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OBJECTIVE: In trials of systemic lupus erythematosus (SLE), the SLE Responder Index (SRI) is the most commonly used primary efficacy end point but has limited validation against long-term outcomes. We aimed to investigate associations of attainment of a modified version of the SRI (mSRI) with key clinical outcomes in SLE patients with up to 5 years of follow-up. METHODS: We used data from a large multicenter, longitudinal SLE cohort in which patients received standard of care. The first visit with active disease (defined as SLE Disease Activity Index 2000 [SLEDAI-2K] score ≥6) was designated as baseline, and mSRI attainment (defined as a reduction in SLEDAI-2K ≥4 points with no worsening in physician global assessment ≥0.3 points) was determined at annual intervals from baseline up to 5 years. Associations between mSRI attainment and outcomes including disease activity, glucocorticoid dose, flare, damage accrual, Lupus Low Disease Activity State (LLDAS), and remission were studied. RESULTS: We included 2,060 patients, with a median baseline SLEDAI-2K score of 8. An mSRI response was attained by 56% of patients at 1 year, with similar responder rates seen at subsequent annual time points. Compared to nonresponders, mSRI responders had significantly lower disease activity and prednisolone dose and higher proportions of LLDAS and remission attainment at each year, and less damage accrual at years 2 and 3. Furthermore, mSRI responder status at 1 year predicted clinical benefit at subsequent years across most outcomes, including damage accrual (odds ratio [OR] range 0.58-0.69, P < 0.05 for damage accrual ORs at all time points). CONCLUSION: In SLE patients with active disease receiving standard of care, mSRI attainment predicts favorable outcomes over long-term follow-up, supporting the clinical meaningfulness of SRI attainment as an SLE trial end point.

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 unmet need in systemic lupus erythematosus (SLE) with the current standard of care is widely recognised, but few studies have quantified this. The recent definition of treat-to-target endpoints and other thresholds of uncontrolled disease activity provide an opportunity to formally define unmet need in SLE. In this study, we enumerated the prevalence of these states and examined their association with adverse outcomes. Method(s): Data were collected prospectively in a 13-country longitudinal SLE cohort between 2013 and 2019. Unmet need was defined as never attaining lupus low disease activity state (LLDAS), a time-adjusted mean SLEDAI-2K (AMS) > 4, or ever experiencing high disease activity status (HDAS; SLEDAI-2K >=10). Health-related quality of life (HRQoL) was assessed using SF36 (v2) and damage accrual using the SLICC-ACR SLE Damage Index (SDI). Result(s): A total of 3384 SLE patients were followed over 30,313 visits (median [IQR] follow-up 2.4 [0.4, 4.3] years). Eight hundred thirteen patients (24%) never achieved LLDAS. Median AMS was 3.0 [1.4, 4.9]; 34% of patients had AMS > 4. Twenty-five per cent of patients had episodes of HDAS. Each of LLDAS-never, AMS>4, and HDAS-ever was strongly associated with damage accrual, higher glucocorticoid use, and worse HRQoL. Mortality was significantly increased in LLDAS-never (adjusted HR [95% CI] = 4.98 [2.07, 12.0], p<0.001) and HDAS-ever (adjusted hazard ratio (HR) [95% CI] = 5.45 [2.75, 10.8], p<0.001) patients. Conclusion(s): Failure to achieve LLDAS, high average disease activity, and episodes of HDAS were prevalent in SLE and were significantly associated with poor outcomes including organ damage, glucocorticoid exposure, poor quality of life, and mortality.Copyright © 2022, The Author(s).

BACKGROUND: The unmet need in systemic lupus erythematosus (SLE) with the current standard of care is widely recognised, but few studies have quantified this. The recent definition of treat-to-target endpoints and other thresholds of uncontrolled disease activity provide an opportunity to formally define unmet need in SLE. In this study, we enumerated the prevalence of these states and examined their association with adverse outcomes. METHODS: Data were collected prospectively in a 13-country longitudinal SLE cohort between 2013 and 2019. Unmet need was defined as never attaining lupus low disease activity state (LLDAS), a time-adjusted mean SLEDAI-2K (AMS) > 4, or ever experiencing high disease activity status (HDAS; SLEDAI-2K ≥10). Health-related quality of life (HRQoL) was assessed using SF36 (v2) and damage accrual using the SLICC-ACR SLE Damage Index (SDI). RESULTS: A total of 3384 SLE patients were followed over 30,313 visits (median [IQR] follow-up 2.4 [0.4, 4.3] years). Eight hundred thirteen patients (24%) never achieved LLDAS. Median AMS was 3.0 [1.4, 4.9]; 34% of patients had AMS > 4. Twenty-five per cent of patients had episodes of HDAS. Each of LLDAS-never, AMS>4, and HDAS-ever was strongly associated with damage accrual, higher glucocorticoid use, and worse HRQoL. Mortality was significantly increased in LLDAS-never (adjusted HR [95% CI] = 4.98 [2.07, 12.0], p<0.001) and HDAS-ever (adjusted hazard ratio (HR) [95% CI] = 5.45 [2.75, 10.8], p<0.001) patients. CONCLUSION: Failure to achieve LLDAS, high average disease activity, and episodes of HDAS were prevalent in SLE and were significantly associated with poor outcomes including organ damage, glucocorticoid exposure, poor quality of life, and mortality.

Systemic lupus erythematosus (SLE) is prevalent in Asia and carries a variable prognosis among patients across the Asia-Pacific region, which could relate to access to health care, tolerability of medications, and adherence to therapies. Because many aspects of SLE are unique among patients from this region, the Asia-Pacific League of Associations for Rheumatology developed the first set of consensus recommendations on the management of SLE. A core panel of 13 rheumatologists drafted a set of statements through face-to-face meeting and teleconferences. A literature review was done for each statement to grade the quality of evidence and strength of recommendation. 29 independent specialists and three patients with SLE were then recruited for a modified Delphi process to establish consensus on the statements through an online voting platform. A total of 34 consensus recommendations were developed. Panellists agreed that patients with SLE should be referred to a specialist for the formulation of a treatment plan through shared decision making between patients and physicians. Remission was agreed to be the goal of therapy, but when it cannot be achieved, a low disease activity state should be aimed for. Patients should be screened for renal disease, and hydroxychloroquine is recommended for all Asian people with SLE. Major organ manifestations of SLE should be treated with induction immunosuppression and subsequently maintenance; options include cyclophosphamide, mycophenolate mofetil, azathioprine, and calcineurin inhibitors, in combination with glucocorticoids. Biologics, combination regimens, plasma exchange, and intravenous immunoglobulins should be reserved for cases of refractory or life-threatening disease. Anticoagulation therapy with warfarin is preferred to the direct oral anticoagulants for thromboembolic SLE manifestations associated with a high-risk antiphospholipid antibody profile.Copyright © 2021 Elsevier Ltd

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.

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.