Gianfranco Ferraccioli

• Professor
• CEO at Università Cattolica del Sacro Cuore

Background Randomized clinical trials have demonstrated the efficacy of secukinumab (SECU) in reducing disease activity in psoriatic arthritis (PsA), while real-world studies prove a broader perspective on SECU’s usefulness in everyday clinical practice. Objectives To assess the effectiveness of SECU by evaluating drug survival and identifying pot...

Objectives: The aim of this study was to evaluate the effectiveness and safety profile of filgotinib, a JAK1 preferential inhibitor, in rheumatoid arthritis (RA) patients included in Italian GISEA (Group for the Study of Early Arthritis) registry. Methods: Data from RA patients treated with filgotinib, recorded in the GISEA registry, were analys...

Primary Sjögren’s disease is primarily driven by B-cell activation and is associated with a high risk of developing non-Hodgkin’s lymphoma (NHL). Over the last few decades, microRNA-155 (miR-155) has arisen as a key regulator of B-cells. Nevertheless, its role in primary Sjögren’s disease remains elusive. Thus, the purpose of this study was (i) to...

Background The SARS‐CoV‐2 pandemic has led to more than 6,870.000 deaths worldwide. Despite recent therapeutic advances, deaths in Intensive Care Units still range between 34 and 72%, comprising substantial unmet need as we move to an endemic phase. The general agreement is that in the first few days of infection, antiviral drugs and neutralizing m...

Objectives: We aimed to investigate the effectiveness of tumour necrosis factor inhibitors (TNFi), anti-interleukin-17 or interleukin-12/23 monoclonal antibodies (anti-IL) on comorbidities in a cohort of patients with spondyloarthritis (SpA), using an average treatment effect (ATE) analysis. Methods: SpA patients from the multicentre Italian GIS...

Despite the relevant advances in our understanding of the pathogenetic mechanisms regulating inflammation in rheumatoid arthritis (RA) and the development of effective therapeutics, to date, there is still a proportion of patients with RA who do not respond to treatment and end up progressing toward the development of joint damage, extra-articular...

Objectives To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active rheumatoid arthritis (RA) who start (new) DMARD-therapy. Methods Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs becau...

Abstract Background Prognostic biomarkers of treatment response to distinct biologic disease-modifying anti-rheumatic drugs (b-DMARDs) are still lacking within the management of rheumatoid arthritis (RA). Methods Thirty-four b-DMARDs naive RA patients, divided by disease duration into early (cohort 1) and long standing (cohort 2), received CTLA4-Ig...

Background A Treat-to-Target approach (T2T) is broadly considered to lead to better clinical outcomes and recommended in patients with RA. However, very few studies have analyzed the effect of T2T on radiographic progression, and any such studies have provided inconsistent results. Objectives To investigate whether meticulously following a treat-t...

Multiple Sclerosis (MS) has been shown to be linked to Epstein Barr Virus (EBV) infection, a virus that infects B cells inside the CNS. The seminal study raises a key interest into the infectious origin of several other autoimmune inflammatory diseases.We will discuss here the infectious agents that have been studied over the years in Rheumatoid Ar...

Vaccination has been a game changer in our efforts to address the coronavirus disease 2019 (COVID-19) pandemic. However, the disease might still represent a clinical crisis for several more years, in part because of the inevitable emergence of variants capable of evading the pre-existing immunity. Drugs affecting viral spread will help curtail tran...

Objective To develop evidence-based European Alliance of Associations for Rheumatology (EULAR) points to consider (PtCs) for the management of difficult-to-treat rheumatoid arthritis (D2T RA). Methods An EULAR Task Force was established comprising 34 individuals: 26 rheumatologists, patient partners and rheumatology experienced health professional...

Background: Haemophilus parasuis ( Hps ; now Glaesserella parasuis ) is an infectious agent that causes severe arthritis in swines and shares sequence similarity with residues 261–273 of collagen type 2 (Coll 261−273 ), a possible autoantigen in rheumatoid arthritis (RA). Objectives/methods: We tested the presence of Hps sequencing 16S ribosomal RN...

Objective This study applied a synovitis score obtained during routine care from ultrasound (US)–guided biopsies of synovial tissue (ST) in patients with rheumatoid arthritis (RA) and patients with other inflammatory and noninflammatory joint diseases to identify pretreatment synovial biomarkers associated with disease characteristics, and to integ...

ObjectivesEULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of rheumatoid arthritis (RA). In particular, few data are available regarding the effectiveness of a second-line bDMARD after failure of abatacept (ABA), tocilizumab (TCZ),...

Objectives: Osteoporosis and bone erosions are hallmarks of rheumatoid arthritis (RA) since disease onset is underpinned by the inflammatory burden. In this observational study, we aimed to dissect the putative RA-related parameters and bone-derived biomarkers associated with systemic and focal bone loss at disease onset and with their progression....

Systemic lupus erythematosus (SLE) and bullous pemphigoid (BP) are chronic autoimmune diseases in which B cells play an important pathogenic role in the different stages of the disease. B cell-targeted therapies have been suggested as a new rational approach for treating SLE. Rituximab (RTX), an anti-CD20 chimeric monoclonal antibody, failed to ach...

Background: Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis (RA) remain symptomatic. These patients can be considered to have 'difficult-to-treat RA'. However, uniform terminology and an appropriate definition are lacking. Objective: The Task Force in charge of...

We read with great interest the Viewpoint by L. H Henderson et al (1) on the therapeutic approach with Glucocorticoids (GC) to the inflammation and Cytokine Storm phases of SARS.CoV 2 infection. We would like to expand their analysis and discuss the data , so far reported in Children and Autoimmune patients ( Rheumatoid Arthritis , Systemic Lupus E...

Immune-regulatory mechanisms of drug-free remission in rheumatoid arthritis (RA) are unknown. We hypothesized that synovial tissue macrophages (STM), which persist in remission, contribute to joint homeostasis. We used single-cell transcriptomics to profile 32,000 STMs and identified phenotypic changes in patients with early/active RA, treatment-re...

Objective: To evaluate the clinical effectiveness of golimumab in biologic inadequate responder (IR) patients with Rheumatoid arthritis (RA), Spondyloarthritis (SpA), and Psoriatic arthritis (PsA). Methods: We analyzed 1424 patients on golimumab from the GISEA registry. Drug survival was estimated by Kaplan-Meier analysis in biologic-naïve, 1-biolo...

COVID‐19 pandemia is a major concern for patients and health care systems. The fear of infection by patients with concomitant rheumatic diseases (either adult or children) and connective tissue diseases is arising worldwide, because of their immunological background and immunological therapies. Analyzing the basic biology of single diseases, the da...

The term “vacuum phenomenon” (VP), is characterized by gas-like density areas due to a rapid increase in the joint space volume (“acute VP”) or represent a chronic gas collection. It can occur within a collapsed vertebral body, the spinal canal, joints but mainly the intervertebral disc. Studies support that VP is originated by a dynamic process in...

OBJECTIVES: To define the prevalence of prolonged QT interval and QT dispersion (QTd) in rheumatoid arthritis (RA) patients and in a control population. METHODS: QT interval corrected by Bazett’s formula (QTc) was calculated from standard 12-lead ECGs in 963 subjects free of previous cardiovascular events (646 RA patients and 317 controls strictly...

Objectives: Systemic sclerosis (SSc) is a rare multi-organ disorder with a prominent gastrointestinal (GI) involvement. Altered gut microbiota is now considered a pivotal factor associated with the development of immune-mediated and inflammatory diseases. We performed a 16S ribosomal RNA (rRNA) gene-sequencing analysis of fecal microbiota in a coh...

Background Ultrasound (US)-guided minimally-invasive synovial tissue (ST) biopsy is a well-tolerated procedure for basic and translational studies on chronic inflammatory joint diseases as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). The aim of the study was to evaluate the utility of histopathologic criteria to...

Background Dendritic cells (DCs) direct immune responses against pathogens while maintaining tolerance to self-antigens. However, their aberrant activation can lead to autoimmunity and inflammation. DCs consist of two subtypes: plasmacytoid and myeloid DCs. Recently, single-cell sequencing has revealed complex heterogeneity within myeloid DCs. Thes...

Purpose To determine the role of antiphospholipid antibodies (aPL) and vascular renal lesions on renal prognosis, in terms of time to achieve remission, number of renal flares and development of chronic renal damage in patients with lupus nephritis (LN). Methods 91 consecutive LN patients have been evaluated and the follow-up data have been collec...

Immune related adverse events (irAEs) have been observed with all checkpoint inhibitors and are very frequent. The evidences coming from experimental models of congenital or acquired deficiency of CTLA-4 or from PD-1 knock-out mice, provided all the informations to interpret the organ or systemic manifestations (endocrine, or systemic autoimmune ch...

Objectives: This study aims to investigate the factors associated with early discontinuation (within one year) of etanercept (ETA) in rheumatoid arthritis (RA) patients who began ETA as first biologic disease-modifying antirheumatic drug (bDMARD) and who were entered into the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the S...

Corpo del lavoro. Il rischio di sviluppare una pa-tologia cardiovascolare (CV) nei pazienti affetti da artrite reumatoide (AR) è aumentato del 50% ri-spetto alla popolazione generale. Gli algoritmi va-lidati nella popolazione generale non consentono una corretta stratificazione del rischio CV nei pa-zienti con AR. L'obiettivo di questo studio è val...

P062 Corpo del lavoro. Lo studio EDRA ha l'obiettivo di determi-nare se la valutazione della disfunzione endoteliale periferica (DE) è utile nel predire l'occorrenza di eventi cardiovascolari in una coorte multicentrica di pazienti affetti da Artrite Reu-matoide (AR). In uno studio cross-sectional su 104 pazien-ti sottoposti a valutazione della DE...

Background. Rheumatoid Arthritis (RA) patients have 50% higher cardiovascular (CV) risk than general population. Diagnosis and treatment of modifiable CV risk factors may reduce CV events and their complications. Herein, we report on the results of a tight screening for modifiable CV risk factors in a large multicentre RA patients cohort. Materials...

Objective Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in rheumatoid arthritis (RA). There is limited knowledge regarding the factors that impede implementation of T2T, particularly in a setting where adherence to T2T is protocol specified. We aimed to assess clinical factors that associate with failure to adhe...

Objective The OMERACT Soluble Biomarker Working Group initiated an international, multicenter, prospective study, The Rheumatoid Arthritis (RA) BIODAM cohort ( NCT01476956 ), to generate resources for the clinical validation of candidate biomarkers predictive of radiographic progression. This first report describes the cohort, clinical outcomes, an...

In the last years, a dramatic amount of research has been performed increasing the knowledge about the biological mechanism underpinning Rheumatoid Arthritis (RA) inflammation, putting B lymphocytes in the center of RA pathogenesis. Nowadays, B cell phenotypes and autoantibodies positivity arose as important biomarkers in early and long-standing di...

Low T‐cell receptor (TCR)/CD28 signaling lymphocytes are expanded in arthritis. We asked whether the down‐expression of TCR‐related molecules correlates with specific arthritis characteristics and if it has clinical implications. TCR‐ZETA, ZAP‐70 and CD28 expression was measured by flow cytometry in synovial fluid (SF) and peripheral blood (PB)‐der...

Overweight/obesity influence disease burden and clinical outcome of Rheumatoid Arthritis (RA). The impact of overweight/obesity on synovial tissue (ST) inflammation is largely unknown. Here, we investigated the histological and transcriptional signature of ST obtained from RA in different disease phases (disease onset, failure to first-line convent...

Methotrexate (MTX) is recognized as the anchor drug in the algorithm treating chronic arthritis (RA, psoriatic arthritis), as well as a steroid sparing agent in other inflammatory conditions (polymyalgia rheumatica, vasculitis, scleroderma). Its main mechanism of action has been related to the increase in extracellular adenosine, which leads to the...

Background Regulatory T cells (Treg) play suppressive functions and are modulated by Abatacept (CTLA4-Ig). Limited data are available on CTLA4-Ig effect on Treg population in Rheumatoid Arthritis (RA). Objectives The aim of the study was to analyze if STAT3/STAT5 expression in CD4+ T cells in peripheral blood (PB) of RA patients at baseline predic...

Background The therapeutic algorithm in persistently active Rheumatoid Arthritis, despite conventional synthetic DMARDs(csDMARDs), identifies TNFα blockers and other biologics as first line treatment, without clear indications of which biologic should be adopted first in persistently active patients. Objectives In the AR-BIOM trial we analyzed sev...

Background Obesity is considered a chronic low-grade inflammatory status due to the release of bioactive substances, as pro-inflammatory cytokines, by the adipose tissue, and it is known negatively affecting some autoimmune inflammatory diseases, like Rheumatoid Arthritis. Few data are available on the role of obesity in Systemic Lupus Erythematosu...

Background According to EULAR recommendations for the management of Rheumatoid Arthritis (RA), if the treatment target is not reached with the first conventional synthetic (cs)-disease modifying antirheumatic drugs (DMARDs), addition of another csDMARD or of a biological (b)-DMARD should be considered [1]. Objectives To evaluate the clinical and r...

Background Xeroftalmia and xerostomia are the hinge symptoms of Sjögren Syndrome and often they negatively influence patients’ quality of life. The eyewashes use based on Platelet Rich Plasma (PRP) has been applicate in the treatment of the xeroftalmia, both primitive and secondary. Objectives To evaluate the effect of subconjunctival injections a...

Background In the treatment strategy of early rheumatoid arthritis (ERA) it is of pivotal importance to detect those patients who are at risk of radiographic progression (RP) in order to avoid decline in both functional capacity and quality of life. Objectives To identify baseline predictive factors for 5-year RP in an observational cohort of ERA...

Background Patients with SLE may have an increased risk of cardiovascular (CV) events due to the contribution of disease-related factors. Objectives: to determine the prognostic role of traditional CV risk factors and SLE-related factors in the assessment of the risk of CV events development in a cohort of patients affected by SLE. Methods Two hun...

Background: Differential diagnosis among psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (Abneg RA) can be challenging particularly in the clinical setting of peripheral phenotype and autoantibodies seronegativity. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and Abneg RA and...

Purpose Body mass index (BMI) demonstrated to influence the clinical response to different drugs in rheumatoid arthritis (RA). The aim of this study was to investigate the role of BMI in the achievement of remission in active RA patients starting the treatment with abatacept. Methods Data regarding 130 RA patients enrolled in the UltraSound-CLinic...

Objective This post hoc analysis of the phase III Active PSoriaTic Arthritis RAndomizEd TriAl (ASTRAEA) evaluated the effect of baseline body mass index (BMI) on subsequent response to subcutaneous (SC) abatacept in patients with psoriatic arthritis (PsA). Methods In ASTRAEA, patients with active PsA were randomised (1:1) to receive blinded weekly...

Background: Anakinra (ANA) is an effective treatment choice in patients with adult onset Still’s disease (AOSD). Variables affecting treatment survival include loss of efficacy or adverse events, but also the decision to discontinue treatment after long-term clinical remission. Objectives: Aims of this study were: (i) to assess the drug retention r...

Autoreactive T cells specific to human collagen type II have a crucial role in the development of rheumatoid arthritis (RA) in the context of MHC class II allele HLA-DRB1-*04. The protein-protein interactions between the T cell receptor (TCR) and the type II collagen bound to the allele MHC of class II may thus represent the target for the developm...

Objectives To evaluate interstitial lung disease associated with systemic sclerosis (SSc-ILD) and its changes during treatment by using quantitative analysis (QA) compared to semi-quantitative analysis (semiQA) of chest computed tomography (CT) scans. To assess the prognostic value of QA in predicting functional changes. Materials and methods We r...

The original version of this article unfortunately contained a mistake in given and family names of all the authors.

Objective: Despite the well-established efficacy of methotrexate (MTX) in rheumatoid arthritis (RA), monotherapy is not sufficient in almost half of patients. The aim of this registry-based study was to detect possible predictive factors for the early failure of MTX as a first-line treatment in early RA patients. Materials and Methods: Five-hundred...

Objective The project aimed to collect expert consensus statements for the profiling of patients with axial spondyloarthritis (axSpA) candidate to biologic agents (bDMARDs) treatment, in order to better define the drivers for the best treatment choice. Methods The 6 more interesting topics about axSpA patient profiling were identified by the proje...

Objectives The aim of our study was to define the role of high-sensitive cardiac troponin T (hs-cTnT) and NT-proBNP in identifying Systemic Sclerosis (SSc) patients with cardiac involvement and at higher risk of cardiac death. Methods Plasma hs-cTnT and NT-proBNP concentrations were measured in 245 SSc-patients. Results hs-cTnT and NT-proBNP leve...

Objectives: To validate enhanced liver fibrosis (ELF) test and its components-amino-terminal propeptide of procollagen type III (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and HA-as biomarkers of fibrosis in SSc in an independent, international, multicentre cohort. Methods: Two hundred and fifty-four SSc patients from six R...

Objective: Obesity is a risk factor for Rheumatoid Arthritis (RA) being associated to low grade inflammation. This study aimed to determine whether PEDF and Chemerin are biomarkers of inflammation related to fat accumulation in RA and to investigate whether weight loss associates with clinical disease improvement through the modification of fat-rel...

Objectives: To examine synovial tissue (ST) predictors of clinical differentiation in patients with seronegative undifferentiated peripheral inflammatory arthritis (UPIA). Methods: Fourty-two patients with IgA/IgM-Rheumatoid Factor and anti-citrullinated peptide antibodies negative UPIA, naive to Disease-Modifying Anti-Rheumatic Drugs, underwent Gr...

Abatacept (CTLA4Ig), a selective T-cell costimulation modulator, has been approved for the treatment of psoriatic arthritis patients with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs, but not for those with uncontrolled skin lesions, nor with axial involvement. In this review, we will try to interpret such...

Background The purpose of this study was to investigate the frequency and the distribution of inflammatory cell infiltrate in two sets of cutaneous biopsies derived from clinically affected and unaffected skin in patients with systemic sclerosis (SSc) and to test correlation between the cell infiltrate and the progression of skin involvement. Meth...

Objective Paradoxical arthritis under tumour necrosis factor inhibitor (TNF-i) for inflammatory bowel disease (IBD) has been described. This study aims to evaluate the histological features of paired synovial tissue (ST) and colonic mucosa (CM) tissue in patients with IBD developing paradoxical arthritis under TNF-i. Methods Patients with IBD with...

Objectives To define the prevalence and determinants of peripheral microvascular endothelial dysfunction (ED) in a large series of rheumatoid arthritis (RA) patients free of previous cardiovascular events. Materials and Methods Data from 874 RA patients enrolled in the EDRA study (Endothelial Dysfunction Evaluation for Coronary Heart Disease Risk...

Table S1: Independent determinants of Ln-RHI according to ACPA status. Table S2: Independent determinants of peripheral ED according to ACPA status.

Aim: Humoral immunity and B cells are thought to play an important role in the pathophysiology of the systemic sclerosis (SSc). The production of free light chains (FLC) of immunoglobulins is abnormally high in several pathological autoimmune conditions and reflects B cell activation. Furthermore, FLCs demonstrated different biological activities...

Acute inflammation is a complex and tightly regulated homeostatic process that includes leukocyte migration from the vasculature into tissues to eliminate the pathogen/injury, followed by a pro-resolving response promoting tissue repair. However, if inflammation is uncontrolled as in chronic diseases such as Rheumatoid Arthritis (RA) it leads to ti...

MicroRNAs (miRNAs) are small non-coding RNAs that fine-tune the cell response to a changing environment by modulating the cell transcriptome. miR-155 is a multifunctional miRNA enriched in cells of the immune system and is indispensable for the immune response. However, when deregulated, miR-155 contributes to the development of chronic inflammatio...

Résumé Objectif Déterminer l’incidence du cancer chez des patients atteints de spondyloarthrite (SpA) traités par inhibiteurs du TNF (anti-TNF) enregistrés dans le registre GISEA et identifier les facteurs associés à l’apparition du cancer. Méthodes Cette étude observationnelle a inclus une cohorte ouverte de 3321 patients atteints de SpA figuran...

Often life-threatening pulmonary fungal infections (PFIs) can occur in patients with rheumatoid arthritis (RA) receiving disease-modifying anti-rheumatic drugs (DMARDs). Most of the data concerning PFIs in RA patients come from case reports and retrospective case series. Of the ve most widely described PFIs, Pneumocystis jirovecii pneumonia (PJP) h...

Objective To describe the effectiveness and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, in a cohort of patients with rheumatoid arthritis (RA) recruited in clinical practice. Methods TRUST was an observational study in RA patients who started treatment with TCZ in the 6 months prior to site activation and were still on treatme...

Atmospheric air pollution has been associated with a range of adverse health effects. The environment plays a causative role in the development of Systemic Sclerosis (SSc). The aim of the present study is to explore the association between particulate (PM10) and benzene (B) exposure in Italian patients with systemic sclerosis and their clinical cha...

Rheumatoid arthritis (RA) is a chronic, definitely disabling, and potentially severe autoimmune disease. Although an increasing number of patients are affected, a key treatment for all patients has not been discovered. High-mobility group box-1 (HMGB1) is a nuclear protein passively and actively released by almost all cell types after several stimu...