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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: 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: 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).

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.

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.

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: 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).

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.

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.

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 ©

Objective Disease severity in SLE is an important concept related to disease activity, treatment burden and prognosis. We set out to evaluate if high disease activity status (HDAS), based on ever attainment of a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) disease activity score of >=10, is an indicator for disease severity in SLE. Methods Using prospectively collected data, we assessed the association of HDAS with sociodemographic and disease characteristics and adverse clinical outcomes using logistic regression or generalised estimating equations. Results Of 286 patients with SLE, who were observed for a median (range) of 5.1 years (1-10.8 years), 43.7% experienced HDAS at least once during the observational period. Autoantibody positivity, particularly anti-dsDNA and anti-Sm positivity, were associated with increased likelihood of HDAS. Age >=45 years at diagnosis was associated with reduced likelihood of HDAS (p=0.002). Patients with HDAS had higher Physician Global Assessment score (>1: OR 8.1, p<0.001) and were more likely to meet criteria for flare (mild/moderate flare: OR 4.4, p<0.001; severe flare: OR 17.2, p<0.001) at the time of experiencing HDAS. They were also more likely to have overall higher disease activity, as defined by time-adjusted mean SLEDAI-2K score in the highest quartile (OR 11.7, 95% CI 5.1 to 26.6; p>0.001), higher corticosteroid exposure (corticosteroid dose in highest quartile: OR 7.7, 95% CI 3.9 to 15.3; p<0.001) and damage accrual (OR 2.3, 95% CI 1.3 to 3.9; p=0.003) when compared with non-HDAS patients. Conclusions HDAS is associated with more severe disease, as measured by higher disease activity across time, corticosteroid exposure and damage accrual. The occurrence of HDAS may be a useful prognostic marker in the management of SLE.Copyright © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Background: The utility of generic health-related quality of life (HRQoL) questionnaires in patients with systemic lupus erythematosus (SLE) is uncertain. We compared the performance of generic (SF36) and specific (SLEQOL) HRQoL surveys by examining their associations with the Global Rating of Change (GRC) and SLE clinical indicators. Method(s): The study included SLE patients who attended a single-center rheumatology clinic between 2013 and 2017. Patients completed both specific (SLEQOL) and generic (SF36) surveys and rated their GRC compared to the previous visit using a 7-point Likert scale on the same day of routine visits. Based on GRC scores, patients' change in HRQoL was categorized as "no change," "deterioration," or "improvement." Disease activity (SLEDAI-2K), flare, and lupus low disease activity state (LLDAS) were assessed at each visit, and organ damage (SDI) was determined annually. Pairwise correlations between SLEQOL and SF36 components were examined, and associations between GRC status and SLE disease indicators were compared using generalized estimating equations (GEE). Result(s): Three hundred thirty-seven patients with 2062 visits were included in the analysis. SLEQOL correlated significantly with SF36. Patients reported improvements in HRQoL in 58%, deterioration in 15%, and "no change" in 27% of all visits. Compared to the "no change" group, mean SF36 and SLEQOL scores were significantly lower in the deterioration group and higher in the improvement group. The magnitude of changes observed with SLEQOL and SF36 in the deterioration and improvement groups was similar. Patients in LLDAS had significantly higher mean scores in both SLEQOL and SF36. In contrast, patients with active disease, especially those with cutaneous, renal, central nervous system, and musculoskeletal activity, had significantly lower SLEQOL and SF36. Flare and organ damage were also associated with lower SLEQOL and SF36-PCS (physical component) but not with SF36-MCS (mental co

Objective Disease severity in SLE is an important concept related to disease activity, treatment burden and prognosis. We set out to evaluate if high disease activity status (HDAS), based on ever attainment of a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) disease activity score of >=10, is an indicator for disease severity in SLE. Methods Using prospectively collected data, we assessed the association of HDAS with sociodemographic and disease characteristics and adverse clinical outcomes using logistic regression or generalised estimating equations. Results Of 286 patients with SLE, who were observed for a median (range) of 5.1 years (1-10.8 years), 43.7% experienced HDAS at least once during the observational period. Autoantibody positivity, particularly anti-dsDNA and anti-Sm positivity, were associated with increased likelihood of HDAS. Age >=45 years at diagnosis was associated with reduced likelihood of HDAS (p=0.002). Patients with HDAS had higher Physician Global Assessment score (>1: OR 8.1, p<0.001) and were more likely to meet criteria for flare (mild/moderate flare: OR 4.4, p<0.001; severe flare: OR 17.2, p<0.001) at the time of experiencing HDAS. They were also more likely to have overall higher disease activity, as defined by time-adjusted mean SLEDAI-2K score in the highest quartile (OR 11.7, 95% CI 5.1 to 26.6; p>0.001), higher corticosteroid exposure (corticosteroid dose in highest quartile: OR 7.7, 95% CI 3.9 to 15.3; p<0.001) and damage accrual (OR 2.3, 95% CI 1.3 to 3.9; p=0.003) when compared with non-HDAS patients. Conclusions HDAS is associated with more severe disease, as measured by higher disease activity across time, corticosteroid exposure and damage accrual. The occurrence of HDAS may be a useful prognostic marker in the management of SLE.Copyright © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Background: The utility of generic health-related quality of life (HRQoL) questionnaires in patients with systemic lupus erythematosus (SLE) is uncertain. We compared the performance of generic (SF36) and specific (SLEQOL) HRQoL surveys by examining their associations with the Global Rating of Change (GRC) and SLE clinical indicators. Method(s): The study included SLE patients who attended a single-center rheumatology clinic between 2013 and 2017. Patients completed both specific (SLEQOL) and generic (SF36) surveys and rated their GRC compared to the previous visit using a 7-point Likert scale on the same day of routine visits. Based on GRC scores, patients' change in HRQoL was categorized as "no change," "deterioration," or "improvement." Disease activity (SLEDAI-2K), flare, and lupus low disease activity state (LLDAS) were assessed at each visit, and organ damage (SDI) was determined annually. Pairwise correlations between SLEQOL and SF36 components were examined, and associations between GRC status and SLE disease indicators were compared using generalized estimating equations (GEE). Result(s): Three hundred thirty-seven patients with 2062 visits were included in the analysis. SLEQOL correlated significantly with SF36. Patients reported improvements in HRQoL in 58%, deterioration in 15%, and "no change" in 27% of all visits. Compared to the "no change" group, mean SF36 and SLEQOL scores were significantly lower in the deterioration group and higher in the improvement group. The magnitude of changes observed with SLEQOL and SF36 in the deterioration and improvement groups was similar. Patients in LLDAS had significantly higher mean scores in both SLEQOL and SF36. In contrast, patients with active disease, especially those with cutaneous, renal, central nervous system, and musculoskeletal activity, had significantly lower SLEQOL and SF36. Flare and organ damage were also associated with lower SLEQOL and SF36-PCS (physical component) but not with SF36-MCS (mental co

Objective Lupus is a complex, heterogeneous autoimmune disease that has yet to see significant progress towards more timely diagnosis, improved treatment options for short-Term and long-Term outcomes, and appropriate access to care. The Addressing Lupus Pillars for Health Advancement (ALPHA) project is the first step in establishing global consensus and developing concrete strategies to address the challenges limiting progress. Methods A Global Advisory Committee of 13 individuals guided the project and began barrier identification. Seventeen expert interviews were conducted to further characterise key barriers. Transcripts were analysed using Nvivo and a codebook was created containing a list of thematic a nodes' (topics) and their descriptions. Findings were used to develop a final survey instrument that was fielded to a diverse, international stakeholder audience to achieve broad consensus. Results Expert interviews identified lupus heterogeneity as the primary barrier hindering advancement. Subsequent barriers were categorised into three areas: (1) Drug development. (2) Clinical care. (3) Access and value. The global survey received 127 completed responses from experts across 20 countries. Respondents identified barriers as high priority including the lack of biomarkers for clinical and drug development use, flawed clinical trial design, lack of access to clinicians familiar with lupus, and obstacles to effective management of lupus due to social determinants of care. Respondents also identified 30 autoimmune conditions that may be lupus-related based on overlapping features, shared autoantibodies and pathophysiology. Conclusions ALPHA is a comprehensive initiative to identify and prioritise the continuum of challenges facing people with lupus by engaging a global audience of lupus experts. It also explored views on lupus as a spectrum of related diseases. Conclusions from this effort provide a framework to generate actionable approaches to the identified high-p

Psychological distress has long been suspected to influence cancer incidence and mortality. It remains largely unknown whether and how stress affects the efficacy of anticancer therapies. We observed that social defeat caused anxiety-like behaviors in mice and dampened therapeutic responses against carcinogen-induced neoplasias and transplantable tumors. Stress elevated plasma corticosterone and upregulated the expression of glucocorticoid-inducible factor Tsc22d3, which blocked type I interferon (IFN) responses in dendritic cell (DC) and IFN-gamma+ T cell activation. Similarly, close correlations were discovered among plasma cortisol levels, TSC22D3 expression in circulating leukocytes and negative mood in patients with cancer. In murine models, exogenous glucocorticoid injection, or enforced expression of Tsc22d3 in DC was sufficient to abolish therapeutic control of tumors. Administration of a glucocorticoid receptor antagonist or DC-specific Tsc22d3 deletion reversed the negative impact of stress or glucocorticoid supplementation on therapeutic outcomes. Altogether, these results indicate that stress-induced glucocorticoid surge and Tsc22d3 upregulation can subvert therapy-induced anticancer immunosurveillance.Copyright © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

Objective: To examine longitudinal associations of active lupus nephritis with organ damage accrual in patients with systemic lupus erythematosus (SLE). Method(s): This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score >0 units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate <50%/proteinuria >3.5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual. Result(s): Patients (N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p < 0.02). Active lupus nephritis was strongly associated with damage accrual in renal but not in non-renal organ domains (hazard ratios = 13.0 (95% CI: 6.58, 25.5) p < 0.001 and 0.96 (95% CI: 0.69, 1.32) p = 0.8, respectively). There was no effect of ethnicity on renal damage accrual, but Asian ethnicity was significantly associated with reduced non-renal damage accrual. Conclusion(s): Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated w

Objective Lupus is a complex, heterogeneous autoimmune disease that has yet to see significant progress towards more timely diagnosis, improved treatment options for short-Term and long-Term outcomes, and appropriate access to care. The Addressing Lupus Pillars for Health Advancement (ALPHA) project is the first step in establishing global consensus and developing concrete strategies to address the challenges limiting progress. Methods A Global Advisory Committee of 13 individuals guided the project and began barrier identification. Seventeen expert interviews were conducted to further characterise key barriers. Transcripts were analysed using Nvivo and a codebook was created containing a list of thematic a nodes' (topics) and their descriptions. Findings were used to develop a final survey instrument that was fielded to a diverse, international stakeholder audience to achieve broad consensus. Results Expert interviews identified lupus heterogeneity as the primary barrier hindering advancement. Subsequent barriers were categorised into three areas: (1) Drug development. (2) Clinical care. (3) Access and value. The global survey received 127 completed responses from experts across 20 countries. Respondents identified barriers as high priority including the lack of biomarkers for clinical and drug development use, flawed clinical trial design, lack of access to clinicians familiar with lupus, and obstacles to effective management of lupus due to social determinants of care. Respondents also identified 30 autoimmune conditions that may be lupus-related based on overlapping features, shared autoantibodies and pathophysiology. Conclusions ALPHA is a comprehensive initiative to identify and prioritise the continuum of challenges facing people with lupus by engaging a global audience of lupus experts. It also explored views on lupus as a spectrum of related diseases. Conclusions from this effort provide a framework to generate actionable approaches to the identified high-p

Psychological distress has long been suspected to influence cancer incidence and mortality. It remains largely unknown whether and how stress affects the efficacy of anticancer therapies. We observed that social defeat caused anxiety-like behaviors in mice and dampened therapeutic responses against carcinogen-induced neoplasias and transplantable tumors. Stress elevated plasma corticosterone and upregulated the expression of glucocorticoid-inducible factor Tsc22d3, which blocked type I interferon (IFN) responses in dendritic cell (DC) and IFN-gamma+ T cell activation. Similarly, close correlations were discovered among plasma cortisol levels, TSC22D3 expression in circulating leukocytes and negative mood in patients with cancer. In murine models, exogenous glucocorticoid injection, or enforced expression of Tsc22d3 in DC was sufficient to abolish therapeutic control of tumors. Administration of a glucocorticoid receptor antagonist or DC-specific Tsc22d3 deletion reversed the negative impact of stress or glucocorticoid supplementation on therapeutic outcomes. Altogether, these results indicate that stress-induced glucocorticoid surge and Tsc22d3 upregulation can subvert therapy-induced anticancer immunosurveillance.Copyright © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

Objective: To examine longitudinal associations of active lupus nephritis with organ damage accrual in patients with systemic lupus erythematosus (SLE). Method(s): This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score >0 units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate <50%/proteinuria >3.5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual. Result(s): Patients (N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p < 0.02). Active lupus nephritis was strongly associated with damage accrual in renal but not in non-renal organ domains (hazard ratios = 13.0 (95% CI: 6.58, 25.5) p < 0.001 and 0.96 (95% CI: 0.69, 1.32) p = 0.8, respectively). There was no effect of ethnicity on renal damage accrual, but Asian ethnicity was significantly associated with reduced non-renal damage accrual. Conclusion(s): Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated w

Objectives Treat-to-target recommendations have identified 'remission' as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE. Methods An international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%. Results The task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions: 1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by ...................... (reference to symptoms, signs, routine labs). 2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment. 3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone <=5 mg/day), maintenance immunosuppressives and/or maintenance biologics. The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life. Conclusions The work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.Copyright © Publish

Objectives Treat-to-target recommendations have identified 'remission' as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE. Methods An international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%. Results The task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions: 1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by ...................... (reference to symptoms, signs, routine labs). 2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment. 3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone <=5 mg/day), maintenance immunosuppressives and/or maintenance biologics. The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life. Conclusions The work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.Copyright © Publish

Objective: Systemic lupus erythematosus (SLE), an autoimmune condition with diverse clinical manifestations, is reported to have different expression in populations of different ancestry. Most previous studies compared patients of different ethnic groups from geographically distinct cohorts. In our study, we aimed to characterize disease manifestations in patients of different ethnic groups from a single centre, and studied patterns of disease activity over time. Method(s): Demographics, baseline disease characteristics and autoantibody profiles, and disease activity (SLEDAI) measured at each visit, were captured from all consenting patients prospectively followed between 2007 and 2011 in an urban teaching hospital lupus clinic. Ethnicity was self-reported. Result(s): Asian ethnicity was significantly associated with more clinically severe SLE. Time-adjusted mean SLEDAI (p=0.01) and maximum SLEDAI (p=0.0018) were significantly higher in Asian patients. Asians were more likely to have renal disease (OR 2.9, 95% CI 1.4-5.98; p=0.004) and persistently active disease (PAD) (OR 2.14, 95% CI 1.05-4.38, p=0.04). Asian lupus patients also had a significantly higher proportion of autoantibody positivity to anti-dsDNA, anti-RNP, anti-Sm, anti-Ro and anti-La, as well as increased likelihood of hypocomplementaemia and immunosuppressant use. Conclusion(s): In this single-cohort study, Asian ethnicity was found to be associated with increased SLE disease activity. This suggests significant inter-ethnic genetic contributions to the regulation of autoimmune responses and disease severity in SLE.

Objective: Systemic lupus erythematosus (SLE), an autoimmune condition with diverse clinical manifestations, is reported to have different expression in populations of different ancestry. Most previous studies compared patients of different ethnic groups from geographically distinct cohorts. In our study, we aimed to characterize disease manifestations in patients of different ethnic groups from a single centre, and studied patterns of disease activity over time. Method(s): Demographics, baseline disease characteristics and autoantibody profiles, and disease activity (SLEDAI) measured at each visit, were captured from all consenting patients prospectively followed between 2007 and 2011 in an urban teaching hospital lupus clinic. Ethnicity was self-reported. Result(s): Asian ethnicity was significantly associated with more clinically severe SLE. Time-adjusted mean SLEDAI (p=0.01) and maximum SLEDAI (p=0.0018) were significantly higher in Asian patients. Asians were more likely to have renal disease (OR 2.9, 95% CI 1.4-5.98; p=0.004) and persistently active disease (PAD) (OR 2.14, 95% CI 1.05-4.38, p=0.04). Asian lupus patients also had a significantly higher proportion of autoantibody positivity to anti-dsDNA, anti-RNP, anti-Sm, anti-Ro and anti-La, as well as increased likelihood of hypocomplementaemia and immunosuppressant use. Conclusion(s): In this single-cohort study, Asian ethnicity was found to be associated with increased SLE disease activity. This suggests significant inter-ethnic genetic contributions to the regulation of autoimmune responses and disease severity in SLE.