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Objective: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. Methods: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria.Results: The Task Force proposed two definitions of remission: ‘cSLE clinical remission on steroids (cCR)’ and ‘cSLE clinical remission off steroids (cCR-0)’. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score < 0.5 (0–3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. Conclusions: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.

Background/Purpose: Cognitive dysfunction (CD) is reported to affect approximately 40% of SLE patients (1). Mood disorders have been associated with both cognitive symptoms and cognitive function in SLE, but the associations of fibromyalgia with these are unclear. We investigated the relationships between patient-reported cognitive symptoms and objective cognitive test results in SLE, and associations of fibromyalgia and mood disorders with both. Method(s): We tested SLE patients (n=87) and demographically matched healthy control (HC) participants (n=48) with the one-hour neuropsychiatric test battery recommended by the ACR for use in SLE (2) and applied three binary defi-nitions of CD and seven cognitive test z-scores. We assessed patient-reported cognitive symptoms, mood disorder symptoms, fibromyalgia symptoms, and fatigue using the Cognitive Symptoms Inventory (CSI), Hospital Anxiety and Depression Scale (HADS), Central Sensitivity Score (CSS) derived from the 2016 ACR fibromyalgia diagnostic criteria (3) and the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT), respectively. We performed multivariate regression analysis to determine associations with cognitive endpoints; likelihood ratio tests were used to select for inclusion from collinear pairs. We used unpaired t tests to compare CSI scores between groups. Result(s): Among SLE patients, the median (range) age was 45 (22-64). Compared to HC, CSS scores were higher (< 0.00001), fibromyalgia was more common (p 0.009) and a history of depression or anxiety was more frequent (p< 0.0001) in SLE patients (Table 1). Cognitive symptoms (CSI score) were worse in SLE patients than HC (median (range) 33 (19-52) vs. 26.5 (21-35), p < 0.0001). At all thresholds, cognitive dysfunction was also more frequent in SLE patients than HC. Age and premorbid IQ were significantly associated with multiple cognitive test endpoints but not with CSI score. On multivariate analysis, CSS, a history of depression, a

Objectives Cognitive dysfunction in SLE is common and associated with significant morbidity but is currently underdetected. Early detection requires the use of screening tests, as formal diagnostic cognitive testing is time-consuming. This study aims to evaluate the Montreal Cognitive Assessment (MoCA) as a screening tool for cognitive dysfunction in SLE. Methods Patients with SLE (n=95) and demographically matched healthy control participants (n=48) underwent cognitive testing using the 1-hour neuropsychiatric test battery recommended by the American College of Rheumatology for use in SLE and the MoCA. We used regression analyses to determine associations between MoCA and cognitive test scores. We assessed several MoCA cut-offs for predicting cognitive impairment in terms of sensitivity, specificity, positive predictive value and negative predictive value. Receiver operating curve analyses were used to determine the diagnostic accuracy of the MoCA cut-off thresholds. Results We found a significant correlation between MoCA score and 9 of the 10 cognitive endpoints studied (all p<0.001). Receiver operating curve analysis suggested that a MoCA cut-off of <27 had highest diagnostic accuracy across the cognitive impairment definitions (area under the curve 0.76-0.78). Using a screening cut-off of <28, the MoCA had sensitivity of 83%-94% and specificity of 46%-59%, depending on the impairment definition used. Conclusions The MoCA correlates strongly with cognitive test results in SLE and has sufficient sensitivity for use as a screening tool with a cut-off of <28 as the optimal threshold. This tool can be incorporated into clinical practice for screening for cognitive dysfunction in SLE. Copyright © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Objectives Cognitive dysfunction in SLE is common and associated with significant morbidity but is currently underdetected. Early detection requires the use of screening tests, as formal diagnostic cognitive testing is time-consuming. This study aims to evaluate the Montreal Cognitive Assessment (MoCA) as a screening tool for cognitive dysfunction in SLE. Methods Patients with SLE (n=95) and demographically matched healthy control participants (n=48) underwent cognitive testing using the 1-hour neuropsychiatric test battery recommended by the American College of Rheumatology for use in SLE and the MoCA. We used regression analyses to determine associations between MoCA and cognitive test scores. We assessed several MoCA cut-offs for predicting cognitive impairment in terms of sensitivity, specificity, positive predictive value and negative predictive value. Receiver operating curve analyses were used to determine the diagnostic accuracy of the MoCA cut-off thresholds. Results We found a significant correlation between MoCA score and 9 of the 10 cognitive endpoints studied (all p<0.001). Receiver operating curve analysis suggested that a MoCA cut-off of <27 had highest diagnostic accuracy across the cognitive impairment definitions (area under the curve 0.76-0.78). Using a screening cut-off of <28, the MoCA had sensitivity of 83%-94% and specificity of 46%-59%, depending on the impairment definition used. Conclusions The MoCA correlates strongly with cognitive test results in SLE and has sufficient sensitivity for use as a screening tool with a cut-off of <28 as the optimal threshold. This tool can be incorporated into clinical practice for screening for cognitive dysfunction in SLE. Copyright © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Objective To achieve consensus on a definition of remission in SLE (DORIS). Background Remission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a framework for such a definition, without reaching a final recommendation. Methods Several systematic literature reviews were performed and specific research questions examined in suitably chosen data sets. The findings were discussed, reformulated as recommendations and voted on. Results Based on data from the literature and several SLE-specific data sets, a set of recommendations was endorsed. Ultimately, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical systemic lupus erythematosus disease activitiy index (SLEDAI)=0, Evaluator's Global Assessment <0.5 (0-3), prednisolone 5 mg/day or less, and stable antimalarials, immunosuppressives, and biologics. Conclusion The 2021 DORIS definition of remission in SLE is recommended for use in clinical care, education, and research including clinical trials and observational studies.Copyright © 2021 BMJ Publishing Group. All rights reserved.

Background/Purpose: Cognitive dysfunction (CD) is reported to affect approximately 40% of SLE patients (1). Mood disorders have been associated with both cognitive symptoms and cognitive function in SLE, but the associations of fibromyalgia with these are unclear. We investigated the relationships between patient-reported cognitive symptoms and objective cognitive test results in SLE, and associations of fibromyalgia and mood disorders with both. Method(s): We tested SLE patients (n=87) and demographically matched healthy control (HC) participants (n=48) with the one-hour neuropsychiatric test battery recommended by the ACR for use in SLE (2) and applied three binary defi-nitions of CD and seven cognitive test z-scores. We assessed patient-reported cognitive symptoms, mood disorder symptoms, fibromyalgia symptoms, and fatigue using the Cognitive Symptoms Inventory (CSI), Hospital Anxiety and Depression Scale (HADS), Central Sensitivity Score (CSS) derived from the 2016 ACR fibromyalgia diagnostic criteria (3) and the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT), respectively. We performed multivariate regression analysis to determine associations with cognitive endpoints; likelihood ratio tests were used to select for inclusion from collinear pairs. We used unpaired t tests to compare CSI scores between groups. Result(s): Among SLE patients, the median (range) age was 45 (22-64). Compared to HC, CSS scores were higher (< 0.00001), fibromyalgia was more common (p 0.009) and a history of depression or anxiety was more frequent (p< 0.0001) in SLE patients (Table 1). Cognitive symptoms (CSI score) were worse in SLE patients than HC (median (range) 33 (19-52) vs. 26.5 (21-35), p < 0.0001). At all thresholds, cognitive dysfunction was also more frequent in SLE patients than HC. Age and premorbid IQ were significantly associated with multiple cognitive test endpoints but not with CSI score. On multivariate analysis, CSS, a history of depression, a

Aim: To describe the evolving demographics of patients recruited to phase 3 randomised controlled trials (RCTs) of biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in Psoriatic Arthritis (PsA). Method(s): A scoping review was conducted to identify placebo-controlled phase 3 RCTs of b/tsDMARDs in PsA published up to January 2022. Inclusion criteria for all studies were reviewed. Demographic data were extracted from the active treatment arms by two authors (WZ, AA) including: age, sex, race, disease duration, swollen joint count (SJC), tender joint count (TJC), and Health Assessment Questionnaire - Disability Index (HAQ-DI). The date of study initiation and countries in which the studies were conducted were extracted from clinicaltrials.gov. Descriptive statistics were used to evaluate the data. Result(s): Thirty-eight eligible RCTs were identified; four were excluded due to a lack of published initiation date. Thirteen (38.2%) were b/tsDMARD-naive cohorts. The mean age of patients did not change over time, however, the proportion of females increased. Females represented 29-43.7% of participants in studies which began recruitment in 2000/01 and 47.7-55.4% in studies recruiting from 2018/19. The mean (range) of countries involved increased from 2 (1-5) in 2000/01 to 26 (14-39) in 2018/19, but 94.0-97.3% of patients in studies from the 2018/19 period were white. The highest percentage of non-white participants in the treatment arm of an RCT was 19.8%. There was minimal evolution in the mean SJC/TJC/HAQ-DI over two decades. Other variables extracted were excluded from analysis due to significant variation in reporting. Conclusion(s): The recruitment of female PsA patients to placebo-controlled phase 3 PsA RCTs has increased over time. Despite the increase in the number of countries in which RCTs are conducted, non-white patients remain sub-optimally represented in treatment data. TJC/SJC/HAQ-DI stability over decades may reflect the inclus

Background: Healthcare quality for systemic lupus erythematosus (SLE) is a modifiable target for improving patient outcomes. We aimed to assess the quality of care processes in different clinic settings, comparing a subspecialty lupus clinic with hospital-based and private general rheumatology clinics. Method(s): Patients with SLE (n = 258) were recruited in 2016 from a subspecialty lupus clinic (n = 147), two hospital general rheumatology clinics (n = 56) and two private rheumatology clinics (n = 55). Data were collected from medical records and patient questionnaires. Quality of care was assessed using 31 validated SLE quality indicators (QI) encompassing diagnostic work-up, disease and comorbidity assessments, drug monitoring, preventative care and reproductive health. Per-QI performance was measured as a percentage of patients that met the QI relative to the number of patients eligible. Per-patient QI performance was calculated as a percentage of QIs met relative to the number of eligible QIs for each patient. Per-QI and per-patient QI performance were compared between the three clinic settings, and multiple regression performed to adjust for sociodemographic, disease and healthcare factors. Result(s): Per-QI performance was generally high across all clinic settings for diagnostic work-up, comorbidity assessment, lupus nephritis, drug monitoring, prednisolone taper, osteoporosis and pregnancy care. Median [IQR] per-patient performance on eligible QIs was higher in the subspeciality lupus clinic (66.7% [57.1-74.1]) than the hospital general rheumatology (52.7% [47.5-58.1]) and private rheumatology (50.0% [42.9-60.9]) clinics (p <0.001) and the difference remained significant after multivariable adjustment. The subspecialty lupus clinic recorded higher per-QI performance for documentation of disease activity, disease damage, cardiovascular risk factor and drug toxicity assessments, pre-immunosuppression hepatitis and tuberculosis screening, new medication counsell

BACKGROUND: Healthcare quality for systemic lupus erythematosus (SLE) is a modifiable target for improving patient outcomes. We aimed to assess the quality of care processes in different clinic settings, comparing a subspecialty lupus clinic with hospital-based and private general rheumatology clinics. METHODS: Patients with SLE (n = 258) were recruited in 2016 from a subspecialty lupus clinic (n = 147), two hospital general rheumatology clinics (n = 56) and two private rheumatology clinics (n = 55). Data were collected from medical records and patient questionnaires. Quality of care was assessed using 31 validated SLE quality indicators (QI) encompassing diagnostic work-up, disease and comorbidity assessments, drug monitoring, preventative care and reproductive health. Per-QI performance was measured as a percentage of patients that met the QI relative to the number of patients eligible. Per-patient QI performance was calculated as a percentage of QIs met relative to the number of eligible QIs for each patient. Per-QI and per-patient QI performance were compared between the three clinic settings, and multiple regression performed to adjust for sociodemographic, disease and healthcare factors. RESULTS: Per-QI performance was generally high across all clinic settings for diagnostic work-up, comorbidity assessment, lupus nephritis, drug monitoring, prednisolone taper, osteoporosis and pregnancy care. Median [IQR] per-patient performance on eligible QIs was higher in the subspeciality lupus clinic (66.7% [57.1-74.1]) than the hospital general rheumatology (52.7% [47.5-58.1]) and private rheumatology (50.0% [42.9-60.9]) clinics (p <0.001) and the difference remained significant after multivariable adjustment. The subspecialty lupus clinic recorded higher per-QI performance for documentation of disease activity, disease damage, cardiovascular risk factor and drug toxicity assessments, pre-immunosuppression hepatitis and tuberculosis screening, new medication counselling

Background/Purpose: Atacicept, a dual inhibitor of the B lymphocyte stimulator and a proliferation-inducing ligand (APRIL), has been associated with a reduction of flares in the Phase II/III APRIL-SLE study (NCT00624338) and disease improvement in a subset of patients (pts) with baseline high disease activity (HDA; SLEDAI-2K >=10) in the Phase IIb ADDRESS II study (NCT01972568). Using immune cell deconvolution of gene expression data, we previously distinguished two pt clusters in the APRIL-SLE study characterized by different rates of flare in the placebo (PBO) group [1]. We proposed an analysis of ADDRESS II to confirm the differential treatment effect observed using baseline gene expression in the APRIL-SLE study. Method(s): In a prior study of APRIL-SLE samples, a cell deconvolution algorithm [2] was used to assess 17 immune cell subsets in gene expression data from mRNA extracted from whole blood at baseline (N=105). Unsupervised clustering revealed five clusters of pts (P1-P5). In two clusters (P1,3), PBO-treated pts, when compared with atacicept-treated pts, had few new BILAG A or B flares. In the other three clusters (P2,4,5), PBO-treated pts had high flare rates. The P2,4,5 subset includes pts with high plasmablasts, high B cells and low neutrophils, or high activated natural killer cells and high activated dendritic cells. Using the cellular modules that defined these clusters, we developed an algorithm to distinguish P1,3 from P2,4,5 and applied it to the ADDRESS II mITT and HDA populations with gene expression data at baseline. Treatment arms in the two resulting subsets were compared using SLE Responder Index (SRI)-4, SRI-6, BILAG-based Combined Lupus Assessment (BICLA), and low disease activity (SLEDAI-2K <=2). Result(s): In ADDRESS II, 179 pts (58.5%) of the mITT and 93 pts (59%) of the HDA subpopulation had RNAseq expression data; their clinical response rates were similar to the overall mITT and HDA populations. The algorithm assigned 93 mITT pts (5

Background/Purpose: Objectives of long-term SLE management are not only to reduce disease activity, but also to prevent flares and minimize exposure to oral corticosteroids (OCS), which are associated with organ damage accrual. 1,2 As tapering OCS increases flare risk, a therapy that both prevents flares and permits safe reductions of OCS is desirable. Flare rates were lower in patients with SLE who received anifrolumab vs placebo, and greater numbers of patients were able to taper OCS with anifrolumab vs placebo in the phase 3 trials, TULIP-1 and TULIP-2.3,4 We evaluated pooled TULIP trial data to further assess the capacity of anifrolumab to simultaneously prevent flares and permit OCS dosage reduction. Method(s): TULIP-1 and TULIP-2 were 52-week trials that evaluated the efficacy and safety of anifrolumab (300 mg IV Q4W for 48 weeks) or placebo in patients with moderately to severely active SLE despite standard-of-care treatment. Flares were defined as >=1 new BILAG-2004 A or >=2 new BILAG-2004 B domain scores vs the prior visit. Patients receiving OCS >=10 mg/day at baseline were required to attempt tapering to <=7.5 mg/day between Weeks 8 and 40; this reduction had to be sustained through Week 52. TULIP-1 and TULIP-2 were analyzed using restricted medication rules per the TULIP-2 protocol, and data from both trials were pooled. We analyzed flare occurrence in all patients, area under the curve (AUC) of OCS dosage among patients on OCS >=10 mg/day at baseline, and flare rates among patients on OCS >=10 mg/day at baseline who were able to sustain OCS dosage reduction to <=7.5 mg/day from Week 40 to Week 52. Result(s): Overall, 360 patients received anifrolumab and 366 received placebo. In total, fewer patients had >=1 flare with anifrolumab vs placebo (33.6% vs 42.9%) (Table 1). In pooled TULIP data, 375/726 (51.7%) patients were taking OCS >=10 mg/day at baseline; among these patients, OCS cumulative dosage through Week 52 was reduced with anifrolumab vs placebo

Background/Purpose: The type 1 interferon (IFN) cytokine family is key to the pathogenesis of SLE, evidenced by the expression of IFN stimulated genes (ISGs) in most patients. Phenotypic differences between SLE patients who express ISGs (IFN high) and those who do not (IFN low) are not well understood. With the emergence of IFN blocking drugs, it is important to examine the clinical utility of IFN status testing. We report the results of longitudinal analysis of IFN and clinical status in SLE. Method(s): 205 patients meeting ACR criteria for SLE were recruited at a tertiary centre where extensive clinical data are collected prospectively on consenting subjects. Whole blood RNA samples were collected in PAXgene tubes. IFN status was determined using the IFN module from Modular Immune Profile Test (DxTerity Diagnostics). Result(s): 729 results (205 patients, 142 with longitudinal samples) were analysed. At baseline, 62.9% of patients were IFN high, 30.2% IFN low and 6.8% borderline. Compared to IFN low patients, IFN high were more likely to be of Eastern Asian ethnicity (45.0 vs 25.8%, p = 0.01), were younger at SLE onset (median [IQR] 27[18-35] vs 33 [25-47] years, p = 0.0001), and were more likely to be positive for anti-Ro (65.3 vs 34.7% p = < 0.0001), anti-La (29.2 vs 11.3% p = 0.01) and anti-RNP (36.1% vs 15.1% p = 0.007) antibodies. In patients with multiple samples, 87.3% had stable ISG status. In longitudinal follow up (median 630 [459-707] days), IFN high patients had higher disease activity (median [IQR] time adjusted mean SLEDAI2K (4.2 [2.8-5.7] vs 2.0 [1.3-4.2], p=< 0.0001), more flares (mild/moderate 53.5 vs 25.8%, p = 0.0003; severe 26.4 vs 6.5%, p = 0.0009) and spent less observed time in lupus low disease activity state (LLDAS) (median 55.5% [26.3-85.5] vs 84.0 [53.0-100]%, p = 0.0003). IFN high patients were more likely to have active arthritis (21.7 vs 6.5%, p = 0.007), skin disease (38.8 vs 14.5%, p = 0.007), leukopenia (26.4 vs 6.5%, p = 0.0009) an

Background/Purpose: BICLA is a validated composite global measure of SLE disease activity that incorporates BILAG, an instrument that distinguishes between partial and complete improvement. BICLA was an endpoint in the phase 3 TULIP-1 and TULIP-2 trials of anifrolumab.1,2 This study investigated the relationships between BICLA response and SLE clinical and laboratory assessments in TULIP-1 and -2, irrespective of treatment assignment. Method(s): This was a post hoc analysis of pooled data from the 52-week (wk), double-blind TULIP-1 and -2 trials. Patients with moderately to severely active SLE, despite standard of care, were randomized to receive anifrolumab (150 or 300 mg IV Q4W) or placebo for 48 wks. BICLA responses were defined by the following: reduction of all baseline BILAG-2004 A and B domain scores to B/C/D and C/D, respectively, and no worsening in any organ system; no worsening of SLEDAI-2K score; and no worsening >=0.3 points in Physician's Global Assessment (range 0-3).3 Attempts to taper oral corticosteroids (OCS) to <=7.5 mg/day between Wks 8 and 40 were required for patients receiving OCS >=10 mg/day at baseline. Sustained OCS dosage reduction was defined as OCS dosage <=7.5 mg/day achieved by Wk 40 and sustained through Wk 52. Result(s): Baseline characteristics were generally similar between BICLA responders (n=318) and nonresponders (n=501). Overall, improved outcomes were observed in BICLA responders vs nonresponders, including numerically greater improvements in SLEDAI-2K (-7.4 [SD: 3.64] vs -4.2 [SD: 4.28]) from baseline to Wk 52 (Table 1). Greater mean daily OCS dosage reduction was observed in BICLA responders vs nonresponders (-5.41 [SD: 6.84] vs -1.67 [SD: 8.08] mg/day) from baseline to Wk 52, and sustained OCS dosage reduction was achieved by more BICLA responders vs nonresponders (79.2% vs 19.1%). A >=50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index activity (CLASI-A) score, for patients with baseline score >

Background: We sought to examine the disease course of High Disease Activity Status (HDAS) patients and their different disease patterns in a real-world longitudinal cohort. Disease resolution till Lupus Low Disease Activity State (LLDAS) has been a general treatment goal, but there is limited information on this subset of patients who achieve this. Method(s): All consenting patients of the Monash Lupus Cohort who had at least 12 months of observation were included. HDAS was defined as SLEDAI-2K >= 10 ever, and HDAS episode as the period from the first HDAS clinic visit until attainment of LLDAS. We examined the associations of different HDAS patterns with the likelihood of damage accrual. Result(s): Of 342 SLE patients, 151 experienced HDAS at least once, accounting for 298 HDAS episodes. The majority of HDAS patients (76.2%) experienced Recurrent HDAS (> 1 HDAS visit), and a smaller subset (47.7%) had Persistent HDAS (consecutive HDAS visits for longer than 2 months). Recurrent or Persistent HDAS patients were younger at diagnosis and more likely to experience renal or serositis manifestations; persistent HDAS patients were also more likely to experience neurological manifestations. Baseline SLEDAI greater than 10 was associated with longer HDAS episodes. Recurrent and Persistent HDAS were both associated with an increased likelihood of damage accrual. The total duration of HDAS episode greater than 2 years and experiencing multiple HDAS episodes (>=4) was also associated with an increased likelihood of damage accrual (OR 1.80, 95% CI 1.08-2.97, p = 0.02, and OR 3.31, 95% CI 1.66-13.26, p = 0.01, respectively). Conclusion(s): HDAS episodes have a highly variable course. Recurrent and Persistent HDAS, and longer duration of HDAS episodes, increased the risk of damage accrual. In addition to a major signifier of severity in SLE, its resolution to LLDAS can determine the subsequent outcome in SLE patients.Copyright © 2021, The Author(s).

Objectives: To evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine acceptance among patients with rheumatic diseases (RMD). Method(s): All rheumatology patients attending a large suburban health network were invited to participate in an anonymized online survey. The primary outcome of interest was SARS-COV-2 vaccine acceptance. Result(s): The mean (SD) age of respondents (n = 641) was 52.7 (15.1) years and 74.4% (n = 474) were female. Sixty-five percent were willing to have a SARS-COV-2 vaccine, while 34.4% were vaccine-hesitant (unwilling or undecided). On multivariate analysis, vaccine acceptance was associated with smoking (OR: 2.25 [95% CI: 1.22-4.15; p = .009]), history of malignancy (OR: 2.51 [95% CI: 1.19-5.26; p = .015]), influenza or pneumococcal vaccination in the preceding year (OR: 2.69 [95% CI: 1.78-4.05; p < .001]) and number of COVID-Safe measures practiced (OR: 1.54 [95% CI: 1.05-2.26; p = .027]). Vaccine acceptance correlated with positive beliefs regarding vaccine efficacy (r = 0.40; p < .001) and safety (r = 0.36; p < .001). Vaccine acceptance correlated negatively with concerns regarding side-effects (r = -0.30; p < .001) and vaccine-associated RMD flare (r = -0.21; p < .001). In vaccine-hesitant respondents, 39.2% were more likely to accept vaccination if given a choice of which vaccine they receive and 54.5% if their rheumatologist recommended it. Twenty-seven percent of patients on immunomodulators were willing to withhold medications while 42.1% were willing if advised by their rheumatologist. Conclusion(s): SARS-COV-2 vaccine hesitancy is prevalent amongst RMD patients and associated with concerns regarding vaccine safety, efficacy, side effects and RMD flare. Clinician recommendation, vaccine choice and communications targeting patient concerns could facilitate vaccine acceptance. Significance and Innovations Vaccine hesitancy is prevalent in RMD patients Vaccine acceptance is associated with beliefs regarding vacc

Background/Purpose: The Lupus Low Disease Activity State (LLDAS) has recently undergone prospective longitudinal validation in a multinational cohort, demonstrating the association of attaining LLDAS with protection from damage accrual and fl are, results that have been replicated in numerous other observational cohorts. Domain 1 of the original LLDAS operational definition captured the absence of significant disease activity by requiring SLEDAI-2K <=4, the absence of SLEDAI activity in major organs, and also the absence of haemolytic anaemia (HA) and gastrointestinal (GI) activity, manifestations not accounted for in the SLEDAI-2K. The requirement for absence of these infrequent clinical features creates the potential to misclassify patients' LLDAS status, as there is no formal definition of HA and GI activity. This has in turn limited regulatory approval of LLDAS as a clinical trial endpoint. To determine the requirement for capture of HA and GI activity in the LLDAS definition we performed a sensitivity analysis. Method(s): We analysed the prospective LLDAS longitudinal validation dataset. To evaluate whether HA and GI activity were captured by the physician global assessment (PGA) criterion of LLDAS, we compared patients with and without HA and GI with respect to median PGA and the proportion of patients with PGA >1. The impact on subsequent damage accrual and fl are of time-dependent associations of criterion 1 of the LLDAS definition, with and without inclusion of HA and GI activity, were assessed using Cox regression analysis. Result(s): Data on 1,707 patients, with 12,689 visits over 2.2 years were analysed. HA and GI activity were recorded in 28 and 73 visits, respectively. The median PGA, and the proportion of patients with PGA >1, were significantly higher in patients with either HA or GI activity (Table 1). Omitting the requirement for absence of HA and GI activity from criterion 1 of the LLDAS definition had no meaningful impact on the protective associ

Preclinical validation of multiple therapeutic targets in mouse studies has not been followed by clinical trial success. Therefore, validationfirst in human SLE has arisen as a new paradigm. The first such target to be translated all the way via clinical trials to submission for approval is type I interferon (IFN). Innate immune mechanisms which evolved to support responses to viral infection, mediated by IFN, are activated by stimuli hypothesized to include nucleic acid immune complexes. Evidence of IFN activation in SLE includes highly reproducible IFN signature gene (ISG) expression in blood and affected tissues, albeit weakly associated with markers of disease activity. IFN is not primarily pathogenic in classic murine lupus models, but it exacerbates murine models of SLE and IFN treatment of other human diseases can induce SLE-like phenotypes. Together, these data supported trialling IFN-targeting treatments in SLE. Studies of antibodies to IFNalpha, and of a vaccine inducing neutralizing IFN antibodies, yielded mixed but overall supportive results. Importantly, three randomized trials of an antibody to the type I IFN receptor, which may cause greater suppression of ISG than other agents, showed reproducible efficacy across composite outcome measures, skin disease, and glucocorticoid tapering, although the primary outcome was not met in one of these trials. Safety issues identified include increased rates of herpes zoster, in line with expectations based on the mechanism of action, but overall suggest an acceptable benefit:risk profile. These findings confirm the role of IFN in the pathogenesis of SLE, solidyfing a key aspect of pathogenesis of lupus from theory to fact. The potential of treatments targeting this pathway to be transformative for SLE patients awaits regulatory approval.

BACKGROUND: Pathology and imaging tests are frequently requested in the outpatient setting despite historically poor completion rates. The impact of COVID-19 telehealth on test completion rates is unknown. AIMS: To examine the impact of the COVID-19 pandemic and telehealth transition on pathology and imaging test request and completion rates in Australian outpatient clinics. METHOD(S): We performed a prospective cohort study with historical controls between March-May 2019 and March-May 2020. Pathology and imaging request and completion rates were collected in review consultation patients attending Gastroenterology and Rheumatology outpatient clinics at a tertiary healthcare system prior and during the early phases of the COVID-19 pandemic in Melbourne. RESULT(S): 1376 patients were included in the study. Pathology tests were requested more frequently in the COVID-19 group (n = 582/684, 85.2%) than control group (n = 492/692, 71.1%, p <0.001) but completion rates were lower in the COVID-19 group (n = 443/582, 76.1%) than control group (n = 426/492 (86.6%), p <0.001). Imaging tests were requested more frequently in the COVID-19 group (n = 345/682, 50.6%) than control group (n = 295/692, 42.6%, p = 0.003) with lower rates of completion in the COVID-19 group (n = 229/345, 66.4%) then control group (n = 247/295, 83.7%, p <0.001). CONCLUSION(S): The COVID-19 pandemic and telehealth transition has resulted in more frequent pathology and imaging requests but fewer test completion in the outpatients setting. This study has identified new clinical risks associated with the abrupt transition to telehealth during COVID-19 that should be explored in future studies and appropriately mitigated. This article is protected by copyright. All rights reserved.

Objective: To determine longitudinal associations between Physician Global Assessment (PGA) and patient-reported outcomes (PROs) in patients with systemic lupus erythematosus (SLE). Method(s): Patients attending a rheumatology clinic between 2013 and 2017 completed specific (SLEQOL) and generic (SF36) health-related quality of life (HRQoL) surveys and rated their global rating of change (GRC) at each visit. PGA, SLEDAI-2K and SLE Flare Index (SFI) were also captured on all visits. Generalised estimating equations (GEE) methods were used to examine longitudinal associations of PGA with PROs and clinical indicators. Result(s): 337 patients were followed for a median [IQR] of 3.2 [1.6, 3.4] years (2,059 visits). High PGA (>1) was strongly associated with high SLEDAI-2K scores, the presence of flares and poor PROs. Odd ratios (OR) [95% CI] of PGA > 1 in patients with SLEDAI-2K >4 & <10 and SLEDAI-2K >=10, compared to SLEDAI-2K <= 4, were 3.46 [2.36, 5.08], p < 0.001 and 6.39 [4.30, 9.49], p < 0.001, respectively. OR [95% CI] of PGA > 1 in patients with mild-to-moderate or severe flares were 2.09 [1.62, 2.71], p < 0.001 and 4.42 [3.21, 6.07], p < 0.001, respectively. Mental components of both SLEQOL (mood, self-image) and SF36 (MCS) surveys demonstrated significant associations with high PGA. After adjusting for SLEDAI-2K, one-point increase in PGA was associated with reductions in SLEQOL total score and SF36-MCS by 2.33 (regression coefficient (RC) [95% CI] = -2.33 [-3.77, -0.88], p = 0.002), and 4.16 (RC [95% CI] = -4.16 [-5.19, -3.13], p < 0.001) points, respectively. Associations of some physical components (SLEQOL-symptoms, and SF36-PCS) with PGA attenuated when adjusted for SLEDAI-2K. Patients who rated low scores of GRC, which indicate health deterioration, were twice as likely to have PGA > 1 (OR [95%CI] 1.99 [1.25, 3.16], p = 0.004). Conclusion(s): High PGA was strongly associated with poor mental health, high disease activity and flares. This study confirms the

Background: Pathology and imaging tests are frequently requested in the outpatient setting despite historically poor completion rates. The impact of COVID-19 telehealth on test completion rates is unknown. Aim(s): To examine the impact of the COVID-19 pandemic and telehealth transition on pathology and imaging test request and completion rates in Australian outpatient clinics. Method(s): We performed a prospective cohort study with historical controls between March-May 2019 and March-May 2020. Pathology and imaging request and completion rates were collected in review consultation patients attending gastroenterology and rheumatology outpatient clinics at a tertiary healthcare system prior and during the early phases of the COVID-19 pandemic in Melbourne. Result(s): A total of 1376 patients was included in the study. Pathology tests were requested more frequently in the COVID-19 group (n = 582/684, 85.2%) than the control group (n = 492/692, 71.1%, P < 0.001), but completion rates were lower in the COVID-19 group (n = 443/582, 76.1%) than the control group (n = 426/492 (86.6%), P < 0.001). Imaging tests were requested more frequently in the COVID-19 group (n = 345/682, 50.6%) than the control group (n = 295/692, 42.6%, P = 0.003), with lower rates of completion in the COVID-19 group (n = 229/345, 66.4%) than the control group (n = 247/295, 83.7%, P < 0.001). Conclusion(s): The COVID-19 pandemic and telehealth transition have resulted in more frequent pathology and imaging requests but fewer test completion in the outpatients setting. This study has identified new clinical risks associated with the abrupt transition to telehealth during COVID-19 that should be explored in future studies and appropriately mitigated.Copyright © 2021 Royal Australasian College of Physicians

Despite promising candidates for new therapeutic options in the treatment of systemic lupus erythematosus (SLE), many clinical trials have failed in the past few years. The disappointing results have been at least partly be attributed to trial designs. With the aim of stimulating new developments in SLE trial design, an international open space meeting was held on occasion of the European Lupus Meeting 2018 in Duesseldorf, Germany about 'What are the topics you care about for making trials in lupus more effective?'. The Open Space is a participant-driven technology, where the discussion topics and schedule are selected during the meeting by all participants and discussion rounds are led by the people attending encouraging active contributions. Eleven topics were selected for further discussion, of which 6 were voted to be more intensively discussed in two consecutive rounds. Major topics were the optimal handling of glucocorticoids in clinical trials, the improvement of outcome measures, reducing or controlling the placebo response and the identification of biomarkers and stratification parameters. Further, the importance of local and international networks was emphasised. By networking, collaborations are facilitated, patient recruitment is more efficient and treatment can be harmonised thus lead to more successful SLE trials. Further discussions are needed to substantiate the results and develop new trial designs. Copyright © 2020 American Society of Mechanical Engineers (ASME). All rights reserved.

Background/Purpose: Metabolic syndrome (MetS) is a chronic pro-inflammatory and pro-thrombotic state associated with increased atherosclerosis, cardiovascular events and type 2 diabetes. It is diagnosed in the presence of at least 3 of 5 metabolic risk factors (obesity, hypertension, hypertriglyceridemia, low high-density lipoproteins (HDL) and insulin resistance [1]). The pathophysiology of MetS remains incompletely understood, but may share mechanisms with inflammatory states such as SLE. Visceral adiposity is known as a source of pro-inflammatory cytokines by adipocytes, the so-called adipokines. The contribution of glucocorticoids to the development of MetS in SLE is not clear, even though their use is associated with cardiovascular comorbidities [2]. We aim to characterize the prevalence and associations of MetS, including serum levels of adipokines, in a multi-ethnic cohort of patients with SLE. Method(s): Using a standardised protocol, baseline demographics, per visit disease activity (SLEDAI2K) and treatment data, and annual recording of organ damage accrual (SLICC damage index (SDI)) were prospectively captured on SLE patients from a single tertiary centre. The presence of MetS,defined using the updated joint consensus criteria [1], was assessed retrospectively at the last recorded visit. Serum levels of adipokines (resistin, lipocalin-2, TNF, MCP-1) and insulin were measured by Quantibody. Result(s): 116 patients (median (IQR) age at enrolment 39.5 (31.4-51.1) years, median disease duration 6.1 (1.4-12) years) were followed for a median of 6.7 (4.1-8.1) years. 80% of patients were exposed to glucocorticoids (median time-adjusted mean dose 3.7 (0.5-7.0) mg/day and 50% accrued organ damage during follow-up. The prevalence of MetS in this cohort was 29%. The prevalence of the components of MetS included: hypertension (59%), low-HDL (51%), hypertriglyceridemia (32%), obesity (16%) and hyperglycaemia (22%). In univariable analysis, MetS was associated with base

Background/Purpose: A key goal of treatment of SLE is the prevention of irreversible organ damage. The ability to identify patients at increased risk for damage could select patients for early intervention but is currently lacking. Conventional studies of damage outcomes in SLE utilize composite disease activity scores, and associations with damage are only modest. We evaluated whether using all available data in an unbiased fashion, including continuous laboratory data usually analysed dichotomously in disease activity scores, could give rise to superior predictive algorithms for organ damage in SLE. Method(s): Prospectively collected longitudinal data from a 13-centre multinational cohort were used. Each visit was assigned yes/no as being in a damage-transition period based on whether the nearest subsequent annual measurement of organ damage (SLICC damage index) increased. Candidate variables included demographic (3), baseline serology (4), medication classes (anti-malarial, immunosuppressant, and glucocorticoid), routine clinical laboratory parameters (14) and SLEDAI-2K. Logistic regression models were selected to predict the probability of damage transition using backward, forward, and hybrid stepwise selection methods, either including or excluding SLEDAI-2K. The primary metric evaluating performance was area under the receiver operating characteristic curve (AUC) for association with damage transition. Result(s): Data from 15,625 visits of 1,621 patients were split randomly 80:20 into training and test datasets; a separate cohort (2,178 visits, 188 patients) was used for independent validation. As there were only 1,157 damage transition visits in the training dataset, oversampling was used to create a dataset with 23,120 visits with a 'transition visit' ratio of 50%. Altogether 221 (~ 2 million) models with different combinations of predictors were analysed. After excluding models with >20 variables or training AUC < 0.62 we ranked 43,332 models excluding SLED

Systemic lupus erythematosus (SLE) is a more common autoimmune rheumatic disease in the Asia-Pacific region. The prognosis of SLE remains unsatisfactory in some Asian countries because of delayed diagnosis, limited access to medications, increased complications and issues of tolerability and adherence to treatment. The Asia-Pacific League of Associations for Rheumatology SLE special interest group has recently published a set of consensus recommendations on the management of SLE for specialists, family physicians, specialty nurses, and other healthcare professionals in the Asia-Pacific region. This article reports a systematic literature review of the infective complications of SLE in Asia and evidence for prevention of these infections by pre-emptive antimicrobial therapy and vaccination.Copyright © 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Systemic lupus erythematosus (SLE) is a more common autoimmune rheumatic disease in the Asia Pacific region. Epidemiological studies have revealed differences in the manifestations and prognosis of the disease among regional ethnicities and populations. To date, the prognosis of SLE remains unsatisfactory in some Asian countries because of limited patient access to medical care and inadequate provider access to educational or practice support. To describe the unique characteristics of the disease in the region and to address the information discrepancy in the area, the Asia-Pacific League of Associations for Rheumatology (APLAR) SLE special interest group has recently published 34 consensus recommendations on the management of SLE for specialists, family physicians, specialty nurses, and other healthcare professionals in the Asia Pacific region. Herein, along with this consensus statement, we detail the infective complications of SLE in Asia and evidence for the prevention of these infections through preemptive antimicrobial therapy and vaccination.

Objective To achieve consensus on a definition of remission in SLE (DORIS). Background Remission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a framework for such a definition, without reaching a final recommendation. Methods Several systematic literature reviews were performed and specific research questions examined in suitably chosen data sets. The findings were discussed, reformulated as recommendations and voted on. Results Based on data from the literature and several SLE-specific data sets, a set of recommendations was endorsed. Ultimately, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical systemic lupus erythematosus disease activitiy index (SLEDAI)=0, Evaluator's Global Assessment <0.5 (0-3), prednisolone 5 mg/day or less, and stable antimalarials, immunosuppressives, and biologics. Conclusion The 2021 DORIS definition of remission in SLE is recommended for use in clinical care, education, and research including clinical trials and observational studies.Copyright © 2021 BMJ Publishing Group. All rights reserved.

Background: The ability to identify lupus patients in high disease activity status (HDAS) without knowledge of the SLEDAI could have application in selection of patients for treatment escalation or enrolment in trials. We sought to generate an algorithm that could calculate via model fitting the presence of HDAS using simple demographic and laboratory values. Method(s): We examined the association of high disease activity (HDA) with demographic and laboratory parameters using prospectively collected data. An HDA visit is recorded when SLEDAI-2K >=10. We utilized the use of combinatorial search to find algorithms to build a mathematical model predictive of HDA. Performance of each algorithm was evaluated using multi-class area under the receiver operating characteristic curve and the final model was compared with the naive Bayes classifier, and analysed using the confusion matrix for accuracy and misclassification rate. Result(s): Data on 286 patients, followed for a median of 5.1 years were studied for a total of 5680 visits. Sixteen laboratory parameters were found to be significantly associated with HDA. A total of 216 algorithms were evaluated and the final algorithm chosen was based on seven pathology measures and three demographic variables. It has an accuracy of 88.6% and misclassification rate of 11.4%. When compared with the naive Bayes classifier [area under the curve (AUC) = 0.663], our algorithm has a better accuracy with AUC = 0.829. Conclusion(s): This study shows that building an accurate model to calculate HDA using routinely available clinical parameters is feasible. Future studies to independently validate the algorithm will be needed to confirm its predictive performance. Copyright © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Objectives To characterise the prevalence and associations of metabolic syndrome (MetS) in a multiethnic cohort of patients with SLE. Methods Using a standardised protocol, baseline demographics, per visit disease activity (Systemic Lupus Erythematosus Disease Activity Index-2K) and treatment data, and annual recording of organ damage accrual (Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC-ACR) Damage Index) were captured on patients with SLE from a single tertiary centre. The presence of MetS, defined using modified updated joint consensus criteria, was assessed at the final visit from patient records. Serum concentrations of adipocytokines were measured by Quantibody. Results 116 patients, with median (Q1, Q3) age at enrolment of 39.5 (31.4-51.1) years and disease duration of 6.1 (1.4-12) years, were followed for a median of 6.7 (4.1-8.1) years. The prevalence of MetS was 29% (34/116), while the prevalence of MetS components varied: hypertension (59%), low high-density lipoproteins (HDLs) (51%), hypertriglyceridaemia (32%), obesity (16%) and hyperglycaemia (22%). In univariable analysis, MetS was associated with baseline organ damage (OR 4.34; 95% CI 1.80 to 10.48; p<0.01) and organ damage accrual (OR 2.34; 95% CI 1.02 to 5.36; p=0.04) but not with disease activity. In multivariable analysis, baseline organ damage remained significantly associated with MetS (adjusted OR 3.36; 95% CI 1.32 to 8.59; p=0.01). Glucocorticoid use was not associated with MetS or any of its five components. High serum concentrations of resistin were significantly negatively associated with MetS (OR 0.17; 95% CI 0.04 to 0.70; p=0.014). Conclusion MetS was common in a multiethnic cohort of patients with SLE, with the most frequent components being hypertension and low HDL. An independent association was found between MetS and organ damage but not glucocorticoid exposure or disease activity.Copyright ©

Background: Pathology and imaging tests are frequently requested in the outpatient setting despite historically poor completion rates. The impact of COVID-19 telehealth on test completion rates is unknown. Aim(s): To examine the impact of the COVID-19 pandemic and telehealth transition on pathology and imaging test request and completion rates in Australian outpatient clinics. Method(s): We performed a prospective cohort study with historical controls between March-May 2019 and March-May 2020. Pathology and imaging request and completion rates were collected in review consultation patients attending gastroenterology and rheumatology outpatient clinics at a tertiary healthcare system prior and during the early phases of the COVID-19 pandemic in Melbourne. Result(s): A total of 1376 patients was included in the study. Pathology tests were requested more frequently in the COVID-19 group (n = 582/684, 85.2%) than the control group (n = 492/692, 71.1%, P < 0.001), but completion rates were lower in the COVID-19 group (n = 443/582, 76.1%) than the control group (n = 426/492 (86.6%), P < 0.001). Imaging tests were requested more frequently in the COVID-19 group (n = 345/682, 50.6%) than the control group (n = 295/692, 42.6%, P = 0.003), with lower rates of completion in the COVID-19 group (n = 229/345, 66.4%) than the control group (n = 247/295, 83.7%, P < 0.001). Conclusion(s): The COVID-19 pandemic and telehealth transition have resulted in more frequent pathology and imaging requests but fewer test completion in the outpatients setting. This study has identified new clinical risks associated with the abrupt transition to telehealth during COVID-19 that should be explored in future studies and appropriately mitigated.Copyright © 2021 Royal Australasian College of Physicians

Background: The ability to identify lupus patients in high disease activity status (HDAS) without knowledge of the SLEDAI could have application in selection of patients for treatment escalation or enrolment in trials. We sought to generate an algorithm that could calculate via model fitting the presence of HDAS using simple demographic and laboratory values. Method(s): We examined the association of high disease activity (HDA) with demographic and laboratory parameters using prospectively collected data. An HDA visit is recorded when SLEDAI-2K >=10. We utilized the use of combinatorial search to find algorithms to build a mathematical model predictive of HDA. Performance of each algorithm was evaluated using multi-class area under the receiver operating characteristic curve and the final model was compared with the naive Bayes classifier, and analysed using the confusion matrix for accuracy and misclassification rate. Result(s): Data on 286 patients, followed for a median of 5.1 years were studied for a total of 5680 visits. Sixteen laboratory parameters were found to be significantly associated with HDA. A total of 216 algorithms were evaluated and the final algorithm chosen was based on seven pathology measures and three demographic variables. It has an accuracy of 88.6% and misclassification rate of 11.4%. When compared with the naive Bayes classifier [area under the curve (AUC) = 0.663], our algorithm has a better accuracy with AUC = 0.829. Conclusion(s): This study shows that building an accurate model to calculate HDA using routinely available clinical parameters is feasible. Future studies to independently validate the algorithm will be needed to confirm its predictive performance. Copyright © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Background: We sought to examine the disease course of High Disease Activity Status (HDAS) patients and their different disease patterns in a real-world longitudinal cohort. Disease resolution till Lupus Low Disease Activity State (LLDAS) has been a general treatment goal, but there is limited information on this subset of patients who achieve this. Method(s): All consenting patients of the Monash Lupus Cohort who had at least 12 months of observation were included. HDAS was defined as SLEDAI-2K >= 10 ever, and HDAS episode as the period from the first HDAS clinic visit until attainment of LLDAS. We examined the associations of different HDAS patterns with the likelihood of damage accrual. Result(s): Of 342 SLE patients, 151 experienced HDAS at least once, accounting for 298 HDAS episodes. The majority of HDAS patients (76.2%) experienced Recurrent HDAS (> 1 HDAS visit), and a smaller subset (47.7%) had Persistent HDAS (consecutive HDAS visits for longer than 2 months). Recurrent or Persistent HDAS patients were younger at diagnosis and more likely to experience renal or serositis manifestations; persistent HDAS patients were also more likely to experience neurological manifestations. Baseline SLEDAI greater than 10 was associated with longer HDAS episodes. Recurrent and Persistent HDAS were both associated with an increased likelihood of damage accrual. The total duration of HDAS episode greater than 2 years and experiencing multiple HDAS episodes (>=4) was also associated with an increased likelihood of damage accrual (OR 1.80, 95% CI 1.08-2.97, p = 0.02, and OR 3.31, 95% CI 1.66-13.26, p = 0.01, respectively). Conclusion(s): HDAS episodes have a highly variable course. Recurrent and Persistent HDAS, and longer duration of HDAS episodes, increased the risk of damage accrual. In addition to a major signifier of severity in SLE, its resolution to LLDAS can determine the subsequent outcome in SLE patients.Copyright © 2021, The Author(s).

Objectives: To evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine acceptance among patients with rheumatic diseases (RMD). Method(s): All rheumatology patients attending a large suburban health network were invited to participate in an anonymized online survey. The primary outcome of interest was SARS-COV-2 vaccine acceptance. Result(s): The mean (SD) age of respondents (n = 641) was 52.7 (15.1) years and 74.4% (n = 474) were female. Sixty-five percent were willing to have a SARS-COV-2 vaccine, while 34.4% were vaccine-hesitant (unwilling or undecided). On multivariate analysis, vaccine acceptance was associated with smoking (OR: 2.25 [95% CI: 1.22-4.15; p = .009]), history of malignancy (OR: 2.51 [95% CI: 1.19-5.26; p = .015]), influenza or pneumococcal vaccination in the preceding year (OR: 2.69 [95% CI: 1.78-4.05; p < .001]) and number of COVID-Safe measures practiced (OR: 1.54 [95% CI: 1.05-2.26; p = .027]). Vaccine acceptance correlated with positive beliefs regarding vaccine efficacy (r = 0.40; p < .001) and safety (r = 0.36; p < .001). Vaccine acceptance correlated negatively with concerns regarding side-effects (r = -0.30; p < .001) and vaccine-associated RMD flare (r = -0.21; p < .001). In vaccine-hesitant respondents, 39.2% were more likely to accept vaccination if given a choice of which vaccine they receive and 54.5% if their rheumatologist recommended it. Twenty-seven percent of patients on immunomodulators were willing to withhold medications while 42.1% were willing if advised by their rheumatologist. Conclusion(s): SARS-COV-2 vaccine hesitancy is prevalent amongst RMD patients and associated with concerns regarding vaccine safety, efficacy, side effects and RMD flare. Clinician recommendation, vaccine choice and communications targeting patient concerns could facilitate vaccine acceptance. Significance and Innovations Vaccine hesitancy is prevalent in RMD patients Vaccine acceptance is associated with beliefs regarding vacc

BACKGROUND: Pathology and imaging tests are frequently requested in the outpatient setting despite historically poor completion rates. The impact of COVID-19 telehealth on test completion rates is unknown. AIMS: To examine the impact of the COVID-19 pandemic and telehealth transition on pathology and imaging test request and completion rates in Australian outpatient clinics. METHOD(S): We performed a prospective cohort study with historical controls between March-May 2019 and March-May 2020. Pathology and imaging request and completion rates were collected in review consultation patients attending Gastroenterology and Rheumatology outpatient clinics at a tertiary healthcare system prior and during the early phases of the COVID-19 pandemic in Melbourne. RESULT(S): 1376 patients were included in the study. Pathology tests were requested more frequently in the COVID-19 group (n = 582/684, 85.2%) than control group (n = 492/692, 71.1%, p <0.001) but completion rates were lower in the COVID-19 group (n = 443/582, 76.1%) than control group (n = 426/492 (86.6%), p <0.001). Imaging tests were requested more frequently in the COVID-19 group (n = 345/682, 50.6%) than control group (n = 295/692, 42.6%, p = 0.003) with lower rates of completion in the COVID-19 group (n = 229/345, 66.4%) then control group (n = 247/295, 83.7%, p <0.001). CONCLUSION(S): The COVID-19 pandemic and telehealth transition has resulted in more frequent pathology and imaging requests but fewer test completion in the outpatients setting. This study has identified new clinical risks associated with the abrupt transition to telehealth during COVID-19 that should be explored in future studies and appropriately mitigated. This article is protected by copyright. All rights reserved.

Objective: To determine longitudinal associations between Physician Global Assessment (PGA) and patient-reported outcomes (PROs) in patients with systemic lupus erythematosus (SLE). Method(s): Patients attending a rheumatology clinic between 2013 and 2017 completed specific (SLEQOL) and generic (SF36) health-related quality of life (HRQoL) surveys and rated their global rating of change (GRC) at each visit. PGA, SLEDAI-2K and SLE Flare Index (SFI) were also captured on all visits. Generalised estimating equations (GEE) methods were used to examine longitudinal associations of PGA with PROs and clinical indicators. Result(s): 337 patients were followed for a median [IQR] of 3.2 [1.6, 3.4] years (2,059 visits). High PGA (>1) was strongly associated with high SLEDAI-2K scores, the presence of flares and poor PROs. Odd ratios (OR) [95% CI] of PGA > 1 in patients with SLEDAI-2K >4 & <10 and SLEDAI-2K >=10, compared to SLEDAI-2K <= 4, were 3.46 [2.36, 5.08], p < 0.001 and 6.39 [4.30, 9.49], p < 0.001, respectively. OR [95% CI] of PGA > 1 in patients with mild-to-moderate or severe flares were 2.09 [1.62, 2.71], p < 0.001 and 4.42 [3.21, 6.07], p < 0.001, respectively. Mental components of both SLEQOL (mood, self-image) and SF36 (MCS) surveys demonstrated significant associations with high PGA. After adjusting for SLEDAI-2K, one-point increase in PGA was associated with reductions in SLEQOL total score and SF36-MCS by 2.33 (regression coefficient (RC) [95% CI] = -2.33 [-3.77, -0.88], p = 0.002), and 4.16 (RC [95% CI] = -4.16 [-5.19, -3.13], p < 0.001) points, respectively. Associations of some physical components (SLEQOL-symptoms, and SF36-PCS) with PGA attenuated when adjusted for SLEDAI-2K. Patients who rated low scores of GRC, which indicate health deterioration, were twice as likely to have PGA > 1 (OR [95%CI] 1.99 [1.25, 3.16], p = 0.004). Conclusion(s): High PGA was strongly associated with poor mental health, high disease activity and flares. This study confirms the

Despite promising candidates for new therapeutic options in the treatment of systemic lupus erythematosus (SLE), many clinical trials have failed in the past few years. The disappointing results have been at least partly be attributed to trial designs. With the aim of stimulating new developments in SLE trial design, an international open space meeting was held on occasion of the European Lupus Meeting 2018 in Duesseldorf, Germany about 'What are the topics you care about for making trials in lupus more effective?'. The Open Space is a participant-driven technology, where the discussion topics and schedule are selected during the meeting by all participants and discussion rounds are led by the people attending encouraging active contributions. Eleven topics were selected for further discussion, of which 6 were voted to be more intensively discussed in two consecutive rounds. Major topics were the optimal handling of glucocorticoids in clinical trials, the improvement of outcome measures, reducing or controlling the placebo response and the identification of biomarkers and stratification parameters. Further, the importance of local and international networks was emphasised. By networking, collaborations are facilitated, patient recruitment is more efficient and treatment can be harmonised thus lead to more successful SLE trials. Further discussions are needed to substantiate the results and develop new trial designs. Copyright © 2020 American Society of Mechanical Engineers (ASME). All rights reserved.

Background/Purpose: Objectives of long-term SLE management are not only to reduce disease activity, but also to prevent flares and minimize exposure to oral corticosteroids (OCS), which are associated with organ damage accrual. 1,2 As tapering OCS increases flare risk, a therapy that both prevents flares and permits safe reductions of OCS is desirable. Flare rates were lower in patients with SLE who received anifrolumab vs placebo, and greater numbers of patients were able to taper OCS with anifrolumab vs placebo in the phase 3 trials, TULIP-1 and TULIP-2.3,4 We evaluated pooled TULIP trial data to further assess the capacity of anifrolumab to simultaneously prevent flares and permit OCS dosage reduction. Method(s): TULIP-1 and TULIP-2 were 52-week trials that evaluated the efficacy and safety of anifrolumab (300 mg IV Q4W for 48 weeks) or placebo in patients with moderately to severely active SLE despite standard-of-care treatment. Flares were defined as >=1 new BILAG-2004 A or >=2 new BILAG-2004 B domain scores vs the prior visit. Patients receiving OCS >=10 mg/day at baseline were required to attempt tapering to <=7.5 mg/day between Weeks 8 and 40; this reduction had to be sustained through Week 52. TULIP-1 and TULIP-2 were analyzed using restricted medication rules per the TULIP-2 protocol, and data from both trials were pooled. We analyzed flare occurrence in all patients, area under the curve (AUC) of OCS dosage among patients on OCS >=10 mg/day at baseline, and flare rates among patients on OCS >=10 mg/day at baseline who were able to sustain OCS dosage reduction to <=7.5 mg/day from Week 40 to Week 52. Result(s): Overall, 360 patients received anifrolumab and 366 received placebo. In total, fewer patients had >=1 flare with anifrolumab vs placebo (33.6% vs 42.9%) (Table 1). In pooled TULIP data, 375/726 (51.7%) patients were taking OCS >=10 mg/day at baseline; among these patients, OCS cumulative dosage through Week 52 was reduced with anifrolumab vs placebo

Background/Purpose: BICLA is a validated composite global measure of SLE disease activity that incorporates BILAG, an instrument that distinguishes between partial and complete improvement. BICLA was an endpoint in the phase 3 TULIP-1 and TULIP-2 trials of anifrolumab.1,2 This study investigated the relationships between BICLA response and SLE clinical and laboratory assessments in TULIP-1 and -2, irrespective of treatment assignment. Method(s): This was a post hoc analysis of pooled data from the 52-week (wk), double-blind TULIP-1 and -2 trials. Patients with moderately to severely active SLE, despite standard of care, were randomized to receive anifrolumab (150 or 300 mg IV Q4W) or placebo for 48 wks. BICLA responses were defined by the following: reduction of all baseline BILAG-2004 A and B domain scores to B/C/D and C/D, respectively, and no worsening in any organ system; no worsening of SLEDAI-2K score; and no worsening >=0.3 points in Physician's Global Assessment (range 0-3).3 Attempts to taper oral corticosteroids (OCS) to <=7.5 mg/day between Wks 8 and 40 were required for patients receiving OCS >=10 mg/day at baseline. Sustained OCS dosage reduction was defined as OCS dosage <=7.5 mg/day achieved by Wk 40 and sustained through Wk 52. Result(s): Baseline characteristics were generally similar between BICLA responders (n=318) and nonresponders (n=501). Overall, improved outcomes were observed in BICLA responders vs nonresponders, including numerically greater improvements in SLEDAI-2K (-7.4 [SD: 3.64] vs -4.2 [SD: 4.28]) from baseline to Wk 52 (Table 1). Greater mean daily OCS dosage reduction was observed in BICLA responders vs nonresponders (-5.41 [SD: 6.84] vs -1.67 [SD: 8.08] mg/day) from baseline to Wk 52, and sustained OCS dosage reduction was achieved by more BICLA responders vs nonresponders (79.2% vs 19.1%). A >=50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index activity (CLASI-A) score, for patients with baseline score >

Background/Purpose: The type 1 interferon (IFN) cytokine family is key to the pathogenesis of SLE, evidenced by the expression of IFN stimulated genes (ISGs) in most patients. Phenotypic differences between SLE patients who express ISGs (IFN high) and those who do not (IFN low) are not well understood. With the emergence of IFN blocking drugs, it is important to examine the clinical utility of IFN status testing. We report the results of longitudinal analysis of IFN and clinical status in SLE. Method(s): 205 patients meeting ACR criteria for SLE were recruited at a tertiary centre where extensive clinical data are collected prospectively on consenting subjects. Whole blood RNA samples were collected in PAXgene tubes. IFN status was determined using the IFN module from Modular Immune Profile Test (DxTerity Diagnostics). Result(s): 729 results (205 patients, 142 with longitudinal samples) were analysed. At baseline, 62.9% of patients were IFN high, 30.2% IFN low and 6.8% borderline. Compared to IFN low patients, IFN high were more likely to be of Eastern Asian ethnicity (45.0 vs 25.8%, p = 0.01), were younger at SLE onset (median [IQR] 27[18-35] vs 33 [25-47] years, p = 0.0001), and were more likely to be positive for anti-Ro (65.3 vs 34.7% p = < 0.0001), anti-La (29.2 vs 11.3% p = 0.01) and anti-RNP (36.1% vs 15.1% p = 0.007) antibodies. In patients with multiple samples, 87.3% had stable ISG status. In longitudinal follow up (median 630 [459-707] days), IFN high patients had higher disease activity (median [IQR] time adjusted mean SLEDAI2K (4.2 [2.8-5.7] vs 2.0 [1.3-4.2], p=< 0.0001), more flares (mild/moderate 53.5 vs 25.8%, p = 0.0003; severe 26.4 vs 6.5%, p = 0.0009) and spent less observed time in lupus low disease activity state (LLDAS) (median 55.5% [26.3-85.5] vs 84.0 [53.0-100]%, p = 0.0003). IFN high patients were more likely to have active arthritis (21.7 vs 6.5%, p = 0.007), skin disease (38.8 vs 14.5%, p = 0.007), leukopenia (26.4 vs 6.5%, p = 0.0009) an

Background/Purpose: Atacicept, a dual inhibitor of the B lymphocyte stimulator and a proliferation-inducing ligand (APRIL), has been associated with a reduction of flares in the Phase II/III APRIL-SLE study (NCT00624338) and disease improvement in a subset of patients (pts) with baseline high disease activity (HDA; SLEDAI-2K >=10) in the Phase IIb ADDRESS II study (NCT01972568). Using immune cell deconvolution of gene expression data, we previously distinguished two pt clusters in the APRIL-SLE study characterized by different rates of flare in the placebo (PBO) group [1]. We proposed an analysis of ADDRESS II to confirm the differential treatment effect observed using baseline gene expression in the APRIL-SLE study. Method(s): In a prior study of APRIL-SLE samples, a cell deconvolution algorithm [2] was used to assess 17 immune cell subsets in gene expression data from mRNA extracted from whole blood at baseline (N=105). Unsupervised clustering revealed five clusters of pts (P1-P5). In two clusters (P1,3), PBO-treated pts, when compared with atacicept-treated pts, had few new BILAG A or B flares. In the other three clusters (P2,4,5), PBO-treated pts had high flare rates. The P2,4,5 subset includes pts with high plasmablasts, high B cells and low neutrophils, or high activated natural killer cells and high activated dendritic cells. Using the cellular modules that defined these clusters, we developed an algorithm to distinguish P1,3 from P2,4,5 and applied it to the ADDRESS II mITT and HDA populations with gene expression data at baseline. Treatment arms in the two resulting subsets were compared using SLE Responder Index (SRI)-4, SRI-6, BILAG-based Combined Lupus Assessment (BICLA), and low disease activity (SLEDAI-2K <=2). Result(s): In ADDRESS II, 179 pts (58.5%) of the mITT and 93 pts (59%) of the HDA subpopulation had RNAseq expression data; their clinical response rates were similar to the overall mITT and HDA populations. The algorithm assigned 93 mITT pts (5

Background/Purpose: SLE is a heterogeneous disease, where a better understanding of molecular differences between patients is needed in order to direct therapy. Existing approaches generally examine mRNA expression, whereas therapeutic targets are mostly soluble or cellular proteins. We aimed to evaluate whether a serum cytokine proteomic profile of SLE patients analysed using an unbiased approach would yield clinically meaningful results. Method(s): Demographic and clinical data of SLE patients (ACR criteria) including disease activity (SLEDAI2K) and organ damage (SLICC Damage Index (SDI)), and matching serum samples, were collected prospectively. A wide-angled serum cytokine proteomics analysis was conducted using Quantibody, Luminex, and ELISA platforms. To reduce heterogeneous data complexity and remove redundant variables, unsupervised feature selection methods were applied. For clustering, machine learning approaches were used, and optimal cluster number confirmed by consensus clustering. Result(s): 198 SLE patients (median [IQR] age 46.7 [36.7, 56.3] years, 88.4% female, median SLEDAI2K 4 [2, 6], 52.5% with organ damage) and 37 sex/ethnicity-matched healthy subjects were recruited. 211 serum analytes were measured. Using unsupervised feature selection methods, we identified a reduced set of 10/211 analytes (MCP-1, GH, CTACK, HCC-1, CD14, ErbB3, E-Selectin, Trappin-2, Cathepsin S and IL-18). The dataset was then clustered, according to the analytes that remained after feature selection, using unsupervised machine learning approaches. k-means analysis produced a distinct result in terms of separability of two clusters that associated only in SLE (Figure 1), and was chosen as the final clustering algorithm. We analysed clinical parameters in patients categorised by these biomarker clusters, and found the clusters differed in clinical characteristics including organ damage (P = 0.04), proportion of patients with high ESR (P = 0.03), and SLEDAI2K (P = 0.08). Using

Preclinical validation of multiple therapeutic targets in mouse studies has not been followed by clinical trial success. Therefore, validationfirst in human SLE has arisen as a new paradigm. The first such target to be translated all the way via clinical trials to submission for approval is type I interferon (IFN). Innate immune mechanisms which evolved to support responses to viral infection, mediated by IFN, are activated by stimuli hypothesized to include nucleic acid immune complexes. Evidence of IFN activation in SLE includes highly reproducible IFN signature gene (ISG) expression in blood and affected tissues, albeit weakly associated with markers of disease activity. IFN is not primarily pathogenic in classic murine lupus models, but it exacerbates murine models of SLE and IFN treatment of other human diseases can induce SLE-like phenotypes. Together, these data supported trialling IFN-targeting treatments in SLE. Studies of antibodies to IFNalpha, and of a vaccine inducing neutralizing IFN antibodies, yielded mixed but overall supportive results. Importantly, three randomized trials of an antibody to the type I IFN receptor, which may cause greater suppression of ISG than other agents, showed reproducible efficacy across composite outcome measures, skin disease, and glucocorticoid tapering, although the primary outcome was not met in one of these trials. Safety issues identified include increased rates of herpes zoster, in line with expectations based on the mechanism of action, but overall suggest an acceptable benefit:risk profile. These findings confirm the role of IFN in the pathogenesis of SLE, solidyfing a key aspect of pathogenesis of lupus from theory to fact. The potential of treatments targeting this pathway to be transformative for SLE patients awaits regulatory approval.

Background/Purpose: The Lupus Low Disease Activity State (LLDAS) has recently undergone prospective longitudinal validation in a multinational cohort, demonstrating the association of attaining LLDAS with protection from damage accrual and fl are, results that have been replicated in numerous other observational cohorts. Domain 1 of the original LLDAS operational definition captured the absence of significant disease activity by requiring SLEDAI-2K <=4, the absence of SLEDAI activity in major organs, and also the absence of haemolytic anaemia (HA) and gastrointestinal (GI) activity, manifestations not accounted for in the SLEDAI-2K. The requirement for absence of these infrequent clinical features creates the potential to misclassify patients' LLDAS status, as there is no formal definition of HA and GI activity. This has in turn limited regulatory approval of LLDAS as a clinical trial endpoint. To determine the requirement for capture of HA and GI activity in the LLDAS definition we performed a sensitivity analysis. Method(s): We analysed the prospective LLDAS longitudinal validation dataset. To evaluate whether HA and GI activity were captured by the physician global assessment (PGA) criterion of LLDAS, we compared patients with and without HA and GI with respect to median PGA and the proportion of patients with PGA >1. The impact on subsequent damage accrual and fl are of time-dependent associations of criterion 1 of the LLDAS definition, with and without inclusion of HA and GI activity, were assessed using Cox regression analysis. Result(s): Data on 1,707 patients, with 12,689 visits over 2.2 years were analysed. HA and GI activity were recorded in 28 and 73 visits, respectively. The median PGA, and the proportion of patients with PGA >1, were significantly higher in patients with either HA or GI activity (Table 1). Omitting the requirement for absence of HA and GI activity from criterion 1 of the LLDAS definition had no meaningful impact on the protective associ

Systemic lupus erythematosus (SLE) is a more common autoimmune rheumatic disease in the Asia-Pacific region. The prognosis of SLE remains unsatisfactory in some Asian countries because of delayed diagnosis, limited access to medications, increased complications and issues of tolerability and adherence to treatment. The Asia-Pacific League of Associations for Rheumatology SLE special interest group has recently published a set of consensus recommendations on the management of SLE for specialists, family physicians, specialty nurses, and other healthcare professionals in the Asia-Pacific region. This article reports a systematic literature review of the infective complications of SLE in Asia and evidence for prevention of these infections by pre-emptive antimicrobial therapy and vaccination.Copyright © 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Background/Purpose: Metabolic syndrome (MetS) is a chronic pro-inflammatory and pro-thrombotic state associated with increased atherosclerosis, cardiovascular events and type 2 diabetes. It is diagnosed in the presence of at least 3 of 5 metabolic risk factors (obesity, hypertension, hypertriglyceridemia, low high-density lipoproteins (HDL) and insulin resistance [1]). The pathophysiology of MetS remains incompletely understood, but may share mechanisms with inflammatory states such as SLE. Visceral adiposity is known as a source of pro-inflammatory cytokines by adipocytes, the so-called adipokines. The contribution of glucocorticoids to the development of MetS in SLE is not clear, even though their use is associated with cardiovascular comorbidities [2]. We aim to characterize the prevalence and associations of MetS, including serum levels of adipokines, in a multi-ethnic cohort of patients with SLE. Method(s): Using a standardised protocol, baseline demographics, per visit disease activity (SLEDAI2K) and treatment data, and annual recording of organ damage accrual (SLICC damage index (SDI)) were prospectively captured on SLE patients from a single tertiary centre. The presence of MetS,defined using the updated joint consensus criteria [1], was assessed retrospectively at the last recorded visit. Serum levels of adipokines (resistin, lipocalin-2, TNF, MCP-1) and insulin were measured by Quantibody. Result(s): 116 patients (median (IQR) age at enrolment 39.5 (31.4-51.1) years, median disease duration 6.1 (1.4-12) years) were followed for a median of 6.7 (4.1-8.1) years. 80% of patients were exposed to glucocorticoids (median time-adjusted mean dose 3.7 (0.5-7.0) mg/day and 50% accrued organ damage during follow-up. The prevalence of MetS in this cohort was 29%. The prevalence of the components of MetS included: hypertension (59%), low-HDL (51%), hypertriglyceridemia (32%), obesity (16%) and hyperglycaemia (22%). In univariable analysis, MetS was associated with base