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Seasonal influenza is a frequent cause of hospitalization and mortality among patients with systemic autoimmune diseases. Despite this evidence, vaccination coverage is generally much lower than the minimum 75% target proposed by the WHO. Therefore, an active campaign was implemented in the years 2019/2020 and 2020/2021 within the Rheumatology Department of the Niguarda Hospital (Milan, Italy) to improve the vaccination coverage in patients with inflammatory arthritis. This study aims to evaluate the vaccination coverage in the 2019/2020 and 2020/2021 (active campaigns) seasons and to compare these results with the 2018/2019 season. A monocenter observational study was conducted among adult patients with rheumatoid arthritis, spondylarthritis, or psoriatic arthropathy, who were referred to the Rheumatology Department of the Niguarda Hospital. Patients were given a questionnaire to investigate previous years' vaccination coverage and to propose an influenza vaccine for the 2020/2021 season. Compared with 2018/2019, a trend for increase in vaccination coverage was reported in 2019/2020 season (+ 10.7%, p = 0.055; 45.5% of coverage) and a statistically significant increase was reported in 2020/2021 (+ 31.2%, p 0.001; 65.9% of coverage). The increase was also significant when comparing the 2020/2021 and 2019/2020 seasons (+ 20.5%, p 0.001). The greatest increase in vaccination coverage was observed among under-65-year-old patients. Obtained results support the implementation of active vaccination campaigns to increase vaccination coverage among patients with systemic autoimmune diseases and highlight the importance of external factors (such as the COVID-19 pandemic) in directing the patient to adopt preventive measures to avoid infections and related complications.

Objective: To evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike (S) IgG antibody production after vaccination with BNT162b2 and the protection from symptomatic breakthrough infections in health care workers. Methods: This prospective observational study (RENAISSANCE) had as a primary end point the evaluation of serologic response to BNT162b2 14 days after a second dose. SARS-CoV-2 anti-S IgG antibodies were evaluated with LIAISON SARS-CoV-2 TrimericS IgG assay (DiaSorin S.p.A.), which is able to detect the presence of both binding and neutralizing antibodies for trimeric spike glycoprotein. Participants were recruited from February 1, 2021, to February 22, 2021. Occurrence of vaccine breakthrough infections was assessed by reverse transcription–polymerase chain reaction on symptomatic and contact cases up to June 6, 2021. Results: Of 2569 staff evaluated, only 4 were nonresponders (0.16%; 95% CI, 0.04% to 0.41%). All 4 nonresponders were severely immunosuppressed and receiving treatment with mycophenolate mofetil or mycophenolic acid. At 14 days after the second dose, 67.5% (1733) of staff had anti-S IgG titers of 2000 BAU/mL or higher; 19.2% (494), between 1500 and 2000 BAU/mL; 9.8% (251), between 1000 and 1500 BAU/mL; and 3.4% (87), 1000 BAU/mL or lower. Women had a higher probability of having higher titers than men (64.5% [1044/1618] vs 58.3% [410/703]; P=.005). This was confirmed after adjustment for age group (odds ratio, 1.275; 95% CI, 1.062 to 1.531; P=.009). Four months after the end of the vaccination program, only 13 participants (0.26%) had experienced a breakthrough SARS-CoV-2 infection, including 1 nonresponder. This was the only participant requiring hospitalization for severe COVID-19. Conclusion: The vaccination campaign among health care workers at the ASST GOM Niguarda has resulted in a marked serologic response and reduction of incident COVID-19 cases. Yet, the lack of protection should not be overlooked in immunocompromised individuals.

Background Among the different CardioVascular (CV) manifestation of the COronaVIrus-related Disease (COVID) particular attention has been paid to arrhythmia and particularly to Atrial fibrillation (AF). The aim of our study was to assess the incidence of AF episodes in patients hospitalized for COVID and to evaluate its predictors and its relationship with in-hospital all-cause mortality. Methods We enrolled 3435 cases of SARS-CoV2 infection admitted in four hospitals in Northern Italy. We collected data on clinical history, vital signs, Intensive Care Unit (ICU) admission, laboratory tests and pharmacological treatment. AF incident and all-cause in-hospital mortality were considered as outcomes. Results 145 (4.2%) patients develop AF during hospitalization, with a median time of 3 days (IQR: 0, 11.5) from admission. Incident AF patients were older and had lower eGFR, lower platelet and lymphocytes count and higher C-Reactive Protein (CRP), were admitted more frequently to ICU and more frequently died compared to subjects that didn't present AF. At the Cox regression model significant determinants of incident AF were older age (HR 1.070; 95% CI: 1.048, 1.092), history of AF (HR 2.800; 95% CI: 1.465, 5.351), ischemic heart disease (HR 0.324; 95% CI: 0.130, 0.811) and ICU admission (HR 8.030; 95% CI: 4.511, 14.292). Incident AF was a predictor of all-cause mortality (HR 1.679; 95% CI: 1.170, 2.410), together with age (HR 1.053; 95% CI: 1.042, 1.065), dementia (HR 1.553; 95% CI 1.151, 2.095), platelet count (HR 0.997; 95% CI: 0.996, 0.999) higher CRP (HR 1.004; 95% CI: 1.003, 1.005) and eGFR (HR: 0.991; 95% CI: 0.986, 0.996) Conclusion AF present as the main arrhythmia in COVID-19 patients and its development during the hospitalization strongly relates with in-hospital mortality.

SARS‐CoV2 infection is a systemic disease that may involve multiple organs, including the central nervous system (CNS). Aims of our study are to describe prevalence and clinical features of neurological manifestations, mortality and hospital discharge in subjects hospitalized with COVID‐19. All individuals admitted for to our hospital COVID‐19 were retrospectively included. Patients were classified according to the symptoms at hospital entry in (1) isolated respiratory, (2) combined respiratory and neurologic, (3) isolated neurologic and (4) stroke manifestations. Descriptive statistics and nonparametric tests to compare the groups were calculated. Kaplan Meier probability curves and multivariable Cox regression models for survival and hospital discharge were applied. The analysis included 901 patients: 42.6% showed a severe or critical disease with an overall mortality of 21.2%. At least one neurological symptom or disease was observed in 30.2% of subjects ranging from dysgeusia/anosmia (9.1%) to postinfective diseases (0.8%). Patients with respiratory symptoms experienced a more severe disease and a higher in‐hospital mortality compared to those who showed only neurologic symptoms. Kaplan Meier estimates displayed a statistically significant different survival among groups (p = 0.003): subjects with stroke had the worst. After adjusting for risk factors such as age, sex and comorbidity, individuals with isolated neurologic manifestations exhibited a better survival (aHR 0.398, 95% CI [0.206, 0.769], p = 0.006). Neurologic manifestations in COVID‐19 are common but heterogeneous and mortality in subjects with isolated neurologic manifestations seems lower than in those with respiratory symptoms., At least one neurologic symptom was observed in 30.2% of subjects. Neurologic manifestations in COVID‐19 are common but heterogeneous. Patients with neurologic symptoms exhibited a less severe pulmonary disease and a lower in‐hospital mortality (aHR 0.398, 95% CI 0.206‐0.769, p = 0.006) compared to those showing respiratory symptoms.

Background: The prognostic impact of electrolyte disorders in hospitalized COVID-19 patients is unclear. Methods: The study included all adult patients hospitalized for COVID-19 in four hospitals in Northern Italy between January 2020 and May 2021 with at least one serum potassium and sodium measurement performed within 3 days since admission. Primary outcome was in-hospital death; secondary outcome was Intensive Care Unit (ICU) admission. A cause-specific Cox proportional-hazards regression model was used for investigating the association between potassium and sodium (as either categorical or continuous variables) and mortality or admission to ICU. Results: Analyses included 3,418 adult hospitalized COVID-19 patients. At multivariable analysis, both hyperkalemia (Hazard Ratio, [HR] 1.833, 95% Confidence Interval [CI] 1.371–2.450) and sK above the median (K 5.1 vs 4.1 mmol/L: HR 1.523, 95% CI 1.295–1.798), and hypernatremia (HR 2.313, 95%CI 1.772–3.018) and sNa above the median (Na 149 vs 139 mmol/L: HR 1.442, 95% CI 1.234–1.686), were associated with in-hospital death, whereas hypokalemia and hyponatremia were not. Hyponatremia was associated with increased hazard of ICU admission (HR 1.884, 95%CI 1.389–2.556). Conclusions: Electrolyte disorders detected at hospital admission may allow early identification of COVID-19 patients at increased risk of adverse outcomes.

The use of a televisit service complying with efficiency and safety regulatory parameters was effective in significantly improving HbA1c levels of people with T1D after a one-year follow-up period. No acute diabetes-related complications occurred. Patients were highly satisfied with the service. Televisit is a valid option for diabetes management.

The most common arrhythmia associated with COronaVIrus-related Disease (COVID) infection is sinus tachycardia. It is not known if high Heart Rate (HR) in COVID is simply a marker of higher systemic response to sepsis or if its persistence could be related to a long-term autonomic dysfunction. The aim of our work is to assess the prevalence of elevated HR at discharge in patients hospitalized for COVID-19 and to evaluate the variables associated with it. We enrolled 697 cases of SARS-CoV2 infection admitted in our hospital after February 21 and discharged within 23 July 2020. We collected data on clinical history, vital signs, laboratory tests and pharmacological treatment. Severe disease was defined as the need for Intensive Care Unit (ICU) admission and/or mechanical ventilation. Median age was 59 years (first-third quartile 49, 74), and male was the prevalent gender (60.1%). 84.6% of the subjects showed a SARS-CoV-2 related pneumonia, and 13.2% resulted in a severe disease. Mean HR at admission was 90 ± 18 bpm with a mean decrease of 10 bpm to discharge. Only 5.5% of subjects presented HR > 100 bpm at discharge. Significant predictors of discharge HR at multiple linear model were admission HR (mean increase = β = 0.17 per bpm, 95% CI 0.11; 0.22, p < 0.001), haemoglobin (β = −0.64 per g/dL, 95% CI −1.19; −0.09, p = 0.023) and severe disease (β = 8.42, 95% CI 5.39; 11.45, p < 0.001). High HR at discharge in COVID-19 patients is not such a frequent consequence, but when it occurs it seems strongly related to a severe course of the disease.

BackgroundAn urgent need exists for an early detection of cases with a high-risk of SARS-CoV-2 infection, particularly in high-flow and -risk settings, such as emergency departments (EDs). The aim of this work is to develop and validate a predictive model for the evaluation of SARS-CoV-2 infection risk, with the rationale of using this tool to manage ED patients.MethodsA retrospective study was performed by cross-sectionally reviewing the electronical case records of patients admitted to Niguarda Hospital or referred to its ED in the period 15 March to 24 April 2020.Derivation sample was composed of non-random inpatients hospitalized on 24 April and admitted before 22 April 2020. Validation sample was composed of consecutive patients who visited the ED between 15 and 25 March 2020. The association between the dichotomic outcome and each predictor was explored by univariate analysis with logistic regression models.ResultsA total of 113 patients in the derivation sample and 419 in the validation sample were analyzed. History of fever, elder age and low oxygen saturation showed to be significant predictors of SARS-CoV-2 infection. The neutrophil count improves the discriminative ability of the model, even if its calibration and usefulness in terms of diagnosis is unclear.ConclusionThe discriminatory ability of the identified models makes the overall performance suboptimal; their implementation to calculate the individual risk of infection should not be used without additional investigations. However, they could be useful to evaluate the spatial allocation of patients while awaiting the result of the nasopharyngeal swab.Key Messages boxWhat is already known on this topic1 year after the onset of the coronavirus disease 2019 (COVID-19) pandemic, the trend of its spread has not shown a substantial global reduction. An urgent need exists for efficient early detection of cases with a high risk of SARS-CoV-2 infection and a number of diagnostic prediction models have been developed, but a few models were externally validated in high-flow and –risk settings, such as emergency departments (EDs).What this study addsThis study develops and validate predictive models for the evaluation of SARS-CoV-2 infection risk, with the rationale of using these tools to promptly manage patients who are afferent to the ED, allocating them accordingly to the risk of infection while awaiting swab result. History of fever, older age and low oxygen saturation showed to be significant predictors of the presence of SARS-CoV-2 infection. The use of laboratory findings, such as neutrophil count, showed to improve the discriminative ability of the model, even if its calibration and usefulness in terms of diagnosis is unclear.

Close follow-up is mandatory in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). During the Coronavirus Disease 2019 (COVID-19) pandemic, rheumatological care was rapidly reorganized during the first peak from March 1, 2020 to May 31, 2020, and all patients with RA, PsA, and AS being treated with a subcutaneous biologic disease-modifying anti-rheumatic drug or oral targeted synthetic disease-modifying anti-rheumatic drug were followed remotely. A retrospective database analysis of these 431 patients before and after this period is presented herein. A rheumatologist directly contacted all patients by telephone. Patients could also enter data on patient-reported outcomes remotely using the digital platform iAR Plus. General health (GH) and visual analog scale (VAS) pain were the main outcomes along with FACIT and disease-specific questionnaires (RADAI, ROAD, PROCLARA for RA, and BASDAI, BASGI, BASFI for AS). In all, 449 visits were postponed (69.9% of all scheduled visits); telephone evaluation was deemed inadequate in 193 instances, and patients underwent a standard outpatient visit. Comparing patients on telemedicine to those who underwent hospital visits, we found no statistically significant differences in GH (35.3 vs 39.3; p = 0.24), VAS (33.3 vs 37.1; p = 0.29), or other specific outcome measures in patients with RA, PsA, or AS. These results show that telemedicine has undoubted benefits, and in light of the ongoing COVID-19 pandemic, it is likely that many patients with these diseases may prefer it. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-04863-x.

SARS-CoV-2 infection determines a disease that predominantly affects lungs. However the cytokines storms, determined by the huge immune response to the infection, could affect also other organs and apparatus such as heart and vessels. Beyond the acute inflammation itself also hypercoagulative status has been linked to SARSCoV-2 infection and this surely relates to the increase seen in prevalence of pulmonary embolism and myocardial infarction. A number of cardiac abnormalities and pathologies have been observed, with special attention to cardiac arrhythmias and myocardial involvement. Furthermore, indirect damages determined by the reduction in acute and chronic cardiovascular care, results in a strong mortality and morbidity outcomes in cardiological patients. In this review we will summarise current knowledge on both direct and indirect cardiovascular damages determined by the SARS-CoV-2 pandemia.

(1) Background: Among the different cardiovascular (CV) manifestations of the coronavirus disease 2019 (COVID-19), arrhythmia and atrial fibrillation (AF) in particular have recently received special attention. The aims of our study were to estimate the incidence of AF in patients hospitalized for COVID-19, and to evaluate its role as a possible predictor of in-hospital all-cause mortality. (2) Methods: We enrolled 3435 people with SARS-CoV2 infection admitted to three hospitals in Northern Italy from February 2020 to May 2021. We collected data on their clinical history, laboratory tests, pharmacological treatment and intensive care unit (ICU) admission. Incident AF and all-cause in-hospital mortality were considered as outcomes. (3) Results: 145 (4.2%) patients developed AF during hospitalization, with a median time since admission of 3 days (I-III quartile: 0, 12). Patients with incident AF were admitted more frequently to the ICU (39.3 vs. 12.4%, p < 0.001), and more frequently died (37.2 vs. 16.9%, p < 0.001). In the Cox regression model, the significant determinants of incident AF were age (HR: 1.041; 95% CI: 1.022, 1.060 per year), a history of AF (HR: 2.720; 95% CI: 1.508, 4.907), lymphocyte count (HR: 0.584; 95% CI: 0.384, 0.888 per 103/µL), estimated glomerular filtration rate (eGFR, HR: 0.988; 95% CI: 0.980, 0.996 per mL/min) and ICU admission (HR: 5.311; 95% CI: 3.397, 8.302). Incident AF was a predictor of all-cause mortality (HR: 1.405; 95% CI: 1.027, 1.992) along with age (HR: 1.057; 95% CI: 1.047, 1.067), male gender (HR: 1.315; 95% CI: 1.064; 1.626), dementia (HR: 1.373; 95% CI: 1.045, 1.803), lower platelet (HR: 0.997; 95% CI: 0.996, 0.998 per 103/µL) and lymphocyte counts (HR: 0.843; 95% CI: 0.725, 0.982 per 103/µL), C-Reactive protein values (HR: 1.004; 95% CI: 1.003, 1.005 per mg/L), eGFR (HR: 0.990; 95% CI: 0.986, 0.994 per mL/min), and ICU admission (HR: 1.759; 95% CI: 1.292, 2.395). (4) Conclusions: Incident AF is a common complication in COVID-19 patients during hospitalization, and its occurrence strongly predicts in-hospital mortality.

BackgroundMost respiratory viruses show pronounced seasonality, but for SARS-CoV-2 this still needs to be documented.MethodsWe examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application.FindingsMeta-analysis of the mortality risk in seven European hospitals estimated odds ratios per one day increase in the admission date to be 0.981 (0.973-0.988, pInterpretationSeverity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.

Objectives: The recent introduction of direct-acting antiviral agents (DAAs) which can eliminate Hepatitis C virus (HCV) had revolutionized the treatment of HCV infections also in a complex clinical setting such as the patients with rheumatoid arthritis (RA). HCV elimination is also opportune due to the availability of more efficient immunosuppressive drugs, whose effect on the course of HCV infection is largely unknown. Methods: Consensus process was endorsed by the Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) to review the available evidence and produce practical, hospital-wide recommendations. The consensus panel consisted of 18 infectious diseases consultants, 20 rheumatologists and one clinical epidemiologist, who used the criteria of the Oxford Centre for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations. Results: A core-set of statements about management of patients with RA and infection by HCV have been developed to help clinicians in their clinical practice. Conclusions: A screening for HCV should be performed in all RA patients and it is mandatory before starting an immunosuppressive therapy. Finally, a DAA treatment should be considered in all HCV-infected patients.Significance and Innovations HCV antibodies should be investigated at the time of diagnosis of RA and, in any case, before starting immunosuppressive therapy with disease-modifying antirheumatic drugs (DMARDs). HCV eradication with DAA should be attempted as soon as possible, depending on patient conditions allowing a continuous oral treatment lasting 8–12 weeks Conventional and biological DMARDs are allowed in patients with HCV infection, but they should be used cautiously in presence of advanced liver disease.

Objective To compare clinical effectiveness between tocilizumab and tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) and inadequate response to conventional synthetic disease-modifying antirheumatic drugs initiating biologic therapy. Methods Patients prescribed tocilizumab (intravenous) or TNFi were prospectively observed in routine clinical practice for 52 weeks across 158 sites in 26 countries. The primary observation was the change from baseline in Disease Activity Score based on 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) at week 24 using analysis of covariance for between-groups comparison. Secondary end points included Clinical Disease Activity Index (CDAI) and patient-reported outcomes at weeks 24 and 52. Results Of 1,216 patients, 35% initiated tocilizumab and 65% initiated TNFi. RA duration was shorter, and disease activity and corticosteroid use were higher in tocilizumab patients. Tocilizumab-treated patients had greater improvement in DAS28-ESR at weeks 24 and 52 (week 24 difference [95% confidence interval] in adjusted means: −0.831 [−1.086, −0.576]; P

Background: SARS-CoV2 infection is a systemic disease that may involve multiple organs, including the nervous system. Aims of our study are to describe prevalence and clinical features of neurological manifestations, mortality and hospital discharge in subjects hospitalized with COVID-19. Methods: All individuals admitted for COVID-19 were retrospectively included. Patients were classified according to the symptoms at hospital entry in 1) isolated respiratory, 2) combined respiratory and neurologic, 3) isolated neurologic and 4) stroke manifestations. Descriptive statistics and non-parametric tests to compare the groups were applied. Kaplan Meier probability curves and multivariable Cox regression models for survival and hospital discharge were applied. Results: The analysis included 901 patients, 42.6% showed a severe or critical disease with an overall mortality of 21.2%. At least one neurological symptom or disease was observed in 30.2% of subjects ranging from dysgeusia/anosmia (9.1%) to post-infective diseases (0.8%). Patients with respiratory symptoms experienced a more severe disease and a higher in-hospital mortality compared to those who showed only neurologic symptoms. Kaplan Meier estimates displayed a statistically significant different survival among groups (p=0.003): subjects with stroke had the worst. After adjusting for risk factors such as age, sex and comorbidity, individuals with isolated neurologic manifestations exhibited a better survival (aHR 0.398, 95% CI 0.206-0.769, p=0.006). Discussion: Neurologic manifestations in COVID-19 are common but heterogeneous. Subjects with isolated neurologic manifestations, experienced a lower mortality than those with respiratory symptoms, suggesting that neurologic disease may have a different course than when the virus involves respiratory system. Funding Statement: None. Declaration of Interests: The authors declare that they have no conflicts of interest for this work. Ethics Approval Statement: The local Ethics Committee approved the protocol under the special conditions indicated by the Italian 648/96 law. All subjects provided written informed consent.

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 several biomarkers to define which one could help to identify the best responder to IL6-R blockade. Methods Sixty-nine RA persistently active despite csDMARDs treatment, were enrolled in this Interventional Phase IV, prospective, multicenter, non-randomized, no-profit study(Clinical Trial:n.2012-001760-30) and followed for 18 months after Tocilizumab(TCZ) treatment monotherapy or in combination with csDMARDs. The study was conducted in 10 outpatient clinics of “Gruppo Italiano di Studio sulle Early Arthritis” network(GISEA Study Group) in Italy. The primary end point was the clinical response to TCZ, as LDA(DAS Results During the 18 months of the study, 9/69 patients(13.0%) discontinued the study because of treatment failure, 2(2.9%) for an AE, 2 for a SAE, and 5(7.2%) for other reasons. At 12 months FU, LDA was achieved in 75.0% and DAS-R and SDAI-R in 63.3% and 41.7% respectively, of RA patients, without significant differences between mono and combination therapy. Considering baseline biomarkers predictive of LDA at 12 months FU, IL23 plasma levels ≥43.6pg/ml arose as potent predictor [OR(95%CIs):20.0(1.9-211.2)], whereas the best predictors of DAS-R were baseline BAFF plasma levels ≥563.3pg/ml [OR(95%CIs):3.9(1.1-14.3)] and IL23 plasma levels ≥43.6pg/ml [OR(95%CIs):4.1(1.1-15.2)]. In addition, Albumin levels ≥4.25g/dl at 3 months FU, arose as a biochemical parameter predicting DAS-R [OR(95%CIs):26.0(3.9-173.1)] and SDAI-R [OR(95%CIs):5.3(1.2-22.9)] at 12 months FU. Conclusion IL23 and BAFF related inflammation are targets of IL6 blockade that significantly increases Albumin levels. High plasma levels of IL23 and BAFF at baseline represent biomarkers for LDA and DAS-R achievement in RA inflammation driven by IL6. Albumin after three months of therapy represents the strongest predictor of remission at 12 months. Disclosure of Interests Gianfranco Ferraccioli Speakers bureau: BMS, Roche, Barbara Tolusso: None declared, Florenzo Iannone Consultant for: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Speakers bureau: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Maurizio Rossini: None declared, Piercarlo Sarzi-Puttini Speakers bureau: Novartis, Marcello Govoni Paid instructor for: Pfizer, Roche, Speakers bureau: Pfizer, Abbvie, MSD, Roche, Eli-Lilly, Celgene, Sanofi, Janssen, Rosario Foti: None declared, Andrea Doria: None declared, Francesco Paolo Cantatore Speakers bureau: PFIZER, ROCHE, Giovanni Francesco Miceli: None declared, oscar massimiliano epis: None declared, Anna Laura Fedele: None declared, Antonio Carletto: None declared, Nicola Maruotti: None declared, Elena De Stefani: None declared, Giorgio Amato: None declared, Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Giovanni Lapadula: None declared

Background: Mixed Cryoglobuminaemia(MC) is a small vessel vasculitis characterized by the presence of a monoclonal rheumatoid factor(RF) and polyclonal immunoglobulins that precipitate at cold temperature, with a large spectrum of clinical manifestations. MC is strongly associated with hepatitis C(HCV) infection>90%. The new direct–acting antivirals(DAA) against HCV, which can eradicate the virus in >95% of patients, are supposed to have benefits on clinical manifestations of MC, nonetheless the amount of data is still limited. Patients with severe vasculitis may require anti-CD20 agent Rituximab(RTX) over DAA. However, despite the strong rationale, the advantage of dual therapy is still debated and the optimal therapeutic schedule unknown. Objectives: To investigate the impact of DAA treatment on clinical manifestations and biochemical parameters of disease activity in HCV-related MC patients who reached complete viral eradication, and if pre-treatment with RTX was able to define a subset of patients with a different outcome. Methods: Data was collected from 31 patients with MC, mean age 68 yrs, female 80%, mean disease duration 10 yrs who were treated with DAA and reached complete viral eradication, at 3 time points: before starting DAA (pre-DDA), after completing DAA (post-DAA), 52 weeks after completing DAA (52w). Additionally, a population of 9 patients with the same disease (mean age 65 yrs, female 77%, mean disease duration 9 yrs) but treated with one or more cycles of RTX prior receiving DAA, was analysed at the same timepoints and additionally before starting RTX(pre-RTX). At each time point clinical data (presence/absence of purpura, neuropathic manifestations, arthralgia, fatigue, nephritis) and biochemical parameters (% cryoglobulins, C3, C4 and RF) were recorded. The change in clinical and biochemical parameters at different timepoints were evaluated. Results: Among patients treated with DAA only, the prevalence of clinical manifestations before starting treatment was the following: purpura 31%,neuropathic manifestations 52%,arthralgia 28%,fatigue 14%, nephritis 3%. We observed a significant reduction in purpura after treatment (pre-DDA vs post-DAA=31% vs 13%,p=0.044) that persisted at 52w (pre-DAA vs 52w=31% vs 0%,p=0.004%). This in parallel with a significant reduction in the level of cryoglobulins (pre-DAA vs 52w=3.99±5.28 vs 1.6 ±1.7,p=0.029 and pre-DAA vs 52w=3.99 ± 5.28 vs 0.92 ± 1.75,p=0.008). Among patients pre-treated with RTX, the prevalence of clinical manifestations before starting RTX was: purpura 78%, neuropathic manifestations 100%,arthralgia 44%,fatigue 50%,nephritis 22%;and before starting DAA was: purpura 22%,neuropathic manifestations 100%,arthralgia 0%,fatigue 0%,nephritis 0%. A significant reduction in the rate of purpura (pre-RTX vs pre-DAA=78% vs 22%, p=0.009%) and arthralgia (44% vs 0%,p=0.012%) after RTX treatment was observed, but no difference in any clinical parameter when comparing pre-RTX with post-DAA and 52w. No significant change in any of the serological parameter was observed. Conclusion: DAA treatment is associated with rapid and sustained decrease in the level of cryoglobulins and related clinical improvement, specifically purpura. Patients who had been pre-treated with RTX showed clinical improvement in terms of purpura and arthralgia, albeit transient; subsequent treatment with DAA did not result in any immediate or long term additional clinical benefit. References [1] Mazzaro C. Clin Exp Rheum2017. Disclosure of Interests: Maria Di Cicco: None declared, Davide Antonio Filippini: None declared, Federica Filippini: None declared, Laura Belloli: None declared, Valeria Campanella: None declared, Cinzia Casu: None declared, Michel Chevallard: None declared, Marina Muscara: None declared, Mariaeva Romano Speakers bureau: janssen, Emanuela Schito: None declared, Elisa Verduci: None declared, Massimo Puoti: None declared, Maria Vinci: None declared, Oscar Massimiliano Epis Speakers bureau: BMS

Background Digital health innovations have opened up several opportunities to help patients with rheumatologic conditions and their treating clinicians in improving routine healthcare. Objectives To evaluate the applicability of a wearable smartwatch for monitoring patients with hip osteoarthritis who received viscosupplementation. Samsung Electronics Italia and MDApp srl supported the present study. Methods Consecutive patients with hip osteoarthritis who received viscosupplementation with jaluronic acid between November 2017 and May 2018 were enrolled in this observational study. All patients gave their informed consent. A Samsung Gear smartwatch was given to each patient and was worn during the day for measuring daily steps, walking distance, and mean velocity. Patients were asked to wear the smartwatch starting from one week before infiltration (T0), until two weeks before (T1). Patients were assessed with Lequesne index and WOMAC score at T0 and T1. Results Overall, 24 patients (7 male and 17 female, mean age 44 years-old) were enrolled. Of these, 70% has worn the smartwatch for most of the time (range 90-100%). An improvement of velocity (45%), an increase of daily steps (29%), and walking distance (25%) were seen. Similarly, Lequesne index and WOMAC score were consistent with subjective improvement. Most of the patients (95%) declared to be satisfied with this digital health study. Conclusion Samsung smartwatches proved to be an effective tool for tracking and recording medical parameters linked with perceived general health. Health technologies are more than an accessories and could be useful in chronic musculo-skeletal diseases because they allow to ease remote diagnosis and to monitor patients’ symptoms and clinical response. Telemedicine could fill the gap between patients and healthcare, with a reproducible and objective tool, enhancing patients’ engagement with the treatment plan. The high patients’ satisfaction further support the use of digital health technology. Reference [1] Kataria S, Digital Health: a new dimension in rheumatology patient care. Rheumatol Int. 2018 Disclosure of Interests Mariaeva Romano Speakers bureau: janssen, Laura Belloli: None declared, Elisa Verduci: None declared, Cinzia Casu: None declared, Valeria Campanella: None declared, Marina Muscara: None declared, Davide Antonio Filippini: None declared, Emanuela Schito: None declared, Maria Di Cicco: None declared, Oscar Massimiliano Epis Speakers bureau: BMS

Background Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disorder of not fully understood aetiology characterized by vascular and fibrotic abnormalities in the skin and internal organs. Musculoskeletal involvement, mainly affecting hands and feet, is frequent in SSc and represents a major cause of disability. Ultrasonography is a non-invasive, cost-effective imaging modality which is able to detect the presence of joint involvement in SSc. Methods 61 consecutive patients (60 women) were enrolled. Each patient has completed a dichotomous survey to evaluate the presence of joint symptoms (presence of pain, swelling, morning stiffness in the last 3 months). Subsequently a rheumatologist - blinded to clinical data and survey results - performed the ultrasound examination of hands and wrists to evaluate the presence of effusion, synovial hypertrophy, power-Doppler signal, erosions and tenosynovitis defined according to the OMERACT definitions. The ultrasound examination was performed using the Esaote MyLab70 with a multifrequency linear probe (6-18 MHz). Results Of the 61 patients analyzed, 29 showned joint involvement on the ultrasound examination (47.54%), in particular, 37.93% had tendon involvement and 72.41% joint involvement (Table 1). 31 patients did not report joint symptoms (50.82%) but 13 (41.93%) still had ultrasound alterations (Table 2). Conclusion Musculoskeletal involvement is frequent in SSc and can be asymptomatic in more than 20% of patients. The ultrasound examination can make it possible to detect articular and periarticular involvement at an early stage of the disease before the onset of disability. Disclosure of interests Laura Belloli: None declared, Cinzia Casu: None declared, Mariaeva Romano Speakers bureau: janssen, Elisa Verduci: None declared, Maria Di Cicco: None declared, Emanuela Schito: None declared, Valeria Campanella: None declared, Michel Chevallard: None declared, Marina Muscara: None declared, Davide antonio Filippini: None declared, Oscar Massimiliano Epis Speakers bureau: BMS

Objective Through a hospital-based SARS-CoV-2 molecular and serological screening, we evaluated the effectiveness of two months of lockdown and two of surveillance, in Milan, Lombardy, the first to be overwhelmed by COVID-19 pandemics during March-April 2020. Methods All subjects presenting at the major hospital of Milan from May-11 to July-5, 2020, underwent a serological screening by chemiluminescent assays. Those admitted were further tested by RT-PCR. Results The cumulative anti-N IgG seroprevalence in the 2753 subjects analyzed was of 5.1% (95%CI = 4.3%-6.0%), with a peak of 8.4% (6.1%-11.4%) 60–63 days since the peak of diagnoses (March-20). 31/106 (29.2%) anti-N reactive subjects had anti-S1/S2 titers >80 AU/mL. Being tested from May-18 to June-5, or residing in the provinces with higher SARS-CoV-2 circulation, were positively and independently associated with anti-N IgG reactivity (OR [95%CI]: 2.179[1.455–3.264] and 3.127[1.18–8.29], respectively). In the 18 RT-PCR positive, symptomatic subjects, anti-N seroprevalence was 33.3% (95% CI: 14.8%-56.3%). Conclusion SARS-CoV-2 seroprevalence in Milan is low, and in a downward trend after only 60–63 days since the peak of diagnoses. Italian confinement measures were effective, but the risk of contagion remains concrete. In hospital-settings, the performance of molecular and serological screenings upon admission remains highly advisable.

Since SARS-CoV-2-based disease (COVID-19) spreads as a pandemic, the necessity of a highly sensitive molecular diagnosis that can drastically reduce false negatives reverse transcription PCR (rtPCR) results, raises as a major clinical need. Here we evaluated the performance of a ddPCR-based assay to quantify SARS-CoV-2 titer in 55 suspected COVID-19 cases with negative rtPCR results thanks to in-house ddPCR assay (targeting RdRp and host RNaseP). Samples were collected at ASST-GOM Niguarda between February and May 2020 at hospital admission. Clinical and imaging data were obtained for clinical staging and definition of disease severity. Patients were mainly female (45.5%) with a median age of 73 (57–84) years. ddPCR-based assay detected SARS-CoV-2 genome in nasopharyngeal samples of 19 (34.5%) patients (median viral-load: 128 copies/mL, IQR: 72–345). In 15 of them (78.9%), chest CT showed a classical COVID-19 bilateral interstitial pneumonia; 14 patients (73.7%) showed severe COVID-19 manifestations. ddPCR did not identify any trace of SARS-CoV-2 genome in the respiratory samples of the remaining 36 patients. The serological assay performed in a subgroup of 34 patients at the later stage of illness (from 3 days to 90 days after) confirmed the presence of SARS-CoV-2 antibodies in all patients tested positive for SARS-CoV-2 in ddPCR (100%). Contrariwise, negative tests were observed in 95.0% ddPCR negative patients (P

Background:Behcet disease is a rare inflammatory disorder with the unique ability to affect vessels of any size. The disease could be associated to thrombosis in both the venous and arterial compartment, and often aneurysms. In particular, the presence of aneurysms of the pulmonary artery is rarely, if ever, seen in conditions other than Behcet. Cardiac involvement, albeit uncommon, is also described and associated to a severe prognosis. The treatment is based on immunosuppressants, meanwhile the use of anticoagulants -especially when aneurysms are present- is debated.Objectives:To describe a complex case of Behcet disease.Methods:We report the case of a 45 years old man of Chinese origin who presented to A&E with fever and acute dyspnea. Blood test revealed raised ESR and CRP and raised neutrophil count. Chest X rays showed bilateral opacities suggesting pneumonia. The patient did not improve over the course of antibiotics. Later on, he presented with an episode of hemoptysis and worsening dyspnea, so he was admitted to the Intensive Care Unit. CT showed bilateral pulmonary thromboembolism and aneurysm of the pulmonary artery. Echocardiogram and cardio-MRI revealed a large, mobile thrombus within the right atrium. Extensive work-up for infections and cancer was unrevealing. ANA, ENA and ANCA antibodies were negative. On the basis of a past medical history of recurrent oral ulcers and papulopustular skin lesions that patient admitted on questioning, a diagnosis of Behcet disease was suspected. In keeping with that, HLA-B51 turned out positive. The patient was promptly started on IV steroid pulses followed by Cyclophosphamide 1 gr IV monthly for six months, then on IV anti-TNF alpha Infliximab. He was also commenced on low molecular weight heparin (LMWH) and subsequently direct factor Xa inhibitor Apixaban.Results:The patient improved significantly with progressive regression of the pulmonary CT changes. He was discharged and able to get back to his daily life activities. After 2 years and a half of treatment, the aneurysm was stable and the intracardiac thrombus completely cleared.Conclusion:This case is of particular interest because of the concomitant presence of two rare vascular complications of Behcet disease-intracardiac thrombosis (Disclosure of Interests :MARIA DI CICCO: None declared, oscar massimiliano epis Consultant of: yes, Speakers bureau: yes, Cinzia Casu: None declared, Antonella Adinolfi: None declared, Luisa Alvaro: None declared, Valeria Campanella: None declared, Michel Chevallard: None declared, Marina Muscarà: None declared, Mariaeva Romano: None declared, Emanuela Schito: None declared, Nicola Ughi: None declared, Elisa Verduci: None declared, Davide Antonio Filippini: None declared

Background: Methotrexate (MTX) is generally recommended as first-line treatment of rheumatoid arthritis (RA). Despite its efficacy is well established, a percentage of patients fails the treatment. Few studies investigated the causes of early discontinuation of MTX; a two-year retention rate of about 66% is described for RA patients with lower age and longer disease duration as independent predictors for discontinuation. Objectives: Aim of this study was to detect possible predictive factors for early discontinuation of MTX prescribed as first line treatment in RA patients enrolled in the GISEA (Italian Group for the Study of Early Arthritis) registry. Methods: RA patients who began MTX as first line treatment were included in the study. For all patients age, sex, disease duration, smoking status, the intake of glucocorticoids, clinical and serological data, comorbidities and extra-articular manifestations were collected. Results: We analyzed 612 RA patients (females/males 477/132, mean age 55.73±14.5 years; mean DAS28 5.35±1.5); rheumatoid factor (RF) was positive in 64.9%, anti-citrullinated peptide antibodies (ACPA) in 42.7%. Comorbidities were observed in 17.5% of patients, while extra-articular RA manifestations were recorded in 1.5%; 68.3% of subjects taken low doses of steroids. One hundred and forty-nine (24.3%) patients discontinued MTX during the first year (for inefficacy in 66/149 (44.3%) patients, adverse events in 51/149 (34.2%), and other reasons in 32/149 (21.5). At univariate analysis early discontinuation of MTX was associated to a lower mean age (p=0.041) and a higher mean tender and swollen joints count (p=0.001 and p=0.024, respectively). Age and tender joints count were confirmed at multivariate analysis (OR 1.014, CI95% 1.001–1.027 and OR 0.951, CI95% 0.923–0.981, respectively) as independent predictors of early withdrawal of MTX. Conclusions: More than 75% of RA patients treated with MTX as first-line therapy remained in treatment after 12 months. Age was directly correlated and tender joints count was inversely correlated with early withdrawal of MTX in RA patients. Disclosure of Interest: None declared

Background The use of glucocorticoid (GC) in Rheumatoid arthritis (RA) is recognised by the current treatment approach as a valid adjunct to DMARDs therapy. Despite its efficacy, safety of GC is still an issue and the best strategy of use is still debated, including patients under bDMARDs therapy Objectives To analyse in RA the differences of GC users versus non-users of baseline features, response to therapy and persistence in bDMARDs from the Italian biologics registry GISEA (Italian Group for the Study of Early Arthritis) Methods Consenting patients satisfying 1987 or 2010 ACR criteria for RA included in the Italian GISEA registry were enrolled. Data recorded comprehend demographic and clinimetric variables. Data are collected at baseline and 6 monthly during follow-up. To be included in the study patients needed a minimum follow-up time of 12 months and if data were not updated after 2012 patients were considered lost to follow-up. EULAR and HAQ responses were calculated. Statistical analysis included descriptive measures, parametric and nonparametric comparisons between groups and univariate analysis of survival on therapy Results A total of 8545 patients were enrolled, of them 4193 (49%) using a variable dose of GC. In 3035 (72%) the dose was ≤5 mg. Baseline demographic and disease-specific features at the start of bDMARD therapy were not different between GC users and non-users, both in 1 st and 2nd line bDMARDs RA patients. EULAR response rates were generally better in GC users at 6 and 12 months, but without statistical significance: good/moderate EULAR responses at 6 months were attained in 76,5% of GC users versus 67% in non users, while at 12 months in 81,5% vs 73% respectively (both Ps not significant). Similarly, HAQ responses ( Conclusions Our data show that GC are used in a high percentage of RA patients on bDMARD therapy. GC significantly improve the persistence on bDMARDs therapy in 1 st and 2nd line. No obvious other differences are evident in baseline, EULAR and HAQ response rates. This fact should be kept in mind when evaluating the persistence on bDMARD treatment reported in different registries. Safety evaluations in individual patients should be further analysed to guide the use of GC in this setting Disclosure of Interest None declared

Background There is evidence that autoimmunity, namely RF and ACPA antibodies, may influence disease activities and impact the clinical outcomes in RA. Objectives There is evidence that autoimmunity, namely RF and ACPA antibodies, may influence disease activities and impact the clinical outcomes in RA. Methods We analysed longitudinal data of consecutive RA patients from the Italian registry GISEA, starting a treatment with golimumab (GOL) and tested for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). Demographic and disease related characteristics were collected at baseline, 6 months, 12, and 24 months or at last observation visit. Primary endpoint was the persistence on GOL in RF/ACPA +ve and RF/ACPA patients. Secondary endpoint was the search of baseline predictors of drug survival and clinical outcomes n the two RA subsets. Drug survival was evaluated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs, 95% confidence intervals (CI)) of drug discontinuation or achievement of low-disease adjusted for patient’s demographics, disease characteristics and prior biologic treatments were computed by Cox-regression stepwise backward models. Results 345 patients had data on RA and ACP testing and were included in this analysis. No significant difference in terms of age, BMI, disease activity, co-therapy with glucocorticoids or methotrexate (MTX) was detected between RF/ACPA+ve and RF/ACPA-ve patients, but the former had significantly higher disease duration (10.6±vs 8.2±6 years) and frequencies of comorbidities (60.6% vs 44.2%). The 2 years global drug retention was 64.5%, and it was almost identical in RF/ACPA+ve 64.2% and in RF/ACPA-ve 65% RA patients. Drug survival was not influenced by the gender or cause of discontinuation (adverse or inefficacy). To note, in 31% of the patients GOL was not associated to MTX. The only predictor of drug discontinuation was the lack of MTX at baseline (HR 1.62, 95 CI 1.07–2.46, p=0.02), and the GOL-naive status (HR 0.62, 95 CI 0.39–0.99, p=0.04). At two years, 44.4% achieved the state of low-disease activity (DAS28 Conclusions In this study, we demonstrated that RF/ACPA positivity does not negatively impact on drug survival on golimumab. This may aid rheumatologists in their clinical decisions. Disclosure of Interest None declared

Background: Tumor necrosis factor-α inhibitors (TNFi) are usually the first biologic drugs employed in rheumatoid arthritis (RA) after failure of conventional disease-modifying antirheumatic drugs (DMARDs). Retention rate is a useful surrogate marker of effectiveness and safety in real life, but few studies investigated the causes of early discontinuation of these drugs. Objectives: Aim of the study was to investigate the possible predictors of early discontinuation (within 1 year of treatment) of etanercept (ETA) in RA patients enrolled into the GISEA (Italian Group for the Study of Early Arthritis) registry. Methods: RA patients who began etanercept as first biologic DMARD were included in the study. For all patients age, sex, disease duration, smoking status, the intake of glucocorticoids and DMARD, clinical and serological data, comorbidities and extra-articular manifestations were collected. Results: We analyzed 477 RA patients (females/males 382/95, mean age 51.3±14.1 years; mean DAS28 5.4±1.5); rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) were positive in 66% and 62.3%, respectively. Comorbidities were observed in 16.6% of patients, mainly cardiovascular diseases, while extra-articular RA manifestations were recorded in 6.3%. Concurrent DMARDs therapies were reported in 54.3% of patients, mainly methotrexate (40.5%), while 52.4% of subjects taken low doses of steroids. Seventy patients (14.7%) discontinued ETA during the first year (for inefficacy in 43 patients, adverse events in 22, and other reasons in 5). The presence of comorbidities and a combination therapy with DMARDs different by MTX were independent predictors of early discontinuation of ETA at multivariate analysis (see table 1). The association with MTX didn’t increase the 1-year retention rate of ETA. No significant associations were observed with steroids, presence of RF or ACPA or the disease activity at baseline. Conclusions: ETA demonstrated a high persistence in RA patients and after 12 months more than 85% of patients continued the treatment. The presence of comorbidities and a combination therapy with DMARDs different by MTX were associated to an early withdrawal of the drug. Disclosure of Interest: None declared

Background Ultrasound (US) has shown to be a sensitive imaging tool for the detection of subclinical signs of synovitis in patients (pts) with rheumatoid arthritis (RA); further studies are still required to delineate the impact of US findings in the management of RA pts in daily clinical practice. Objectives To investigate the relationship between US findings indicative of joint inflammation and US bone erosions at joint level in pts with RA. Methods In 2015 an educational event focused on the added value of US in RA pts was held in 22 rheumatology centers in Italy. In every center, the local rheumatologists provided RA pts to be examined by US. Pts signed an informed consent and a brief history of them was collected by the local rheumatologists (previous and current therapy, DAS28, HAQ score). Bilateral US examinations of wrists, metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints were performed by rheumatologists expert in US, to assess synovitis (joint effusion, synovial proliferation, and power Doppler (PD) signal), and bone erosions, using a Logiq E R7, General Electrics, with a 4.2–13 MHz linear probe. All US findings were scored using a 4 degree semiquantitative scoring system. Results In 465 RA pts, a total of 10.230 joints were scanned. Of these joints, 3.969 (39%) showed joint effusion and/or synovial proliferation and 1.784 (17%) were found positive for PD signal. The most frequently involved joints were the wrists followed by the second MCP joints and first MTP joints. In 749 joints US detected at least one bone erosion. The most frequently eroded joints were the wrists, the second and fifth MCP joints and the first and fifth MTP joints. A total of 226 RA pts showed at least one bone erosions and in 181 (80%) of these pts the eroded joints were found positive for PD signal. Conclusions A high prevalence of PD signal was found in the joints found eroded by US. This is the first study providing such an evidence using a portable US equipment. Disclosure of Interest None declared

Background Ultrasound (US) examination is able to show subclinical synovitis and structural changes of joints in patients (pts) with RA in clinical remission (CR). Objectives To investigate the differencies of US examination of small joints of hands, feet and wrists in pts with very early (VERA, 7 y duration) in clinical remission (CR). Methods In 2015 an educational event (RECALL survey) focused on the added value of US in RA pts was held in 22 rheumatology centers in Italy. In every center, the local rheumatologists provided RA pts to be examined by US. Pts signed an informed consent and a brief history of them was collected by the local rheumatologists (previous and current therapy, DAS28, HAQ score). Bilateral US examinations of wrists, metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints were performed by rheumatologists expert in US, to assess synovitis (joint effusion, synovial proliferation, and power Doppler (PD) signal), and bone erosions, using a Logiq E R7, General Electrics, with a 4.2–13 MHz linear probe. All US findings were scored using a 4 degree semiquantitative scoring system. Results Eighty-eight pts were classified as VERA, 183 as ERA and 165 as LRA. Drug usage was not different among the three groups of pts. LRA patients were older (p Conclusions At US examination VERA, ERA and LRA pts in CR have the same degree of synovial hyperplasia and PD signal despite the differences of duration of CR. Higher degree of erosive disease (at wrist and MTP joints), lower degree of MTP effusion and higher prevalence of joint effusion at MTP joints were present among LRA vs ERA and VERA pts. Disclosure of Interest None declared

Background In Rheumatoid Arthritis (RA) treatment response is assessed using standard clinical disease activity measure. However ultrasound (US) is able to show subclinical synovitis in patients (pts) with RA who are in clinical remission (CR); further studies are still required to delineate the impact of US findings in the management of RA pts in daily clinical practice. Objectives to investigate the influence of US on the clinicians9 treatment choices in pts with RA. Methods in 2015 an educational event (RECALL Survey) focused on the added value of US in RA pts was held in 22 rheumatology centers in Italy.In every center, the local rheumatologists provided RA pts to be examined by US. Pts signed an informed consent and a brief history of them was collected by the local rheumatologists (previous and current therapy, DAS28, HAQ score). Bilateral US examinations of wrists, metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints were performed by rheumatologists expert in US, to assess synovitis (joint effusion, synovial proliferation, and power Doppler (PD) signal), and bone erosions, using a Logiq E R7, General Electrics, with a 4.2–13 MHz linear probe. All US findings were scored using a 4 degree semiquantitative scoring system. Results 465 pts were evaluated. Clinicians, after US evaluations, changed therapy in 23.7% of pts, did not change therapy in 35.5% of pts.In general changes of therapy tended to be made by clinicians when joint effusion or power Doppler signal were present (table 1–2). The presence of erosion did not influence the clinicians9 decisions. Conclusions Ultrasound may be an useful tool in daily rheumatologic practice to help clinicians make decisions about how to treat patients with RA. US results, especially joint effusion and Power Doppler signal, may influence the choice of clinicians to modify a patient9s treatment regime. Disclosure of Interest None declared

To assess validity, responsiveness and interpretability of the UltraSound-CLinical ARthritis Activity (US-CLARA) index in patients with rheumatoid arthritis (RA).In this longitudinal study were involved RA patients starting treatment with abatacept. Subjects were followed along three visits in the first 6 months of therapy and underwent a comprehensive clinimetric evaluation. Validity was explored correlating the baseline scores and the cumulative inflammatory burden of the US-CLARA with the other composite indices applied. Sensitivity to change was assessed after 6 months of treatment in terms of internal and external responsiveness. Interpretability was defined in terms of determination of cutoffs against external criteria for remission (REM), low disease activity (LDA), moderate disease activity (MDA), and high disease activity (HDA) of SDAI.One-hundred and thirty patients completed the study.moderate correlations were observed between US-CLARA and both DAS28-CRP and DAS28-ESR. Higher correlations were also found between US-CLARA and both SDAI and CDAI scores. Responsiveness: internal responsiveness was wide, with SRM and ES ranging from 0.91 to 1.51. US-CLARA responsiveness was similar to that of DAS28, SDAI, or CDAI. Similarly, the area under ROC curve (AUC-ROC) of US-CLARA gives identical results. The AUC of cumulative inflammatory burden, calculated during the 6-months follow-up of all combinations were highly correlated (p0.0001). Interpretability: cutoff values for REM, US-CLARA2.0; for LDA, 2.0 ≤US-CLARA3; for MDA, 3 ≤US-CLARA ≤4.8; for HDA, US-CLARA4.8.The US-CLARA is valid and sensitive tool to assess disease activity in RA.

Introduction Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX). Objectives To evaluate the efficacy and safety of RTX–MTX combination therapy compared with RTX alone in the treatment of RA. Methods We analyzed data from a prospective cohort study, the Italian biologic register GISEA, to investigate the efficacy and safety of rituximab. Moreover, the adverse events (AE) and the causes of discontinuation therapy were analyzed. Results We identified 338 RA patients, 162 treated with RTX and 176 with RTX–MTX. After 52 and 104 weeks of therapy the disease activity score in 28 joints and the Health Assessment Questionnaire Score were available in 168 patients (78 with RTX–MTX and 60 with RTX alone), showing significant reduction without differences among the two groups. AE were reported in 142 patients (42%), for a total of 368 recorded side effects. The majority (90.5%) of AE were mild to moderate in severity. Comparable percentages of severe AE were reported in the 2 groups (9.9% for RTX alone and 9.3% for RTX + MTX). A poor disease control was observed in 14.2% and 13.5% of patients treated with RTX + MTX and RTX, respectively; while 12 patients (4.5% in RTX + MTX, and 2.5% in RTX group) suspended therapy for AE. Conclusions RTX showed a good efficacy and safety profile in the real-life management of RA patients regardless of the association with MTX.

In primary care and internal medicine settings clinicians are often reluctant to take advantage of the resources that ultrasonography (US) offers as a diagnostic tool in the initial management of patients with inflammatory arthritis, despite the recognised importance of an accurate and timely diagnosis of rheumatoid arthritis (RA) and of early referral to ensure optimal patient management. Both grey-scale (GS) and power Doppler (PD) imaging have been extensively used in early detection of synovitis and bone erosions in patients with inflammatory arthritides. We reviewed the main data on the clinical use of US in the initial management of patients with inflammatory arthritis, focusing on RA diagnosis in patients with undifferentiated arthritis, prediction of disease severity, differential diagnoses and assessment of synovitis in children with juvenile idiopathic arthritis (JIA). The role of US in assessing treatment response and monitoring disease activity in clinical remission was also briefly evaluated. The reliability of US as a diagnostic tool in rheumatological diseases has greatly advanced in the last years and the use of this imaging technique, in association with conventional assessments such as physical examination and serological tests, should be considered more often also in primary care settings.

This case series evaluates the clinical and ultrasound response to tocilizumab treatment in patients with rheumatoid arthritis (RA). Six patients with active RA (DAS28 ≥ 3.2) for ≥6 months, refractory to conventional DMARDs or anti-TNF agents, received tocilizumab 8 mg/kg every 4 weeks, as monotherapy or in combination with DMARDs, for 6 months. The following clinical parameters were assessed monthly: number of tender joints (28 and 44 joints), number of swollen joints (28 and 44 joints), DAS28-ESR, DAS28-CRP, VAS score, global health status, health assessment questionnaire, patient global assessment of disease activity, physician global assessment of disease activity, functional assessment of chronic illness therapy (FACIT), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). All patients also underwent a gray-scale ultrasonography (US) assessment with power Doppler evaluation at each visit. All clinical parameters improved during the study, versus baseline. This improvement was statistically significant for most parameters 2 months following tocilizumab initiation and was sustained to the end of the observation period. The number of tender joints (44-joint evaluation), the FACIT score, and ESR and CRP concentrations were significantly improved versus baseline values after the first month of tocilizumab treatment. The course of US evaluations mirrored that of clinical parameters; a faster and more evident response was observed for foot joints, with respect to hand joints. This case series suggested the rapid clinical benefit of tocilizumab. Ultrasound assessment showed that the onset of this effect was faster in the foot joints than in the hand joints.

Objective To compare clinical effectiveness between tocilizumab and tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) and inadequate response to conventional synthetic disease‐modifying antirheumatic drugs initiating biologic therapy. Methods Patients prescribed tocilizumab (intravenous) or TNFi were prospectively observed in routine clinical practice for 52 weeks across 158 sites in 26 countries. The primary observation was the change from baseline in Disease Activity Score based on 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) at week 24 using analysis of covariance for between‐groups comparison. Secondary end points included Clinical Disease Activity Index (CDAI) and patient‐reported outcomes at weeks 24 and 52. Results Of 1,216 patients, 35% initiated tocilizumab and 65% initiated TNFi. RA duration was shorter, and disease activity and corticosteroid use were higher in tocilizumab patients. Tocilizumab‐treated patients had greater improvement in DAS28‐ESR at weeks 24 and 52 (week 24 difference [95% confidence interval] in adjusted means: −0.831 [−1.086, −0.576]; P

Objective To compare clinical evaluation and ultrasonography (US) in the assessment of joint synovitis in children with juvenile idiopathic arthritis (JIA). Methods Thirty-two patients underwent clinical evaluation of 52 joints by 2 pediatric rheumatologists. Joints were assessed for swelling, tenderness/pain on motion, and restricted motion. The same joints were scanned independently by an experienced sonographer for synovial hyperplasia, joint effusion, and power Doppler (PD) signal. Results In total, 1,664 joints were assessed both clinically and with US. On clinical examination, 98 joints (5.9%) were swollen, 59 joints (3.5%) were tender, and 40 joints (2.4%) had restricted motion. On US evaluation, 125 joints (7.5%) had synovial hyperplasia, 153 joints (9.2%) had joint effusion, and 53 joints (3.2%) had PD signal. A total of 104 (6.3%) and 167 (10%) joints had clinical and US synovitis, respectively. Of the 1,560 clinically normal joints, 86 (5.5%) had subclinical synovitis (i.e., had synovitis on US). US led to classifying 5 patients as having polyarthritis who were classified as having oligoarthritis or were found to have no synovitis on clinical evaluation. US variables were moderately correlated with clinical measures of joint swelling, but poorly correlated with those of joint tenderness/pain on motion and restricted motion. Overall, correlations were lower for PD signal than for synovial hyperplasia and joint effusion. Conclusion We found that subclinical synovitis as detected by US is common in children with JIA. This finding may have important implications for patient classification and may affect the choice of the optimal therapeutic strategy in individual patients.

Objective To evaluate the prevalence of undiagnosed rheumatic diseases in the first trimester of pregnancy. Design We screened for rheumatic diseases in 1210 consecutive pregnant women during the first trimester of pregnancy using a 10-item questionnaire. Setting A university hospital in northern Italy. Population One hundred and thirty-seven (11.3%) women who answered positively to at least one question constituted the cases and were compared with 107 negative controls. Methods Cases and controls were tested for rheumatic autoantibodies (antinuclear antibody, anti-double-stranded DNA, anti-extractable nuclear antigen, anticardiolipin antibody, anti-β2-glycoprotein I antibodies and lupus anticoagulant) and were evaluated by a rheumatologist for a definite diagnosis of rheumatic disease. Main outcome measures Prevalence of undiagnosed rheumatic disease in the first trimester of pregnancy. Results The overall rate of positivity to the antibodies tested was 43.1% (59/137) among cases and 9.3% (10/107) in the controls (P < 0.001). A definitive diagnosis of rheumatic disease was made in 35 cases (25.5%) and in none of the controls (P

Objective Rheumatoid arthritis (RA) with concomitant hepatitis B virus (HBV) infection represents a therapeutic challenge due to the risk of HBV reactivation under immunosuppressive treatment. To date there are few data coming from anecdotal case reports that concern HBV reactivation following treatment with abatacept. This observational retrospective study was aimed to assess the safety profile of abatacept in this particular clinical setting. Methods Eleven Italian rheumatologic centers provided data from patients with RA and positive HBV serology treated with intravenous abatacept. HBV markers and clinical and laboratory data were checked at followup visits every 3 months. Results In total, 72 patients were included in the study: 47 inactive carriers, 21 occult carriers, and 4 chronic active carriers for HBV. At baseline all of the patients had normal liver function tests and low or undetectable HBV DNA levels, except for those with chronic active hepatitis. Thirteen patients received prophylaxis with lamivudine, and 4 received treatment with adefovir or tenofovir. At the end of the 24-month followup period, 49 patients were being treated. Data from 316 followup visits showed that abatacept was safe. No patients experienced reactivation of hepatitis B. Treatment withdrawals (23 patients) were due to lack of efficacy, subject decision/lost at followup, or adverse events not related to HBV infection. Conclusion Our study provides reassuring data about the safety profile of abatacept in RA with concomitant HBV infection without universal antiviral prophylaxis. Further prospective studies are needed to confirm these preliminary results.

In the last decade, treatment strategies for rheumatoid arthritis (RA) have included the early use of disease-modifying anti-rheumatic drugs, since prompt suppression of disease activity is associated with a reduction in radiological damage. This strategy has now been incorporated into the broader concept of “tight control”, defined as a treatment strategy tailored to each patient with RA, which aims to achieve a predefined level of low disease activity or remission within a certain period of time. To pursue this goal, tight control should include careful and continuous monitoring of disease activity, and early therapeutic adjustments or switches should be considered as necessary. It is noteworthy that the key role of tight control of RA has been stressed by the recent EULAR Guidelines. This review discusses the most recent evidence concerning the role of a tight control strategy in the treatment of RA, and on how this strategy should be pursued.

We have evaluated bone marrow morphology, percentage of bone marrow CD34(+) cells, proliferative activity of bone marrow precursors, clonogenic assay (BFU-E and CFU-GM) in short-term bone marrow cultures, and bone marrow cell apoptosis, together with serum TNF-alpha and IL-6, in 16 chronic, refractory RA patients, as well as in five healthy controls. Of 16 RA patients (68.7%), 11 showed a reduced bone marrow cellularity, while it was normal in all the controls. In RA patients, the median percentage of CD34(+) bone marrow cells, the median percentage of proliferating bone marrow myeloid precursors, and the median number of both BFU-E and CFU-GM colonies were significantly lower than observed in the controls. As far as TNF-alpha and IL-6 titers is concerned, the latter did not significantly differ from controls' values, while TNF-alpha titers were significantly lower in healthy controls. Finally, the median apoptotic index of early bone marrow myeloid cells of RA patients was significantly higher compared with controls. These observations may identify the biological risk factors for impaired mobilization and/or engraftment when RA patients are candidates for autologous hematopoietic stem cell grafting.

Technological advances in ultrasonography (US) in recent years has allowed for improvements to the imaging quality of gray-scale ultrasound and the development of more advanced forms of this imaging technique such as 3D and Doppler US. These improvements mean that US now has an accepted place in rheumatology not only in diagnosis, but also in the determination of disease progression and pathology and in facilitating guidance of interventional therapies. The increasing use of US-guided intervention by rheumatologists in the last 20 years is evidenced by the almost exponential increase in the number of publications in the relevant subjects.

The paper reports the results from the observational retrospective-prospective RUBINO study conducted in Italy to assess the safety of rituximab in the treatment of rheumatoid arthritis (RA) in routine clinical practice. The percentage of patients who manifested at least one grade 3 or 4 adverse event (AE) assessed by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v.3) during the observation period (primary objective) was evaluated. The percentage of patients manifesting a severe AE (SAE), clinical response to rituximab treatment, clinical remission according to disease activity score for 28 joints (DAS28) criteria, markers of disease and quality of life were also assessed. Fifty-three Italian rheumatology centers took part in the study. Patients with a diagnosis of RA and inadequate response to anti-tumor necrosis factor b (anti-TNFa) drugs were enrolled. Participating patients had previously received at least one cycle of rituximab, and treatment was still ongoing at the time of recruitment. Out of 205 patients enrolled, 60% manifested no form of AE, 14.2% had at least one grade 3 or 4 AE, and 11.2% patients reported an SAE. The overall percentage of patients manifesting AEs (40%) was lower compared to the DANCER (81% and 85%), REFLEX (85%) and RESET (85% and 69%) studies, but higher than that observed in the CERERRA registry (from 10.2% to 13.9%). This difference may be due to the shorter observation period applied in the CERERRA registry (only 12 months) compared to the RUBINO study (up to 3 years). All parameters of RA activity (erythrocyte sedimentation rate, C-reactive protein, health assessment questionnaire score, DAS28) improved significantly during the study.

Anti-Ro(SS-A) 52 kDa and 60 kDa specificities in undifferentiated connective tissue disease. — Objective. Autoantibodies to Ro(SS-A) may recognize two different polypeptides, of 52 kDa and 60 kDa, respectively. Methods. We used an ELISA with purified human recombinant antigens to conduct a detailed analysis of the specificities of anti-Ro(SS-A) antibodies from 170 patients with definite diagnoses (systemic lupus erythematosus [SLE], n = 55; primary Sjogren's syndrome [PSS], n = 39; systemic sclerosis, n = 9; rheumatoid arthritis [RA], n = 10) or undifferentiated connective tissue disease (UCTD, n = 57). Most of the patients with SLE or PSS had both anti-52 kDa and -60 antibodies; isolated anti-60 kDa antibodies were found in 13 % of the SLE patients and in none of the PSS patients, whereas high titers of anti-52 kDa were more common in the PSS than in the SLE patients. Results. In the UCTD patients, the anti-Ro(SS-A) profile showed no significant correlations with clinical features but was associated with the clinical outcome. Over the mean follow-up of five years, definite SLE developed in four of the five UCTD patients with isolated anti-60 kDa vs only one of the remaining 52 patients (p < 0.0001); progression to PSS was seen in seven of the 34 patients with both anti-52 kDa and anti-60 kDa vs none of the remaining 23 patients (ρ = 0.03); none of the 12 patients with isolated anti-52 kDa developed a definite connective tissue disease. Conclusion. Our study suggests that analysis of anti-Ro(SS-A) specificity may provide useful information for predicting the course of UCTD.

The real role of anti‐neutrophil cytoplasmic antibodies (ANCA) in systemic lupus erythematosus (SLE) patients is not well defined [1–3]; recently in our centre we observed two SLE cases in which AN...

disease activity after dose reduction regained low disease activity after returning to the standard dose. The study by van Herwaarden et al. paved the way for further investigation on the effectiveness of reduced-dose TCZ in clinical practice. At our center, we conducted a small pilot, descriptive-only observation in ten RA patients who were under therapy with standard-dose TCZ from at least 12 months and in clinical remission from at least 6 months. After informed consent, TCZ therapy was reduced to 4 mg/kg. Each month, at the infusion visit, patients were monitored using approved clinical scales (VAS, HAQ, CDAI, and SDAI) and by ultrasound (US) examination, which is increasingly used in the determination of disease progression [5]. One patient developed a neoplasia and was then excluded from the analysis. Two patients experienced reactivation of disease, 2 and 4 months since the initiation of reduced-dose TCZ, respectively; standard-dose TCZ therapy was then reinstituted, and clinical remission was observed at the following visit in both patients. We report here the data reported at 12 months after the initiation of reduced-dose TCZ, in the remaining seven patients. Overall, at the end of the observation period, all patients showed stable disease remission, although a minor worsening in all scales was observed (mean DAS28-VES: 1.7 ± 1.1 at baseline vs. 2.4 ± 1.2 at 12 months; DAS28-PCR: 1.5 ± 0.8 vs. 2.2 ± 0.5; HAQ: 0.1 ± 0.4 vs. 0.2 ± 0.4; CDAI: 3.1 ± 2.9 vs. 4.7 ± 2.8; SDAI: 3.2 ± 2.9 vs. 4.8 ± 2.8). Disease remission was also confirmed at US (number of joints with articular effusion: 4.0 ± 2.5 vs. 5.7 ± 4.1; number of joints with synovial hypertrophy: 4.7 ± 2.8 vs. 6.6 ± 4.4; number of positive joints at Power Doppler: 0.7 ± 1.0 vs. 0.6 ± 0.8). Although the preliminary and descriptive-only nature of our pilot analysis does not allow to retrieve any definite conclusion, our findings lend further support to the Tocilizumab (TCZ) is a humanized monoclonal interleukin-6 (IL-6) receptor antibody which has demonstrated clinical efficacy in the treatment of patients with moderate–severe rheumatoid arthritis (RA) who experienced inadequate response to methotrexate and one or more antiTNFα agent [1, 2]. The efficacy of TCZ in the treatment of RA is supported by a bulk of evidence which includes randomized clinical trials and observational, ‘field-practice’ studies [2]. TCZ can be administered intravenously at the standard dose of 8 mg/kg either in combination with other disease-modifying antirheumatic drugs (DMARDs) or as a monotherapy [2]. The favorable efficacy and tolerability profile of TCZ is sustained over a long term (up to 9 years) [2]. Although the above-mentioned evidence supports the use of TCZ in clinical practice, additional data are required to fully explore the optimal individualization of this treatment for each single patient [3]. For instance, it has been recently suggested that some of patients on TCZ achieve low disease activity with a lower than registered starting dose, i.e., 4 mg/kg [4]. In a retrospective study by van Herwaarden et al. [4] on 22 RA patients treated with TCZ 8 mg/kg for about 6 months and tapered to 4 mg/kg because of low disease activity, 55 % of patients remain in disease remission at 6 months since the reduction in dose; however, a slight increase in the disease activity score 28 (DAS28) was observed at the end of the observation period. Interestingly, all patients with worsened

The 'real time' capability of ultrasound (US) allows dynamic assessment of joint and tendon movements, which can often aid in the detection of structural abnormalities. The simultaneous use of arthroscopy (AS) and US is therefore a logical progression. Here the results of a series of 11 patients with different rheumatic diseases in whom a combined use of US and AS was adopted are reported.

Objective: The role of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) in the response to treatment for rheumatoid arthritis (RA) such as tocilizumab (TCZ) is still not completely understood. This study investigates the relationship between the presence and levels of RF and anti-CCP and clinical response to TCZ in patients with RA. Methods: This was an observational longitudinal study in 27 patients with active, long-standing RA despite previous treatment with >2 Disease-Modifying Anti Rheumatic Drugs (DMARDs) and/or steroids. Patients were treated with TCZ 8 mg/kg every 4 weeks. The following parameters were assessed: Erythro Sedimentation Rate (ESR), C - reactive protein (CRP), Health Assessment Questionnaire (HAQ), Disease Activity Score of 28 joints (DAS28), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI). IgM-, IgA- and IgGRFs and anti-CCP antibodies were measured using ELISA at baseline, 3 months (T1), 6 months (T2), and 12 months (T3). Results: All patients showed significant and sustained clinical response to TCZ treatment. All clinical scales with the exception of HAQ significantly decreased. There was a significant correlation (p=0.03) between anti-CCP and SDAI changes from baseline at T1 and T2. However, no significant correlation was measured between antibody count at T0 and changes in the DAS-28 ESR at T1 and at T2. Also, there was no correlation between clinical scales and antibody levels RF-IgG, IgA, IgM as well as between clinical scales and anti-CCP levels. Conclusions: Tocilizumab is effective in treating the clinical symptoms of RA, and the efficacy of this molecule was not correlated with either RF or anti-CCP levels.