Publications by authors named "Mariele Gatto"

67 Publications

What are the topics you care about making trials in lupus more effective? Results of an Open Space meeting of international lupus experts.

Lupus Sci Med 2021 05;8(1)

Policlinic and Hiller Research Unit, Heinrich Heine University Düsseldorf, Dusseldorf, Nordrhein-Westfalen, Germany.

Despite promising candidates for new therapeutic options in the treatment of systemic lupus erythematosus (SLE), many clinical trials have failed in the past few years. The disappointing results have been at least partly be attributed to trial designs. With the aim of stimulating new developments in SLE trial design, an international open space meeting was held on occasion of the European Lupus Meeting 2018 in Duesseldorf, Germany about 'What are the topics you care about for making trials in lupus more effective?'. The Open Space is a participant-driven technology, where the discussion topics and schedule are selected during the meeting by all participants and discussion rounds are led by the people attending encouraging active contributions. Eleven topics were selected for further discussion, of which 6 were voted to be more intensively discussed in two consecutive rounds. Major topics were the optimal handling of glucocorticoids in clinical trials, the improvement of outcome measures, reducing or controlling the placebo response and the identification of biomarkers and stratification parameters. Further, the importance of local and international networks was emphasised. By networking, collaborations are facilitated, patient recruitment is more efficient and treatment can be harmonised thus lead to more successful SLE trials. Further discussions are needed to substantiate the results and develop new trial designs.
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http://dx.doi.org/10.1136/lupus-2021-000506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141446PMC
May 2021

Immunosuppressive therapy withdrawal after remission achievement in patients with lupus nephritis.

Rheumatology (Oxford) 2021 Apr 28. Epub 2021 Apr 28.

Rheumatology Unit, Department of Medicine, University of Padova, Padua, Italy.

Aim: Whether immunosuppressive therapy (IS) may be safely withdrawn in lupus nephritis (LN) is still unclear. We assessed rate and predictors of flare after IS withdrawal in patients with LN in remission.

Methods: Patients with biopsy-proven LN treated with IS between 1980 and 2020 were considered. Remission was defined as normal serum creatinine, proteinuria <0.5 g/24h, inactive urine sediment, and no extra-renal SLE activity on stable immunosuppressive and/or antimalarial therapy and/or prednisone ≤5mg/day. IS discontinuation was defined as the complete withdrawal of immunosuppressants, flares according to SLEDAI Flare Index. Predictors of flare were analyzed by multivariate logistic regression analysis.

Results: Among 513 SLE patients included in our database, 270 had LN. Of them, 238 underwent renal biopsy and were treated with ISs. Eighty-three patients (34.8%) discontinued IS, 46 ± 30 months after remission achievement. During a mean±SD follow-up of 116.5 ± 78 months, 19 patients (22.8%) developed a flare (8/19 renal) and were re-treated; 14/19 (73.7%) re-achieved remission after restarting therapy. Patients treated with IS therapy for at least three years after remission achievement had the lowest risk of relapse (OR 0.284, 95% CI 0.093-0.867, p= 0.023). At multivariate analysis, antimalarial maintenance therapy (OR 0.194, 95%CI 0.038-0.978, p= 0.047), age at IS discontinuation (OR 0.93, 95%CI 0.868-0.997, p= 0.040), remission duration >3 years before IS discontinuation (OR 0.231, 95%CI 0.058-0.920, p= 0.038) were protective against disease flares.

Conclusions: Withdrawal of IS is feasible in LN patients in remission for at least 3 years and on antimalarial therapy. Patients who experience flares can re-achieve remission with an appropriate treatment.
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http://dx.doi.org/10.1093/rheumatology/keab373DOI Listing
April 2021

Belimumab: a step forward in the treatment of systemic lupus erythematosus.

Expert Opin Biol Ther 2021 May 12;21(5):563-573. Epub 2021 Mar 12.

Division of Rheumatology, University of Padova, Padova, Italy.

: 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 a complexity of genetic, hormonal and environmental factors leading to immune deregulation and production of autoantibodies. Therefore, novel therapies have focused on B cells as key effectors of SLE pathogenesis. Belimumab is a fully humanized monoclonal antibody that antagonizes B-lymphocyte stimulator (BLyS); it is the first and the only biological drug approved for SLE in over 50 years.: In this review we discuss the pharmacological properties of belimumab, new recommendations for its use in clinical practice and its evidence of efficacy and safety based on clinical trial and real-life data.: Efficacy and safety of belimumab in clinical practice have been well established. To date, it is known that early introduction of belimumab in SLE can maximize the efficacy of the drug. A number of questions are still open, such as the timing of belimumab discontinuation and its possible association with other biological drugs, which need to be assessed in future studies.
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http://dx.doi.org/10.1080/14712598.2021.1895744DOI Listing
May 2021

Lupus nephritis: clinical presentations and outcomes in the 21st century.

Rheumatology (Oxford) 2020 12;59(Suppl5):v39-v51

Nephrology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Lupus nephritis (LN) is a frequent and severe manifestation of SLE. Along the decades, the epidemiology of LN and its clinical presentation have been changing. However, even though retrospective cohort studies report a decreased mortality rate and an improvement in the disease prognosis, the percentage of patients progressing into end stage renal disease (ESRD) keeps steady despite the improvements in therapeutic strategies. Current in-use medications have been available for decades now, yet over the years, regimens for optimizing their efficacy and minimizing toxicity have been developed. Therapeutic research is now moving towards the direction of precision medicine and several new drugs, targeting selectively different pathogenetic pathways, are currently under evaluation with promising results. In this review, we address the main changes and persistent unmet needs in LN management throughout the past decades, with a focus on prognosis and upcoming treatments.
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http://dx.doi.org/10.1093/rheumatology/keaa381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751166PMC
December 2020

Prevalence, outcome and management of patients with SLE and secondary antiphospholipid antibody syndrome after aPL seroconversion.

Rheumatology (Oxford) 2021 03;60(3):1313-1320

Division of Rheumatology, Department of Medicine DIMED, University of Padua, Padova, Italy.

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.
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http://dx.doi.org/10.1093/rheumatology/keaa463DOI Listing
March 2021

Nonimmune mechanisms in idiopathic inflammatory myopathies.

Curr Opin Rheumatol 2020 11;32(6):515-522

Unit of Rheumatology, Department of Medicine (DIMED), University of Padova, Padova, Italy.

Purpose Of Review: This review encompasses the main novelties regarding nonimmune mechanisms implicated in the pathogenesis of idiopathic inflammatory myopathies (IIM).

Recent Findings: In recent years, growing data support a role for endoplasmic-reticulum (ER) stress as a propagator of muscular damage, together with the release of interferon type I and reactive oxygen species in hypoxemic muscle fibers. Other studies evaluating the relationship between autophagy and Toll-like receptors (TLRs) in IIM subtypes have shown increased TLR3 and TLR4 expression in fibers of IIM patients and colocalization with LC3, an autophagy marker, submitting autophagy as a likely player in IIM pathogenesis. Most novel evidences concern the potential role of denervation of the neuromuscular junction in IIM, possibly connected to hyperexpression of MHC-I, and trafficking of extracellular vesicles, which may represent a connection between nonimmune and immune-mediated mechanisms of muscle inflammation and damage.

Summary: Nonimmune mechanisms contribute to the pathogenesis of IIM, likely cooperating with immune-mediated inflammation. Consistent data were released for ER stress, autophagy, mitochondrial dysfunction and hypoxia; in addition to, neuromuscular denervation and extracellular vesicles have been proposed as thoughtful links between muscle inflammation, damage and atrophy. Further understanding of nonimmune abnormalities and potential reversible pathways is needed to improve the management of IIM.
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http://dx.doi.org/10.1097/BOR.0000000000000748DOI Listing
November 2020

Frequency and clinical correlates of antiphospholipid antibodies arising in patients with SARS-CoV-2 infection: findings from a multicentre study on 122 cases.

Clin Exp Rheumatol 2020 Jul-Aug;38(4):754-759. Epub 2020 Jul 28.

Rheumatology Unit, Department of Medicine, University of Perugia, Italy.

Objectives: COVID-19 features include disseminated intravascular coagulation and thrombotic microangiopathy indicating a hypercoagulable state. We aimed to investigate antiphospholipid antibodies (aPL) prevalence and clinical relationships in a large cohort of COVID-19 patients.

Methods: We analysed the prevalence and titres of serum aPL in 122 patients with COVID-19 and 157 with primary antiphospholipid syndrome (PAPS) and 91 with other autoimmune rheumatic diseases (oARD) for comparison. IgG/IgM anticardiolipin (aCL) and IgG/IgM anti-beta2glycoprotein I (β2GPI) were assayed using homemade ELISA, IgA aCL and anti-β2GPI by commercial ELISA kits and lupus anticoagulant (LAC) by multiple coagulation tests following updated international guidelines.

Results: Prevalence of IgG and IgM aCL and of IgG and IgM anti-β2GPI across COVID-19 patients were 13.4%, 2.7%, 6.3% and 7.1%, being significantly lower than in PAPS (p<0.0001 for all). Frequency of IgG aCL and IgM anti-β2GPI was comparable to oARD (13.4% vs. 13.2% and 7.1% vs. 11%, respectively), while IgG anti-β2GPI and IgM aCL were lower (p<0.01). IgA aCL and IgA anti-β2GPI were retrieved in 1.7% and 3.3% of COVID-19 patients, respectively. Positive LAC was observed in 22.2% COVID-19 vs. 54.1% of PAPS (p<0.0001) and 14.6% of oARD (p=0.21). Venous or arterial thromboses occurred in 18/46 (39.1%) COVID-19 patients and were not associated with positive aPL (p=0.09).

Conclusions: Thrombosis is a frequent manifestation during COVID-19 infection. However, prevalence and titres of aPL antibodies or LAC were neither consistently increased nor associated with thrombosis when measured at a single timepoint, therefore not representing a suitable screening tool in the acute stage of disease.
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July 2020

Lack of EULAR/ERA-EDTA response at 1 year predicts poor long-term renal outcome in patients with lupus nephritis.

Ann Rheum Dis 2020 08 5;79(8):1077-1083. Epub 2020 Jun 5.

Division of Rheumatology, Department of Medicine, DIMED, University of Padova, Padova, Italy.

Objectives: Short-term predictive endpoints of chronic kidney disease (CKD) are needed in lupus nephritis (LN). We tested response to therapy at 1 year.

Methods: We considered patients with LN who underwent renal biopsy followed by induction therapy between January 1970 and December 2016. LN was assessed using the International Society of Nephrology/Renal Pathology Society (2003) criteria and the National Institute of Health (NIH) activity and chronicity index. The renal outcome was CKD. Response was defined according to EULAR/European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations: proteinuria <0.5 g/24 hours, (near) normal estimated glomerular filtration rate (eGFR); ≥50% proteinuria reduction to subnephrotic levels, (near) normal eGFR; and all the other cases. Logistic regression analysis was employed for 12-month response and Cox regression for CKD prediction.

Results: We studied 381 patients (90.5% Caucasians). After 12-month therapy, 58%, 26% and 16% of patients achieved complete, partial and no response, respectively, according to EULAR/ERA-EDTA. During a median follow-up of 10.7 (IQR: 4.97-18.80) years, 53 patients developed CKD. At 15 years, CKD-free survival rate was 95.2%, 87.6% and 55.4% in patients with complete, partial and no response at 12 months, respectively (p<0.0001). CKD-free survival rates did not differ between complete and partial responders (p=0.067). Serum creatinine (HR: 1.485, 95% CI 1.276 to 1.625), eGFR (HR 0.967, 95% CI 0.957 to 0.977) and proteinuria at 12 months (HR 1.234, 95% CI 1.111 to 1.379) were associated with CKD, yet no reliable cut-offs were identified on the receiver operating characteristic curve. In multivariable analysis, no EULAR/ERA-EDTA response at 12 months (HR 5.165, 95% CI 2.770 to 7.628), low C4 (HR 1.053, 95% CI 1.019 to 1.089) and persistent arterial hypertension (HR 3.154, 95% CI 1.500 to 4.547) independently predicted CKD.

Conclusions: Lack of EULAR/ERA-EDTA response at 12 months predicts CKD.
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http://dx.doi.org/10.1136/annrheumdis-2020-216965DOI Listing
August 2020

Multicentric study comparing cyclosporine, mycophenolate mofetil and azathioprine in the maintenance therapy of lupus nephritis: 8 years follow up.

J Nephrol 2021 04 27;34(2):389-398. Epub 2020 May 27.

Divisione di Nefrologia e Dialisi-Padiglione Croff, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico Milano, Via della Commenda 15, 20122, Milano, Italy.

Background: The ideal long-term maintenance therapy of Lupus Nephritis (LN) is still a matter of debate. The present study was aimed at comparing the efficacy/safety profile of cyclosporine (CsA), mycophenolate mofetil (MMF) and azathioprine (AZA) in long-term maintenance therapy of LN.

Methods: We performed a retrospective study of patients with biopsy-proven active LN. After induction therapy, all patients received maintenance therapy with CsA, MMF or AZA based on medical decision. Primary endpoint was complete renal remission (CRR) after 8 years (defined as proteinuria < 0.5 g/24 h, eGFR > 60 ml/min/1.73 mq); secondary endpoints were: CRR after 1 year, renal and extrarenal flares, progression of chronic kidney disease (CKD stage 3 or above) and side-effects.

Results: Out of 106 patients, 34 received CsA, 36 MMF and 36 AZA. Clinical and histological characteristics at start of induction therapy were comparable among groups. At start of maintenance therapy, CsA patients had significantly higher proteinuria (P = 0.004) or nephrotic syndrome (P = 0.024) and significantly lower CRR (23.5% vs 55.5% on MMF and 41.7% on AZA, P = 0.024). At one year, CRR was similar in the three groups (79.4% on CsA, 63.8% on MMF, 58.3% on AZA, P = 0.2). At 8 years, the primary endpoint was achieved by 79.4% of CsA vs 83.3% of MMF and 77.8% of AZA patients (P = 0.83); 24 h proteinuria, serum creatinine, eGFR were similar. CKD stage 3 or above developed in 8.8% of CsA, in 8.3% of MMF and in 8.3% of AZA patients (P = 0.92). Flares-free survival curves and incidence of side-effects were not different.

Conclusions: This is the first study comparing CsA, MMF and AZA on long-term LN maintenance therapy. All treatments had similar efficacy in achieving and maintaining CRR, despite more severe baseline clinical features in patients treated with CsA.
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http://dx.doi.org/10.1007/s40620-020-00753-wDOI Listing
April 2021

Rituximab-associated hypogammaglobulinaemia in ANCA-associated vasculitis and connective tissue diseases: a longitudinal observational study.

Clin Exp Rheumatol 2020 Mar-Apr;38 Suppl 124(2):188-194. Epub 2020 May 22.

Rheumatology Unit, Department of Medicine DIMED, University of Padova, Italy.

Objectives: The burden of hypogammaglobulinaemia following rituximab (RTX) treatment in rheumatic diseases has not been fully elucidated yet. Our aim was to evaluate the frequency and predictors of hypogammaglobulinaemia in patients affected by ANCA-associated vasculitis (AAV) and connective tissue diseases (CTD).

Methods: We retrospectively reviewed prospectively collected data of patients receiving RTX. Immunoglobulins (Ig) levels and lymphocyte subsets were recorded at RTX administration and 3-6 months later. We assessed frequency of hypogammaglobulinaemia (serum IgG<6 g/L) and its related events. Univariate and multivariable analysis were performed using SPSS 20.0 package.

Results: Sixty-eight patients (30 AAV, 25 systemic lupus erythematosus, 9 systemic sclerosis and 4 idiopathic inflammatory myopathies) were treated with RTX (95 infusions, median 2 [2-6]). Following RTX, IgG<6 g/L were observed in 15/68 patients (15.8%), IgM<0.4 g/L in 28/68 (41%) and IgA<0.7 g/L in 7/68 (10.2%). Hypogammaglobulinaemia was more common in patients with AAV (p=0.008), short disease duration (p=0.001), low IgG levels at baseline (p=0.008), high cyclophosphamide exposure (p=0.018), high daily and cumulative prednisone dosage (p=0.001 and p=0.006). At multivariate analysis, cumulative cyclophosphamide dosage (OR 1.1 [1.0-1.3] p=0.045), daily prednisone intake >15mg (OR 9.5 [2.2-41.7] p=0.03) and IgG levels before RTX (OR 0.74 [0.59-0.93] p=0.009) were independent predictors of hypogammaglobulinaemia. Five patients experienced severe infections within 12 months, more frequently in those with IgG<6 g/L (26.7% vs 1.9%, p=0.007).

Conclusions: Hypogammaglobulinaemia following RTX is uncommon in AAV and CTD and is more likely in patients with high glucocorticoids and cyclophosphamide exposure and low IgG levels at baseline.
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September 2020

Physician's global assessment is often useful in SLE, but not always: the case of clinical remission.

Ann Rheum Dis 2020 May 20. Epub 2020 May 20.

Department of Medicine DIMED, Division of Rheumatology, University of Padua, Padova, Italy

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http://dx.doi.org/10.1136/annrheumdis-2020-217611DOI Listing
May 2020

Remission in systemic lupus erythematosus: testing different definitions in a large multicentre cohort.

Ann Rheum Dis 2020 07 22;79(7):943-950. Epub 2020 Apr 22.

Department of Medicine, Division of Rheumatology, University of Padua, Padova, Italy

Objectives: Remission in systemic lupus erythematosus (SLE) is defined through a combination of 'clinical SLE Disease Activity Index (cSLEDAI)=0', 'physician's global assessment (PGA) <0.5' and 'prednisone (PDN) ≤5 mg/day'. We investigated the performance of these items, alone or in combination, in defining remission and in predicting SLICC/ACR Damage Index.

Methods: We tested seven potential definitions of remission in SLE patients followed-up for ≥5 years: PDN ≤5 mg/day; PGA <0.5; cSLEDAI=0; PGA <0.5 plus PDN ≤5 mg/day; cSLEDAI=0 plus PGA <0.5; cSLEDAI=0 plus PDN ≤5 mg/day; cSLEDAI=0 plus PDN ≤5 mg/day plus PGA <0.5. The effect of these definitions on damage was evaluated by Poisson regression analysis; the best performance was identified as the lowest Akaike and Bayesian information criterion (AIC and BIC). Positive and negative predictive values in identifying no damage increase were calculated.

Results: We 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 <0.5 0.631, 0.444 to 0.896; cSLEDAI=0 0.531, 0.371 to 0.759; PGA <0.5 plus PDN ≤5 mg/day 0.554, 0.381 to 0.805; cSLEDAI=0 plus PGA <0.5 0.574, 0.400 to 0.826; cSLEDAI=0 plus PDN ≤5 mg/day 0.543, 0.376 to 0.785; cSLEDAI=0 plus PDN ≤5 mg/day plus PGA <0.5 0.532, 0.363 to 0.781, p<0.01 for all), except PDN ≤5 mg/day, which required four consecutive years (OR 0.534, 95% CI 0.325 to 0.877, p=0.013). Positive and negative predictive values were similar; however, cSLEDAI=0 showed the best performance (AIC 1082.90, BIC 1109.72, p<0.0001). Adding PGA <0.5 and/or PDN ≤5 mg/day to cSLEDAI=0 decreased remission duration (-1.8 and -1.5 year/patient, respectively) without increasing cSLEDAI=0 performance in predicting damage accrual.

Conclusions: cSLEDAI=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.
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http://dx.doi.org/10.1136/annrheumdis-2020-217070DOI Listing
July 2020

Early Disease and Low Baseline Damage as Predictors of Response to Belimumab in Patients With Systemic Lupus Erythematosus in a Real-Life Setting.

Arthritis Rheumatol 2020 08 12;72(8):1314-1324. Epub 2020 Jun 12.

Università degli Studi di Genova, Genoa, Italy.

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.
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http://dx.doi.org/10.1002/art.41253DOI Listing
August 2020

Immunization with Pentraxin3 prevents transition from subclinical to clinical lupus nephritis in lupus-prone mice: Insights from renal ultrastructural findings.

J Autoimmun 2020 07 4;111:102443. Epub 2020 Apr 4.

Unit of Rheumatology, Department of Medicine (DIMED), University of Padova, Padova, Italy. Electronic address:

Background: Pentraxin3 (PTX3) is an emerging player in lupus nephritis (LN). Anti-PTX3 antibodies showed to delay LN occurrence in vivo.

Aim: To evaluate renal changes following immunization with PTX3 in a murine model of LN.

Materials And Methods: Twenty-two lupus-prone New Zealand Black/White (NZB/W)F1 mice were divided into two groups (n = 11) and subcutaneously injected with human recombinant (hr)PTX3 100 μg or phosphate buffer saline (PBS) 200 μl, three times 3 weeks apart, starting before development of proteinuria. Five mice from each group were scheduled for sacrifice at week 22 and 6 from each group at week 29. Renal lesions included electron-dense deposits (EDD), glomerular deposition of IgG, complement and PTX3 as markers of renal inflammation. They were evaluated by immunofluorescence (IF), confocal and immunoelectron microscopy (IEM). Validated semiquantitative scores were used when available to score renal lesions. Chi-squared test with Fisher exact test was used for comparison.

Results: Nineteen out of 22 mice were sacrificed as scheduled. Only hrPTX3-immunized mice developed anti-PTX3 antibodies. Compared to PBS-injected mice, they displayed a dramatic decrease in glomerular deposits of IgG, C1q and PTX3, as well as in the amount of EDD (p = 0.006) and podocyte effacement (p = 0.043). Importantly, PTX3 was pinpointed inside the EDD and co-localized with nuclear material.

Conclusions: Immunization with PTX3 prevented progression from the preclinical to the clinical stage of LN, inciting anti-PTX3 antibodies and preventing renal PTX3 deposition. PTX3 is a novel component of EDD, submitting it as one initiating autoantigen in LN and as potential target for early treatment.
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http://dx.doi.org/10.1016/j.jaut.2020.102443DOI Listing
July 2020

Preclinical and early systemic lupus erythematosus.

Best Pract Res Clin Rheumatol 2019 08 12;33(4):101422. Epub 2019 Jul 12.

Division of Rheumatology, Department of Medicine, University of Padova, Italy. Electronic address:

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.
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http://dx.doi.org/10.1016/j.berh.2019.06.004DOI Listing
August 2019

Prevalence and predictors of flare after immunosuppressant discontinuation in patients with systemic lupus erythematosus in remission.

Rheumatology (Oxford) 2020 07;59(7):1591-1598

Rheumatology Unit, Department of Medicine, University of Padova, Padova, Italy.

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.
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http://dx.doi.org/10.1093/rheumatology/kez422DOI Listing
July 2020

Pulmonary involvement in antisynthetase syndrome.

Curr Opin Rheumatol 2019 11;31(6):603-610

Division of Rheumatology, Department of Medicine, University of Padua, Padua, Italy.

Purpose Of Review: Lung involvement is a distinctive feature of antisynthetase syndrome (ASS) and it is considered a basic disease-classifying criterion. In this review, we go over clinical features, radiological patterns, prognostic factors, pathogenesis and treatment of lung involvement in ASS patients, focusing on the clinical differences linked to the different antibody specificities known so far.

Recent Findings: The lung is the most common extramuscular organ involved in ASS and has the greatest impact on patient prognosis. The pulmonary disease-defining manifestation in ASS is interstitial lung disease (ILD), yet a proportion of patients also develop pulmonary arterial hypertension and, less frequently, obstructive bronchiolitis or acute respiratory failure according to drivers not yet fully understood but likely associated with the underlying autoantibody pattern. Clinical presentation of pulmonary involvement can range from milder forms to a rapidly progressive disease which may lead to chronic lung damage if misdiagnosed and not properly treated.

Summary: The knowledge of risk factors associated with progressive or refractory lung damage is important to identify and properly treat patients with the poorest prognosis. For those with a disease not responsive to conventional therapy the efficacy of other therapeutic option is under evaluation.
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http://dx.doi.org/10.1097/BOR.0000000000000663DOI Listing
November 2019

Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis.

Front Immunol 2019 25;10:29. Epub 2019 Jan 25.

Unit of Rheumatology, Department of Medicine, University of Padova, Padua, Italy.

Pentraxin3 (PTX3) is overexpressed in kidneys of patients developing lupus nephritis (LN). Active LN is associated with reduced anti-PTX3 antibodies. However, abnormalities of B cell differentiation against PTX3 have not been characterized in systemic lupus erythematosus (SLE). Characterization of PTX3-specific (PTX3) B cells in peripheral blood of SLE patients with or without LN and healthy donors (HD). SLE patients without LN, biopsy-proven LN and matched HD were analyzed. Active LN was defined as proteinuria>0.5 g/day or CrCl<60 ml/min/1.73 m with active urinary sediment. Peripheral B cells were analyzed for direct PTX3 binding by flow cytometry using PTX3 labeled with cyanine 5 (Cy5) and phycoerythrin (PE). Initially, a flow cytometry based assay to identify PTX3 B cells was developed by demonstrating simultaneous binding of PTX3-Cy5 and PTX3-PE. Specificity of B cells was validated by blocking experiments using unlabeled PTX3. We could identify circulating PTX3 B-cells in HD and patients. Notably, LN patients showed a significantly diminished number of PTX3 B cells (SLE vs. LN = 0.033; HD vs. LN = 0.008). This decrease was identified in naïve and memory B cell compartments (naïve: SLE vs. LN = 0.028; HD vs. LN = 0.0001; memory: SLE vs. LN = 0.038, HD vs. LN = 0.011). Decreased PTX3 B cells in LN within the naïve and memory compartment suggest their negative selection at early stages of B cell development potentially related to a decreased regulatory function. PTX3 B cells could candidate for autoantigen-defined regulatory B cells as a striking abnormality of LN patients.
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http://dx.doi.org/10.3389/fimmu.2019.00029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355680PMC
December 2019

IL-12 and IL-23/Th17 axis in systemic lupus erythematosus.

Exp Biol Med (Maywood) 2019 01 21;244(1):42-51. Epub 2019 Jan 21.

1 Department of Medicine-DIMED, Division of Rheumatology, University of Padova, 35128 Padova, Italy.

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.
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http://dx.doi.org/10.1177/1535370218824547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362534PMC
January 2019

New therapeutic strategies in systemic lupus erythematosus management.

Nat Rev Rheumatol 2019 01;15(1):30-48

Unit of Rheumatology, Department of Medicine, University of Padova, Padova, Italy.

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.
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http://dx.doi.org/10.1038/s41584-018-0133-2DOI Listing
January 2019

SERPINB3 Delays Glomerulonephritis and Attenuates the Lupus-Like Disease in Lupus Murine Models by Inducing a More Tolerogenic Immune Phenotype.

Front Immunol 2018 11;9:2081. Epub 2018 Sep 11.

Rheumatology Unit, Department of Medicine (DIMED), University of Padova, Padova, Italy.

To explore the effects of SERPINB3 administration in murine lupus models with a focus on lupus-like nephritis. 40 NZB/W F1 mice were subdivided into 4 groups and intraperitoneally injected with recombinant SERPINB3 (7.5 μg/0.1 mL or 15 μg/0.1 mL) or PBS (0.1 mL) before (group 1 and 2) or after (group 3 and 4) the development of proteinuria (≥100 mg/dl). Two additional mice groups were provided by including 20 MRL/ mice which were prophylactically injected with SERPINB3 (10 mice, group 5) or PBS (10 mice, group 6). Time of occurrence and levels of anti-dsDNA and anti-C1q antibodies, proteinuria and serum creatinine, overall- and proteinuria-free survival were assessed in mice followed up to natural death. Histological analysis was performed in kidneys of both lupus models. The Th17:Treg cell ratio was assessed by flow-cytometry in splenocytes of treated and untreated MRL/ mice. Statistical analysis was performed using non parametric tests and Kaplan-Meier curves, when indicated. Autoantibody levels and proteinuria were significantly decreased and time of occurrence significantly delayed in SERPINB3-treated mice vs. controls. In agreement with these findings, proteinuria-free and overall survival were significantly improved in SERPINB3-treated groups vs. controls. Histological analysis demonstrated a lower prevalence of severe tubular lesions in kidneys of group 5 vs. group 6. SERPINB3-treated mice showed an overall trend toward a reduced prevalence of severe lesions in both strains. Th17:Treg ratio was significantly decreased in splenocytes of MRL/ mice treated with SERPINB3, compared to untreated control mice. SERPINB3 significantly improves disease course and delays the onset of severe glomerulonephritis in lupus-prone mice, possibly inducing a more tolerogenic immune phenotype.
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http://dx.doi.org/10.3389/fimmu.2018.02081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141748PMC
September 2019

Correction to: Effectiveness, Tolerability, and Safety of Belimumab in Patients with Refractory SLE: a Review of Observational Clinical-Practice-Based Studies.

Clin Rev Allergy Immunol 2018 10;55(2):237

Division of Rheumatology, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.

The following changes are made for this article: (1.) Maddalena Larosa's given name and surname were inadvertently interchanged. The authorgroup section is now corrected. (2.) The author(s)' decision to opt for Open Choice.
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http://dx.doi.org/10.1007/s12016-018-8704-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182622PMC
October 2018

Changing patterns in clinical-histological presentation and renal outcome over the last five decades in a cohort of 499 patients with lupus nephritis.

Ann Rheum Dis 2018 09 5;77(9):1318-1325. Epub 2018 May 5.

Division of Rheumatology, Department of Medicine, DIMED, University of Padua, Padua, Italy.

Objectives: To evaluate changes in demographic, clinical and histological presentation, and prognosis of lupus nephritis (LN) over time.

Patients And Methods: We 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.

Results: A progressive increase in patient age at the time of LN diagnosis (p<0.0001) and a longer time between systemic lupus erythematosus onset and LN occurrence (p<0.0001) was observed from 1970 to 2016. During the same period, the frequency of renal insufficiency at the time of LN presentation progressively decreased (p<0.0001) and that of isolated urinary abnormalities increased (p<0.0001). No changes in histological class and activity index were observed, while chronicity index significantly decreased from 1970 to 2016 (p=0.023). Survival without end-stage renal disease (ESRD) was 87% in P1, 94% in P2% and 99% in P3 at 10 years, 80% in P1 and 90% in P2 at 20 years (p=0.0019). At multivariate analysis, male gender, arterial hypertension, absence of maintenance immunosuppressive therapy, increased serum creatinine, and high activity and chronicity index were independent predictors of ESRD.

Conclusions: Clinical presentation of LN has become less severe in the last years, leading to a better long-term renal survival.
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http://dx.doi.org/10.1136/annrheumdis-2017-212732DOI Listing
September 2018

Effectiveness, Tolerability, and Safety of Belimumab in Patients with Refractory SLE: a Review of Observational Clinical-Practice-Based Studies.

Clin Rev Allergy Immunol 2018 04;54(2):331-343

Division of Rheumatology, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.

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.
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http://dx.doi.org/10.1007/s12016-018-8675-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132773PMC
April 2018

Controversies in Rheumatology and Autoimmunity: Approaching the truth by the discussion.

Autoimmun Rev 2018 01 3;17(1):1-3. Epub 2017 Nov 3.

Rheumatology Unit, L. Sacco University Hospital, Milan, Italy.

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http://dx.doi.org/10.1016/j.autrev.2017.11.001DOI Listing
January 2018

Can we withdraw immunosuppressants in patients with lupus nephritis in remission? An expert debate.

Autoimmun Rev 2018 Jan 3;17(1):11-18. Epub 2017 Nov 3.

Joint Rheumatology Program, 4th Department of Medicine, "Attikon" University Hospital, National and Kapodistrian University of Athens Medical School and Biomedical Research Foundation of the Athens Academy, Athens, Greece; Medical School, University of Cyprus, Nicosia, Cyprus. Electronic address:

Lupus nephritis (LN) treatment requires an initial intensive period of therapy followed by a long-term maintenance treatment in order to stabilize disease control and eventually reach renal remission. In this section, Authors discuss the feasibility of safely lowering and even suspending maintenance therapy in LN patients having entered remission, highlighting hurdles in predicting the depth and durability of disease quiescence together with the need for minimizing potentially toxic therapies. Even though no firm conclusions can still be drawn, the treating physician has to find the wise balance between disease control and treatment-related drawbacks by following patients closely and recognizing as early as possible the ones who are likely to reach a deep and durable renal remission; there is consensus that is these are the only patients in whom a potential safe complete withdrawal can be foreseen so far.
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http://dx.doi.org/10.1016/j.autrev.2017.11.003DOI Listing
January 2018

Lupus low disease activity state is associated with a decrease in damage progression in Caucasian patients with SLE, but overlaps with remission.

Ann Rheum Dis 2018 Jan 26;77(1):104-110. Epub 2017 Sep 26.

Department of Medicine, University of Padova, Division of Rheumatology, Padova, Italy.

Objective: To 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).

Methods: We 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.

Results: LLDAS 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, p<0.001). On average, 84% of patients in LLDAS also fulfilled the criteria for remission.

Conclusions: LLDAS 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.
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http://dx.doi.org/10.1136/annrheumdis-2017-211613DOI Listing
January 2018

Clinical predictors of response and discontinuation of belimumab in patients with systemic lupus erythematosus in real life setting. Results of a large, multicentric, nationwide study.

J Autoimmun 2018 01 19;86:1-8. Epub 2017 Sep 19.

Division of Rheumatology, Department of Medicine-DIMED, University of Padova, Padova, Italy. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jaut.2017.09.004DOI Listing
January 2018

Unresolved and critical issues in autoimmune rheumatic diseases.

Autoimmun Rev 2017 11 12;16(11):1093-1095. Epub 2017 Sep 12.

Rheumatology Unit, L. Sacco University Hospital, Milan, Italy.

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http://dx.doi.org/10.1016/j.autrev.2017.09.001DOI Listing
November 2017

The new targeted therapy in systemic lupus erythematosus: Is the glass half-full or half-empty?

Autoimmun Rev 2017 Nov 9;16(11):1119-1124. Epub 2017 Sep 9.

Policlinic and Hiller Research Unit for Rheumatology, UKD, Heinrich-Heine-University Duesseldorf, Germany.

Biologic therapy is still limited in lupus, where chronic steroid exposure and wide-spectrum immunosuppression are major triggers of organ damage. In this viewpoint, the authors summarize their views for a "half-full or half-empty" glass on targeted therapy in SLE. The are several reasons for seeing the glass half-empty and in this section the authors propose a critical reflection on scarceness of novel targeted lupus therapies. They show how hard it is to identify suitable biological and clinical targets and to choose the patients that may best fit those targets, as well as to stratify patients according to disease subtype and response, all contributing to the final outcome. On the other hand, reasons are emerging to see the glass half-full, including the growing evidence that disease activity and damage can both be hindered by the proper use of novel drugs and that promising molecules are upcoming. In this section, the authors contextualize potentials and failures of new drugs, providing a critical reading of disappointing results and underlining the concrete benefits obtainable through a wise use of available treatments. Indeed, combining medications with new therapeutic strategies such as the treat-to-target seems the right approach to add some water to a filling glass.
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http://dx.doi.org/10.1016/j.autrev.2017.09.006DOI Listing
November 2017