The SLE-DAS provides an accurate and feasible flare tool in the clinical setting: a validation study.

OBJECTIVE: To assess the criterion validity of the SLE disease activity score (SLE-DAS) flare tool and compare its performance in identifying flares against other instruments. METHODS: Patients with SLE fulfilling SLE-DAS low disease activity at baseline were included from two academic lupus clinics. During follow-up, flares were identified by the senior attending clinician, applying the expert-consensus-based definition as gold-standard. The first clinical flare from flaring patients, and the first visit after baseline in patients without flares were analysed. In each no flare/flare visits, we assessed flares by SLE-DAS (score increase ≥1.72), classic-SELENA Flare Index (c-SELENA FI), revised-SELENA FI (r-SELENA FI), and SLEDAI-2K (score increase ≥4). We estimated the sensitivity, specificity, and Cohen's Kappa agreement of each flare tool against the gold-standard. RESULTS: A total of 442 patients were included and followed-up for 22.9 (14.2) months. Incidence of flares was 8.19/100 patient-years, with 69 patients experiencing flares. The SLE-DAS identified 96.6% of the expert-defined flares implying a treatment change and classified 28.0% of those as moderate/severe. Sensitivity and specificity for the gold-standard flare definition were: SLE-DAS 97.1% and 97.3%, c-SELENA FI 88.4% and 98.1%, r-SELENA FI 88.4% and 96.8%, SLEDAI-2K 56.5% and 99.2%, respectively. Kappa coefficients of these instruments were 0.902 (95% CI: 0.847, 0.957), 0.870 (95% CI: 0.805, 0.935), 0.832 (95% CI: 0.761, 0.903), and 0.663 (95% CI: 0.557, 0.769), respectively. The number of flare misclassifications was lowest with the SLE-DAS, and highest with the SLEDAI-2K. CONCLUSION: The SLE-DAS accurately identifies and categorizes flares as mild or moderate/severe. It is feasible and, thus, may help the physicians' treatment decisions in the clinical practice setting.

What is the best instrument to measure disease activity in SLE? - SLE-DAS vs Easy BILAG.

Systemic lupus erythematosus (SLE) is a heterogeneous condition making assessment of disease activity challenging. However, thorough assessment is essential to evaluate patients longitudinally, to guide therapeutic decisions, and for clinical trials. Currently, the most popular disease activity index in clinical practice and trials is SLEDAI-2K. Its main advantage is ease of use, but significant weaknesses of SLEDAI-2K are omission of several serious manifestations, inability to capture change within an organ system, and fixed severity weightings that are often inappropriate. Recently several groups have developing improved tools. We report here the debate held at CORA meeting on this issue. SLE-DAS includes 17 weighted clinical and laboratory parameters including continuous measures in 4 items with an online calculator. A higher sensitivity to change compared to SLEDAI-2K has been demonstrated in its validation studies. Easy BILAG is an improved format of the BILAG-2004 that retains its content but greatly simplified. Its scoring using a single-page form that incorporates concise definitions for key terms next to clinical items. Easy-BILAG demonstrates higher accuracy and less variability and increased and better user feedback compared to the standard BILAG-2004 format. Both the indices discussed at CORA showed an advantage in measuring disease activity compared to SLEDAI.

EULAR recommendations for the management of systemic lupus erythematosus: 2023 update.

OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence. METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item. RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease. CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.

Creation and Validation of the European Portuguese Version of the Systemic Lupus Erythematous Quality of Life Questionnaire.

(1) Background: Patients with systemic lupus erythematous (SLE) experience profound effects on health-related quality of life (HRQoL) that cannot be explained by objective indicators of mortality and morbidity. This study aimed to adapt the SLE Quality of Life (SLEQoL) questionnaire to the European Portuguese population and to assess its reliability and validity for patients with SLE. (2) Methods: Two independent translators translated the original version of the SLEQoL questionnaire into Portuguese. A back-translated version was produced. The Portuguese version of the questionnaire was reviewed and tested for validity and reliability. Cronbach's alpha and the internal validity index were calculated to verify the internal reliability and validity of the content. Rheumatologists filled out the SLE Disease Activity Score (SLE-DAS) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index SLICC/ACR-DI questionnaires. (3) Results: This study involved 180 patients, of which 93.8% were females. The results indicated very high internal consistency reliability (α = 0.949), low correlations between the SLEQoL and the SLE-DAS, a correlation between all SLEQoL dimensions and all SF-36 dimensions (except for "response to treatment" and "self-image"), and good correlation scores with both the EQ-5D-5L index and VAS. (4) Conclusion: The Portuguese version of the SLEQoL questionnaire is valid and reliable for the measurement of HRQoL in SLE patients.

Antimalarial treatment and minimizing prednisolone are associated with lower risk of infection in SLE: a 24-month prospective cohort study.

INTRODUCTION/OBJECTIVES: Infections are a major cause of morbidity and death in systemic lupus erythematosus (SLE). Perfecting the understanding of contributors to infection burden in SLE is pivotal to improve management and outcomes. This study aims to identify clinical predictors of infection in SLE. METHOD: We conducted a prospective cohort study at a referral SLE clinic. Infections were identified at each visit and categorized as (a) any type, (b) serious, (c) non-serious, and (d) bacterial. Survival analysis followed by multivariate Cox regression with an estimation of hazard ratios (HR) with 95% confidence intervals (95%CI) was performed. RESULTS: We included 259 patients during a mean follow-up of 23.3 ± 5.7 months. The incidence rate of infection of any type was 59.3 cases per 100 patient-years. Multivariate Cox models showed that (a) prednisolone ≥ 7.5 mg/day (HR = 1.95, 95%CI 1.26-3.03) and female gender (HR = 2.08, 95%CI 1.12-3.86) were associated with higher risk of infection of any type; (b) prednisolone ≥ 10 mg/day was associated with higher (HR = 4.32, 95%CI 1.39-13.40), and antimalarials with lower risk (HR = 0.18, 95%CI 0.06-0.51) of serious infection; (c) female gender (HR = 1.92, 95%CI 1.04-3.57) and prednisolone ≥ 7.5 mg/day (HR = 1.89, 95%CI 1.21-2.96) were associated with higher risk of non-serious infection; (d) antimalarials were associated with lower (HR = 0.49, 95%CI 0.26-0.93) and female gender (HR = 5.12; 95%CI 1.62-16.18) with higher risk of bacterial infection. CONCLUSIONS: The risk of infection was higher in females in this young, well-controlled, low-comorbidity SLE cohort. Antimalarials were associated with lower and prednisolone ≥ 7.5 mg with higher risk of infection. Key Points • Lupus patients treated with prednisolone ≥ 7.5 mg/day were 89% more likely to present infections. • Lupus patients receiving prednisolone ≥ 10 mg/day were four times more likely to present serious infections. • Lupus patients receiving antimalarials were 82% less likely to present serious infections.

Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) enables accurate and user-friendly definitions of clinical remission and categories of disease activity.

OBJECTIVES: There is an unmet need for accurate and user-friendly definitions of systemic lupus erythematosus (SLE) disease activity and remission. We aimed to derive and validate the SLE Disease Activity Score (SLE-DAS) definitions for disease activity categories and clinical remission state. METHODS: Derivation was conducted at Padova Lupus Clinic (Italy). Validation was prospectively performed at Cochin Lupus Clinic (France) and by post hoc analysis of BLISS-76 trial. At each clinic, an expert classified patients in three categories: remission, mild or moderate/severe activity. The SLE-DAS cut-offs were derived using the receiver operating characteristic curve analysis in Padova cohort; its performance was assessed against expert classification in Cochin cohort and British Isles Lupus Assessment Group (BILAG) index in BLISS-76. Gold standard for clinical remission state was the fulfilment of Definition Of Remission In SLE. A Boolean and an index-based definitions of remission were sustained by chi-square automatic interaction detection algorithm. An SLE-DAS online calculator was developed and tested. RESULTS: We included 1190 patients with SLE: 221 in the derivation cohort and 969 in the validation cohorts (150 from Cochin; 819 from BLISS-76). Derived cut-offs were: remission, SLE-DAS ≤2.08; mild activity, 2.087.64. Regarding validation in Cochin cohort, sensitivity and specificity are above 90%, 82% and 95% for remission, mild and moderate/severe activity, respectively. The SLE-DAS Boolean-based and index-based remission showed sensitivity of 100% and specificity above 97%. CONCLUSION: The SLE-DAS is an accurate and easy-to-use tool for defining SLE clinical remission state and disease activity categories, validated against expert assessment and BILAG.

Derivation and validation of the SLE Disease Activity Score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity.

OBJECTIVES: To derive and validate a new disease activity measure for systemic lupus erythematosus (SLE), the SLE Disease Activity Score (SLE-DAS), with improved sensitivity to change as compared with SLE Disease Activity Index (SLEDAI), while maintaining high specificity and easiness of use. METHODS: We studied 520 patients with SLE from two tertiary care centres (derivation and validation cohorts). At each visit, disease activity was scored using the Physician Global Assessment (PGA) and SLEDAI 2000 (SLEDAI-2K). To construct the SLE-DAS, we applied multivariate linear regression analysis in the derivation cohort, with PGA as dependent variable. The formula was validated in a different cohort through the study of: (1) correlations between SLE-DAS, PGA and SLEDAI-2K; (2) performance of SLEDAI-2K and SLE-DAS in identifying a clinically meaningful change in disease activity (ΔPGA≥0.3); and (3) accuracy of SLEDAI-2K and SLE-DAS time-adjusted means in predicting damage accrual. RESULTS: The final SLE-DAS instrument included 17 items. SLE-DAS was highly correlated with PGA (r=0.875, p<0.0005) and SLEDAI-2K (r=0.943, p<0.0005) in the validation cohort. The optimal discriminative ΔSLE-DAS cut-off to detect a clinically meaningful change was 1.72. In the validation cohort, SLE-DAS showed a higher sensitivity than SLEDAI-2K (change ≥4) to detect a clinically meaningful improvement (89.5% vs 47.4%, p=0.008) or worsening (95.5% vs 59.1%, p=0.008), while maintaining similar specificities. SLE-DAS performed better in predicting damage accrual than SLEDAI-2K. CONCLUSION: SLE-DAS has a good construct validity and has better performance than SLEDAI-2K in identifying clinically significant changes in disease activity and in predicting damage accrual.

Differential male and female adrenal cortical steroid hormone and cortisol responses to interleukin-6 in humans.

Evidence from experimental animal studies show that sex hormones influence the glucocorticoid response to a variety of inflammatory and noninflammatory stimuli. In this study we assessed gender differences in the response of ACTH and cortisol in normal young male and female humans following intravenous infusion of human IL-6 in various dosages. Males presented a significantly stronger ACTH production in response to IL-6 than females. Peak cortisol response, however, was similar in males and females. Cortisol/ACTH ratios were significantly higher in females than in males, both at baseline and after each of the IL-6 dosages. These results suggest that an effective glucocorticoid response requires similar levels of IL-6 in males and females. However, they also suggest that the adrenals of males and females have different sensitivities to ACTH (higher in females) and possibly also to direct IL-6 stimulation.