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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.

The current treatment approach for systemic lupus erythematosus (SLE), as outlined in the recommendations by international medical associations including EULAR and the ACR, is mostly eminence-based rather than evidence-based. However, knowledge on SLE is growing quickly, and such new advances need to be translated into clinical practice. Questions remain regarding the choice and timing of drug administration and tapering until withdrawal, which both can affect the balance between the control of disease activity and damage to organs triggered by long-standing and/or disproportionate immunosuppression. Currently, the treating physicians of patients with SLE are required to weigh the present with the future situation of their patients in an optimized balance between therapeutic harm and benefit. In this Review, the available therapeutic strategies and main challenges in the approach to SLE treatment are discussed. Remission and low disease activity are desirable therapeutic goals. Although the drug armamentarium for SLE has not expanded much in the past few decades, there are nonetheless opportunities to make better choices and explore combination therapies; such opportunities offer the potential of a personalized medicine strategy. The treatment of systemic lupus erythematosus involves a balance between control of disease activity and prevention of therapeutic harm that requires careful optimization. In this Review, the authors discuss available and emerging therapeutic strategies that exploit the current drug armamentarium.

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.

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

Remission has recently emerged as a potential target in the management of systemic lupus erythematosus (SLE), indeed remission is not uncommon and is associated with improved prognosis.1 2 Nevertheless, the best management of remitted patients, especially those in stable remission, remains elusive. In particular, whether immunosuppressive therapy (IS) may be safely discontinued, without exposing remitted patients to a significant risk of flare, has not yet been clearly determined. Accordingly, available recommendations for the management of SLE underline the importance of progressive tapering of glucocorticoids (GCs) until withdrawal, but do not remark on the possibility of discontinuing IS in remitted patients. Moreover, the timing of IS discontinuation has not yet been established and in clinical practice it is quite common that remitted patients continue to receive the same treatment which led to remission, with the aim of preventing flares, for an indefinite period of time. It has been recently reported that ISs were safely withdrawn after remission achievement in more than 75% of patients with SLE in a cohort of 319 patients treated with IS for different manifestations, including lupus nephritis (LN) (47%), arthritis (15.7%), haematological abnormalities (5.3%), skin rash (6.3%), neuropsychiatric SLE (1.9%), vasculitis (1.3%), serositis (0.6%), and multi-organ involvement (21.9%).3 The independent predictors of a safe discontinuation were hydroxychloroquine (HCQ) maintenance therapy after IS discontinuation and a longer duration of remission at IS discontinuation. Notably, being on HCQ and in remission for at least two consecutive years reduced the risk of flare by 81% and being on HCQ and in remission for at least three consecutive years by 86%. These findings are in keeping with recent recommendations, as antimalarials have been regarded as standard of care in all SLE patients unless contraindicated, including patients with LN, where antimalarials are proposed as an additional therapy. Interestingly, in this study maintenance therapy with 5 mg/day prednisolone equivalent alone did not protect against flares, as patients with low-dose maintenance therapy experienced a similar flare-rate compared to patients who discontinued all treatment at the time of IS withdrawal. In LN, different studies found a variable flare rate after IS discontinuation due to achievement of stable remission, ranging from 15% to 38.7%. Antimalarial therapy and a longer duration of remission at IS discontinuation resulted predictive of flare-free remission in some but not all these studies. Notably, the protective role of HCQ therapeutic levels against LN flares has recently been reported.4 Indeed, among remitted patients, those with a subsequent renal flare during the follow-up had significantly lower HCQ levels compared with those in persistent remission. To date, different authors suggested a wide range of duration of IS maintenance therapy after remission achievement in LN, varying from 3 to 6.5 years. Based on available data, we can conclude that IS may be withdrawn in selected SLE patients, based on the characteristics of the individual patient, including their maintenance therapy and the duration of remission, which requires a personalised approach. In this regard, long-term therapy with antimalarials should be recommended in all SLE patients.5 Continuous surveillance should be planned during treatment tapering and after withdrawal, to ensure any early signs or symptoms of disease relapse are detected. Learning Objectives Explain why, although GCs should be de-escalated and withdrawn as early as possible in remitted patients, the timing of IS tapering until discontinuation in these patients is still an unresolved issue Describe the recent data suggesting that maintenance therapy with HCQ and a longer duration of remission at the time of IS withdrawal are protective against lupus flares Explain the importance of tight surveillance of lupus patients, during IS therapy tapering and after IS withdrawal in order to detect early signs or symptoms predictive of a disease relapse References Zen M, Iaccarino L, Gatto M, et al. Prolonged remission in Caucasian patients with SLE: prevalence and outcomes. Ann Rheum Dis 2015;74(12):2117–22. van Vollenhoven R, Voskuyl A, Bertsias G, et al. A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). Ann Rheum Dis 2017;76(3):554–61. Zen M, Saccon F, Gatto M, et al. Prevalence and predictors of flare after immunosuppressant discontinuation in patients with systemic lupus erythematosus in remission. Rheumatology (Oxford) 2020;59(7):1591–98. Cunha C, Alexander S, Ashby D, et al. Hydroxycloroquine blood concentration in lupus nephritis: a determinant of disease outcome?Nephrol Dial Transplant 2018 Sep 1;33(9):1604–10. Gatto M, Zen M, Iaccarino L, Doria A. New therapeutic strategies in systemic lupus erythematosus management. Nat Rev Rheumatol 2019;15:30–48.

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:Belimumab (BEL) is a monoclonal antibody approved for SLE treatment but few data are available about its use before or during pregnancy.Objectives:Our study aims to describe pregnancies in SLE patients who have discontinued BEL before conception, at positive pregnancy test or during pregnancy.Methods:Data from prospectively-followed pregnancies (2014-2020) in SLE patients treated with BEL in 3 Italian centers where retrospectively collected, focusing on maternal disease activity, obstetric and neonatal outcome. Continuous data are expressed as median [min-max].Results:Thirteen SLE pregnancies were analyzed (median age at conception 32 [24-41] years; 77% spontaneous, 69% primigravidae). All patients had positive ANA and anti-dsDNA antibodies; 4 had anti-Ro antibodies (31%); 4 had anti-phospholipid antibodies (aPL; 1 single, 2 double and 1 triple positivity). Seven patients (54%) had a history of lupus nephritis (LN); 2 patients (15%) had a concomitant diagnosis of antiphospholipid syndrome (1 thrombotic-APS and 1 thrombotic+obstetric-APS).Ten (77%) pregnancies were planned and the use of BEL with regard to pregnancy was agreed with the patient during preconception counseling. At preconception visit, 8 patients were in remission while 5 had active disease (median SLEDAI 3 [0-8]).BEL (11 intravenous, 2 subcutaneous) was stopped in 2 cases before conception, in 7 at positive pregnancy test and in 4 during pregnancy (2 at 11th week, 1 at 22nd, 1 at 24th); median duration of treatment at discontinuation was 29 [4-68] months. Other treatments during pregnancy were: oral prednisone in 12 cases (92%); intravenous methylprednisolone in 1 (8%); hydroxychloroquine in 10 (77%); chloroquine in 1 (8%); azathioprine in 5 (39%); calcineurin inhibitors in 5 (39%); low-dose acetylsalicylic acid in 10 (77%); low molecular weight heparin in 9 (69%).Three flares occurred during the 3rd trimester in patients who stopped BEL at positive pregnancy test.Live-births occurred in 92% of the pregnancies. A patient with thrombotic+obstetric-APS and LN, underwent assisted reproductive technology (embryo donation) and developed eclampsia (25thweek), an urgent cesarean section was performed and the newborn died after 3 days. One pre-eclampsia occurred in a patient with history of LN, double aPL positivity and active disease. One miscarriage at 11th week occurred; no early miscarriages (th week) were recorded. Pregnancy complications and outcomes are reported in Table 1.Table 1.Pregnancy complications and outcomes according to the timing of discontinuation of BEL.BEL STOPPED PRECONCEPTIONALLY(2)BEL STOPPED AT POS PREGNANCY TEST(7)BEL STOPPED DURING PREGNANCY(4)Pre-eclampsia0/20/71/4 (25%)Eclampsia0/20/71/4* (25%)Gestational Diabetes0/21/7 (14%)0/4IUGR0/21/7 (14%)1/4* (25%)pPROM/PROM0/20/71/4 (25%)Live birth1/2 (50%)7/7 (100%)4/4 (100%)Severe pre-term birth(≤ 34thweek)0/20/71/4* (25%)Late pre-term birth(35th- 37thweek)0/23/7 (43%)0/4Small for Gestational age neonate0/24/7 (54%)1/4 (25%)Late miscarriage (>10thweek)1/2 (50%)0/70/4Perinatal death0/20/71/4* (25%)IUGR: IntraUterine Growth Restriction; PROM: Premature Rupture of Membrane; pPROM: pretermPROM; *in the same patient (history of thrombotic and obstetric-APS and lupus nephritis) who underwent Assisted Reproductive Technologies (embryo donation).No malformations were recorded. Two newborns were transferred to the Intensive Care Unit (1 for milk protein intolerance and 1 for desaturation).Eight newborns received vaccinations according to national schedule (missing data for 3). Five newborns were breastfed, 1 received formula milk and 5 mixed-feeding. BEL was resumed in 7/13 patients after pregnancy (in 4 cases for flare), after a median period of 5 [4-22] months.Conclusion:While more data are needed, this small series suggests that BEL might be a therapeutic option for SLE patients during pregnancy planning, similarly to other biological drugs used in chronic forms of arthritis.Disclosure of Interests:None declared

Background:Anti-citrullinated alpha enolase antibodies have been investigated in rheumatoid arthritis and associated with bone erosion and interstitial lung disease but little is known about their prevalence and role in connective tissue diseases (CTDs).Objectives:The aim of this study was to investigate the prevalence and relevance of anti-CEP1 antibodies in CTDs.Methods:Serum samples from five independent patient cohorts were assessed: 1) established (est) primary Sjogren’s syndrome (pSS) N=78, 2) est-systemic lupus erythematosus (SLE) N=52, 3) est-systemic sclerosis (SSc) N=71, 4) pSS at disease onset N=30, 5) SLE at disease onset N=46 (cohorts 4 and 5 had at least 3 years of follow-up). Samples from ninety sex and age matched healthy donors (HD) and 200 patients with est-RA (disease controls) were also tested. Anti-CEP1 IgG antibodies were measured with a commercially available ELISA kit (Euroimmun, Luebeck, Germany).Results:Anti-CEP1 titer was significantly higher in est-pSS, est-SLE and est-SSc compared to HD, significantly lower in est-pSS and est-SSc compared to est-RA and comparable in est-SLE versus est-RA. We divided patients in every CTD group based on whether their anti-CEP1 titer was below or above the 25th, 50th and 75th percentile. In est-SLE anti-CEP1 values over the 25th percentile were associated with articular involvement (odds ratio, OR (95% confidence interval, CI)=11.5; 1.9-70.6, p=0.008). In est-pSS, no relationship between anti-CEP1>25th percentile and articular involvement was found but rather an association with rheumatoid factor positivity (OR (95% CI)=4.8, 1.6-14.1, p=0.004) and salivary gland swelling (OR (95% CI)=6.2, 1.3-29.1, p=0.021). In est-SSc no difference could be detected across the 3 groups. Anti-CEP-1 titers in pSS and SLE at onset did not differ from each other, were comparable also to those of HD and significantly lower than those of est-pSS, est-SLE and est-RA patients (all pConclusion:Anti-CEP-1 antibodies can be detected in CTDs at different title during the disease course and may increase overtime, at least in pSS. Although anti-CEP1 antibodies are associated with specific clinical manifestation in est-CTDs, such as articular involvement in est-SLE, they seem to lack a predictive value for future manifestations when measured at disease onset.References:[1]Alunno A, Bistoni O, Pratesi F et al Rheumatology (Oxford) 2018.[2]Manca ML, Alunno A, D’Amato C et al. Joint Bone Spine 2018.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...

Objective To investigate effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a clinical practice setting. Methods Sixty-seven patients with active SLE, mean ± SD age 39.3 ± 10.2 years, from 2 Italian prospective cohorts were treated with belimumab (10 mg/kg on day 0, 14, 28, and then every 28 days) added to background therapy. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, the Disease Activity Score in 28 joints (DAS28), 24-hour proteinuria, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score, anti–double-stranded DNA (anti-dsDNA), C3 and C4 levels, and prednisone daily dose were recorded at baseline, month 3, 6, 9, 12, 18, and 24. Arthritis was subdivided into “classical” (CLP) and “rheumatoid-like”; skin manifestations into acute (ACLE), subacute (SCLE), and chronic. SLE flares, defined according to the SLEDAI Flare Index, were calculated before and after belimumab initiation. Adverse events were carefully evaluated during treatment. Statistics were performed by the SPSS package (version 21.0). Results Mean ± SD followup was 16.2 ± 9.5 months. Main refractory manifestations treated with belimumab were musculoskeletal (37.3%), mucocutaneous (22.4%), and renal (23.9%). SLEDAI-2K, prednisone daily dose, anti-dsDNA, DAS28, CLASI, and 24-hour proteinuria decreased during treatment. DAS28 score decreased in patients with polyarthritis (P

Retrospective studies reported a high incidence of maternal complications in pregnant women with lupus. In this paper we prospectively assessed the rate of risk and the risk factors of maternal outcome in women with stable lupus nephritis who received pre-pregnancy counseling. This prospective multicenter study includes 71 pregnancies in 61 women with lupus nephritis who became pregnant between 2006 and 2013. Complete renal remission was present before pregnancy in 56 cases (78.9%) and mild active nephritis in 15 cases. All women underwent a screening visit before pregnancy and were closely monitored by a multidisciplinary team. Lupus anticoagulant, serum C3 and C4 complement fractions, anti-DNA antibodies, anti-C1q antibodies, anticardiolipin IgG and IgM antibodies, anti-beta2 IgG and IgM antibodies were tested at screening visit, at first, second, third trimester of pregnancy, and one year after delivery. Renal flares of lupus during or after pregnancy, pre-eclampsia, and HELLP syndrome were defined as adverse maternal outcomes. Fourteen flares (19.7%), six cases of pre-eclampsia (8.4%) and two cases of HELLP (2.8%) occurred during the study period. All flares responded to therapy and the manifestations of pre-eclampsia and HELLP were promptly reversible. Low C3, high anti-DNA antibodies and predicted all renal flares. High anti-C1q antibodies and low C4 predicted early flares. The body mass index (BMI) was associated with increased risk of late flares. History of previous renal flares and the presence of clinically active lupus nephritis at conception did not increase the risk of renal flares during pregnancy. History of renal flares before pregnancy, arterial hypertension, and longer disease predicted pre-eclampsia/HELLP. In pregnant women with lupus nephritis adverse maternal outcomes were relatively common but proved to be reversible when promptly diagnosed and treated. Immunological activity, arterial hypertension and BMI may predispose to maternal complications.

Patients affected with systemic lupus erythematosus (SLE) still display increased mortality and decreased quality of life in respect to general population. The major determinant of poor long term prognosis is organ damage, which is predictive of more damage and death. Damage is in turn triggered by uncontrolled disease activity and especially by the long-standing corticosteroid use which often accompanies SLE patients over their disease course, owing both to the need of reaching disease remission and to the habit of keeping patients on a small steroid dose for an indefinite period of time. Hence, the need for new drugs and therapeutic strategies aiming at minimizing damage accrual through a better control of disease activity and a steroid-sparing potential is paramount. So far, however, the therapeutic strategy in SLE requires a multitarget approach which is not devoid of widespread immunesuppression. In fact, several studies have been carried out in recent years targeting both the adaptive and the innate immune system, the majority of which did not achieve their primary endpoint, being often divergent from successful clinical experience and thereby committing physician to off-label use of targeted therapies in face of refractory SLE manifestations. The study designs and the chosen endpoints were often blamed for inadequacy, being at least in part responsible for study failures. In this review, we go over major clinical trials conducted in SLE by analyzing any critical aspects related to study design, predefined endpoints and biological activity of novel compounds that may have hampered study outcome, despite the great effort of providing less toxic drugs within a targeted, pathogenic-based approach.

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.

Background Patients with Systemic Lupus Erythematosus (SLE) are often exposed to prolonged treatment with immunosuppressants (IS). Remission of disease activity should conceptually enable IS withdrawal, but no enough evidence is available regarding the benefits of IS discontinuation, especially in non-renal SLE, or the risk of a subsequent flare. Our aims were to assess the rate of IS withdrawal in SLE remitted patients and the predictors of a subsequent flare and flare-free survival; moreover, to evaluate the effect of IS withdrawal on damage accrual. Methods We studied patients diagnosed with SLE between 1990 and 2018 treated with IS over their disease course who discontinued ISs. IS discontinuation was defined as complete withdrawal of any IS. Reasons for discontinuation were: remission, defined as clinical SLE Disease Activity Index (SLEDAI)−2K=0, or poor compliance/intolerance. Flares were defined according to SLEDAI Flare Index. Predictors of a subsequent flare and flare-free survival were analyzed by multivariate logistic regression and Cox regression analysis, respectively. Results Eligible patients ever treated with IS were 319 out of 456. 139 patients discontinued ISs, 105 of them (75.5%) due to remission. Mean ±SD follow-up after IS withdrawal was 91±71 months (range 6–372). 26/105 remitted (24.7%) and 23/34 unremitted patients (67.6%) experienced a flare (p Table 1 reports characteristics of remitted patients, overall and according to flare occurrence after IS discontinuation. At multivariate logistic regression analysis, antimalarial intake (OR, 95% CI 0.103, 0.023–0.452, p=0.003), older age (OR 0.943, 0.892–0.997, p=0.039) and the duration of remission before IS discontinuation (OR 0.943, 0.938–0.996, p=0.025) were independent protective factors against flares after IS discontinuation. Conversely, no predictive factors of a longer time-to-flare were identified by multivariate Cox-regression analysis. Median damage accrual was similar in patients who discontinued (1, range 0–8) or not IS (1, range 0–9) after adjusting for age, disease duration and cumulative prednisone dose. We separately analyzed data of non-renal remitted patients (37 patients, 35.2%). The only variable associated with a lower flare rate was antimalarial intake (OR 0.048, 0.005–0.503, p=0.002). Conclusions In our cohort, one third of patients treated with IS discontinued the drug during the follow-up, in most cases due to remission. The use of antimalarials after IS discontinuation was independently associated with a significant decrease in the risk of flare. Funding Source(s): None Table 1 reports characteristics of remitted patients, overall and according to flare occurrence after IS discontinuation.

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 …

It was with great interest that we read the letter ‘Performance of the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) in a Latin American population’.1 Rodriguez-Gonzalez et al commented on our recent manuscript reporting the derivation and validation of Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS),2 which demonstrated a much higher performance to detect clinical meaningful changes of SLE disease activity, as compared with SLE Disease Activity Index 2000 (SLEDAI-2K).3 In their letter, Rodriguez-Gonzalez et al reported a cross-sectional monocentric cohort study of 227 Mexican Mestizo SLE patients, in which they found a very high positive correlation between the SLE-DAS and the SLEDAI-2K (rho=0.92, p

Systemic lupus erythematosus (SLE) is a very complex disease where multiple immunological pathways can concur in inducing tissue damage. Cytokines are key mediators in this process and among them the role of interleukin (IL)-12 and the IL-23/Th17 axis has recently emerged. IL-12 and IL-23 have a heterodimeric structure with a common subunit, named p40. Although they share a partially common structure, their functions appear slightly different. Indeed, IL-12 is a key cytokine in inducing an efficient T helper 1 (Th1) response and in Th differentiation, while IL-23 plays a crucial role in chronic inflammation and Th17 cell activation, which results in IL-17 secretion. The increasing knowledge on the interaction between IL-12 and IL-23/Th17 axis in the development of autoimmune diseases has led to the identification of new therapeutic strategies targeting these immunological pathways. IL-23/Th17 axis has recently been suggested to be essential in developing lupus nephritis, both in mice and in humans. In keeping with these observations, ustekinumab, a fully human IgG1κ monoclonal antibody (mAb) directed towards p40 subunit, has been investigated in SLE. Promising data from a phase II randomized controlled trial in SLE patients suggest that this mAb might be a potential novel therapeutic strategy in SLE. In this review, we summarize the complex interaction between IL-12 and IL-23/Th17 axis in SLE with a special focus on drugs which affect this immune pathway. Impact statement Our article is focused on emerging pathogenetic pathways in systemic lupus erythematosus (SLE). Notably, IL-12 and IL-23 have been described as emerging cytokines in SLE pathogenesis. We know that IL-23 stimulates Th17 cells to produce IL-17. We try to point out the importance of IL-23/Th17 axis in SLE and to focus on the interaction between this axis and IL-12. Ustekinumab, a fully human IgG1κ monoclonal antibody directed towards the p40 shared subunit of IL-12 and IL-23, has been recently investigated in SLE, suggesting a potential novel therapeutic strategy in SLE. To our knowledge, there are no reviews which simultaneously focus on IL-12 an IL-23/Th17 axis in SLE. Thus, we believe our work will be of interest to the readers.

It was with great interest that we read the letter ‘Assessment of responsiveness of the musculoskeletal component of SLE-DAS in an independent cohort’ by Hassan et al .1 We recently published the derivation and validation of the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS), a new continuous measure of SLE disease activity with high sensitivity and specificity to change.2 Hassan et al report in their letter that in an analysis of 20 SLE …

Background Whether patients with autoimmune rheumatic diseases (ARD) have a higher risk for SARS-CoV-2 infection (COVID-19) and how SARS-CoV-2 pandemic impacts on adherence to therapy has not been fully elucidated. We assessed the rate and clinical presentation of COVID-19, and adherence to therapy in a large cohort of patients with ARD followed-up in a tertiary University-Hospital in Northeast Italy. Methods Between April 9th and April 25th, 2020, after SARS-CoV-2 infection peak, a telephone survey investigating the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), ANCA-associated vasculitis (AAV), and idiopathic inflammatory myopathies (IIM) was administered. Demographics, disease activity status, therapy, occupational exposure, and adherence to social distancing advise were also collected. Results 916 patients (397 SLE, 182 AAV, 176 SSc, 111 RA, 50 IIM) completed the survey. 148 patients developed at least one symptom compatible with COVID-19 (cough 96, sore throat 64, fever 64, arthromyalgias 59, diarrhea 26, conjunctivitis 18, ageusia/hyposmia, 18). Among the 916 patients, 65 (7.1%) underwent SARS-CoV-2 nasopharyngeal swab (18 symptomatic and 47 asymptomatic), 2 (0.21%) tested positive, a proportion similar to that observed in the general population of the Veneto region. No deaths occurred. 31 patients (3.4%) withdrew ≥1 medication, mainly immunosuppressants or biologics. Adoption of social distancing was observed by 860 patients (93.9%), including 335 (36.6%) who adopted it before official lockdown. Conclusions COVID-19 incidence seems to be similar in our cohort compared to the general population. Adherence to therapy and to social distancing advise was high., Highlights • SARS-CoV-2 infection rate in ARDs seems to be similar to that of the general population. • Adoption of social distancing measures was prevalent among different ARD groups. • Earlier social distancing was more common in unremitted patients, treated with multiple drugs. • Therapy discontinuation due to COVID-related concerns was rare, but undertaken even by active patients. • Therapeutic regimens based on ≥3 drugs were associated with therapy discontinuation in our cohort.

Background:Whether and when immunosuppressive therapy may be safely withdrawn in patients with lupus nephritis (LN) is still poorly defined. Indeed, there is no clear agreement about the optimal duration of maintenance treatment.Objectives:We aimed at assessing the rate and predictors of flare after IS withdrawal in patients with LN in remission.Methods:Patients with systemic lupus erythematosus (SLE) (ACR criteria) and biopsy-proven LN diagnosed between 1990 and 2019, ever treated with IS and currently in follow-up were considered. IS discontinuation was defined as the complete withdrawal of any immunosuppressive drug in patients in remission. Remission was defined as normal serum creatinine, proteinuria 0.5 g/24h requiring an increase in corticosteroid therapy or the reintroduction of IS. Predictors of a subsequent flare were analyzed by multivariate logistic regression analysis.Results:Out of 456 SLE patients regularly followed-up, 206 (45.1%) had LN and were considered in our study. Eighty-three patients (40.3%) discontinued IS after remission achievement (Table 1). After stopping therapy, patients were followed for a mean±SD of 99±77 months (range 12-378). Nineteen patients (22.8%) developed a flare after IS discontinuation, after a mean±SD follow-up of 78±68 months (range 7-312), and were re-treated; among them, 6 patients (7.2%) experienced a renal and 13 (15.6%) an extra-renal flare. Compared to patients who flared, patients in persistent IS-free remission had longer remission before IS withdrawal (51.2±31.5 vs. 29.3±16.5 months, pTable 1.Characteristics of 83 patients with LN in remission who discontinued immunosuppressive therapy, overall and according to flare occurrenceTotal patients (83)Patients with flare (19)Patients without flare (64)P valueFemale, N(%)72 (88.7)16 (84.2)56 (87.5)nsAge at 2019, years43±1139±11.545±10.40.049SLE duration at 2019, years18±916.7±9.018.6±8.6nsSLE duration at IS discontinuation, years9.7±7.67.1±6.110.5±7.8nsTime to achieve remission, months27±3722.1±35.628.5±37.6nsRemission duration at IS discontinuation, months46±3029 ±16.551±31.5IS therapy duration, years6.7±4.35.2±3.87.1±4.20.061Anti dsDNA, N(%)65 (78.3)18 (95)47 (73)0.059HCQ after IS discontinuation, N(%)67 (80.7)12 (63.1)55 (85.9)0.005IS, immunosuppressant; HCQ, hydroxychloroquineTable 2.Multivariate logistic regression: predictors of flare occurrenceDependent variable: flare occurrenceOR95% CIp valueNumber of ISs, ever3.2641.030-10.3420.044HCQ therapy after IS discontinuation0.0960.014-0.6520.017Remission duration at IS discontinuation0.9540.912-0.9970.037Cyclophosphamide, ever0.0650.008-0.5480.012IS, immunosuppressant; HCQ, hydroxychloroquineConclusion:Based on our experience, withdrawal of IS is feasible in selected patients with LN, i.e. patients who achieved stable remission and received maintenance therapy with antimalarials. Patients who experience new flares can re-achieve remission with an appropriate treatment.Disclosure of Interests: :Margherita Zen Speakers bureau: BMS, Ely Lilly, Janssen, GSK, Mariele Gatto Speakers bureau: GSK, Francesco Benvenuti: None declared, Francesca Saccon: None declared, Maddalena Larosa: None declared, Luca Iaccarino Speakers bureau: GSK, Pfizer, Janssen, Novartis, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS

Background The efficacy of tacrolimus (TAC) in lupus nephritis (LN) has been recently demonstrated in several randomised controlled trials in asian cohorts.1 Nevertheless, data on real-life experience and long-term safety of TAC are still lacking. Objectives To assess efficacy and safety of TAC in SLE patients with refractory LN in a multi-centric prospective cohort. Methods Adult SLE patients with refractory LN from 4 Italian centres were prospectively followed for at least 12 months. Clinical and serological variables and previous/concomitant medications were collected at baseline,3,6,12 months after starting TAC. Renal response was assessed by using EULAR/ERA-EDTA definitions.2 Adverse events (AEs) included non-infectious and infectious AEs; they were defined severe (SAE) when hospitalisation and/or death and/or life-threatening manifestations occurred. Data were analysed using SPSS (v.24.0). Results Thirteen SLE patients (8 females,5 males, mean age 33.7±10.2, mean disease duration 11.9±5.9) were enrolled (table 1). Concomitant medications included: prednisone(100%), mycophenolate mofetil(92.3%), hydroxychloroquine(53.8%), azathioprine(7.7%), belimumab(7.7%) and cyclosporine(7.7%). The average number of previous immunosuppressants taken by each patient was 3.15±1.90. Six-months renal response was achieved by 5/13 patients (38.5%): complete renal response (CRR) in 3 (60.0%) and partial renal response (PRR) in 2 patients (40.0%). Twelve-months renal response occurred in 4/13 patients (30.8%): CRR in 2/13 (50.0%) and PRR in 2/13 (50.0%). One patient achieved CRR at 6 and 12 months; one patient achieved PRR at 6 months and CRR at 12 months. Six patients (46.1%) discontinued TAC after an average follow up period of 10.2±7.8 months. Causes of discontinuation were: 3 non-infectious non-SAEs, 1 flare, 1 non-infectious SAE, and 1 non-response. Concerning AEs, no severe infections or deaths occurred. Conclusions Our preliminary data from clinical practice setting suggest that TAC could be a therapeutic rescue strategy for refractory LN. Further studies are needed to prove TAC efficacy in the long term. References [1] Mok CC, Ying KY, Yim CW, et al. Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: a randomised controlled trial and long-term follow-up. Ann Rheum Dis2016;75:30e6. [2] Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis2012;0:1–12. Disclosure of Interest None declared

Background: SLEDAI is a widely used instrument to measure disease activity of systemic lupus erythematosus (SLE). However, it lacks sensitivity to discriminate improvement/worsening as it only scores items categorically and does not include several relevant lupus features, such as hemolytic anemia. Objectives: To derive and validate a SLE Disease Activity Score (SLE-DAS) with improved sensitivity to change, while maintaining the high specificity and simplicity of use of the SLEDAI. Methods: 324 patients fulfilling ACR’97 and/or SLICC’12 classification criteria for SLE and regularly followed at a tertiary care lupus clinic from January 2014 to December 2017 were included. At each outpatient visit, clinical and laboratory data were collected and disease activity (last 30 days) was scored with Physician Global Assessment (PGA) (0–3 scale) and SLEDAI-2K. To derive the SLE-DAS we analyzed data from the study visit with higher disease activity from each patient, applying multivariate linear regression analysis, with PGA as dependent variable/gold-standard. Independent variables tested in the models included items from SLEDAI-2K and continuous variables for swollen joint count, proteinuria, platelet and white blood cells counts. Some features absent from SLEDAI, such as hemolytic anemia, gastrointestinal and cardiopulmonary involvement were added to the model. To assess correlation validity we performed a Spearman’s correlation between the SLE-DAS, PGA and SLEDAI-2K at last follow-up visit. We tested performance of SLEDAI-2K (change ≥4) and SLE-DAS to discriminate a clinically meaningful worsening and improvement in SLE disease activity (change in PGA ≥0.3) using Receiver Operating Characteristic (ROC) curve analysis. We determined the best cut-offs values of SLE-DAS to detect changes in PGA ≥0.3 and calculated the sensitivity, specificity, positive and negative predictive values (PPV, NPV). Statistical significance was set at 0.05. Results: The final SLE-DAS model included 17 items. The SLE-DAS score at last follow-up visit presented high correlation with PGA (rho=0.975, p Conclusions: The SLE-DAS presents good construct validity and much higher discriminative power to detect changes in SLE disease activity as compared to SLEDAI-2K. External validation in another SLE cohort is underway. Disclosure of Interest: None declared

Background Prolonged treatment with immunosuppressants (IS) has been associated with long-term complications in Systemic Lupus Erythematosus (SLE); however, few data on IS discontinuation in remitted patients are available to date. Objectives We conducted an observational study to describe the proportion of SLE patients who discontinued IS and to assess the potential predictors of a subsequent flare. Methods We used data from Padua Cohort, which includes 454 SLE patients followed up from 1990 to 2017. Patients treated with IS over the disease course who discontinued IS and seen at least once in 2017 were studied. Reasons for discontinuation were: remission (defined by clinical SLE disease activity Index=0) or poor compliance/intolerance. Flares were defined according to SLEDAI Flare Index. Predictors of a subsequent flare were analysed by multivariate logistic regression analysis. Results Eligible patients who were ever treated with IS were 297. IS were discontinued in 106 patients (35.7%): mycophenolate (50, 47.2%), azathioprine (27, 25.5%), cyclophosphamide (11, 10.4%), methotrexate (10, 9.4%), cyclosporine (8, 7.5%). Mean ±SD follow-up duration after IS withdrawal was 82±64 months (range 6–320). 83 out of 106 patients (78.4%) discontinued IS due to remission (mean remission duration at IS discontinuation 39±28 months), and 23 (21.6%) due to poor compliance/intolerance. Among remitted patients, 18 (78.3%) experienced a flare after IS discontinuation (9/55 patients with nephritis, 5/10 with arthritis, 2/9 with skin involvement, 1/3 with neuroSLE, 1/4 with haematological involvement) after a mean of 65±52 months (range 6–180). Conversely, in patients with poor compliance/intolerance, 17 relapsed (73.9%) after a mean of 22±16 months. Flare-free 10 year-survival rate was higher in patients who discontinued IS due to remission than to poor compliance/intolerance (p In patients who discontinued IS due to remission, a shorter duration of remission at IS discontinuation was associated with disease relapse (p=0.006). Patients who were on IS due to nephritis had a lower risk of flare after IS discontinuation compared with patients with other manifestations (16.4% vs 32.1%, OR 0.58, 95% 0.32–0.98, p=0.049); patients with arthritis were those who were more likely to flare (OR 4.61, 95% CI 1.16–18.29, p=0.035). Positive anti-SSA/SSB (OR 0.45, 95% CI 0.26–0.78, p=0.012) and antimalarials intake after IS discontinuation (OR 0.22, 95% CI 0.07–0.73, p=0.015) were associated with a lower risk of flare. No clinical features over the disease course were associated with flare occurrence. At multivariate analysis, antimalarial use was the strongest protective factor against flares after IS discontinuation (OR 0.22, 95% CI 0.05–0.85, p=0.029). Conclusions In our cohort, one third of patients treated with IS discontinued the drug during the follow-up, in most cases due to a prolonged remission. Patients who discontinued IS due to remission had a higher free-survival rate than those who discontinued these drugs due to poor compliance/intolerance. The use of antimalarials after IS discontinuation was independently associated with a significant decrease in the risk of flare. IS discontinuation in patients with arthritis requires particular caution. Disclosure of Interest None declared

Background The treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) is extremely challenging and only a few clinical trials have been performed to establish optimal management. Objectives To describe the therapeutic approach and the short-term outcome of a multi-centre cohort of patients with NPSLE, enrolled at the time of the first NP event. Methods This is a retrospective cohort study. All NP events were defined according to American College of Rheumatology (ACR) case definition and divided into 3 clusters: central/diffuse (C/D), central/focal (C/F) and peripheral (P). A validated attribution algorithm was used to determine the attribution of all NP events. Demographic variables, global SLE disease activity Index 2000 (SLEDAI-2K), cumulative organ damage (SLICC/ACR Damage Index (SDI)) and treatment adopted for NP manifestations were collected. The clinical outcome of all NP events was determined by a physician-completed seven-point Likert scale (1=patient demise, 2=much worse, 3=worse, 4=no change, 5=improved, 6=much improved, 7=resolved). The relationship between the variables of interest and the outcome was analysed by crude and adjusted logistic models and reported as Odds Ratio (OR) and 95% confidence intervals (95% CI). Results 461 SLE patients with at least one NP event were included. 91.8% of patients were female, mean (SD) age 35.4 (13.6) years. 19.7% (91) of events were observed at diagnosis of SLE, 13.4% (62) before and 66.8% (308) after the diagnosis. 111 events (24.1%) were C/F, 286 (62%) C/D and 64 (13.9%) P. 198 (42.95%) of all NP events were attributed to SLE. The overall probability of immunosuppressive therapy was 28.4% (95% CI 24.3–32.8), 38.7% (95% CI 29.6–48.5) in C/F, 21.3% (95%CI 16.7–26.5) in C/D and 42.2% (95%CI 16.7–26.5) in P manifestations. The probability of immunosuppressive therapy was 47.9% (95% CI 40.8–55.2) in attributed events. The one-year outcome was available in 355 patients. Physician assessment indicated resolution (76 patients) or improvement (150 patients) in 49% (226/461) of cases. The crude and adjusted OR of attributed NP events and immunosuppressants on a favourable outcome is illustrated in Figure 1. The multivariable logistic regression analysis was done adjusting for age at diagnosis of SLE [OR 0.96, 0.94–0.98] p=0.001, female gender [OR 0.97, 0.33–2.7] p=0.959, SDI [0.85, 0.68–1.08] p=0.202, SLEDAI-2K [1.06, 1.01–1.11] p=0.008 and type of event (F/C [REF], C/D [0.37, 0.16–0.83] p=0.016, P [0.54, 0.21–1.42] p=0.215). Conclusions In our study, the therapeutic immunosuppressive approach was mostly used in attributed, C/F and P manifestations. In patients treated with immunosuppressants, the favourable outcome was lower in C/D phenotype. Disclosure of Interest None declared

Objective To evaluate the prevalence of different definitions of remission and their effect on damage in systemic lupus erythematosus (SLE). Design and method We considered 293 caucasian SLE patients followed-up for 7 years (2009–2015): 253 (86.3%) were female, mean ±SD disease duration 11.1±7.8 years. Disease activity was assessed by clinical SLEDAI-2K (c-SLEDAI) and damage by SLICC/ACR Damage Index (SDI). We evaluate the effect of different definitions of remission (c-SLEDAI=0; c-SLEDAI ≤1; c-SLEDAI=0 and prednisone ≤5 mg/day; c-SLEDAI ≤1 and prednisone ≤5 mg/day; c-SLEDAI=0 and PGA Results Frequency of remission achieved during the 7 year follow-up are reported in table 1 according to the different definitions. The mean increase in SDI and the percentage of patients with increased of SDI from the baseline to the end of follow-up were significantly higher in unremitted and 1 year remitted patients compared with patients with 2-, 3-, 4- and ≥5 year remission, irrespective of the definition of remission. 5 year remitted patients had lower damage compared with 2 year (p Conclusions The inclusion of PGA

ObjectiveTo evaluate the prevalence, duration and effect on damage accrual of the ‘Lupus Low Disease Activity State’ (LLDAS) in a monocentric cohort of patients with systemic lupus erythematosus (SLE).MethodsWe studied 293 Caucasian patients with SLE during a 7-year follow-up period. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and SELENA-SLEDAI physician global assessment (PGA), and damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We considered the following definition of LLDAS: SLEDAI-2K ≤4 without major organ activity, no new disease activity, PGA (0–3)≤1, prednisone ≤7.5 mg/day and well-tolerated immunosuppressant dosages. The effect of LLDAS on SDI was evaluated by multivariate regression analysis. We also evaluated remission defined as clinical SLEDAI-2K=0 and prednisone ≤5 mg/day in patients treated with/without stable immunosuppressants and/or antimalarials.ResultsLLDAS lasting 1, 2, 3, 4 or ≥5 consecutive years was achieved by 33 (11.3%), 43 (14.7%), 39 (13.3%), 31 (10.6%) and 109 (37.2%) patients, respectively. Patients who spent at least two consecutive years in LLDAS had significantly less damage accrual compared with patients never in LLDAS (p=0.001), and they were significantly less likely to have an increase in SDI (OR 0.160, 95% CI 0.060 to 0.426, pConclusionsLLDAS was associated with a decrease in damage progression in Caucasian patients with SLE. The majority of patients in LLDAS were in remission, which can largely contribute to the protective effect of LLDAS on damage accrual.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ, The term 'undifferentiated connective tissue disease' (UCTD) is generally used to describe clinical entities characterised by clinical and serological manifestations of systemic autoimmune diseases but not fulfilling the criteria for defined connective tissue diseases (CTDs). In this narrative review, we summarise the results of a systematic literature research, which was performed as part of the ERN ReCONNET project, aimed at evaluating existing clinical practice guidelines (CPGs) or recommendations. No specific CPG on UCTD were found, potential areas of intervention are absence of a consensus definition of UCTD, need for specific monitoring and therapeutic protocols, stratification of UCTD based on the risk of developing a defined CTD and preventive measure for the future development of a more severe condition. Patients feel uncertainty regarding the name of the disease and feel the need of a better education and understanding of these conditions and its possible changes over time., This publication was funded by the European Union’s Health Programme (2014-2020).

Objective To investigate efficacy, safety and survival of belimumab and to identify predictors of drug response and drug discontinuation in patients with active SLE in clinical practice. Patients and methods Data of SLE patients, treated with belimumab, from 11 Italian prospective cohorts were analyzed. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24-h proteinuria, CLASIa (Cutaneous LE Disease Area and Severity Index Activity) were recorded at baseline and every 6 months. SLE Responder Index-4 (SRI-4) was calculated at 12 and 24 months. Demographic and clinical features and comorbidities were included in the univariate and multivariate analysis. Adverse events were recorded at each visit. Statistics was performed using the SPSS software. Results We studied 188 SLE patients, mean follow-up 17.5 ± 10.6 months. The most frequent manifestations, which required the use of belimumab, were polyarthritis (45.2%) and skin rashes (25.5%). SRI-4 was achieved by 77.0% and 68.7% of patients at 12 and 24-months. Independent predictors of 12-month response were SLEDAI-2K ≥ 10 (OR 40.46, p = 0.001) and polyarthritis (OR 12.64, p = 0.001) and of 24-month response were SLEDAI-2K ≥ 10 (OR 15.97, p = 0.008), polyarthritis (OR 32.36, p = 0.006), and prednisone ≥7.5 mg/day (OR 9.94, p = 0.026). We observed a low rate of severe adverse events. Fifty-eight patients (30.8%) discontinued belimumab after a mean follow-up of 10.4 ± 7.5 months. The drug survival was 86.9%, 76.9%, 69.4%, 67.1%, and 61.9% at 6, 12, 18, 24, and 30 months, respectively. No factors associated with drug discontinuation were found. Conclusion Belimumab is effective and safe when used in clinical practice setting.