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Systemic Lupus Erythematosus: HELP
Articles by Luca Iaccarino
Based on 38 articles published since 2010
(Why 38 articles?)
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Between 2010 and 2020, L. Iaccarino wrote the following 38 articles about Lupus Erythematosus, Systemic.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial When to use belimumab in SLE. 2017

Gatto, Mariele / Iaccarino, Luca / Zen, Margherita / Doria, Andrea. ·a Division of Rheumatology , University of Padova , Padova , Italy. ·Expert Rev Clin Immunol · Pubmed #28463023.

ABSTRACT: -- No abstract --

2 Review Preclinical and early systemic lupus erythematosus. 2019

Gatto, Mariele / Saccon, Francesca / Zen, Margherita / Iaccarino, Luca / Doria, Andrea. ·Division of Rheumatology, Department of Medicine, University of Padova, Italy. · Division of Rheumatology, Department of Medicine, University of Padova, Italy. Electronic address: adoria@unipd.it. ·Best Pract Res Clin Rheumatol · Pubmed #31810542.

ABSTRACT: 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.

3 Review New therapeutic strategies in systemic lupus erythematosus management. 2019

Gatto, Mariele / Zen, Margherita / Iaccarino, Luca / Doria, Andrea. ·Unit of Rheumatology, Department of Medicine, University of Padova, Padova, Italy. · Unit of Rheumatology, Department of Medicine, University of Padova, Padova, Italy. adoria@unipd.it. ·Nat Rev Rheumatol · Pubmed #30538302.

ABSTRACT: 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.

4 Review Effectiveness, Tolerability, and Safety of Belimumab in Patients with Refractory SLE: a Review of Observational Clinical-Practice-Based Studies. 2018

Trentin, Francesca / Gatto, Mariele / Zen, Margherita / Larosa, Maddalena / Maddalena, Larosa / Nalotto, Linda / Saccon, Francesca / Zanatta, Elisabetta / Iaccarino, Luca / Doria, Andrea. ·Division of Rheumatology, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy. · Division of Rheumatology, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy. adoria@unipd.it. ·Clin Rev Allergy Immunol · Pubmed #29512034.

ABSTRACT: 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.

5 Review Rheumatic diseases and autoimmune vascular dementia. 2017

Atzeni, Fabiola / Pipitone, Nicolò / Iaccarino, Luca / Masala, Ignazio Francesco / Weiss, Ronen / Alciati, Alessandra / Doria, Andrea / Chapmanand, Joab / Sarzi-Puttini, Piercarlo. ·IRCCS Orthopedic Institute of Galeazzi, Milan, Italy. Electronic address: atzenifabiola@hotmail.com. · Rheumatology Department, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. · Division of Rheumatology, University of Padoa, Italy. · Orthopedic and Trauma Unit, Santissima Trinità Hospital, Cagliari, Italy. · Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel; Department of Neurology, Chaim Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Hashomer, Israel. · Department of Clinical Neurosciences, Villa San Benedetto Menni, Hermanas Hospitalarias, FoRiPsi, Albese con Cassano, Como, Italy. · Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel; Department of Neurology, Robert and Martha Harden Chair in Mental and Neurological Diseases, Sackler Faculty of Medicine, Tel Aviv University, Israel. · Rheumatology Unit, L. Sacco University Hospital, Milan, Italy. ·Autoimmun Rev · Pubmed #29037904.

ABSTRACT: Vascular dementia (VD) comes second after Alzheimer's disease (AD) as a cause of impaired cognition. VD is not a specific nosological entity, but rather a syndrome encompassing a number of diseases caused by impaired supply of blood to the brain. Systemic autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis and antiphospholipid syndrome (APS) can be associated with dementia. VD is often related to the presence of traditional cardiovascular risk factors, but it may also be associated with a host of disorders affecting the brain blood vessels, neuronal cells, or both. It is important to entertain in the differential diagnosis of VD, to recognize and to cure them accurately in order to preserve life's quality of our patients.

6 Review The Management of Systemic Lupus Erythematosus (SLE) Patients in Remission. 2017

Zen, Margherita / Gatto, Mariele / Nalotto, Linda / Larosa, Maddalena / Iaccarino, Luca / Doria, Andrea. ·Division of Rheumatology, Department of Medicine, DIMED, University of Padua, Italy. ·Isr Med Assoc J · Pubmed #28786263.

ABSTRACT: -- No abstract --

7 Review Role of galectin-3 in autoimmune and non-autoimmune nephropathies. 2017

Saccon, Francesca / Gatto, Mariele / Ghirardello, Anna / Iaccarino, Luca / Punzi, Leonardo / Doria, Andrea. ·Division of Rheumatology, Department of Medicine (DIMED), University of Padova, Italy. · Division of Rheumatology, Department of Medicine (DIMED), University of Padova, Italy. Electronic address: adoria@unipd.it. ·Autoimmun Rev · Pubmed #27666815.

ABSTRACT: Galectins are evolutionary conserved β-galactoside binding proteins with a carbohydrate-recognition domain (CRD) of approximately 130 amino acids. In mammals, 15 members of the galectin family have been identified and classified into three subtypes according to CRD organization: prototype, tandem repeat-type and chimera-type galectins. Galectin-3 (gal-3) is the only chimera type galectin in vertebrates containing one CRD linked to an unusual long N-terminal domain which displays non-lectin dependent activities. Although recent studies revealed unique, pleiotropic and context-dependent functions of gal-3 in both extracellular and intracellular space, gal-3 specific pathways and its ligands have not been clearly defined yet. In the kidney gal-3 is involved in later stages of nephrogenesis as well as in renal cell cancer. However, gal-3 has recently been associated with lupus glomerulonephritis, with Familial Mediterranean Fever-induced proteinuria and renal amyloidosis. Gal-3 has been studied in experimental acute kidney damage and in the subsequent regeneration phase as well as in several models of chronic kidney disease, including nephropathies induced by aging, ischemia, hypertension, diabetes, hyperlipidemia, unilateral ureteral obstruction and chronic allograft injury. Because of the pivotal role of gal-3 in the modulation of immune system, wound repair, fibrosis and tumorigenesis, it is not surprising that gal-3 can be an intriguing prognostic biomarker as well as a promising therapeutic target in a great variety of diseases, including chronic kidney disease, chronic heart failure and cardio-renal syndrome. This review summarizes the functions of gal-3 in kidney pathophysiology focusing on the reported role of gal-3 in autoimmune diseases.

8 Review Success and failure of biological treatment in systemic lupus erythematosus: A critical analysis. 2016

Gatto, Mariele / Saccon, Francesca / Zen, Margherita / Bettio, Silvano / Iaccarino, Luca / Punzi, Leonardo / Doria, Andrea. ·Division of Rheumatology, Department of Medicine, University of Padova, Via Giustiniani 2, 35123, Padova, Italy. · Division of Rheumatology, Department of Medicine, University of Padova, Via Giustiniani 2, 35123, Padova, Italy. Electronic address: adoria@unipd.it. ·J Autoimmun · Pubmed #27373904.

ABSTRACT: 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.

9 Review Advances in the diagnosis and classification of systemic lupus erythematosus. 2016

Larosa, Maddalena / Iaccarino, Luca / Gatto, Mariele / Punzi, Leonardo / Doria, Andrea. ·a Department of Medicine - DIMED, Division of Rheumatology , University of Padova , Padova , Italy. ·Expert Rev Clin Immunol · Pubmed #27362864.

ABSTRACT: INTRODUCTION: Systemic lupus erythematosus (SLE) is the prototype of systemic autoimmune diseases. Patients with SLE display a wide spectrum of clinical and serological findings that can mislead and delay the diagnosis. Diagnostic criteria have not been developed yet, whereas several sets of classification criteria are available; however, none of them has 100% sensitivity and 100% specificity, i.e. the hallmark of diagnostic criteria. Nevertheless, classification criteria are often misused as diagnostic criteria, which may affect earliness of diagnosis and lead to more misdiagnosed cases. Areas covered: In this review, we compare old and new classification criteria, discussing their application and pinpointing their limitations in the management of patients. Moreover, we will focus on current and novel biomarkers for SLE diagnosis, highlighting their predictive value and applicability in clinical practice. Expert commentary: SLE diagnosis still represents a challenge, remaining largely based on a clinical judgment. Besides SLE diagnosis, even its classification is still challenging to date. Indeed, although classification of SLE seems to be achieved more frequently with the 2012 SLICC criteria than with the previous 1997 ACR criteria, this last-updated 2012 set might be improved. Notably, diagnostic and classification criteria should be applied to any subject in the world, and consequently they should include immunological variables validated in different populations, which is still an unmet need.

10 Review Clinical and pathologic considerations of the qualitative and quantitative aspects of lupus nephritogenic autoantibodies: A comprehensive review. 2016

Gatto, Mariele / Iaccarino, Luca / Ghirardello, Anna / Punzi, Leonardo / Doria, Andrea. ·Division of Rheumatology, Department of Medicine, University of Padova, Via Giustiniani 2, 35123 Padova, Italy. · Division of Rheumatology, Department of Medicine, University of Padova, Via Giustiniani 2, 35123 Padova, Italy. Electronic address: adoria@unipd.it. ·J Autoimmun · Pubmed #26879422.

ABSTRACT: Autoantibodies are key mediators in determining the clinical manifestations of systemic lupus erythematosus (SLE). The mechanisms by which antibodies may be harmful to self tissues encompass complement mediated inflammation, cell apoptosis and immune-complexes mediated damage, however the precise cooperation of antibodies in SLE have not been unravelled so far. Lupus nephritis (LN) is a protean feature of SLE resulting in wide variety of symptoms including asymptomatic proteinuria, mild renal disease until end-stage renal failure which are triggered by complex autoantibody interactions. Novel clues concerning development and self-maintenance of LN have come to light in recent times, pointing straight to a multistep inflammatory process which is incited by anti-chromatin antibodies, the best known being anti-DNA and anti-nucleosome antibodies, culminating in a self-maintaining inflammatory loop with spreading of glomerular inflammation. In the maintenance of the inflammatory process pro-inflammatory antibodies are involved, among which anti-C1q are thought to play a major role, whereas hindrance of the nephritic process could be actively mediated by protective autoantibodies. Despite being so relevant in occurrence of LN, nor anti-chromatin neither anti-C1q antibodies have been precisely characterized in terms of origin, antigen specificity and mechanisms of action. Moreover, novel autoantibodies are emerging in LN which can modify disease course, whereas the pathogenic value of a myriad of cross-reactive antibodies has been progressively challenged. The aim of this review is to give a comprehensive view of known and emerging autoantibody reactivities involved in renal inflammation and damage going over their origin, mechanisms of action and interactions in determining LN course.

11 Review Cardiovascular risk factors, burden of disease and preventive strategies in patients with systemic lupus erythematosus: a literature review. 2015

Benvenuti, Francesco / Gatto, Mariele / Larosa, Maddalena / Iaccarino, Luca / Punzi, Leonardo / Doria, Andrea. ·a 1 University of Padova, Division of Rheumatology, Department of Medicine , Via Giustiniani 2, 35128 Padova, Italy +390 498 212 202, +393 388 072 644 ; +390 498 212 191 ; adoria@unipd.it. ·Expert Opin Drug Saf · Pubmed #26212119.

ABSTRACT: INTRODUCTION: Risk of developing cardiovascular disease (CVD) is increased in systemic lupus erythematosus (SLE) compared with the general population. Traditional risk factors cannot account for the totality of CV events and adequate prevention may be challenging. AREAS COVERED: This review summarizes traditional and emerging risk factors of CVD in SLE patients and goes over potential pathogenic mechanisms involved in CVD development. Role of commonly used drugs and preventive strategies exploitable in everyday clinical practice are also discussed. EXPERT OPINION: SLE-related risk factors involve both disease- and treatment-related features, including disease activity, disease phenotype, corticosteroid misuse and alterations of innate and adaptive immunity. Primary prevention is mandatory in management of lupus patients through appropriate disease control, corticosteroid tapering, use of antimalarials and eventually vitamin D supplementation.

12 Review Value and goals of treat-to-target in systemic lupus erythematosus: knowledge and foresight. 2015

Doria, A / Gatto, M / Iaccarino, L / Punzi, L. ·Division of Rheumatology, Department of Medicine, University of Padova, Padova, Italy adoria@unipd.it. · Division of Rheumatology, Department of Medicine, University of Padova, Padova, Italy. ·Lupus · Pubmed #25801894.

ABSTRACT: Treat-to-target is a therapeutic strategy aimed at improving disease outcome through the achievement of shared treatment goals, which has dramatically ameliorated the prognosis of widespread disorders, such as hypertension or diabetes. Conversely, efforts to delineate treat-to-target in systemic lupus erythematosus (SLE) have failed in pinpointing common goals and treatment strategies, probably because of disease heterogeneity and lack of measurable biomarkers predicting disease course and ensuring a safe treatment tapering during quiescence. Given the detrimental effects of persistent disease activity and protracted corticosteroid therapy on patients' outcome in lupus, disease remission should be pursued whenever possible. Fortunately, clinical remission is currently realistic for a greater number of patients than it was in the past, yet tight monitoring is required in order for patients to benefit from disease- and corticosteroid-free intervals, while minimizing the risk of disease flares. In everyday practice, patients should be brought to the lowest level of disease activity ensuring a significant benefit over a persistently active disease, being either clinical remission or low disease activity.

13 Review Optimizing outcome in SLE: treating-to-target and definition of treatment goals. 2014

Doria, Andrea / Gatto, Mariele / Zen, Margherita / Iaccarino, Luca / Punzi, Leonardo. ·Division of Rheumatology, University of Padova, Padua, Italy. Electronic address: adoria@unipd.it. · Division of Rheumatology, University of Padova, Padua, Italy. ·Autoimmun Rev · Pubmed #24480071.

ABSTRACT: Patients affected with systemic lupus erythematosus (SLE) display poor-long term prognosis and increased mortality in respect of general population. This may be due to continuous organ damage accrual which is fostered both by persistent disease activity (mainly in the short term) and prolonged corticosteroid exposure (mainly in the long term). The effort of defining novel therapeutic goals to which patients should be treated in order to have their prognosis improved is named treat-to-target. Remission in SLE was shown to be associated with better outcome and prolonged survival; in clinical practice, patients may experience either complete or clinical remission, which are defined as complete clinical/serological healing or no clinical signs of lupus with active serology, respectively. The main treat-to-target in SLE is complete remission, however since longitudinal observations suggest that clinical remission or low disease activity even with minimal corticosteroid intake do improve patients prognosis and survival as well, they may be assumed as acceptable alternative targets. Suitable therapeutic strategies have to be defined in order for these goals to be achieved including early diagnosis, effective treatment and proper corticosteroid tapering which in turn require development of more reliable serum biomarkers for early disease detection and less toxic targeted therapies with a steroid-sparing potential.

14 Review Serpins, immunity and autoimmunity: old molecules, new functions. 2013

Gatto, Mariele / Iaccarino, Luca / Ghirardello, Anna / Bassi, Nicola / Pontisso, Patrizia / Punzi, Leonardo / Shoenfeld, Yehuda / Doria, Andrea. ·Division of Rheumatology, Department of Medicine, University of Padua, Via Giustiniani 2, 35128, Padua, Italy. ·Clin Rev Allergy Immunol · Pubmed #23325331.

ABSTRACT: Serine protease inhibitors (serpins) are evolutionary old, structurally conserved molecules which encompass nearly all branches of life. More than 1,000 serpins were characterized to date which are subdivided into 16 subgroups (A-P) according to their common ancestry; among them, 37 are found in humans. Serpins were termed after their capability to inhibit serine proteases, but mounting evidence suggests that they may achieve a greater deal of functions, ranging from embryological growth to synaptic plasticity, development of both myeloid and lymphoid immune cells, and modulation of apoptosis. Serpins are mainly extracellular molecules, although some of them (namely, ov-serpins or clade B serpins) mostly act inside the cells, being either ubiquitously or tissue-specifically expressed. Among newly characterized serpin functions, regulation of cellular proliferation through apoptosis modulation and proteasome disturbance seems to play a major role. Accordingly, several serpins were found to be hyperexpressed in tumor cells. Indeed, apoptosis dysregulation is likely to be a cornerstone in both tumorigenesis and autoimmunity, since uncontrolled cellular viability results in tumor proliferation, while inefficient disposal of apoptotic debris may favor the rescue of autoreactive immune cells. Such a process was widely documented in systemic lupus erythematosus (SLE). Interestingly, alterations in the expression of some serpins, e.g., the ov-serpin SERPINB3, are being unraveled in patients affected with SLE and other autoimmune disorders, suggesting that a failure in serpin function might affect immune homeostasis and self-tolerance, thereby contributing to autoimmunity. Here, we provide an overview of serpin origin, function, and dysfunction, focusing on human serpins and ov-serpins, with a hub on SERPINB3.

15 Review Emerging and critical issues in the pathogenesis of lupus. 2013

Gatto, Mariele / Zen, Margherita / Ghirardello, Anna / Bettio, Silvano / Bassi, Nicola / Iaccarino, Luca / Punzi, Leonardo / Doria, Andrea. ·Division of Rheumatology, Department of Medicine, University of Padova, Via Giustiniani 2, 35128 Padova, Italy. ·Autoimmun Rev · Pubmed #23000207.

ABSTRACT: Systemic lupus erythematosus (SLE) is a multisystemic, autoimmune disease, encompassing either mild or severe manifestations. SLE was originally labeled as being an immune complex-mediated disease, but further knowledge suggested its pathogenesis is motlier than that, involving complex interactions between predisposed individuals and their environment. People affected with SLE have their immune system skewed toward aberrant self-recognition usually after encountering a triggering agent. Defeats in early and late immune checkpoints contribute to tolerance breakdown and further generation and expansion of autoreactive cell-clones. B and T cells play a master role in SLE, however clues are emerging about other cell types and new light is being shed on SLE autoantibodies, since some of them display really harmful potential (pathogenic antibodies), while others are just connected with disease development (pathological antibodies) and may even be protective. Autoantibody generation is elicited by abnormal apoptosis and inefficient clearance of cellular debris causing intracellular autoantigens (e.g. nucleosomes) to persist in the extracellular environment, being further recognized by autoreactive cells. Here we explore the complexity of SLE pathogenesis through five core issues, i.e. genetic predisposition, B and T cell abnormalities, abnormal autoantigen availability, autoantibody generation and organ damage, relying on current knowledge and recent insights into SLE development.

16 Review SLE diagnosis and treatment: when early is early. 2010

Doria, Andrea / Zen, Margherita / Canova, Mariagrazia / Bettio, Silvano / Bassi, Nicola / Nalotto, Linda / Rampudda, Mariaelisa / Ghirardello, Anna / Iaccarino, Luca. ·Division of Rheumatology, Department of Clinical and Experimental Medicine, University of Padova, Italy. adoria@unipd.it ·Autoimmun Rev · Pubmed #20813207.

ABSTRACT: Around 1980 antinuclear antibody testing became widely used in routine laboratory practice leading to a tapering in the lag time between SLE onset and diagnosis. Since then nothing relevant has been introduced which could help us in making the diagnosis of SLE earlier than now. Notably, there is increasing evidence that early diagnosis and treatment could increase SLE remission rate and improve patient prognosis. Although it has been shown that autoantibodies appear before clinical manifestations in SLE patients, currently we cannot predict which autoantibody positive subjects will eventually develop the disease. Thus, great effort should be made in order to identify new biomarkers able to improve our diagnostic potential. B lymphocyte stimulator (BLyS), anti-ribosomal P protein and anti-C1q antibodies are among the most promising. In recent years, some therapeutic options have emerged as appropriate interventions for early SLE treatment, including antimalarials, vitamin D, statins and vaccination with self-derived peptides. All these immune modulators seem to be particularly useful when introduced in an early stage of the disease.

17 Review Hormones, immune response, and pregnancy in healthy women and SLE patients. 2010

Zen, Margherita / Ghirardello, Anna / Iaccarino, Luca / Tonon, Michele / Campana, Carla / Arienti, Silvia / Rampudda, Mariaelisa / Canova, Mariagrazia / Doria, Andrea. ·Division of Rheumatology, Clinical and Experimental Medicine, University of Padova, Padova, Italy. adoria@unipd.it ·Swiss Med Wkly · Pubmed #20175004.

ABSTRACT: During pregnancy the maternal immune system is modified in order to achieve immune tolerance toward paternal antigen expressed on foetal cells. These modifications, which occur both at the foeto-maternal interface and in the systemic circulation, are driven by oestrogens and progesterone whose blood concentrations increase during pregnancy. The cytokine profile is also modified. Th2 cytokines are enhanced while the Th1 response is inhibited. This could explain why Th1-mediated autoimmune diseases tend to improve and Th2-mediated diseases, such as systemic lupus erythematosus (SLE), tend to worsen during pregnancy. However, whether or not SLE relapses more frequently during pregnancy is still a matter of debate. Steroid hormone and cytokine profiles differ in SLE patients compared with healthy subjects during pregnancy leading to a dysregulation of the balance between cell-mediated and humoral immune response, which, in turn, could explain the variability of the SLE course during gestation. This review focuses on hormonal-related cytokine changes observed during pregnancy in healthy subjects and SLE patients.

18 Clinical Trial Effects of Belimumab on Flare Rate and Expected Damage Progression in Patients With Active Systemic Lupus Erythematosus. 2017

Iaccarino, Luca / Bettio, Silvano / Reggia, Rossella / Zen, Margherita / Frassi, Micol / Andreoli, Laura / Gatto, Mariele / Piantoni, Silvia / Nalotto, Linda / Franceschini, Franco / Larosa, Maddalena / Fredi, Micaela / Punzi, Leonardo / Tincani, Angela / Doria, Andrea. ·University of Padova, Padova, Italy. · Spedali Civili and University of Brescia, Brescia, Italy. ·Arthritis Care Res (Hoboken) · Pubmed #27390293.

ABSTRACT: 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 < 0.001), particularly in those with CLP (P < 0.001), and CLASI decreased in patients with skin manifestation (P = 0.003), either ACLE (P = 0.051) or SCLE (P = 0.047). Flare rate was lower 1 and 2 years after belimumab initiation than in the periods before (P = 0.001). Belimumab was well-tolerated and no damage accrual was observed after initiation. CONCLUSION: Belimumab was effective and safe in a clinical practice setting; it decreased the number of flares and hindered damage progression in patients with active SLE.

19 Clinical Trial Efficacy and safety of off-label use of rituximab in refractory lupus: data from the Italian Multicentre Registry. 2015

Iaccarino, Luca / Bartoloni, Elena / Carli, Linda / Ceccarelli, Fulvia / Conti, Fabrizio / De Vita, Salvatore / Ferraccioli, Gianfranco / Galeazzi, Mauro / Gatto, Mariele / Gerli, Roberto / Govoni, Marcello / Gremese, Elisa / Iuliano, Annamaria / Mansutti, Elena / Moroni, Gabriella / Mosca, Marta / Nalli, Cecilia / Naretto, Carla / Padovan, Melissa / Palma, Lavinia / Raffiotta, Francesca / Roccatello, Dario / Tincani, Angela / Valesini, Guido / Zen, Margherita / Doria, Andrea. ·Department of Medicine-DIMED, Division of Rheumatology, University of Padova, Italy. · Department of Medicine, Rheumatology Unit, University of Perugia, Perugia, Italy. · Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy. · Department of Internal Medicine and Medical Specialities, Rheumatology, La Sapienza University, Roma, Italy. · Department of Medical and Biological Sciences, Rheumatology Clinic, University Hospital Santa Maria della Misericordia, Udine, Italy. · Institute of Rheumatology and Affine Sciences, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy. · Research Centre of Systemic Autoimmune and Autoinflammatory Diseases, Rheumatology Unit, Policlinico Le Scotte, University of Siena, Siena, Italy. · Department of Medical Sciences, University of Ferrara, Italy. · Division of Nephrology, Fondazione Ca' Granda Ospedale Maggiore IRCCS, Milano, Italy. · Rheumatology and Clinical Immunology, Department of Clinical and Experimental Sciences, Spedali Civili and University of Brescia, Italy. · Department of Rare Disease, Immunology, Haematology and Immunohaematology, Research Centre of Immunopathology of Rare Diseases (CMID), Hospital Torino Nord Emergenza San G. Bosco and University of Torino, Italy. ·Clin Exp Rheumatol · Pubmed #26053285.

ABSTRACT: OBJECTIVES: To evaluate the efficacy and safety of rituximab (RTX) in patients with systemic lupus erythematosus (SLE) refractory to standard therapy in the clinical practice setting. METHODS: 145 SLE patients (ACR criteria) were treated with RTX in 11 Italian Centres: 118 with two infusions (1 g), two weeks apart; 27 with 4 infusions (375 mg/m2), one week apart, followed in 10 cases by two further doses, after 1 and 2 months. Systemic complete response (CR) was defined as European Consensus Lupus Activity Measurement (ECLAM) score ≤1 and partial response (PR) as 1< ECLAM ≤3. Renal CR (RCR) and renal PR (RPR) were defined according to EULAR recommendations for management of lupus nephritis. RESULTS: Data from 134 (92.4%) patients were available. The mean±SD follow-up was 27.3±18.5 months. After the first course of RTX, CR or PR were observed in 85.8% and CR in 45.5% of cases; RCR or RPR in 94.1% and RCR in 30.9% of patients after 12-month follow-up. Disease flares occurred in 35.1% and renal flares in 31.2% of patients during observational period. Among patients retreated, CR or PR were observed in 84.4% and CR in 57.8% of cases. Adverse events, infections, and infusion reactions occurred after first RTX course in 23.8%, 16.4%, and 3.8% of patients and after retreatment in 33.3%, 22.2% and 11.1%, respectively. No severe infusion reactions or deaths occurred. CONCLUSIONS: Data from Italian multicentre RTX Registry confirmed the efficacy and safety of RTX in SLE patients refractory to standard treatment in clinical practice setting.

20 Article Remission in systemic lupus erythematosus: testing different definitions in a large multicentre cohort. 2020

Saccon, Francesca / Zen, Margherita / Gatto, Mariele / Margiotta, Domenico Paolo Emanuele / Afeltra, Antonella / Ceccarelli, Fulvia / Conti, Fabrizio / Bortoluzzi, Alessandra / Govoni, Marcello / Frontini, Giulia / Moroni, Gabriella / Dall'Ara, Francesca / Tincani, Angela / Signorini, Viola / Mosca, Marta / Frigo, Anna Chiara / Iaccarino, Luca / Doria, Andrea. ·Department of Medicine, Division of Rheumatology, University of Padua, Padova, Italy. · Unit of Allergology, Immunolgy, Rheumatology, Department of Medicine, Universita Campus Bio-Medico di Roma, Roma, Italy. · Dipartimento di Medicina Interna e Specialità Mediche, Reumatologia, Sapienza University of Rome, Roma, Lazio, Italy. · Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Rheumatology Unit, Sapienza University of Rome, Roma, Lazio, Italy. · University Hospital Arcispedale Sant'Anna, Department of Medical Sciences, Division of Rheumatology, University of Ferrara, Ferrara, Emilia-Romagna, Italy. · Nephrology Unit, La Fondazione IRCCS Ca' Granda Ospedale Maggiore di Milano Policlinico, Milano, Lombardia, Italy. · ASST-Spedali Civili, Rheumatology and Clinical Immunology, University of Brescia, Brescia, Lombardia, Italy. · Department of Clinical and Experimental Medicine, Rheumatology Unit, University of Pisa, Pisa, Toscana, Italy. · Department of Cardiac-Thoracic-Vascular Sciences and Public Health, Biostatistics, Epidemiology and Public Health Unit, University of Padua, Padova, Veneto, Italy. · Department of Medicine, Division of Rheumatology, University of Padua, Padova, Italy adoria@unipd.it. ·Ann Rheum Dis · Pubmed #32321721.

ABSTRACT: 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.

21 Article Prevalence and predictors of flare after immunosuppressant discontinuation in patients with systemic lupus erythematosus in remission. 2019

Zen, Margherita / Saccon, Francesca / Gatto, Mariele / Montesso, Giulia / Larosa, Maddalena / Benvenuti, Francesco / Iaccarino, Luca / Doria, Andrea. ·Rheumatology Unit, Department of Medicine, University of Padova, Padova, Italy. ·Rheumatology (Oxford) · Pubmed #31642908.

ABSTRACT: 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.

22 Article Derivation and validation of the SLE Disease Activity Score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity. 2019

Jesus, Diogo / Matos, Ana / Henriques, Carla / Zen, Margherita / Larosa, Maddalena / Iaccarino, Luca / Da Silva, José António Pereira / Doria, Andrea / Inês, Luís Sousa. ·Rheumatology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. · School of Technology and Management, Polytechnic Institute of Viseu, Viseu, Portugal. · Centre for the Study of Education, Technologies and Health, Viseu, Portugal. · Centre for Mathematics, University of Coimbra, Coimbra, Portugal. · Rheumatology Unit, Department of Medicine, University of Padova, Padova, Italy. · Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal. · Rheumatology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal luisines@gmail.com. · School of Health Sciences, University of Beira Interior, Covilhã, Portugal. ·Ann Rheum Dis · Pubmed #30626657.

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

23 Article Early Lupus Project: one-year follow-up of an Italian cohort of patients with systemic lupus erythematosus of recent onset. 2018

Sebastiani, G D / Prevete, I / Iuliano, A / Piga, M / Iannone, F / Coladonato, L / Govoni, M / Bortoluzzi, A / Mosca, M / Tani, C / Doria, A / Iaccarino, L / Tincani, A / Fredi, M / Conti, F / Spinelli, F R / Galeazzi, M / Bellisai, F / Zanetti, A / Carrara, G / Scirè, C A / Mathieu, A. ·1 UOC Reumatologia, Azienda Ospedaliera San Camillo-Forlanini, Roma, Italy. · 2 Cattedra e Struttura Complessa di Reumatologia, Università degli Studi e AOU di Cagliari, Italy. · 3 Dipartimento Interdisciplinare di Medicina - Sezione di Reumatologia, Universita' di Bari, Italy. · 4 UO e Sezione di Reumatologia - Dipartimento di Scienze Mediche, Università degli Studi di Ferrara, Italy. · 5 UO Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa, Italy. · 6 Rheumatology Unit, Department of Medicine, University of Padova, Italy. · 7 UOC Reumatologia e Immunologia Clinica, Dipartimento di Scienze Cliniche e Sperimentali, Università degli Studi di Brescia, ASST Spedali Civili - Brescia, Italy. · 8 Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Italy. · 9 UOC di Reumatologia, Azienda Ospedaliera Universitaria Senese, Italy. · 10 Centro Studi SIR (Società Italiana di Reumatologia), Italy. ·Lupus · Pubmed #29779436.

ABSTRACT: Objective To describe the clinical and serological features of a prospectively followed cohort of early diagnosed systemic lupus erythematosus (SLE) patients during a one-year follow-up period. Methods SLE patients with disease duration less than 12 months were consecutively enrolled in a multicentre, prospective study. At study entry and then every 6 months, a large panel of data was recorded. Results Of 260 patients enrolled, 185 had at least 12 months of follow-up; of these, 84.3% were female, 92.4% were Caucasians. Mean diagnostic delay was about 20 months; higher values of European Consensus Lupus Activity Measurement (ECLAM) and of organs/systems involved were both associated with shorter diagnostic delay. Clinical and serological parameters improved after study entry. However, patients' quality of life deteriorated and cardiovascular risk factors significantly increased. About one-third of patients with active disease at study entry went into remission (ECLAM = 0). Negative predictors for remission were: oral ulcers, arthritis, low C4, anti-SSB (Ro) antibodies and therapy with mycophenolate. There was a widespread use of glucocorticoids both at baseline and during follow-up. Conclusion Clinical symptoms and serological parameters improve during the first period after diagnosis. However, patients' quality of life deteriorates. The widespread use of glucocorticoids is probably the reason for the early significant increase of some cardiovascular risk factors.

24 Article Lupus low disease activity state is associated with a decrease in damage progression in Caucasian patients with SLE, but overlaps with remission. 2018

Zen, Margherita / Iaccarino, Luca / Gatto, Mariele / Saccon, Francesca / Larosa, Maddalena / Ghirardello, Anna / Punzi, Leonardo / Doria, Andrea. ·Department of Medicine, University of Padova, Division of Rheumatology, Padova, Italy. ·Ann Rheum Dis · Pubmed #28970217.

ABSTRACT: 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.

25 Article 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. 2018

Iaccarino, Luca / Andreoli, Laura / Bocci, Elena Bartoloni / Bortoluzzi, Alessandra / Ceccarelli, Fulvia / Conti, Fabrizio / De Angelis, Rossella / De Marchi, Ginevra / De Vita, Salvatore / Di Matteo, Andrea / Emmi, Giacomo / Emmi, Lorenzo / Gatto, Mariele / Gerli, Roberto / Gerosa, Maria / Govoni, Marcello / Larosa, Maddalena / Meroni, Pier Luigi / Mosca, Marta / Pazzola, Giulia / Reggia, Rossella / Saccon, Francesca / Salvarani, Carlo / Tani, Chiara / Zen, Margherita / Frigo, Anna Chiara / Tincani, Angela / Doria, Andrea. ·Division of Rheumatology, Department of Medicine-DIMED, University of Padova, Padova, Italy. · Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Brescia, Italy. · Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy. · Medical Sciences, UOC of Rheumatology, University Hospital S. Anna, Ferrara, Italy. · Rheumatology Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. · Rheumatology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy. · Clinic of Rheumatology, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy. · Internal Interdisciplinary Medicine, Centre for Rare Cardiovascular and Immunological Diseases, Lupus Clinic, AOU Careggi, Florence, Italy. · Department of Surgery and Translational Medicine, University of Florence, Italy. · Rheumatology Department, University of Milan, Istituto Ortopedico Gaetano Pini, Milano, Italy. · Rheumatology Unit, University of Pisa, Pisa, Italy. · Rheumatology Unit, Internal Medicine Department, Arcispedale Santa Maria Nuova - IRCCS, Reggio Emilia, Italy. · Biostatistics, Epidemiology and Public Health Unit, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Italy. · Division of Rheumatology, Department of Medicine-DIMED, University of Padova, Padova, Italy. Electronic address: adoria@unipd.it. ·J Autoimmun · Pubmed #28935492.

ABSTRACT: 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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