Search

This review summarizes the recent developments about anti-MDA5 antibody positive dermatomyositis with a focus on its pathogenesis, clinical features and treatment options of rapidly progressive interstitial lung disease, its most ominous complication.Anti-MDA5+ dermatomyositis has a heterogeneous clinical spectrum with different patient subsets exhibiting widely different outcomes; severe acute interstitial lung disease is the main factor impacting prognosis. The pathogenetic role of anti-MDA5 antibodies is an active area of investigation.Anti-MDA5+ dermatomyositis has a wider spectrum of manifestations than previously thought. A high index of suspicion is needed not to miss atypical presentations. In the setting of acute interstitial lung involvement, once a confident diagnosis is made, an aggressive approach with early combined immunosuppression affords the best chances of survival.

The short and long-term outcomes of children with anti-Ro/La-related congenital heart block treated with a combined maternal-neonatal therapy protocol were compared with those of controls treated with other therapies.Sixteen mothers were treated during pregnancy with a therapy consisting of daily oral fluorinated steroids, weekly plasma exchange and fortnightly intravenous immunoglobulins and their neonates with intravenous immunoglobulins (study group); 19 mothers were treated with fluorinated steroids alone or associated to intravenous immunoglobulins or plasma exchange (control group).The combined-therapy children showed a significantly lower progression rate from 2nd to 3rd degree block at birth, a significant increase in heart rate at birth and a significantly lower number of pacemaker implants during post-natal follow-up with respect to those treated with the other therapies.The combined therapy produced better short and long term outcomes with respect to the other therapies studied.

Objectives We aimed at estimating the incidence and prevalence of SLE in northeastern Italy over the period 2012–20. Methods A retrospective population-based study was conducted in Veneto Region (4.9 million people) using the population registry, an administrative health database where all residents are recorded. Between 2012 and 2020, SLE prevalence was defined by a healthcare co-payment exemption for SLE (national registry code 028) or any hospital diagnosis of SLE (International Classification of Disease , Ninth Revision, Clinical Modification 710.0), whichever came first. Incident SLE was defined from 2013 to 2020 to exclude prevalent cases. Standardized incidence and prevalence rates were reported by age and sex. Results During the study period, we identified 4283 SLE patients (85% female), with 1092 incident cases. Across the study period, SLE standardized point prevalence increased from 63.5 (95% CI 61.2, 65.8) to 70.6 (95% CI 68.3, 73.0) per 100 000 residents, corresponding to an annual increment of 1.14% (P Conclusions Over the last decade, SLE prevalence has increased, while incidence has stably declined. In view of the introduction of new high-cost drugs, a clear definition of the epidemiology of SLE is crucial for all healthcare stakeholders.

Objectives To demonstrate that unsuccessful treatment optimization in early disease is associated with difficult-to-treat RA (D2T-RA). Methods In this retrospective multicentre cohort study conducted from 09/2021–03/2022, we enrolled individuals fulfilling the 2010 ACR/EULAR RA criteria diagnosed 2000–2019. The outcome was D2T-RA by the EULAR definition. We used robust regression to examine the associations with delay, dose, duration of methotrexate and discontinuation of glucocorticoids. We tested through multinomial regression which factors were associated with persistent inflammatory refractory RA (PIRRA) or non-inflammatory refractory RA (NIRRA). Sensitivity analysis included a case-control study matching the year of diagnosis. Results We enrolled 48 D2T-RA patients and 145 non-D2T-RA controls. Methotrexate was started within 3 months in 16.7% of D2T-RA vs 33.1% of non-D2T-RA (P = 0.011). Adequate duration of methotrexate was obtained in significantly fewer D2T-RA patients (70.8% vs 85.5%). Glucocorticoids were continued beyond 6 months in a higher proportion of D2T-RA patients (70.8% vs 33.8%, P Conclusion Failure to start methotrexate within 3 months and not being off glucocorticoids within 6 months are early predictive features of D2T-RA.

The aim of this study was to examine whether scar imaging echocardiography with ultrasound multi-pulse scheme (eSCAR) can detect subclinical myocardial involvement in systemic lupus erythematosus (SLE). We consecutively recruited SLE patients and controls matched for age, sex, and cardiovascular risk factors. Participants with cardiac symptoms or a prior history of heart disease were excluded. All participants underwent eSCAR and speckle tracking echocardiography (STE) with global longitudinal strain (GLS) assessment. SLE patients were assessed for disease activity and were followed up for 12 months. Myocardial scars by eSCAR were observed in 19% of SLE patients, almost exclusively localized at the inferoseptal myocardial segments, and in none of the controls. GLS was significantly lower in most myocardial segments of SLE patients compared with the controls, especially in the inferoseptal segments. eSCAR-positive SLE patients received a higher cumulative and current dose of prednisone, and had significantly higher levels of anti-dsDNA antibodies (p = 0.037). eSCAR-positive patients were at higher risk of having SLE flares over follow-up (hazard ratio: 4.91; 95% CI 1.43–16.83; p = 0.0001). We identified inferoseptal myocardial scars by eSCAR in about one-fifth of SLE patients. Subclinical myocardial involvement was associated with glucocorticoid use and anti-dsDNA antibodies.

The treat-to-target strategy has been recently suggested in the management of Systemic Lupus Erythematosus (SLE). Lupus Low Disease Activity State (LLDAS) and Definitions Of Remission In SLE (DORIS) remission were outlined as two concentric targets. The achievement of LLDAS was shown to be associated with lower frequency of SLE flare, decreased damage progression, better quality of life, and reduced mortality. In addition, LLDAS has successfully been tested in post-hoc analyses of a number of randomized controlled trials. However, it has been recently underlined that LLDAS includes a high proportion of patients in remission, raising the question if these endpoints are sufficiently distinct to consider their separation clinically relevant. Some studies suggest that the protective effect of LLDAS on damage might be due to the inclusion of patients who are in remission. Notably, clinical low disease activity (LDA) seems to be uncommon in SLE due to the relapsing-remitting pattern of the disease, in which low level of activity only occurs transiently. Moreover, since the domains included in LLDAS have several limitations, such as the use of a binomial disease activity index, the exclusion of some mild manifestations and the consideration of items subjected to variability (physician global assessment and glucocorticoids dose), not all patients in LDA are adequately represented by LLDAS.

Aim. To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE. Methods. All patients with skin and joint involvement enrolled in the BeRLiSS cohort were considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission (

Objective The withdrawal of oral anticoagulation (OAC) in patients with SLE and secondary aPL syndrome (SAPS) who become seronegative has not been clearly investigated to date. Our aim was to evaluate the prevalence of aPL seroconversion and the prognosis of SLE patients with SAPS who withdrew OAC after aPL negativization. Methods We retrospectively analysed data of all SLE patients (ACR criteria) with SAPS (Sydney criteria) prospectively followed-up in our clinic. aPL seroconversion was defined as negativization of lupus anticoagulant, aCL, and anti-β2glycoprotein-1 antibodies on two or more consecutive measurements, at least 12 weeks apart. OAC discontinuation was defined as the definitive withdrawal of all anticoagulants. Results Fifty-five out of 513 (10.7%) SLE patients had vascular SAPS. Sixteen patients (29.1%) became aPL seronegative during follow-up. Immunosuppressive therapy predicted aPL negativization (odds ratio 5.211, 95%CI 1.341, 20.243), whereas APS diagnosis prior to that of SLE (odds ratio 0.078, 95%CI 0.008, 0.799) and triple-positive profile (odds ratio 0.264, 95%CI 0.115, 0.609) were negative predictors of aPL negativization. OAC was discontinued in 13/55 patients (23.6%), after a median follow-up of 45 months (range 1–276) from aPL seroconversion. SLE-related modifiable risk factors for thrombosis were observed in 10/13 patients (77%) at the time of the thrombotic event. No thrombotic recurrences were observed during a mean follow-up time of 44 (19) months from OAC discontinuation. Conclusions Our results suggest that OAC can be safely discontinued in SLE patients who became persistently seronegative for aPL, at least when aPL-related thrombotic events occurred in presence of other thrombotic risk factors.

High plasma C5a and C5b-9 levels are considered a clear sign of complement activation. We aimed to evaluate the clinical significance of these two complement activation products during quiescent phases of thrombotic antiphospholipid syndrome (APS) by comparing their plasma levels in the different clinical subsets and relating them to the clinical characteristics and antiphospholipid antibody profile of the patients.The three patient subsets studied were: i) thrombotic patients responsive to anti-vitamin K therapy (TAPS); ii) patients with refractory to vitamin K antagonists recurrent thrombosis (RAPS); iii) patients diagnosed with catastrophic APS (CAPS). Plasma C5a and C5b-9 levels were assessed using commercial ELISA assays.Sixty-two quiescent APS patients were recruited: 40 were affected by TAPS, 13 by RAPS and 9 by CAPS. Data analysis showed that the TAPS patients had significantly lower levels of both complement activation products with respect to the RAPS and CAPS patients. In addition, C5a and/or C5b-9 significantly prevailed in the patients with small-vessel thrombosis, just as C5b-9 did in the triple antiphospholipid antibody positive patients. The ROC curve showed that the best cut-offs for C5a and C5b-9 levels had a higher sensitivity, specificity and likelihood ratio in the CAPS and RAPS groups than they did in the TAPS subset.These results suggest that the persistence of high plasma C5b-9 and C5a levels during quiescent phases identifies APS patients with more severe disease who may develop rethrombosis and benefit from complement inhibition treatment during an acute disease phase.

ObjectiveTo investigate second kidney biopsy as predictor of end-stage kidney disease (ESKD) in active lupus nephritis (LN).MethodsPatients with biopsy-proven LN (International Society of Nephrology/Renal Pathology Society 2003) who had undergone a second kidney biopsy between January 1990 and December 2018 were included. Clinical and histological findings at first and at second biopsy were analysed with Cox proportional hazard models to predict ESKD, defined as start of kidney replacement therapy. Survival curves were calculated with Kaplan-Meier method.ResultsNinety-two patients with LN were included, 87% females, mean follow-up 17.9±10.1 years. Reasons for second kidney biopsy encompassed nephritic flares (n=28, 30.4%), proteinuric flares (n=46, 50%) or lack of renal response (n=18, 19.5%). Class switch from first biopsy occurred in 50.5% of cases, mainly from non-proliferative towards proliferative classes. Class IV remained stable in over 50% of cases. Twenty-five patients (27.2%) developed ESKD, mostly belonging to the nephritic flare group (17/28, 60.7%). Independent predictors of ESKD at second biopsy were activity index (AI; (HR 95% CI) 1.20 (1.03 to 1.41), p=0.022), chronicity index (CI; 1.41 (1.09 to 1.82), p=0.008) and 24h-proteinuria (1.22 (1.04 to 1.42), p=0.013). AI≥2 (log-rank p=0.031), CI >4 (log-rank p=0.001) or proteinuria ≥3.5 g/day (log-rank=0.009) identified thresholds for higher ESKD risk. In a subgroup analysis, glomerular activity and tubular chronicity mostly accounted for AI and CI association with ESKD. No histological or laboratory predictors emerged at first biopsy (95% CI): AI: 0.88 to 1.19; CI: 0.66 to 1.20; proteinuria 0.85 to 1.08.ConclusionsFindings at second but not at first kidney biopsy in patients with persistently active or relapsing LN inform about ESKD development in a long-term follow-up.

Anti-COVID-19 vaccines have proved to be effective and well tolerated. Great attention is now being paid to the characterisation of possible adverse events associated to their administration. We report a case series of suspected rheumatic diseases (RDs) following anti-COVID-19 vaccination.We included patients evaluated at first-aid rheumatologic consultancy and at rheumatologic outpatient and inpatient clinic at Padova University Hospital between May and September 2021 presenting with a RD within 30 days after an anti-COVID-19 vaccine dose. Our selection was in accordance with the World Health Organisation guidelines for adverse event following immunisation (AEFI) surveillance. Patients were regularly re-evaluated by telemedicine or face-to-face visit.We identified 30 cases of RD following vaccination: 24 (80.0%) new onsets and 6 (20.0%) flares. Most of patients (76.6%) received the BNT162b2 vaccine. The mean time to RD onset/flare was 12±9 days. The most common manifestations were inflammatory arthritis (40.0%), rheumatic polymyalgia (33.3%) and adult-onset Still's disease (13.3%). At the last FU visit (9.6±2.2 months), 83.3% of patients showed complete response to first- or second-line therapy, 13.3% a partial response and one patient (3.3%) was still experiencing an active disease.Considering the amount of vaccine doses administered during the evaluation period we overall detected a limited number of cases. We noted a clear prevalence of autoinflammatory conditions and seronegative manifestations. The great majority of patients had mild features and showed a good response to therapy.

Introduction: Systemic Lupus Erythematosus (SLE) is a chronic B cell-mediated autoimmune disease which can potentially involve several organs and systems. The development of SLE is associated with ...

Objective To report baseline data of SLE patients enrolled in the Lupus Italian Registry (LIRE). Methods Patients affected by SLE aged ≥ 16 years were consecutively recruited in a multicenter prospective study comparing two cohorts: patients starting biologic immunosuppressants (BC) and patients starting non-biologic immunosuppresants (NBC). Results 308 patients were enrolled, 179 in NBC and 129 in BC. Mean age at disease onset and at diagnosis was significantly higher in NBC (p = 0.023, p = 0.045, respectively). Disease duration was longer in BC (p = 0.022). Patients in BC presented arthritis more frequently (p = 0.024), those in NBC nephropathy (p = 0.03). Quality of life was worse in BC (p = 0.031). Anti-dsDNA, low C3, were significantly more frequent in BC (p Conclusion The predominant organ involvement was different in the two cohorts: kidney involvement predominated in NBC, joint involvement in BC. Despite the younger age at disease onset, patients of the BC had a longer disease duration and more frequently had taken a cumulative prednisone dosage greater than 10 g. Even the pattern of clinical manifestations inducing to prescribe biological rather than conventional immunosuppressants was quite different. Keywords: Autoantibody(ies), autoimmune disease, belimumab, cohort studies, glucocorticoids, immunosuppressants, rituximab, systemic lupus erythematosus

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

ObjectivesThere 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.MethodsDerivation 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.ResultsWe 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%.ConclusionThe 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.

We read with interest the paper by Aranow et al 1 where physician’s global assessment (PGA) displayed excellent inter-rater reliability, which could rely on the inclusion of highly selected lupus experts, as stated by the authors themselves. Indeed, in previous studies, PGA showed a high intra-rater and inter-rater variability,2 3 consistently with PGA being a subjective measure. The high inter-rater reliability observed by the authors is surprising considering that the timeframe for assessing disease activity significantly varied among respondents: 36.7% scored PGA over the previous 7–10 days, 36.7% over the previous month, the remainder over shorter or longer periods of time. Additionally, in almost one-third of respondents, lupus damage was considered when scoring PGA. Notably, the authors suggest that PGA should be scored after considering laboratory results, owing to a better correlation with systemic lupus erythematosus (SLE) disease activity index-2000 (SLEDAI-2K) of postlaboratory versus prelaboratory PGA. …

Background/Purpose Systemic lupus erythematosus (SLE) is an autoimmune disease, mostly affecting women during their childbearing age. Disease remission before conception is pivotal for a favorable pregnancy outcome. The aims of our study were: 1)to evaluate maternal and fetal complications in a cohort of pregnant SLE patients; 2)to compare Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) in the 6 months before conception as predictors of maternal/fetal complications. Methods All SLE pregnancies were prospectively included until August 2019 at our Unit (Rheumatology Department, University of Padova). All women were monthly followed throughout gestation and at least in one occasion in the 6 months before conception. Disease activity was assessed before pregnancy by SLEDAI-2k and SLEDAS. During gestation, we evaluated SLE activity by the Systemic Lupus Erythematosus Pregnancy Disease Activity Index (SLEPDAI) and the SLEDAS index adapted to pregnancy (SLEPDAS). At conception, we considered ‘active’:1)patients with a SLEDAS>2.08; 2)clinically active patients according SLEDAI-2k treated with ≥5 mg/day of prednisone (immunosuppressants and antimalarials were allowed). Statistics were performed with SPSS (V.24.0). Results We enrolled 115 pregnancies in 76 patients (table 1). We found 29 (25.2%) pregnancies with at least one maternal complication and 39 (33.9%) with at least 1 fetal adverse outcome. Positive anti-dsDNA and active disease according SLEDAS (SLEDAS>2.08) at conception resulted to be predictors of maternal complications (p=0.036, OR=2.71, CI 95% 1.07–6.87; p=0.008, OR=4.46, CI 95% 1.48–13.49, respectively). Conversely, active disease according SLEDAI-2k did not result predictive of maternal complications (p=0.255, OR=2.16, CI 95% 9.57–8.16). No predictors of fetal complications were observed. Conclusions SLE-DAS>2.08 and positive anti-dsDNA are risk factors of maternal complications while active SLE according to SLEDAI-2k does not seem to be a predictor of such complications.

ObjectivesRemission in systemic lupus erythematosus (SLE) is defined through a combination of ‘clinical SLE Disease Activity Index (cSLEDAI)=0’, ‘physician's global assessment (PGA) MethodsWe tested seven potential definitions of remission in SLE patients followed-up for ≥5 years: PDN ≤5 mg/day; PGA ResultsWe included 646 patients (mean±SD disease duration 9.2±6.9 years). At multivariate analysis, ≥2 consecutive year remission according to all definitions protected against damage (OR, 95% CI: PGA ConclusionscSLEDAI=0 is the most attainable definition of remission, while displaying the best performance in predicting damage progression in the short-to-mid-term follow-up.

Objective To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (SLE) who were treated with belimumab. Methods In this retrospective study of a multicenter cohort of SLE patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the SLE Responder Index 4 (SRI-4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to score disease damage yearly over the follow-up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results The study included 466 patients with active SLE from 24 Italian centers, with a median follow-up period of 18 months (range 1-60 months). An SRI-4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of ≥10 on the SLE Disease Activity Index 2000 (SLEDAI-2K) (OR 3.14 [95% CI 2.033-4.860]) and a disease duration of ≤2 years (OR 1.94 [95% CI 1.078-3.473). Baseline predictors of response at 12 months included a score of ≥10 on the SLEDAI-2K (OR 3.48 [95% CI 2.004-6.025]) and an SDI score of 0 (OR 1.74 [95% CI 1.036-2.923]). Baseline predictors of response at 24 months included a score of ≥10 on the SLEDAI-2K (OR 4.25 [95% CI 2.018-8.940]) and a disease duration of ≤2 years (OR 3.79 [95% CI 1.039-13.52]). Baseline predictors of response at 36 months included a score of ≥10 on the SLEDAI-2K (OR 14.59 [95% CI 3.54-59.79) and baseline status of current smoker (OR 0.19 [95% CI 0.039-0.69]). Patients who were in remission for ≥25% of the follow-up period (44.3%) or who had low disease activity for ≥50% of the follow-up period (66.1%) accrued significantly less damage (P = 0.046 and P = 0.007). A baseline SDI score of 0 was an independent predictor of achieving low disease activity in ≥50% of the follow-up period and remission in ≥25% of the follow-up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of ≥25% of the follow-up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy (P = 0.009). Conclusion In patients with active SLE and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real-life setting.

The challenge of early diagnosis and treatment is a timely issue in the management of systemic lupus erythematosus (SLE), as autoimmunity starts earlier than its clinical manifestations. Hence, growing efforts for stratification of patients according to the individual risk of developing specific clinical manifestations and/or predicting a better response to a given treatment have led to the proposal of several biomarkers, which require validation for use in clinical practice. In this viewpoint, we aim at distinguishing and discussing the features and the approach to asymptomatic immunological abnormalities potentially heralding the development of SLE, defined as preclinical lupus, and clinical manifestations consistent with SLE not yet fulfilling classification criteria, defined as early lupus. In case of preclinical SLE, careful surveillance using available screening tools is paramount, while patients with early lupus deserve an appropriate and timely diagnosis and, consequently, a proper treatment including hydroxychloroquine as the anchor drug.

ObjectivesTo evaluate changes in demographic, clinical and histological presentation, and prognosis of lupus nephritis (LN) over time.Patients and methodsWe studied a multicentre cohort of 499 patients diagnosed with LN from 1970 to 2016. The 46-year follow-up was subdivided into three periods (P): P1 1970–1985, P2 1986–2001 and P3 2002–2016, and patients accordingly grouped based on the year of LN diagnosis. Predictors of patient and renal survival were investigated by univariate and multivariate proportional hazards Cox regression analyses. Survival curves were compared using the log-rank test.ResultsA progressive increase in patient age at the time of LN diagnosis (pConclusionsClinical presentation of LN has become less severe in the last years, leading to a better long-term renal survival.

To date, belimumab is the only biological drug approved for the treatment of patients with active refractory SLE. We compared and critically analyzed the results of 11 observational clinical-practice-based studies, conducted in SLE referral centers. Despite the differences in endpoints and follow-up duration, all studies remarked that belimumab provides additional benefits when used as an add-on to existing treatment, allowing a higher rate of patients to reach remission and to taper or discontinue corticosteroids. In the OBSErve studies, 2–9.6% of patients discontinued corticosteroids and 72–88.4% achieved a ≥ 20% improvement by physician’s judgment at 6 months. In Hui-Yuen’s study, 51% of patients attained response by simplified SRI at month 6. In Sthoeger’s study, 72.3% of patients discontinued corticosteroids and 69.4% achieved clinical remission by PGA after a median follow-up of 2.3 years. In the multicentric Italian study, 77 and 68.7% of patients reached SRI-4 response at months 6 and 12, respectively. In all the studies, disease activity indices decreased over time. Retention rates at 6, 9, and 12 months were 82–94.1, 61.2–83.3, and 56.7–79.2%, respectively. The main limitations of these studies include the lack of a control group, the short period of observation (6–24 months) and the lack of precise restrictions regarding concomitant medication management. This notwithstanding, these experiences provide a more realistic picture of real-life effectiveness of the drug compared with the randomized controlled clinical trials, where stringent inclusion/exclusion criteria and changes in background therapy could limit the inference of data to the routine clinical care.

Background:LN is still a severe manifestation of Systemic lupus erythematosus (SLE) and multitarget therapy is needed to control the disease especially in refractory cases.Objectives:To evaluate renal response in SLE patients with glomerulonephritis (GN) treated with Belimumab in real-life setting.Methods:Patients with proteinuria >0.5 g/24 h and/or active sediment at baseline enrolled in a multicentre Italian cohort of SLE patients (BeRLiSS study), treated with monthly iv Belimumab 10 mg/kg plus standard of care were considered in this study. Complete renal response (CRR) was defined as proteinuria 2 and no rescue therapy. Primary efficacy renal response (PERR) was defined as proteinuria ≤0.7 g/24 h, eGFR ≥60ml/min/1.73m2 and no rescue therapy. Prevalence and predictive factors of CRR and PERR at 12 and 24 months after Belimumab initiation were analyzed by multivariate logistic regression analysis.Results:A total of 91 patients were considered in this study, 79 female, mean age 40.51±9.03 years, mean disease duration 12.18±8.15 years, median follow-up time after Belimumab initiation 22 months. Twenty patients had baseline proteinuria ≥0.5 2 at baseline. Immunosuppresants were taken by 70 (76.9%) patients: 47 micofenolate, 15 azathioprine and 5 ciclosporine. Sixty patients (65.9%) were on antimalarials. During follow-up 34 (37.4%) patients achieved CRR. Among them 5 (14.7%) patients relapsed and 29 (85.3%) patients maintained remission. Mean time to achieved CRR was 9.71±5.91 months.High levels of baseline proteinuria were a negative independent predictor of CRR and PERR at 6 months (OR 0.044 CI95% 0.006-0.320 p=0.002 and OR 0.232 CI95% 0.091-0.596 p=0.002) and 12 months (OR 0.029 CI95% 0.002-0.556 p=0.019 and OR 0.056 CI95% 0.009-0.327 p=0.001). High levels of baseline creatinine were a negative independent predictor of renal response. Renal response at 6 months was a strong predictive factor of renal response at 12 and 24 months.Conclusion:Belimumab is an effective add-on therapy in the treatment of GN in real-life practice setting.Disclosure of Interests:None declared

Background:Treatment of systemic lupus erythematosus (SLE) is tailored according to the intensity of SLE disease activity and aims to achieve remission. Current definitions of remission and disease activity categories are mostly based on the SLE Disease Activity Index (SLEDAI), which has important limitations. The SLE Disease Activity Score (SLE-DAS) is a validated continuous disease activity score with higher accuracy in measuring SLE activity and higher sensitivity-to-change as compared to SLEDAI1. SLE-DAS is user-friendly with its online calculator.Objectives:To derive and validate the SLE-DAS cut-off values for defining SLE disease activity categories and SLE clinical remission state.Methods:Derivation study was conducted at the Padova Lupus Clinic. Validation was performed prospectively in patients from the Cochin Lupus Clinic and by post-hoc analysis of BLISS-76 (NCT00410384) trial. Gold-standard for clinical remission state was fulfillment of Definition Of Remission In SLE (DORIS). In Padova and Cochin Clinics, at time of inclusion, a senior clinician classified each patient as presenting: (i) remission, (ii) mild, or (iii) moderate/severe disease activity. Derivation of the SLE-DAS cut-offs for disease activity categories was performed using ROC curve analysis against this expert clinical classification. Performance of these SLE-DAS categories of disease activity was assessed as compared with: (i) expert classification (in Cochin cohort); (ii) British Isles Lupus Assessment Group (BILAG) index (in BLISS-76). An index-based and a Boolean definition of remission were tested applying decision trees, using CHAID (chi-square automatic interaction detection) algorithm and their performance estimated.Results:We included 1190 SLE patients (221 in Padova, 150 in Cochin and 819 from BLISS-76 cohorts). In the derivation cohort, best SLE-DAS cut-off values for disease activity categories were: (i) remission, SLE-DAS≤2.08; (ii) mild activity, 2.087.10. Table 1 shows the performance of these SLE-DAS cut-offs. The SLE-DAS Boolean-based definition of remission (all SLE-DAS clinical items scores = 0 and prednisone ≤5mg/day) showed sensitivity and specificity of 100% in the derivation (Padova) and validation (Cochin) clinical cohorts. The SLE-DAS index-based definition of remission (SLE-DAS ≤2.08 and prednisone ≤5mg/day) presented sensitivity =100% and specificity =97.4% in the derivation and validation clinical cohorts. The SLE-DAS definitions of remission were fully substantiated by CHAID.Table 1.Performance of SLE-DAS cut-offs for remission and disease activity categories compared to physician’s classification and BILAG (n =1190).Disease activity categorySensitivity (%)Specificity (%)Accuracy (%)DerivationPadova CohortRemission(SLE-DAS≤2.08)99.397.198.6Mild Disease Activity(2.0874.298.995.5Moderate and Severe Disease Activity(SLE-DAS>7.10)97.496.796.8ValidationCochin CohortRemission(SLE-DAS≤2.08)99.193.998.0Mild Disease Activity(2.0882.699.296.7Moderate and Severe Disease Activity(SLE-DAS>7.10)100.098.698.7ValidationBLISS-76Remission and Mild Disease Activity§vs. Moderate and Severe Disease Activity§§ (SLE-DAS≤7.10 vs. >7.10)91.484.190.8§ Remission/Mild: No BILAG B or A scores§§ Moderate/severe: ≥1 BILAG B or A scoresConclusion:The SLE-DAS is an accurate and easy to use tool for defining clinical remission state and SLE disease activity categories, validated with both the expert assessment and BILAG.References:[1]Jesus D, et al. Derivation and validation of the SLE Disease Activity Score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity. Ann Rheum Dis 2019;78:365-71.Acknowledgements:The authors would like to thank GlaxoSmithKline (Uxbridge, UK) for granting access to the data from the BLISS-76 trial through the Clinical Study Data Request consortium.Disclosure of Interests:None declared

Belimumab is a monoclonal IgGʎ antibody targeting soluble B lymphocyte stimulator (BLyS) and aimed at lowering available BLyS levels for autoreactive B cells selection and survival.Belimumab was ap...

Background Belimumab is the unique biologic therapy available for patients with SLE. Objectives To investigate effectiveness and safety of belimumab in SLE patients in clinical practice. Methods 458 active SLE patients (ACR criteria) from 24 Italian Centers, mean±SD age 43.5±11.3 years; mean±SD disease duration 12.3±8.7 years, were treated with belimumab (10 mg/kg day 0, 14, 28 and then every 28 days), as add-on therapy. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24H proteinuria, CLASI, PGA, Fatigue (VAS 0-10) were recorded at baseline and every 6 months. Flares were defined according to SFI. Response was evaluated according to SRI-4. Statistics were performed by pairs T-test, chi-square test and multiple logistic regression (SPSS, version 22.0). Results Mean±SD follow-up was 21.2±15.3 months (range 3-60). Most common features treated with belimumab were articular in 67%, mucocutaneous in 55%, and renal in 17% of cases. Improvement of clinical and serological variables, including daily prednisone dosage, was observed (Table). SRI-4 is summarized in the Figure. At the end of follow-up 293 patients (66%) were still on belimumab. Most common cause of discontinuation were inadequate response (36%), AEs (31%), and pregnancy (8%). Mean number of flare during belimumab treatment compared with the corresponding period before belimumab initiation decreased (p 9,998 infusions were analyzed. 784 AEs were observed in 330 patients, SAEs were 43 in 36 patients. No severe infusion reactions were observed; 16 patients had infective SAEs, and 22 non infective SAEs. Conclusion We confirmed the effectiveness, the steroid sparing effect and good safety profile of belimumab in our cohort. Disclosure of Interests Luca Iaccarino: None declared, Francesca Saccon: None declared, Alessandro Mathieu: None declared, Matteo Piga: None declared, Angela Ceribelli: None declared, Carlo Selmi Grant/research support from: Abbvie, Janssen, MSD, Novartis, Pfizer, Consultant for: Abbvie, Alfa-Sigma, Biogen, BMS, Celgene, Eli-Lilly, GSK, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, YCB, Speakers bureau: Abbvie, Alfa-Sigma, Biogen, BMS, Celgene, Eli-Lilly, GSK, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, YCB, Paolo Cardinaletti: None declared, Armando Gabrielli: None declared, Andrea Di Matteo: None declared, Rossella De Angelis: None declared, Paola Faggioli: None declared, Antonella Laria: None declared, Micaela Fredi: None declared, Francesca Regola: None declared, Laura Andreoli: None declared, Giulia Pazzola: None declared, Carlo Salvarani: None declared, Francesco Puppo: None declared, Simone Negrini: None declared, Marcella Prete: None declared, Vito Racanelli: None declared, Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Maria Gerosa: None declared, Tania Ubiali: None declared, Enrica Bozzolo: None declared, Valentina Canti: None declared, Fabrizio Conti: None declared, Fulvia Ceccarelli: None declared, Elena Bartoloni Bocci: None declared, Roberto Gerli: None declared, Antonio Lobasso: None declared, Amato De Paulis: None declared, Ginevra De Marchi: None declared, Salvatore De Vita Grant/research support from: Roche, Pfizer, Abbvie, Novartis, BMS, MSD, Celgene, Janssen, Consultant for: Roche, Alessandra Bortoluzzi: None declared, Marcello Govoni Paid instructor for: Pfizer, Roche, Speakers bureau: Pfizer, Abbvie, MSD, Roche, Eli-Lilly, Celgene, Sanofi, Janssen, Francesco Benvenuti: None declared, Margherita Zen: None declared, Marta Mosca Paid instructor for: GlaxoSmithKline, Lilly, UCB, Chiara Tani: None declared, Maurizio Rossini: None declared, Giovanni Orsolini Speakers bureau: Grunenthal, Mariele Gatto: None declared, Salvatore Scarpato: None declared, Enrico Brunetta: None declared, Aurora Zumbo: None declared, Gabriele Valentini: None declared, SERENA FASANO: None declared, Giacomo Emmi: None declared, Maria Letizia Urban: None declared, Giacomo Tanti: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis, Andrea Doria: None declared

Background Patients with Systemic Lupus Erythematosus (SLE) are often treated with prolonged maintenance therapy with immunosuppressants (ISs) after remission achievement, with the aim of avoiding disease flares and subsequent organ damage. Data on the risk of flare after IS discontinuation and the effect of IS discontinuation on damage accrual are scanty. Objectives Our aims were to analyze damage progression in remitted SLE patients who did or did not discontinued ISs, to assess flare rate after IS withdrawal and to compare damage accrual in patients who did or did not flare after IS discontinuation. Methods We considered all SLE patients included in our lupus database, diagnosed between 1990 and 2018 (ACR criteria), treated with immunosuppressants over their disease course, who discontinued IS due to remission. IS discontinuation was defined as complete withdrawal of any immunosuppressive drug, and remission as clinical SLE Disease Activity Index (SLEDAI)-2K=0. Flares were defined according to SLEDAI Flare Index, and damage according to SLICC damage Index (SDI). Results Eligible patients ever treated with ISs were 319 out of 456 (69.9%) currently in follow-up. Remission lasting at least 6 months was achieved by 206 patients treated with IS (64.6%) (Table 1); among them 105 (51%) discontinued ISs during the follow-up. Mean±SD follow-up after IS withdrawal was 91±71 months (range 6-372). No difference in damage accrual between remitted patients who discontinued or did not discontinue ISs was observed at the end of follow-up, after adjusting for disease duration: median (range) SDI 1 (0-6) and 0 (0-4), respectively. Accordingly, the proportion of remitted patients who accrued damage during the follow-up was similar between those who did or did not discontinue ISs (55% vs. 48%). Among patients who discontinued ISs, 26 (24.7%) experienced a flare after a median (range) of 57 (6-264) months from IS discontinuation. Flares were severe in 50% of cases (Table 2). No difference in damage progression between patients who flared and did not flare after IS withdrawal was found at the end of follow-up: median (range) SDI 1 (0-5) and 1 (0-6), respectively. Moreover, the proportion of patients with damage accrual was similar among patients with and without flare after IS discontinuation (56% vs. 54%). Conclusion In our SLE cohort, the withdrawal of IS therapy in remitted patients did not seem to influence damage progression in the medium-term. Disclosure of Interests: None declared

Background: The treat-to-target strategy in Systemic Lupus Erythematosus (SLE) aims to achieve remission. However, to define a target based on the SLE Disease Activity Index (SLEDAI) is questionable, due to its limitations (especially its dichotomous nature). The SLE Disease Activity Score (SLE-DAS) is a recently validated continuous disease activity score which has a higher accuracy in measuring SLE activity and a higher sensitivity-to-change compared to SLEDAI.1 Objectives: To assess the ability of SLE-DAS to define SLE remission and other disease activity states. Methods: Cross-sectional study of SLE patients fulfilling the ACR’97 and/or SLICC’12 classification criteria and followed at the Padua Lupus Clinic from March to June 2018. At each outpatient visit, the attending clinician scored SLE disease activity (in the last 30 days) using Physician Global Assessment (PGA) (0-3 points, 10 cm scale), SLEDAI-2K and SLE-DAS. A senior rheumatologist expert in SLE, blinded to the disease activity scores, classified each patient in 1 of 4 categories: (i) remission, (ii) low disease activity (LDA), (iii) mild disease activity and (iv) moderate/severe disease activity. The best cut-off values of SLE-DAS to define these categories were estimated using Receiver Operating Characteristic (ROC) curve analysis. Accuracy, precision, sensitivity and specificity values for these cut-off values were then calculated. The agreement between the SLE-DAS and physician’s classification was measured using Kappa coefficient. Statistical significance was set at 0.05. Results: We included 221 patients (84.2% female, mean age of 45.4±13.5 years, mean disease duration of 15.4±9.5 years). In this preliminary study, the proposed cut-off values of SLE-DAS to define each disease activity category were: remission SLE-DAS≤2.08, LDA 2.08 7.64 for (Table 1). The overall accuracy of these SLE-DAS cut-off values to identify each disease activity state was 96.4%. The agreement between SLE-DAS and physician’s classification was very high (k=0.925, p According to the SLE-DAS cut-offs, 68.8% of the patients were in remission, 2.3% in LDA, 10.9% in mild disease activity and 18.1% in moderate/severe disease activity. Conclusion: The SLE-DAS has a high precision in identifying remission, LDA, and other disease activity states in SLE. These results suggest that the SLE-DAS is an accurate tool in defining achievable targets in SLE management. References: [1] Jesus D, Matos A, Henriques C, et al. Derivation and validation of the SLE Disease Activity Score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity. Ann Rheum Dis 2019, Epub ahead of print 9 January 2019. DOI: 10.1136/annrheumdis-2018-214502. Disclosure of Interests: None declared

Background: Remission is the most desirable target in the treatment systemic lupus erythematosus (SLE) however, a universally accepted definition of remission in SLE is still missing. Objectives: To test the contribution of the different items included into the currently used definitions of remission in SLE. Methods: We studied 646 Caucasian patients from a multicentre lupus cohort followed for at least 5-years: female 585 (90.6%), mean age at baseline 40.59±12.14 years, mean disease duration 9.18±6.86 years. Disease activity was assessed by clinical SLE Disease Activity Index 2000 (cSLEDAI) and SELENA-SLEDAI physician global assessment (PGA), and damage by Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI). To test the performance of the different items included in the definitions of SLE remission [1, 2] we identify 7 subtypes of remission: (1) PGA (0-3) Results: The number of patients achieving remission according to the different definitions is show in Figure 1. The proportion of patients who maintained prolonged remission (5-consecutive years) was: PGA When PGA Conclusion: The prevalence and extent of damage significantly decreased as the time spent in remission increased, irrespective of the remission subtype. The addition of PGA References [1] van Vollenhoven R, et al. 2014 [2] Zen M, et al. 2015 Disclosure of Interests: Francesca Saccon: None declared, Margherita Zen: None declared, Mariele Gatto: None declared, Domenico PE Margiotta: None declared, Fulvia Ceccarelli: None declared, Giulia Frontini: None declared, Gabriella Moroni: None declared, Alessandra Bortoluzzi: None declared, Marcello Govoni: None declared, Viola Signorini: None declared, Marta Mosca Paid instructor for: GlaxoSmithKline, Lilly, UCB, Francesca Dall’Ara: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis, Anna Chiara Frigo: None declared, Antonella Afeltra Grant/research support from: MSD, PFIZER, ABBVIE, ROCHE, UCB, Speakers bureau: MSD, PFIZER, BMS, ROCHE, SANOFI, fabrizio conti: None declared, Andrea Doria: None declared

Objectives Patients with SLE are often exposed to prolonged immunosuppression since few data on flare recurrence in remitted patients who discontinued immunosuppressants are available. We aimed to assess the rate and predictors of flare after immunosuppressant withdrawal in SLE patients in remission. Methods SLE patients diagnosed between 1990 and 2018 (according to the ACR criteria), ever treated with immunosuppressants and currently in follow-up were considered. Immunosuppressant discontinuation was defined as complete withdrawal of any immunosuppressive drug. Reasons for discontinuation were remission, defined as clinical SLEDAI-2K = 0 on a stable immunosuppressive and/or antimalarial therapy and/or on prednisone ⩽5 mg/day, or poor adherence/intolerance. Flares were defined according to the SLEDAI Flare Index. Predictors of a subsequent flare were analysed by multivariate logistic regression. Results There were 319 eligible patients out of 456 (69.9%). Of the 319 patients, 139 (43.5%) discontinued immunosuppressants, 105 (75.5%) due to remission, 34 (24.5%) due to poor adherence/intolerance. The mean (s.d.) follow-up time after immunosuppressant withdrawal was 91 (71) months (range 6–372). Among the patients who discontinued immunosuppressants, 26/105 remitted (24.7%) and 23/34 unremitted patients (67.6%) experienced a flare (P < 0.001) after a median (range) follow-up of 57 (6–264) and 8 months (1–72), respectively (P = 0.009). In patients who discontinued immunosuppressants due to remission, maintenance therapy with antimalarials (OR 0.243, 95% CI 0.070, 0.842) and the duration of remission at immunosuppressant discontinuation (OR 0.870, 0.824–0.996) were independent protective factors against disease flare. Conclusion SLE flares are not uncommon after immunosuppressant discontinuation, even in remitted patients; however, antimalarial therapy and durable remission can significantly reduce the risk of flare.

It was with great interest that we read the letter ‘SLE-DAS: Ready for routine use?’ by Mathew and coauthors.1 Mathew et al commented on our recent article reporting the derivation and validation of the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS),2 which demonstrated a much higher sensitivity to change of SLE disease activity, as compared with SLE Disease Activity Index 2000 (SLEDAI-2K). Mathew et al ’s main concern is in regard of the SLE-DAS scoring of active lupus nephritis (LN). The SLE-DAS renal component is measured continuously, applying a logarithmic scale of proteinuria absolute value (to be scored only if above 500 mg/day and provided it is attributable to active LN). This is very different of the SLEDAI-2K renal component that comprises four dichotomous variables (proteinuria above 500 mg/day, pyuria, haematuria and urinary casts, each one scored solely as present or absent with a weight of 4 points if present and regardless of severity).3 In the derivation of the SLE-DAS, we modelled the renal component using longitudinal data of real patients with active LN from a large, well-characterised tertiary lupus cohort.4 5 The SLE-DAS with its continuous scoring of the absolute value of proteinuria amends risks of major bias of SLEDAI-2K regarding renal involvement. In patients with active LN, the …