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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.

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.

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).