate regression. Results Of 1631 patients 89.4% were female and the mean (± SD) age was 35.0±13.4 years. The mean disease duration at enrollment was 5.6±4.8 months and the mean followup was 3.5±2.9 years. A total of 75/1631 (4.6%) patients had ≥1 seizure with the majority (79%) having a single event. In these 75 patients there were 91 seizures (66% generalized; 34% focal) of which 78/91 (86%) were attributed to SLE. The majority presented early in the disease course with a median (range) interval from the time of diagnosis of SLE to onset of first seizure of 0.14 (-0.50 – 7.57) years. There was a higher risk of seizures in those with African race/ethnicity (HR (CI): 1.97 (1.07-3.63); p=0.02) and lack of post-secondary education (1.97 (1.21-3.19); p Conclusions Most seizures in SLE patients are attributable to lupus in close proximity to the time of diagnosis of SLE. The risk of seizures is higher in patients of African race/ethnicity, lower educational status and organ damage outside of the nervous system. In the majority of cases the seizures resolve, do not require long-term anti-seizure medication and are not associated with a negative impact on mental or physical health-related quality of life. The association with lupus related therapies is complex but anti-malarial drugs may have a protective effect. Disclosure of Interest None Declared

Objectives To evaluate the annual direct medical costs and the impact of SLE disease severity and flares on incremental costs in autoantibody positive SLE patients (pts) managed by specialists. Methods A retrospective study was conducted in three Canadian academic medical centers with established cohorts of SLE patients. Data on patient characteristics, disease activity and severity, and medical resource utilization were collected through chart review. Consecutive pts seen in clinic between July 2007 and June 2008 were screened for SLE flares and disease severity using predefined decision rules for both. The number and proportion of pts with severe and non-severe SLE was also defined a priori. Patients who met the inclusion criteria were stratified by disease severity (severe and non-severe active SLE) and followed for 2 yrs (±6 mths after the inclusion visit). Severe disease was defined as involvement of renal, neurological, cardiovascular or respiratory systems which required >7.5 mg/day of corticosteroids and/or immunosuppressants or any SLE manifestation that required at least 30mg/day of corticosteroids at the inclusion visit. A modified SELENA-SLEDAI Flare Index was used to identify mild/moderate and severe flares. Costs were calculated by multiplying each health resource utilized (i.e., lab and imaging tests, biopsies, meds, specialist visits, day hospitalizations, emerg visits, inpatient and rehab stays) by its corresponding CAD unit cost. Total unadjusted mean costs and costs associated with flares were assessed over 2 yrs and expressed in CAD dollars. The analyses were primarily performed using appropriate descriptive statistics for continuous and categorical data. Multiple regression analyses was used to identify the association between 2 yr costs and number of mild/moderate flares and number of severe flares, adjusting for age and SLICC/ACR damage index score. Results A total of 109 pts, 93.6% female, with a mean (SD) age of 41.4 (±15.4) yrs and mean disease duration of 11.9 (±12.6) yrs were studied. At enrollment, 56 pts had severe active SLE and 53 had non-severe active SLE. The mean number of flares for severe and non-severe pts over the study period was 2.68 and 1.91 respectively (p=0.005). Patients in the severe patient group had a higher number of severe flares compared to pts with non-severe SLE (1.82 vs. 0.70; p Conclusions Patients with severe active SLE have 2.7 times higher annual costs compared to pts with non-severe disease. Patients experiencing at least one flare incurred 2 times more costs annually than those without flares. Direct healthcare costs in Canada are influenced by SLE disease severity in addition to the type and frequency of SLE flares. Disclosure of Interest A. Clarke Consultant for: the study and received funds from GSK/HGS, is a consultant for MedImmune and Bristol Myers Squibb, and received research grants from GSK and funds from GSK/HGS for the writing of this abstract. M. Urowitz Consultant for: the study and received funds from GSK/HGS, is a consultant for UCB, Merck/Serono, and received funds from GSK/HGS for the writing of this abstract., N. Monga Employee of: GlaxoSmithKline, N. Topors Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, J. Hanly Consultant for: the study and received funds from GSK/HGS, received a grant from GSK, and received funds from GSK/HGS for the writing of this abstract.