Actigraphic and self-reported characterization of sleep in systemic lupus erythematosus patients.

OBJECTIVES: In a cross-sectional study, we explored possible differences in sleep parameters between SLE patients and age- and gender-matched healthy controls through actigraphic and self-reported measures. Furthermore, we aimed to identify possible predictors of such disturbances in the patient cohort. METHODS: Participants' sociodemographic data and sleep parameters were collected. Sleep parameters were evaluated through the Pittsburgh Sleep Quality Index, the Insomnia Severity Index and 7-day actigraphic monitoring. The 10-item Perceived Stress Scale was used to investigate stress. Disease activity and daily glucocorticoid dose were assessed in SLE patients. Possible predictors of the SLE group were explored through two binomial logistic models. Within the SLE group, possible predictors of sleep parameters were tested estimating multiple linear regression models. RESULTS: A total of 40 SLE patients and 33 controls were included in the study. The SLE group showed worse sleep maintenance actigraphic parameters (i.e. sleep efficiency and wake after sleep onset), higher total sleep time and higher perceived stress. Within the SLE cohort, the daily glucocorticoids dose was associated with an impairment in sleep maintenance despite no reduction in sleep duration, typical of normal sleep duration insomnia, whereas perceived stress was associated with short sleep duration insomnia. CONCLUSION: Compared with healthy controls, SLE patients showed worse sleep quality and greater perceived stress severity. As glucocorticoids and perceived stress are associated with different types of insomnia in these patients, a multidimensional approach to both sleep characterization and therapy might be preferred.

Which extra-renal flare is 'difficult to treat' in systemic lupus erythematosus? A one-year longitudinal study comparing traditional and machine learning approaches.

OBJECTIVES: To describe phenotypes and outcomes of extra-renal flares in SLE, to identify clusters of extra-renal flares based on baseline features, and to develop a machine learning (ML) tool capable of predicting 'difficult to treat' (D2T) flares. METHODS: Extra-renal flares that occurred in our cohort over the last five years with at least one year of follow-up were included. Baseline clinical variables were described and flares assigned to clusters. Attainment of remission and low disease activity state (LLDAS) at 12 months were compared. Flares were then considered 'D2T' in case of non-attainment of LLDAS at 6 and 12 months. Baseline features were used to train a ML model able to predict future D2T-flares, at admission. Traditional approaches were then compared with informatic techniques. RESULTS: Among 420 SLE patients of the cohort, 114 flares occurred between 2015 and 2021; 79 extra-renal flares, predominantly mucocutaneous (24.1%) and musculoskeletal (45.6%), were considered. After 12 months, 79.4% and 49.4% were in LLDAS and in remission, respectively, while 17 flares were classified as D2T (21.5%); D2T flares received a higher cumulative and daily dose of glucocorticoids. Among the clusters, cluster 'D' (mild-moderate flares with mucocutaneous manifestations in patients with history of skin involvement) was associated with the lowest rate of remission. Among clinical data, not being on LLDAS at 3 months was the unique independent predictor of D2T flares. CONCLUSIONS: Our clusterization well separates extra-renal flares according to their baseline features and may propose a new identification standard. D2T flares, especially refractory skin manifestations, are frequent in SLE and represent an unmet need in the management of the disease as they are associated with higher glucocorticoid (GC) dosage and risk of damage accrual. Our ML model could help in the early identification of D2T flares, flagging them to elevate the attention threshold at admission.

Anifrolumab In Refractory Systemic Lupus Erythematosus: A Real-Life, Multicenter Study.

OBJECTIVE: To report the real-world experience on the use of ANI in refractory SLE. METHODS: Multicenter retrospective study involving 9 Italian SLE referral centers participating in a compassionate use program for the use of ANI in active adult SLE patients in whom all the available treatment choices failed, were not tolerated or contraindicated.At baseline, at 1, 3, 6, 9 and 12 months of treatment, overall and organ specific disease activity, flares, daily glucocorticoid (GC) dose, and adverse events were recorded. RESULTS: A total of 26 patients were enrolled. At 4 weeks after starting ANI, a significant decrease in SLEDAI-2K (p=0.005), SLEDAS (p=0.005) and PGA (p=0.001) was recorded, and the same trend was maintained over time. A significant reduction in CLASI-activity (p<0.001) and in tender (p=0.026) and swollen (p=0.017) joint count was also recorded. At 3 months of follow-up, 33% of patients already achieved a remission state, while 46% were in LLDAS; at 6 months, 50% were in remission and 80% in LLDAS. A significant reduction in the mean GC daily dose was observed, starting from week 4 (p=0.04). A total of 4 disease flares according to the SELENA-SLEDAI Flare Index were recorded (three mild-moderate and one severe). Overall, 4 out of 20 patients with at least 24 weeks of follow-up (20%) were considered "non responders". CONCLUSION: This study provides a real-world experience on the use of ANI in refractory SLE patients, confirming its rapid effectiveness and an overall acceptable safety profile.

Adherence to medication during pregnancy in systemic autoimmune diseases: results from a prospective study.

OBJECTIVES: To evaluate adherence to medication in patients with systemic autoimmune diseases (SAD), comparing pregnant and non-pregnant women. METHODS: 200 patients with SAD were consecutively enrolled, 100 pregnant and 100 non-pregnant women. Each patient completed the 8-item Morisky Medication Adherence Scale (MMAS-8), one copy for hydroxychloroquine (HCQ) and one for other treatments for rheumatic disease, and Hospital Anxiety and Depression Scale (HADS). RESULTS: No significant differences were found in ongoing therapies between pregnant and non-pregnant women. 148 patients (74.0%) were taking HCQ and 160 (80.0%) other therapies for rheumatic disease. The mean MMAS-8 score was >6 in all groups indicating a good adherence, on average. The rate of patients with good medication adherence was higher in pregnant patients (73.9% vs. 63.3% and 76.5% vs. 64.5%, for HCQ and other therapies, respectively) although this difference was not statistically significant. Eight patients had very poor medical adherence, and all were non-pregnant women. Anxiety (15% of patients) was associated to low medication adherence for drugs other than HCQ (p=0.02), while depression (4% of patients) did not seem to have an impact on adherence. CONCLUSIONS: In our cohort we recorded a good adherence to prescribed medication, although adequate adherence was not achieved in about 30% of patients, confirming that non-adherence is an important issue in SAD. It is difficult to define a profile of patients at risk of poor adherence, but it appears important to implement communication and adherence monitoring strategies since strict monitoring also during pregnancy could improve medical adherence.

Environment and systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations and a relapsing-remitting course. SLE pathogenesis is the result of complex interactions between ethnic, genetic, epigenetic, immunoregulatory, hormonal and environmental factors, and several aspects of these multifactorial connections are still unclear. Overall, for the disease development, an environmental trigger may induce immunological dysfunction in genetically predisposed individuals. This review aims to summarise the most relevant data on the impact of environmental factors on the incidence of SLE and on disease activity and damage in patients with an established diagnosis of SLE.

Systemic lupus erythematosus: one year in review 2024.

Systemic lupus erythematosus (SLE) is classically regarded as the landmark of systemic autoimmune diseases, characterised by protean, multi-systemic manifestations and a highly variable clinical course.Over the last years, both clinical and translational clinical research efforts led to significant steps forward in management and treatment of SLE. However, numerous aspects of SLE, from pathogenesis to treatment, still remain challenging, and several unmet needs persist for both patients and physicians. Following the previous annual reviews of this series, herewith, we aim to report the most relevant new updates on SLE, issued in 2023. In particular, we focused on biomarkers, clinical aspects and outcomes, comorbidities, as well as new treatment targets and real-world evidence.

Post-traumatic stress disorder and post-traumatic stress symptoms in patients with systemic autoimmune diseases during the COVID-19 pandemic.

OBJECTIVES: The COVID-19 outbreak led to an increase in mental disorders, particularly post-traumatic stress disorder (PTSD), in the general population and especially in high-risk populations such as patients with rheumatologic conditions. Although these latters are considered vulnerable to developing PTSD, few specific data have been particularly reported in the framework of the pandemic. The aim of the present study was to investigate PTSD and post-traumatic stress symptoms (PTSS) in a sample of patients with systemic autoimmune disease (SAD), followed in the framework of a prospective observational study during the pandemic. METHODS: The PERMAS project is a prospective observational study including patients with SAD and involving the Rheumatology and the Psychiatric Clinics of the Azienda Ospedaliero Universitaria Pisana (AOUP, Pisa, Italy) and the Institute of Management of the Scuola Superiore Sant'Anna (Pisa, Italy). The assessments included: a data-sheet for sociodemographic and clinical characteristics; the Trauma and Loss Spectrum-Self Report (TALS-SR) and the Impact of Event Scale-Revised (IES-R), for PTSD and PTSS; the 36-item Short Form Survey (SF-36) to assess quality of life. RESULTS: The total sample consisted of 252 patients with SAD, including 131 with connective tissue disease, 101 with arthritis and 20 with systemic vasculitis. The diagnostic groups differed significantly in age (p<0.001), gender (p<0.001), prevalence of full-blown and partial PTSD (p=0.001), and other psychopathologic variables. Connective tissue disease and SF-36 were significantly associated with the TALS-SR scores in both univariate (p<0.001) and multivariate (p<0.025; p<0.001) analyses. CONCLUSIONS: Patients with SAD, and, in particular, patients with connective tissue diseases reported an increased risk of developing stress-related psychopathological symptoms, indicating the need for special psychological monitoring of this high-risk group.

Systemic lupus erythematosus: one year in review 2023.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations and a relapsing-remitting course. New data regarding pathogenic pathways, biomarkers and clinical manifestations of SLE are emerging, and new drugs and therapeutic protocols have been proposed to improve the control of disease activity. Furthermore, new insights into comorbidities and reproductive health in SLE patients are constantly emerging.This annual review aims to summarise the most relevant data on SLE that was published in 2022.

Similarities and differences between younger and older disease onset patients with newly diagnosed systemic lupus erythematosus.

OBJECTIVES: Several studies show that age at onset has an impact on the clinical-serological presentation, comorbidities and disease course of patients with systemic lupus erythematosus (SLE). We evaluated whether, in patients with recent onset SLE, the age at onset correlates with clinical-serological manifestations and with comorbidities. METHODS: We analysed 171 patients with a SLE diagnosis obtained within 12 months of diagnosis enrolled in the Early Lupus project. Based on the age of onset of the first disease symptom, they were stratified into 2 groups: early onset (18-45 years) and late onset (>45 years). The analysis was replicated by stratifying patients based on age at diagnosis (fulfillment of ACR classification criteria). Each comparison was made at baseline and at 36 months of follow-up. RESULTS: Baseline: patients with late onset displayed comorbidities (hypertension, dyslipidemia and osteoporosis) more frequently than early onset group. 11.4% of late onset patients had a malignancy in medical history, not recorded in the early onset cohort. The two groups differed neither in organ involvement (domain BILAG) nor in disease activity (ECLAM). Patients with early onset showed a disease with signs of higher serologic activity (higher frequency of anti-dsDNA positivity and lower mean C3 and C4 levels) and had malar rash more frequently than the late onset group (36.2% vs. 18.2%, p=0.042). Similar results were obtained by stratifying patients by age of diagnosis (18-45 years and >45 years), except for the higher frequency of discoid rash in the group with age at diagnosis >45 years (18% vs. 6.6%, p=0.045). 36 months: the 2 groups of patients independently of the stratification applied did not differ in the accumulation of damage, but showed a different pattern of 8 organ involvement. Musculoskeletal involvement was more frequent both in the late onset group (18.6% vs. 7.3%, p=0.043) and in the group with age at diagnosis >45 years (20.4% vs. 5.9%, p=0.009) compared to their counterparts, while renal involvement was more frequent in the group with age at diagnosis 18-45 years (21.4% vs. 6.1%, p=0.03).A sub analysis at 36 months on patients without hypertension and osteoporosis at enrollment showed that patients with older age at onset had a higher frequency of these comorbidities, compared to their counterparts. CONCLUSIONS: In our cohort, younger disease SLE onset seems to correlate with a more active immunological profile, while late onset with a higher incidence of comorbidities.

ERN ReCONNET points to consider for treating patients living with autoimmune rheumatic diseases with antiviral therapies and anti-SARS-CoV-2 antibody products.

Recent studies have shown that people who are immunocompromised may inadvertently play a role in spurring the mutations of the virus that create new variants. This is because some immunocompromised individuals remain at risk of getting COVID-19 despite vaccination, experience more severe disease, are susceptible to being chronically infected and remain contagious for longer if they become infected and considering that immunocompromised individuals represent approximately 2% of the overall population, this aspect should be carefully considered. So far, some autoimmune rheumatic disease (ARD) patients with COVID-19 have been treated with antiviral therapies or anti-SARS-CoV-2 antibody products. However, there is no homogeneous approach to these treatment strategies. This issue was addressed within the European Reference Network (ERN) on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ReCONNET) in a discussion among experts and patient's representatives in the context of the rare and complex connective tissue diseases (rCTDs) covered by the Network. ERN ReCONNET is one of the 24 ERNs launched by the European Commission in 2017 with the aim of tackling low prevalence and rare diseases that require highly specialised treatment and promoting concentration of knowledge and resources through virtual networks involving healthcare providers (HCPs) across the European Union (EU). Considering the urgent need to provide guidance not only to the rCTDs community, but also to the whole ARDs community, a multidisciplinary Task Force, including expert clinicians and European Patient Advocacy Group (ePAG) Advocates, was created in the framework of ERN ReCONNET with the aim of developing overarching principles (OP) and points-to-consider (PtC) on a homogenous approach to treat immunocompromised patients with ARDs (with a particular focus on CTDs) affected by COVID-19 using antiviral therapies and anti-SARS-CoV-2 antibody products. The present work reports the final OP and PtC agreed by the Task Force.

One year in review 2022: systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic multisystem auto-immune disease with extremely varied clinical manifestations and a complex pathogenesis. New insights in SLE about pathogenetic pathways, biomarkers, and data on clinical manifestations are progressively emerging, and new drugs and new therapeutic strategies have been proposed to improve the control of disease activity. Thus, this review is aimed to summarise the most relevant data about SLE emerged during 2021, following the previous annual review of this series.

Rare clinical manifestations in systemic lupus erythematosus: a review on frequency and clinical presentation.

OBJECTIVES: The purpose of this study was to review the frequency and clinical presentation of the rarest clinical manifestations of systemic lupus erythematosus (SLE). METHODS: A list of 6 rare SLE manifestations were defined: gastrointestinal, liver, pulmonary, cardiac, ocular and neurological manifestations. Each topic was assigned to a pair of authors to perform a literature search and article review. RESULTS: In total, 149 articles were included in the literature review: 37 for gastrointestinal manifestations, 6 for liver manifestations, 27 for pulmonary manifestations, 50 for cardiac manifestations, 16 for ocular manifestations, 13 for neurological manifestations. Gastrointestinal disorders included several clinical presentations with variable frequency (from 0.5% to 10.7% of the cases); liver involvement included lupus-related hepatitis (9.3%) and autoimmune hepatitis (2.3%). The rarest pulmonary manifestations identified were shrinking lung syndrome, described in 1.5% of patients, while interstitial lung disease and lupus pneumonia were reported in 4% and 3% of patients respectively. Myocarditis and pulmonary hypertension were also rarely described in SLE patients although ranging from 0.4-16% and 1-14% respectively, depending on the methodology used for its identification. Ocular manifestations in SLE included some rare manifestations (reported in less than 5% of patients) and lupus retinopathy that is described in 1.2-28.8% of patients depending on methods of ascertainment. Aseptic meningitis and chorea were also confirmed as very rare manifestations being reported in less than 1% and in 0.3-2.4% of cases respectively. CONCLUSIONS: The results of this literature review provide the basis for a better understanding of some less-known manifestations of SLE and for stressing the need for a higher awareness in diagnostic and therapeutic protocols regarding these rare disease aspects.

European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance.

BACKGROUND/OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. METHODS: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. RESULTS: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement. CONCLUSIONS: Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.

Durable renal response and safety with add-on belimumab in patients with lupus nephritis in real-life setting (BeRLiSS-LN). Results from a large, nationwide, multicentric cohort.

BACKGROUND: Belimumab was recently approved for treatment of lupus glomerulonephritis (LN). AIM: To evaluate renal response and its predictors in LN patients receiving belimumab in real-life. PATIENTS AND METHODS: We considered all patients fulfilling the SLEDAI-2K renal items and/or having estimated glomerular filtration rate (eGFR)≤60 ml/min/1.73 m2, with positive anti-dsDNA and/or low C3/C4 enrolled in the multicentre Italian lupus cohort BeRLiSS (BElimumab in Real LIfe Setting Study), treated with monthly IV Belimumab 10 mg/kg over standard treatment. Primary efficacy renal response (PERR), defined as proteinuria ≤0.7 g/24 h, eGFR≥60 ml/min/1.73 m2 without rescue therapy, was considered as primary outcome. Complete renal response (CRR; proteinuria <0.5 g/24 h, eGFR≥90 ml/min/1.73 m2) was considered as secondary outcome. Prevalence and predictors of PERR were evaluated at 6, 12, 24 months by multivariate logistic regression. RESULTS: Among the 466 SLE patients of BeRLiSS, 91 fulfilled the inclusion criteria, 79 females, median age 41.0 (33.0-47.0) years, median follow-up 22.0 (12.0-36.0) months. Sixty-four (70.3%) achieved PERR, of whom 38.4% reached CRR. Among patients achieving PERR at 6 months, 86.7% maintained response throughout the follow-up. At multivariable analysis, hypertension (OR [95%CI]: 0.28 [0.09-0.89], p = 0.032), high baseline serum creatinine (0.97 [0.95-0.99], p = 0.01) and high baseline proteinuria (0.37, [0.19-0.74], p = 0.005) negatively predicted PERR. Positive predictors of PERR at 12 and 24 months were baseline anti-Sm positivity (OR [95%CI]: 6.2 [1.21-31.7], p = 0.029; 19.8 [2.01-186.7], p = 0.009, respectively) and having achieved PERR at 6 months (14.4 [3.28-63.6]; 11.7 [2.7-48.7], p = 0.001 for both). CONCLUSIONS: Add-on therapy with belimumab led to durable renal response in patients with LN in a real-life setting.

Are remission and low disease activity state ideal targets for pregnancy planning in systemic lupus erythematosus? A multicentre study.

OBJECTIVES: To determine whether disease remission or low disease activity state at the beginning of pregnancy in SLE patients is associated with better pregnancy outcome. METHODS: Pregnancies in SLE patients prospectively monitored by pregnancy clinics at four rheumatology centres were enrolled. Patient demographics and clinical information were collected at baseline (pregnancy visit before 8 weeks of gestation) including whether patients were in remission according to the Definition of Remission in SLE (DORIS) criteria and and/or Lupus Low Disease Activity State (LLDAS). Univariate and multivariate analysis were performed to determine predictors of disease flare and adverse pregnancy outcomes (APOs) including preeclampsia, preterm delivery, small for gestational age infant, intrauterine growth restriction and intrauterine fetal death. RESULTS: A total of 347 pregnancies were observed in 281 SLE patients. Excluding early pregnancy losses, 212 pregnancies (69.7%) occurred in patients who were in remission at baseline, 33 (10.9%) in patients in LLDAS, and the remainder in active patients. Seventy-three flares (24%) were observed during pregnancy or puerperium, and 105 (34.5%) APOs occurred. Multivariate analysis revealed that patients in disease remission or taking HCQ were less likely to have disease flare, while a history of LN increased the risk. The risk of APOs was increased in patients with shorter disease duration, while being on HCQ resulted a protective variable. An almost significant association between complete remission and a decreased risk of APOs was observed. CONCLUSIONS: Prenatal planning with a firm treat-to-target goal of disease remission is an important strategy to reduce the risk of disease flares and severe obstetric complications in SLE pregnancies.

UCTD and SLE patients show increased levels of oxidative and DNA damage together with an altered kinetics of DSB repair.

Immunological tolerance is a critical feature of the immune system; its loss might lead to an abnormal response of lymphocytes causing autoimmune diseases. One of the most important groups belonging to autoimmune disorders is the connective tissue diseases (CTD). CTD are classified among systemic rheumatic diseases and include pathologies such as systemic lupus erythematosus (SLE), and undifferentiated CTD (UCTD). In this study, we evaluated oxidative and genome damage in peripheral blood lymphocytes from patients with SLE and UCTD, further classified on the basis of disease activity and the presence/absence of a serological profile. Oxidative damage was evaluated in cell membrane using the fluorescent fatty acid analogue BODIPY581/591 C11. The percentage of oxidised lymphocytes in both SLE and UCTD patients was higher than in the control group, and the oxidative stress correlated positively with both disease activity and autoantibody profile. The γH2AX focus assay was used to quantify the presence of spontaneous double strand breaks (DSBs), and to assess the abilities of DSBs repair system after T cells were treated with mitomycin C (MMC). Subjects with these autoimmune disorders showed a higher number of γH2AX foci than healthy controls, but no correlation with diseases activity and presence of serological profile was observed. In addition, patients displayed an altered response to MMC-induced DSBs, which led their peripheral cells to greatly increase apoptosis. Taken together our results confirmed an interplay among oxidative stress, DNA damage and impaired DNA repair, which are directly correlated to the aggressiveness and clinical progression of the diseases. We propose the evaluation of these molecular markers to better characterise SLE and UCTD, aiming to improve the treatment plan and the quality of the patients' life.

How do systemic lupus erythematosus patients with very-long disease duration present? Analysis of a monocentric cohort.

OBJECTIVE: to describe the disease path and the very long-term outcome in a monocentric cohort of patients with Systemic Lupus Erythematosus (SLE). METHODS: SLE patients with a disease duration of at least 15 years from diagnosis were enrolled. The number of hospitalizations, the disease flares occurred over the disease course and the organ damage accumulation were evaluated at 1, 2, 3, 4, 5, 10 years from diagnosis and at last observation in 2019 as well. Disease state, ongoing therapies and quality of life measures were also assessed at last visit. RESULTS: 126 Caucasian SLE patients were included in the analysis (95% female, median age 47.5 IQR 41-53, median disease duration 21 IQR19-26). At last visit, the majority of the patients (78.6%) was on LLDAS (remission included), 53.4% were on GC treatment and 35.7% on immunosuppressant. Furthermore, 53.2% had at least one organ damage. The majority of patients (66.7%) presented a relapsing-remitting course, for a total of 158 flares during the disease course (incidence rate: 0.79/patient-year); moreover, 84.9% of the cohort experienced at least one hospital admission, amounting to a total of 328 hospitalizations (incidence rate: 0.85/patient-year). The main reason for admission was disease activity, while the percentage of hospitalizations due to other causes has been growing over the 10 years of follow-up. CONCLUSION: after a very long period of disease, most of the patients with SLE are in remission and are not taking GC therapy; however, the risk of incurring in disease flare remains a real problem.

One year in review 2021: systemic lupus erythematosus.

In 2020 many contributions have been produced on SLE. Our critical digest of the recent literature will be focused on genetic factors that contribute to the development of the disease, novel potential therapeutic targets (including IL-23, IL-17, interferons and JAKs), diagnostic and prognostic biomarkers, classification criteria, clinical manifestations and comorbidities. We will then present new treatment options (with a special focus on belimumab, anifrolumab, tacrolimus, voclosporin and EULAR/ERA-EDTA recommendations for the management of LN) and treat-to-target strategy. Lastly, we will concentrate on some of the aspects that influence patients' disease perception and quality of life.

Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes and ethnicities.

OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. METHODS: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. RESULTS: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%). CONCLUSIONS: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.

The patient's perspective: are quality of life and disease burden a possible treatment target in systemic lupus erythematosus?

A few decades ago, the therapy goal of patients with systemic lupus erythematosus (SLE) was survival and the prevention of organ failure. Today, clinical remission and low disease activity are believed to be the optimal therapeutic targets. These aims are difficult to reach for many patients, but they still do not address the health-related quality of life (QoL) that is significantly impaired in SLE patients. Even in the state of remission, QoL and fatigue are insufficient controlled. Thus, patient-oriented research is essential to design new strategies for the management of lupus patients. The INTEGRATE project analyses the patients' and physicians' perspectives to pave the way to design an innovative therapeutic strategy for lupus and focuses on the multifaceted dimensions of the disease burden. Shared decision making (SDM) could include the patient's perspective of SLE to treatment strategy and consider QoL and the burden of lupus into the process of therapy decision.