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Objectives The present study validates the 2022 ACR/European Alliance of Associations for Rheumatology (EULAR) classification criteria for Takayasu’s arteritis (TAK), compared with the 1990 ACR TAK classification criteria. Methods The fulfilment of 2022 ACR/EULAR and 1990 ACR TAK criteria from four referral centres was assessed for TAK compared with extracranial giant cell arteritis (EC-GCA) and other controls. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio of a positive test (LR+) or negative test (LR–), and area under receiver operating characteristics curve (AUC) were calculated. Results Among 504 patients with TAK (404 females) and 222 controls (151 females, 144 patients with EC-GCA), the 2022 ACR/EULAR criteria had better sensitivity (95.83% vs 82.94%) and NPV, but poorer specificity (63.51% vs 90.54%), PPV, LR+, LR– and AUC at the pre-determined cut-offs than the 1990 ACR criteria. The 2022 ACR/EULAR criteria had greater specificity (76.06% vs 57.62%) and AUC (0.845 vs 0.771), with similar sensitivity (93% vs 96.53%) in males as in females. The 2022 ACR/EULAR criteria performed similarly with only EC-GCA as controls (sensitivity 95.83%, specificity 60.42%, AUC 0.781). Sensitivity remained similar, whereas specificity was higher for 40–60 years vs Conclusion The poor specificity of the 2022 ACR/EULAR TAK criteria in real-life settings was improved by increasing the cut-off to 6 or 7, or removing the point for female sex.

Objectives To evaluate effectiveness and safety of infliximab dose escalation in Takayasu arteritis (TAK) patients. To identify factors associated with refractoriness to standard-dose infliximab. Methods Medical records of infliximab-treated TAK patients from a large single-centre observational cohort were reviewed. Infliximab therapy duration, concomitant therapies, and reasons for dose escalation and therapy suspension were evaluated. Occurrence of adverse events was recorded. A comparison between patients who maintained infliximab standard-dose and those who needed dose-escalation was performed. Factors associated with refractoriness to standard dose were analysed. Results Forty-one patients were included. Starting infliximab dose was 5 mg/kg 6-weekly and 28 patients (68%) needed dose escalation. Persistence/recurrence of clinical symptoms was the most frequent reason for escalation. Median therapy duration was 39 (IQR, 26–61) months in the standard-dose group and 68 (38–87) months in the intensified-dose group. In the intensified-dose-group, infliximab was suspended in eight patients (29%) after a median of 38 (31–71) months, due to loss of response (n = 7) or patient’s request (n = 1). Patients in the intensified-dose group had a higher number of relapses (3.4 vs 0.8 events/patient) and received a higher cumulative steroid dose (1.7 [1.6–2.3] vs 1.3 [1–1.6] g/month of prednisone). Three patients from the intensified-dose group had serious infections; one patient from the standard-dose group developed paradoxical psoriasis. At univariate analysis, age at diagnosis and age at infliximab start were associated with infliximab escalation. Conclusion In TAK, dose escalation is safe and allows to optimise infliximab durability in refractory patients. Younger patients seem to be more refractory to standard dosages.

Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 x 10(-s)) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets., National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [R01 AR070148]; National Institute of Arthritis and Musculoskeletal and Skin DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [U54 AR057319, U01 AR51874 04]; National Center for Research ResourcesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [U54 RR019497]; Office of Rare Diseases Research of the National Center for Advancing Translational Sciences; Imperial College, National Institute for Health Research, Biomedical Research Centre; Wellcome TrustWellcome TrustEuropean Commission [WT107881]; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MC_UU_00002/4], This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health grant R01 AR070148 to A.H.S. The Vasculitis Clinical Research Consortium has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319 and U01 AR51874 04), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research of the National Center for Advancing Translational Sciences. J.C.M., A.P.K., and R.M.M. acknowledge support from the Imperial College, National Institute for Health Research, Biomedical Research Centre. C.W. and G.R. acknowledge support from The Wellcome Trust (WT107881) and the Medical Research Council (MC_UU_00002/4). This work was supported by the use of study data downloaded from the dbGaP website, under dbGaP: phs000272.v1.p1, phs000431.v2.p1, phs000583.v1.p1, and phs000444.v1.p1.

Introduction: Adult onset Still disease (AOSD) is a rare systemic inflammatory condition. The clinical spectrum of this disease ranges from self-limiting forms with mild symptoms to life-threatening cases. Glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs) represent the first line of therapy for AOSD, with add-on therapy with second-line drug reserved to steroid-dependent patients and in life-threatening cases. Currently, early treatment with conventional disease modifying anti-rheumatic drugs (DMARDs) and biologic agents blocking causal cytokines is advocated in patients with severe and recalcitrant clinical manifestations. Areas covered: This review analyzes the available controlled evidence and observational data regarding the efficacy and safety of conventional and biological pharmacological agents in the treatment of AOSD. Expert opinion: Non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids are effective in controlling clinical manifestations in the majority of AOSD patients. Conventional DMARDs can be 20 effective in some severe and steroid-dependent cases of AOSD; however, anti-cytokine agents represent an effective and overall more suitable alternative in this specific subset of patients. IL-1 and IL-6 blockade are effective in treating systemic and articular inflammation of AOSD patients. IL-1 blockade also has an excellent safety profile and therefore represent the first choice of biologic treatment in this clinical scenario.

Objective Memory stem T (Tscm) cells are long-lived, self-renewing T cells that play a relevant role in immunologic memory. This study was undertaken to investigate whether Tscm cells accumulate in rheumatoid arthritis (RA). Methods The polarization and differentiation profiles of circulating T cells were assessed by flow cytometry. Antigen-specific T cells were characterized by staining with major histocompatibility complex class II tetramers. The T cell receptor (TCR) repertoire was analyzed by high-throughput sequencing using an unbiased RNA-based approach in CD4+ T cell subpopulations sorted by fluorescence-activated cell sorting. Results We analyzed the dynamics of circulating Tscm cells (identified as CD45RA+CD62L+CD95+ T cells) by flow cytometry in 27 RA patients, 16 of whom were also studied during treatment with the anti-tumor necrosis factor (anti-TNF) agent etanercept. Age-matched healthy donors were used as controls. CD4+ Tscm cells were selectively and significantly expanded in RA patients in terms of frequency and absolute numbers, and significantly contracted upon anti-TNF treatment. Expanded CD4+ Tscm cells displayed a prevalent Th17 phenotype and a skewed TCR repertoire in RA patients, with the 10 most abundant clones representing up to 53.7% of the detected sequences. CD4+ lymphocytes specific for a citrullinated vimentin (Cit-vimentin) epitope were expanded in RA patients with active disease. Tscm cells accounted for a large fraction of Cit-vimentin-specific CD4+ cells. Conclusion Our results indicate that Tscm cells, including expanded clones specific for relevant autoantigens, accumulate in RA patients not exposed to biologic agents, and might be involved in the natural history of the disease. Further analysis of Tscm cell dynamics in autoimmune disorders may have implications for the design and efficacy assessment of innovative therapies.

Objective To assess the safety and the efficacy of TNF-α antagonists and tocilizumab in patients with Takayasu arteritis (TAK). Methods A total of 209 patients with TAK [median age 29 years (interquartile range 7–62)], 186 (89%) females] were included. They received either TNF-α antagonists [n = 132 (63%) with 172 lines; infliximab (n = 109), adalimumab (n = 45), golimumab (n = 8), certolizumab (n = 6) and etanercept (n = 5)] or tocilizumab [n = 77 (37%) with 121 lines; i.v. and s.c. in 95 and 26 cases, respectively]. Results A complete response at 6 months was evidenced in 101/152 (66%) patients on TNF-α antagonists and 75/107 (70%) patients on tocilizumab. Age ≥30 years [odds ratio 2.09 (95% CI 1.09, 3.99)] was associated with complete response, whereas vascular signs [OR 0.26 (95% CI 0.1, 0.65)], baseline prednisone ≥20 mg/day [OR 0.51 (95% CI 0.28, 0.93)] were negatively associated with the complete response to TNF-α antagonists or tocilizumab. During a median follow-up of 36 months, 103 relapses were noted. Supra-aortic branches and thoracic aorta involvement [HR 2.44 (95% CI 1.06, 5.65) and 3.66 (1.18, 11.4), respectively] and systemic signs at baseline [HR 2.01 (95% CI 1.30, 3.11)] were significantly associated with relapse. The cumulative incidence of treatment discontinuation and relapse were similar in TNF-α antagonists and tocilizumab. Fifty-eight (20%) adverse effects occurred on biologic targeted therapies [37 (21%) on TNF-α antagonists and 21 (17%) on tocilizumab (P = 0.4), respectively]. Conclusion This large multicentre study shows high efficacy of biologic targeted treatments in refractory TAK. Efficacy, relapse and drug retention rate were equivalent with TNF-α antagonists and tocilizumab.

The concern about the offspring’s health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.

Objectives: To compare the presenting features and outcomes of patients with cranial-limited (C-) and large-vessel (LV-) giant cell arteritis (GCA). Methods: Data from our GCA cohort were collected retrospectively. Patients who underwent total-body large-vessel imaging within 10 days after commencing steroid therapy were included. Patients with LV involvement were classified as LV-GCA. Presenting features, treatments, and outcomes of LV-GCA and C-GCA patients were compared. Results: 161 patients were included (LV-GCA, n = 100). At baseline, LV-GCA patients were younger than those with C-GCA (73.2 �� 8.9 vs 76 �� 8.8 years, p = 0.018) and had a longer delay to diagnosis (3.5 �� 4.6 vs 2.3 �� 4.9 months, p = 0.001). C-GCA patients had a higher incidence of headache (p = 0.006) and ischaemic optic neuropathy (p Conclusion: LV-GCA patients were younger at diagnosis and suffered a longer diagnostic delay. The outcomes of the two subgroups were similar. An earlier introduction of steroid-sparing agents in LV-GCA patients might have played a positive role.

Objectives To assess drug retention rates (DRRs) and reasons for discontinuation of biologic disease-modifying antirheumatic drugs (bDMARDs) in a large monocentric cohort of patients with adult onset Still's disease (AOSD). Methods Clinical data of AOSD patients treated with at least one bDMARD and followed up at our Center were retrospectively evaluated. Data about disease duration, number of previous bDMARDs, concomitant treatments, and reasons for therapy discontinuation were collected. Survival curves were examined by the Kaplan-Meier method and compared using a stratified log-rank test. 24-month DRRs were calculated for each bDMARD. Hazard ratio (HR) for previous bDMARD use was evaluated. Results Forty-two AOSD patients received a total of 79 bDMARD-courses. Anakinra (ANK; n = 41) was the most frequently used bDMARD, followed by tocilizumab (TCZ; n = 21) and Tumor Necrosis Factor inhibitors (TNFi; n = 17). Biologic agents were administered concomitantly with prednisone in all cases (mean dose, 23 ± 18 mg/day) and with csDMARD therapy in 54 (68%) of courses. Thirty-six (46%) treatment courses were discontinued by 24 months. DRRs at 24 months were 62.5% for TCZ, 53.1% for ANK, and 11.8% for TNFi. ANK and TCZ DRRs were similar (p = 0.576), but significantly higher than TNFi (p = 0.015). Previous biologic therapies did not impact DRR (HR 0.73, 95% CI = 0.40 - 1.31, p = 0.288). Conclusions In our AOSD study population, 24 months DRRs of TCZ and ANK were similar and significantly higher than the TNFi DRR. Previous use of biologic agents did not affect DRRs.

Objective We retrospectively investigated drug retention rate (DRR) and reasons for discontinuation of seven biologic disease-modifying anti-rheumatic drugs (bDMARDs) in Takayasu's arteritis (TA) in a real-world setting. Methods TA patients followed-up in our center fulfilling the 1990 ACR criteria and treated with ≥1 bDMARD were selected. Data about disease duration, number of bDMARDs, reasons for bDMARDs discontinuation, and concomitant conventional synthetic (cs)DMARDs were collected. Survival curves were examined by the Kaplan-Meier method and compared using a stratified log-rank test. 24-month DRR was calculated. Hazard ratio (HR) for concomitant csDMARDs and for previous bDMARDs was evaluated. A comparative sub-analysis between anti-TNFα drugs and tocilizumab was performed. Results We identified 50 patients and 86 bDMARD-courses. No significant differences were observed in age and disease duration between the seven groups. Infliximab was the most frequent first-line bDMARD (78.6%). At bDMARDs initiation, all patients were prescribed prednisone (mean dose, 13.5 ± 10.3 mg/day) and 85.2% concomitant csDMARD therapy. 43% of treatment courses were stopped by 24 months. Golimumab had the highest DRR (71.4%), followed by infliximab (69%), adalimumab (56.3%), abatacept (50%), tocilizumab (41.1%), anakinra (0%) and rituximab (0%), p = 0.016. Concomitant csDMARDs therapy showed positive effects on DRR (HR=2.87, 95% CI=1.19–6.92, p = 0.019). Anti-TNFα drugs had significantly higher DRR compared to tocilizumab (67.2% vs 41.1%, p = 0.028). Even in these subgroups, csDMARDs showed positive effects on DRR (HR=3.79, 95% CI=1.49–9.6, p = 0.005). Conclusions Anti-TNFα agents had the highest DRR overall and a higher DRR in a head-to-head comparison with tocilizumab. Concomitant csDMARDs had a significant positive effect on bDMARDs DRR.

The provisional EULAR recommendations address several aspects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus, and the disease caused by SARS-CoV-2, COVID-19 and are meant for patients with rheumatic and musculoskeletal diseases (RMD) and their caregivers. A task force of 20 members was convened by EULAR that met several times by videoconferencing in April 2020. The task force finally agreed on five overarching principles and 13 recommendations covering four generic themes: (1) General measures and prevention of SARS-CoV-2 infection. (2) The management of RMD when local measures of social distancing are in effect. (3) The management of COVID-19 in the context of RMD. (4) The prevention of infections other than SARS-CoV-2. EULAR considers this set of recommendations as a 'living document' and a starting point, which will be updated as soon as promising new developments with potential impact on the care of patients with RMD become available.

Severe infections represent one of the major complications of immunosuppressive therapy.1 Great concern among rheumatologists has consequently raised by the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19).2 3 Italy has represented the European epicentre of this global pandemic, with more than 140 000 confirmed cases as of 11 April 2020.4 We evaluated the impact of SARS-CoV-2 infection among patients with large-vessel vasculitis (LVV) followed up at our LVV-Clinic in Milan, Lombardy, the Italian region with the highest rate of SARS-CoV-2 infections.5 A phone survey was conducted among these patients between 2 and 10 April 2020, 6 weeks after the COVID-19 outbreak in Italy. The survey consisted of the following questions: (1) Have you been diagnosed with COVID-19? (2) Since the beginning of COVID-19 outbreak, have you experienced one of the following symptoms: sore throat, non-productive cough, fever >37.5°C, reduced smelling or tasting, flu-like symptoms? (3) Have you been in contact with a COVID-19 patient? (4) Have you regularly been taking your LVV medications? …

ObjectiveTo describe the features of large-vessel vasculitis (LVV) as it affects the aorta and its branches in patients with relapsing polychondritis (RP).MethodsRetrospective data and systematic literature review.ResultsTwenty-one patients were identified. LVV diagnosis was subsequent to RP and associated with extrachondral involvement in the majority of patients. Supraaortic vessels were more frequently involved (82%). Fourteen patients (67%) were treated with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) and 7 (33%) with a biological DMARD (bDMARD). Vascular interventional procedures were performed in 10 patients (48%). Premature death due to cardiovascular complications was reported in 3 cases (14%).ConclusionExtraaortic LVV is a serious and overlooked RP manifestation. All patients with RP should be investigated for LVV.

Purpose: The object of this study was to assess whether18F-fluorodeoxyglucose PET/CT (FDG PET/CT) provides novel information in patients with Takayasu’s arteritis (TA) in addition to that provided by current activity assessment, to analyse the effects of possible confounders, such as arterial grafts, and to verify whether PET/CT could be informative in lesions

Background:Adult onset Still’s disease (AOSD) is a rare systemic inflammatory disease. Glucocorticoids represents first-line therapy and conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) play a central role as steroid-sparing agents. Patients refractory to csDMARD may require the introduction of a biological DMARD (bDMARD). There is paucity of data about the efficacy and drug retention rate (DRR) of bDMARDs used in the treatment of AOSD.Objectives:To retrospectively evaluate DRR and reasons for discontinuation of five different bDMARDs in a monocentric cohort of AOSD patients in a real-world setting.Methods:AOSD patients followed at our Center who received at least one bDMARD were selected. Data about disease duration, number of bDMARDs, reasons for bDMARDs discontinuation, concomitant csDMARDs were collected. Survival curves were determined by the Kaplan-Meier method and compared using a stratified log-rank test. 24-month DRRs were then calculated. Hazard ratio (HR) for previous bDMARDs was also evaluated.Results:We identified 42 patients and 79 bDMARD-courses (Table 1). Anakinra (ANK, n = 41) was the most used bDMARD, followed by tocilizumab (TCZ, n=21) and Tumor Necrosis Factor inhibitors (TNFi, n = 17). At bDMARDs initiation, all patients were being given prednisone (mean dose, 23 ± 18 mg/day) and 76% were on concomitant csDMARD therapy. 36 (46%) treatment courses were stopped by 24 months; discontinuation causes are shown inTable 2. 14 treatment courses were started in the previous 24 months (ANK = 9, TCZ = 5), without being stopped before the study time but not reaching 2-year treatment duration. Overall retention rates at 24 months were the following: TCZ, 62.5%; ANK, 53.1%; TNFi, 11.8% (p = 0.021). Survival curves are shown inFigure 1. DRRs of ANK and TCZ were statistically comparable (p = 0.576), and they were both significantly higher than the DRR of TNFi (p = 0.015). Previous bDMARDs therapy showed no effect on DRR (HR 0.73, 95% CI = 0.40 - 1.31, p = 0.288).Table 1.Clinical characteristics at initiation of biologic agents in adult onset Still’s Disease. TNFi = Tumor Necrosis Factor inhibitorsAnakinra (n=41)Tocilizumab (n=21)TNFi (n=17)p - valueAge (years)38 ± 1643 ± 1938 ± 130.601Female sex (%)61%48%35%0.443Mean disease duration (months)49 ± 6072 ± 7561 ± 640.445Systemic disease (%)61%38%29%0.213C-reactive protein (mg/l)99 ± 84111 ± 10066 ± 520.445Erythrocyte sedimentation rate (mm/h)71 ± 3265 ± 2777 ± 410.617White blood cells (cells/ul)14640 ± 454014116 ± 372416870 ± 55040.361Ferritin (ng/ml)10114 ± 186576327 ± 80616295 ± 95730.591Previous therapy (%)100%100%100%1.000csDMARD (%)88%90%94%0.973bDMARD (%)22%81%59%0.003Mean prednisone dose (mg die)20.3 ± 18.115.8 ± 14.427.3 ± 14.40.252Concomitant csDMARD therapy (%)71%71%59%0.865Table 2.Causes of treatment discontinuation of biologic agents in adult onset Still’s Disease. TNFi = Tumor Necrosis Factor inhibitorsAnakinra (n=41)Tocilizumab (n=21)TNFi (n=17)Total (n=79)Inefficacy24%14%65%30%Adverse events10%10%24%13%Other reasons 2% 5% 0% 3%Total37%29%88%46%Figure 1.Kaplan-Meier curves comparing anakinra (ANK), tocilizumab (TCZ) and Tumor Necrosis Factor inhibitors (TNFi) at 24 months in adult onset Still’s disease.Conclusion:In our AOSD cohort, DRRs at 24 months of TCZ and ANK were not statistically different, and they were both significantly higher than the DRR of TNFi. Previous use of biologic agents was found to have no effect on bDMARDs retention probability.References:[1]Efficacy and safety of biological agents in adult-onset Still’s disease; Cavalli et al; Scand J Rheumatol. 2015;44(4):309-14.Disclosure of Interests:Nicola Farina: None declared, Alessandro Tomelleri: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Giulio Cavalli Speakers bureau: SOBI, Novartis, Pfizer, Elena Baldissera Speakers bureau: Novartis, Pfizer, Roche, Alpha Sigma, Sanofi, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI

Objectives Takayasu arteritis (TA), a systemic vasculitis typically occurring in female patients aged ≤ 40, can affect coronary arteries and cause ischemic heart disease (IHD). In this study, we investigated the prevalence of TA in young women presenting with IHD in the Emergency Department. Methods We evaluated hospital records of 158,860 consecutive female patients aged < 40, who accessed the Emergency Department of our institution over 8 consecutive years (2007–2015). The prevalence of different etiologies of IHD was determined. Diagnosis of TA was established based on the 1990 ACR criteria. Results Overall, 1950 women aged < 40 presented to the Emergency Department with chest pain, dyspnea, palpitations, angina, heart failure, or cardiac arrest; 40 had acute IHD. The etiology was ‘classic’ atherosclerosis in 24 cases (60%), TA in 4 cases (10%), vasospasm and sympathomimetic drug abuse in 3 cases each (7.5%), coronary artery dissection and microvascular angina in 2 cases each (5%), Takotsubo and radiation-induced cardiomyopathy in 1 case each (2.5%). Discussion Although a diagnosis of TA is likely to be overlooked, TA is not infrequent in younger females presenting with acute IHD, a finding relevant to the diagnosis and management of these patients.

Background IgG4-Related Disease (IgG4-RD) promptly responds to glucocorticoids but relapses in most patients. Rituximab (RTX) represents a promising strategy to avoid IgG4-RD flares but its administration for maintaining disease remission has never been assessed in terms of optimal timing of infusion, dosage, and duration of treatment. In the present study we aimed to evaluate the efficacy and safety of RTX for maintenance of IgG4-RD remission. Methods Fourteen patients with IgG4-RD were treated with RTX as induction of remission therapy at the San Raffaele Scientific Institute in Milan, Italy. The cohort was then divided into two study groups: patients re-treated only in case of disease relapse (Group 1, n = 7), and patients regularly re-treated with RTX every 6 months for maintenance therapy (Group 2, n = 7). Data on free-relapse rate and adverse events were collected and retrospectively analysed. Results Median follow-up time and baseline clinical-serological features were similar between Group 1 and 2 (p > 0.05). The free relapse rate 18 months after induction of remission treatment was significantly lower in Group 1 (29%) than in Group 2 (100%) (p = 0.006). Infectious complications developed in 6/14 patients (3 in Group 1 and 3 in Group 2). Conclusion Administration of RTX every 6 months as maintenance of remission therapy prevents IgG4-RD flares.

Background: Takayasu arteritis (TA) is a large-vessel vasculitis usually affecting young women. The age of onset is though variable. Controversial data are reported about differences in disease features according to the age of onset. Objectives: To compare clinical and vascular TA features according to TA age of onset. Methods: We retrospectively evaluated onset demographic and disease features in TA patients followed-up at our Hospital between January 2000 and august 2018. We divided our cohort into 3 groups according to the age of onset: ≤20 (Group 1), 21-40 (Group 2), >40 (Group 3) years. Diagnostic delay (DD) was defined as the time interval between the first TA symptom and TA diagnosis. Non parametric statistic tests were used. Results: 126 patients (12 male, 114 female) were analyzed. Mean age at onset was 31.46±13.38 years. Group 1 and 3 included 30 (23.81%) patients each, Group 2 66 (52.38%). Mean age at onset was 16.23±3.20 years in Group 1, 29.59±5.80 in Group 2 and 50.8±7.16 in Group 3. Mean DD was different between the 3 groups: 117.63±129.79 months in Group 1, 56.47±76.98 in Group 2 and 30.80±40.53 in Group 3 (Group 1 vs 2, p=0.021; Group 1 vs 3, p Conclusion: TA patients 40 years. Vascular involvement seems also be influenced by the age of onset with the abdominal aorta being more frequently affected in younger patients and iliac arteries in older patients. Disclosure of interests: Silvia Sartorelli: None declared, Corrado Campochiaro Consultant for: Dr Corrado Campochiaro received consultation honoraria from Pfizer., alessandro Tomelleri: None declared, Elena Baldissera Consultant for: Consultation honoraria from Novartis and Rottapharm, Speakers bureau: Pfeizer, Sobi, Novartis, Lorenzo Dagna Consultant for: Prof Lorenzo Dagna received consultation honoraria from abbvie, amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI.

Background Takayasu arteritis (TAK) is a chronic large-vessel vasculitis that predominantly affects aorta and its major branches. Although it is more commonly observed in asian population, it can occur worldwide. TAK affects more frequently women in their second and third decades of life, but occurrence in patients older than 40 years is not rare1. Female to male ratio is commonly reported as 9:12. Objectives To compare clinical characteristics and pattern of vascular involvement at disease onset according to gender specificity in patients affected by TAK. Methods Data from 117 TAK patients (11 male, 106 female) diagnosed according to the aCR criteria from our Centre were retrospectively collected. Differences between men and women with regard to demographic features, diagnostic delay, signs and symptoms attributed to TAK, and arteries involved at diagnosis were compared. Data from 3 published articles describing sex differences in TAK patients were obtained3,4,5. A global analysis of these 3 cohorts plus ours (for a total of 578 patients, 108 men and 470 women) was performed. Results In our TAK cohort, age at disease onset and age at diagnosis were not significantly different between men and women. Diagnostic delay was slightly higher in men. Male patients showed higher involvement of iliac arteries (right, p=0.016; left, p=0.021); female patients suffered more frequently from upper limbs claudication (p=0.026). In the overall analysis, men had higher prevalence of arterial hypertension (p=0.007) and more frequent involvement of abdominal aorta (p=0.026), renal arteries (right, p Conclusion In TAK patients, gender has a strong influence on pattern of vascular involvement and consequently on clinical presentation. Specifically, women have higher involvement of the supradiaphragmatic vessels, whereas in men the abdominal vessels are more frequently affected. References [1] Numano, et al. Takayasu arteritis. Lancet (2000). [2] Fatos, et al. Epidemiology of Takayasu arteritis. Presse Med (2017) [3] Lim aY, et al. Gender differences in clinical and angiographic findings of patients with Takayasu arteritis. Clin Exp Rheumatol (2015) [4] Sharma BK, et al. A possible role of sex in determining distribution of lesions in Takayasu arteritis. Int J Cardiol (1998) [5] Mont’Alverne aR de S, et al. Features of the onset of Takayasu’s arteritis according to gender. Arq Bras Cardiol (2013) Disclosure of interests Alessandro Tomelleri: None declared, Corrado Campochiaro Consultant for: Dr Corrado Campochiaro received consultation honoraria from Pfizer., Silvia Sartorelli: None declared, Giulio Cavalli Consultant for: Dr Giulio Cavalli received consultation honoraria from Pfizer, Novartis and SOBI., Giacomo De Luca Speakers bureau: Pfeizer, Sobi, Elena Baldissera Consultant for: Consultation honoraria from Novartis and Rottapharm, Speakers bureau: Pfeizer, Sobi, Novartis, Lorenzo Dagna Consultant for: Prof Lorenzo Dagna received consultation honoraria from abbvie, amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI.

Background Adult-onset Still’s disease (AOSD) is a rare auto-inflammatory condition characterized by fever, arthritis, skin rash, and multi-organ inflammation. The pathogenesis of AOSD is centrally mediated by the pro-inflammatory cytokine interleukin (IL)-1β; anakinra, a recombinant inhibitor of the IL-1β receptor, has thereby become the cornerstone of biologic therapy for AOSD. More recently, a new agent blocking IL-1β has become available, that is, the monoclonal antibody canakinumab. Objectives So far, canakinumab has been used in the treatment of AOSD following failure of multiple lines of biologic therapy, including anakinra. Here, we describe the use of canakinumab as first-line biologic agent in 6 patients with AOSD, and report the highly promising results of this treatment approach. Methods Six patients with severe, DMARD-refractory AOSD received canakinumab at the approved dose of 4 mg/kg once every 4 weeks following failure of conventional treatment with corticosteroids and methotrexate. Patient characteristics and response to therapy were recorded. Results In all patients, treatment with canakinumab led to striking and rapid clinical responses, within days of initiation. Fever and skin rash disappeared first and did not recur, followed by progressive and sustained improvement in arthritis. Inflammatory organ involvement also responded to treatment: for example, we observed resolution of pericardial inflammation in two patients, as revealed by cardiac ultrasound; another patient had hepatosplenomegaly, which also reverted to normal upon treatment. A striking reduction in serum pro-inflammatory markers C-reactive protein, erythrocyte sedimentation rate, and ferritin mirrored the efficacy on clinical manifestations. These effects amounted to a significant decrease in the modified Pouchot score for measuring disease severity (average score before canakinumab treatment: 6; after: 1.25; statistical significance of difference evaluated with Mann-Whitney: p=0.02), and allowed for tapering or discontinuation of concomitant therapy: specifically, corticosteroid treatment was completely discontinued in two patients and substantially reduced in two patients, whereas methotrexate was stopped in one patient. Conclusion In this study, first-line biologic therapy of AOSD with canakinumab resulted in rapid and marked efficacy, ultimately leading to full clinical remissions in all patients, and allowing for robust steroid-sparing effects. So far, canakinumab in AOSD has mostly been used as a last line of treatment following failure of multiple other agents, including anakinra. Early treatment, as described in this study, is nevertheless advisable and may reduce chances of chronic disease and permanent damage. References [1] Cavalli G, Dinarello CA: Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology (Oxford)2015, 54(12):2134-2144. [2] Cavalli G, Franchini S, Aiello P, Guglielmi B, Berti A, Campochiaro C, Sabbadini MG, Baldissera E, Dagna L: Efficacy and safety of biological agents in adult-onset Still’s disease. Scand J Rheumatol2015, 44(4):309-314. Disclosure of Interests Giulio Cavalli: None declared, Alessandro Tomelleri: None declared, Giacomo De Luca Speakers bureau: Pfeizer, Sobi, Corrado Campochiaro Consultant for: Dr Corrado Campochiaro received consultation honoraria from Pfizer., Elena Baldissera Consultant for: Consultation honoraria from Novartis and Rottapharm, Speakers bureau: Pfeizer, Sobi, Novartis, Lorenzo Dagna: None declared

Background IgG4-related disease(IgG4-RD) is a systemic fibro-inflammatory disease. Treatment is based on corticosteroids(CS) but up to 50% of patients may relapse. Rituximab(RTX) has emerged as an effective treatment option[1]. Objectives To assess the free relapse rate(FRR) in patients receiving or not maintenance RTX therapy. Secondary outcomes: time to relapse, incidence of adverse events and differences in FRR between Group 2a and 2b patients. Methods Data of IgG4-RD patients treated with RTX and followed-up for >18 months were reviewed. Patients were treated with two 1 g RTX doses 15 days apart(standard dose,SD) and then divided into: patients receiving RTX in case of relapse(Group 1) and patients receiving maintenance RTX treatment 6 monthly(Group 2). Patients in Group 2 received a first maintenance treatment RTX SD and were then further divided into patients receiving RTX SD(Group 2a) or single 1 g RTX dose(Group 2b). Results 14 IgG4-RD patients were included. Median number of organs involved was 3(1-5). Baseline median physician global assessment(PGA) was 70(50-90), IgG4-RD responder index(IgG4-RD RI) 12(6-12). Median eosinophil count, ESR, CRP, and serum IgG4 level were 100cells/μL(50–1.800), 19mm/h(6-64), 3.7mg/L(0.1–36) and 3.17mg/L(470–21.800) respectively. Indications for RTX were: relapse in 10/14(71%), partial response in 3/14(21%) and first-line treatment in 1(7%) patient. CS were stopped in 5 patients and reduced by month 3 in remaining patients(27.14±13.06 vs 6.43±2.45 mg daily,p=0.012). 3 patients were on concomitant methotrexate(MTX) therapy at RTX induction, MTX was stopped in all patients at month 3. At month 6 PGA, IgG4-RD RI, and serum IgG4 decreased to a median value of 10(0-50), 2(0-6), and 822 mg/L(380–7.313), respectively(p Conclusion RTX is a safe and effective treatment in IgG4-RD. Both SD and single 1 g RTX dose seem effective in maintenance. References [1] CarruthersMN.Rituximab for IgG4-related disease:a prospective,open-label trial.Ann Rheum Dis.2015. Disclosure of Interests Corrado Campochiaro Consultant for: Dr Corrado Campochiaro received consultation honoraria from Pfizer., Emanuel Della Torre: None declared, Marco Lanzillotta: None declared, Enrica Bozzolo: None declared, Elena Baldissera Consultant for: Consultation honoraria from Novartis and Rottapharm, Speakers bureau: Pfeizer, Sobi, Novartis, Lorenzo Dagna Consultant for: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI.

Background Takayasu arteritis (TAK) is an inflammatory disease which primarily affects large vessels1. However, as a systemic disease, the spectrum of its manifestations is not limited to the arterial wall2. Objectives To describe characteristics of extravascular manifestations of TAK patients from a single Italian Centre. Methods Data records of TAK patients diagnosed according to the 1990 ACR criteria and followed-up at our Large Vessel Vasculitis Clinic were reviewed. Any significant inflammatory/autoimmune comorbidity and family history for inflammatory/autoimmune diseases were considered. For each comorbidity, temporal correlation with TAK diagnosis was assessed. Need for biological therapy for TAK control, as an indirect measure of TAK aggressiveness, was evaluated. Non-parametric statistic tests were used. Results In our cohort of 129 TAK patients, 46 patients (35.7%) were identified as having an inflammatory/autoimmune comorbidity, for a total of 64 comorbidities (14 patients experienced >1 comorbidity). Comorbidities were classified into 6 categories: systemic inflammatory diseases (17.2%); gastro-intestinal (9.4%), articular (10.9%), ocular (20.3%) and muco-cutaneous (39.1%) involvement; miscellaneous (autoimmune hepatitis (1.6%), retroperitoneal fibrosis (1.6%)). In 33 cases (51.6%) the comorbidity onset preceded, in 25 (39%) followed and in 6 (9.4%) was synchronous with TAK diagnosis (Table 1). In 25 patients (54.3%) use of a biological therapy to control TAK activity was needed (versus 35.4% in patients without comorbidities, p=0.042). Having a comorbidity increased the risk for the introduction of a biologic therapy, odds ratio=2.176 (1.042-4.541). Of the 129 TAK patients, 17 (13.2%) had a positive family history for inflammatory/autoimmune diseases (8 psoriasis, 5 rheumatoid arthritis, 3 inflammatory bowel disease, 1 sarcoidosis). Conclusion In TAK patients, extravascular involvement is a common finding and usually precedes the vascular involvement (the only significant exception is represented by inflammatory arthritis). Inflammatory and autoimmune extravascular comorbidities seem to be associated with a significant higher burden of vascular inflammation, as inferred by the higher rate of biological therapies use in these TAK patients. References [1] Numano, et al. Takayasu arteritis. Lancet (2000). [2] Kwon, et al. Extravascular manifestations of Takayasu arteritis: focusing on the features shared with spondyloarthritis. Arthritis Res Ther (2018) Disclosure of Interests Alessandro Tomelleri: None declared, Corrado Campochiaro Consultant for: Dr Corrado Campochiaro received consultation honoraria from Pfizer., Silvia Sartorelli: None declared, Veronica Bandini: None declared, Elena Baldissera Consultant for: Consultation honoraria from Novartis and Rottapharm, Speakers bureau: Pfeizer, Sobi, Novartis, Lorenzo Dagna Consultant for: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI.

Background Biologic disease-modifying anti-rheumatic drugs(bDMARDs) have been showed to be effective in refractory Takayasu arteritis(TA) [1]. Data about bDMARDs drug retention rate(DRR) in TA are scarce. Objectives To investigate DRR and reasons for discontinuation of 7 bDMARDs in a real-world setting Methods TA patients fulfilling the 1990 ACR criteria and treated with ≥1 bDMARD were selected. Data about disease duration, number of bDMARDs, reasons for bDMARDs discontinuation (classified as inefficacy, toxic reactions, non-toxic reasons), concomitant conventional synthetic (cs)DMARDs were collected. Survival curves were examined by the Kaplan-Meier method and compared using a stratified log-rank test. DRR was evaluated at 24 months. Hazard ratio(HR) for concomitant csDMARDs therapy and for previous bDMARDs was performed. A comparative sub-analysis between antiTNFα drugs and tocilizumab(TCZ) was performed Results We identified 50 patients and 86 bDMARD-courses. At baseline, mean age was 39.1±12.1 years, mean disease duration was 119.5±110.1 months. No significant differences were observed in age and disease duration between the 7 groups. 31 patients were treated with 1 bDMARD, 11 with 2, 4 with 3, 2 with 5, 1 with 6, 1 with 7. Infliximab was the most frequent first-line bDMARD(78.6%). At bDMARDs initiation all patients were on prednisone(mean dose 13.5±10.3 mg), 85.2% on csDMARD(53 methotrexate, 13 azathioprine, 6 sirolimus, 3 mycophenolate-mofetil, 1 sulfasalazine). 43% of treatment courses were stopped by 24 months. Table1 summarizes DRR and reasons for treatment discontinuation for each bDMARD. Golimumab had the highest DRR(71.4%), followed by infliximab (69%), adalimumab (56.3%), abatacept (50%), tocilizumab (41.1.%), anakinra (0%) and rituximab (0%), p=0.016. Only concomitant csDMARDs therapy (HR=2.87,95%CI=1.19-6.92,p=0.019) showed positive effects on DRR. AntiTNFα drugs had significantly higher DRR compared to TCZ (67.2% vs 41.1%,p=0.028). Even in these subgroups csDMARDs(HR=3.79,95% CI=1.49-9.6,p=0.005) showed positive effects on DRR Conclusion In our TA cohort, antiTNFα agents had the highest DRR and, notably, they had a higher DRR in a head-to-head comparison with TCZ. Concomitant use of csDMARDs had a significant positive effect on bDMARDs DRR References [1] Management of large-vessel vasculitis. Salvarani C, Hatemi G. Curr Opin Rheumatol. 2019 Jan;31 Disclosure of Interests Corrado Campochiaro Consultant for: Dr Corrado Campochiaro received consultation honoraria from Pfizer., Alessandro Tomelleri: None declared, Silvia Sartorelli: None declared, Giulio Cavalli Consultant for: Dr Giulio Cavalli received consultation honoraria from Pfizer, Novartis and SOBI., Giacomo De Luca Speakers bureau: Pfeizer, Sobi, Elena Baldissera Consultant for: Consultation honoraria from Novartis and Rottapharm, Speakers bureau: Pfeizer, Sobi, Novartis, Lorenzo Dagna Consultant for: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI.

Background Giant cell arteritis (GCA) is a large-vessel vasculitis that generally affects people older than 50 years1. Glucocorticoids are the mainstay treatment2. Tocilizumab (TCZ) has recently been shown in clinical trials to be effective and safe for the treatment of GCA3. Objectives To describe our real-life experience with TCZ in a cohort of GCA patients from a single Italian Centre. Methods We included GCA patients diagnosed according to the 1990 aCR criteria, followed-up at our Large Vessel Vasculitis Clinic, and treated with TCZ. We retrospectively evaluated demographic features, disease characteristics, reasons for TCZ introduction and discontinuation, concomitant therapies and response to treatment. For each patient we evaluated potential eligibility for GiACTA trial. For statistical comparisons, we used non-parametric tests. Results 40 patients (32 women, mean age 71±10 years) were included. Table 1 summarizes clinical features, tools for GCA diagnosis (imaging and/or biopsy) and reasons for TCZ introduction. Mean disease duration before TCZ introduction was 21.5±29.1 months. Only 12 patients (30%) met both GiACTA inclusion and exclusion criteria at TCZ introduction. 31 patients were followed-up for 3 months, 23 for 6 months, 17 for 12 months. Mean prednisone (PDN) dose at TCZ introduction was 21.9±13.2 mg. Mean PDN dose was 8.4±6.5 mg (p Conclusion Our data confirm TCZ is highly effective in GCA treatment and has a significant steroid-sparing effect. In our real-life retrospective study, TCZ was also shown to be a safe option in patients with relapsing or refractory GCA. References [1] Salvarani C., et al. Polymyalgia rheumatica and giant-cell arteritis. Lancet (2008) [2] Proven a., et al. Glucocorticoid therapy in giant cell arteritis. Arthritis Rheum (2003) [3] Stone JH, et al. Trial of Tocilizumab in Giant-Cell arteritis. N Engl J Med (2017) Disclosure of interests Alessandro Tomelleri: None declared, Corrado Campochiaro Consultant for: Dr Corrado Campochiaro received consultation honoraria from Pfizer., Silvia Sartorelli: None declared, adriana cariddi: None declared, Elena Baldissera Consultant for: Consultation honoraria from Novartis and Rottapharm, Speakers bureau: Pfeizer, Sobi, Novartis, Lorenzo Dagna Consultant for: Prof Lorenzo Dagna received consultation honoraria from abbvie, amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI.

Background Adult-onset Still’s disease (AOSD) is a rare autoinflammatory disease characterised by fever, arthritis, and multi-organ involvement. Inflammation in AOSD is mediated by interleukin (IL)−1β, as confirmed by the dramatic clinical efficacy of selective blockers of this cytokine. The genetic predisposition to this rampant IL-1-driven inflammation remains nevertheless elusive. Previous studies failed to identify associations between polymorphisms in the genes encoding IL-1 and AOSD, thus pointing at more complex genetic mechanisms. This ‘missing heritability’ cannot be adequately investigated with traditional techniques for genetic partitioning, such as GWAS, which only assess common variants and polymorphisms. Studies focusing on highly penetrant rare variants or different types of mutations (i.e. small copy-number variations; insertions/deletions) are warranted. Objectives We hypothesised that genetically determined changes in IL-1-related pathways resulting in excessive IL-1β activity lead to the development of autoinflammation in AOSD. Scope of this study was to unravel the combined mutational variation of a network of IL-1-related receptors, pathways, counter-regulators, and cellular processes possibly involved in the pathogenesis of AOSD and IL-1-mediated inflammation in general. Methods We collected clinical, demographic, and genetic data from a large cohort of 76 AOSD patients and developed an innovative platform based on molecular inversion probes (MIP) technology for performing highly multiplexed targeted-resequencing. This allows efficient sequencing of the coding sequence of 48 genes related to the IL-1-pathway, and allows studying rare and common variants in one assay. We have also screened 500 healthy controls, and 1000s of samples with other disorders using the same assay. Results We identified rare and unique (i.e. private variants) in the IL1 pathway in several individuals with AOSD. Whether any these are involved in a strong predisposition to AOSD is currently followed-up. Rare genetic variants have been identified in six IL-1-pathway ‘clusters’: Deregulated activation of the inflammasome and release of IL–1β and IL–18. IL–1 family receptors and intracellular signalling mediators. Other pro–inflammatory cytokines and receptors. Regulatory molecules, including IL–1Ra or IL–37. Cellular processes regulating production of IL–1 and IL–18 (i.e. autophagy). Production of ROS, which function as markers of cellular damage and trigger inflammation. Conclusions Unravelling the genetic bases of inflammation in AOSD deepens our understanding of the human innate immunome. Of note, this study platform may serve for the genetic analysis of other IL-1-mediated conditions, including gout and other autoinflammatory diseases, whose genetic predisposition remains elusive. Equally important, the identification of pathways amenable to targeting with small molecules or biologics may translate into remarkable clinical implications. Disclosure of Interest None declared

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Objective: To compare clinical characteristics and pattern of vascular involvement at disease onset according to gender specificity in patients with Takayasu arteritis (TA). Methods: Data from 117 TA patients (11 male, 106 female), diagnosed according to the American College of Rheumatology criteria, from our centre were retrospectively collected. Differences between men and women regarding demographic features, diagnostic delay, signs and symptoms attributed to TA, and arteries involved at diagnosis were compared. Data were obtained from three published articles describing gender differences in TA. A global analysis of these three cohorts plus ours (a total of 578 patients; 108 men, 470 women) was performed. Results: In our TA cohort, age at disease onset and age at diagnosis were not significantly different between genders. Diagnostic delay was higher in men. Male patients showed higher involvement of iliac arteries (right, p =0.016; left, p =0.021); females suffered more frequently from upper limb claudication (p=0.026). In the overall analysis, men had higher prevalence of arterial hypertension (p=0.007) and more frequent involvement of abdominal aorta (p=0.026), renal arteries (right, p

Objective The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age. Methods We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18–55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149). Results At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A “Disease Knowledge Index” (DKI) was created to investigate the degree of patients’ information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning. Conclusion Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.

Background:Large-vessel vasculitides comprise Takayasu arteritis (TA)and giant cell arteritis (GCA). Arterial stenosis and dilatation directly affect prognosis but the mechanism(s) underlying remodeling of the vessel wall have not been identified. Microvesicles (MVs) are membrane-enclosed extracellular vesicles released upon cellular activation and stress and as a consequence of environmental inflammation. MVs maintain features and constituents of their parental cells. They have been proposed to serve as potential liquid biopsies in oncology.Objectives:To verify whether arterial wall derived-MVs are recognizable in the blood of TA patients and express bioactive molecules potentially involved in arterial injury, inflammation and remodeling.Methods:Platelet was obtained from 112 LVV pts (73 TA, 39 GCA), 42 age and age- and sex-matched healthy controls (HC) and 30 pts with severe carotid atherosclerosis requiring vascular surgery. Plasma flow cytometry was performed with anti-CD14, CD16, anti-CD144 (VE-cadherin, an endothelial marker), anti-CD140a/b (PDGF receptor A/B a vascular stromal marker), anti-HMGB1, anti-PTX3, mitotracker green (that identifies mithochondrial moieties) and mitosox (that revels mitochondrial reactive oxygen species). MVs were identified by physical parameters using Gigamix beads. Medium- to large-sized MVs were defined as MVs with >240nm-eq diameter.Results:Preliminary results are available for 49 LVV (42 TA, 7 GCA), 8 severe carotidatherosclerosis and 14 age- and sex-matched HC. As compared to HC or CA, LVV plasma contains a higher number of MVs and in particular of medium- to large- sized MVs (pConclusion:MVs, including those expressing arterial stromal biomarkers, are increased in LVV plasma, suggesting a communication between the vessel wall and peripheral blood. MV express signals that may in turn contribute to persisting vascular inflammation in large vessel vascultis Further analysis is required to dissect their potential use as disease biomarkersReferences:[1]van Niel G et al, Nat Rev Mol Cell Biol. 2018[2]Mason JC. Nat Rev Rheumatol. 2010Disclosure of Interests:None declared

Background:Most published evidence on infliximab (IFX) in Takayasu arteritis (TAK) refers to its use at the standard dose of 5 mg/kg every 6-8 weeks1. However, in other diseases such as rheumatoid arthritis or Crohn’s disease2,3, it has been already demonstrated that IFX often requires a dose escalation to maintain its response.Objectives:To evaluate effectiveness and safety of IFX dose escalation in TAK patients. To identify predictors of refractoriness to standard-dose IFX.Methods:Medical records of IFX-treated TAK patients from a large single-centre observational cohort were reviewed. Decisions on IFX start, interruption, and dose modification were always made by the same experienced physician (EB). IFX therapy duration and reasons for dose escalation and therapy suspension were evaluated. Occurrence of adverse events was recorded. A comparison between patients who maintained IFX standard-dose and those who needed dose-escalation was performed. Factors predicting standard-dose refractoriness were analyzed.Results:Forty-one patients were included (38 women; median age at IFX start, 36 [IQR, 28-45] years; median disease duration, 22 [13-60] months). Starting IFX dose was 5 mg/kg 6-weekly; 39 patients (95%) were on concomitant csDMARD and 38 patients (93%) on systemic glucocorticoids (GC). IFX dose escalation was performed in the majority of patients (n=28, 68%) (Figure 1). Persistence/recurrence of clinical symptoms was the most frequent reason for dose escalation (62%). Median IFX therapy duration was 39 (26-61) months in the standard-dose and 68 (38-87) months in the intensified-dose group. Patients in the intensified-dose group had a higher number of relapses (3.4 vs 0.8 events/patient), expression of a more aggressive disease phenotype. Nevertheless, in only 8 patients (29%) from this group IFX was suspended, after a median of 38 (31-71) months. Causes of suspension were loss of response (n=7) or patient’s request (n=1). GC were successfully suspended in 4 patients from the standard-dose (36%) and 3 patients from intensified-dose (11%) group. Median daily prednisone dose was reduced from 10 (6-10) to 3 (0-5) mg in the standard-dose group, and from 13 (9-18) to 5 (4-5) mg in the intensified-dose group. Three patients from the intensified-dose group had a serious infection; one patient from the standard-dose group developed paradoxical psoriasis. At univariate analysis, younger age at diagnosis and at IFX start were associated with IFX escalation (Table 1).Table 1.Factors influencing IFX dose escalation in patients with TAK (Cox proportional hazards model)Standard-dose IFXIntensified-dose IFXP-valueAge at diagnosis, years40 (34-46)30 (23-40)0.031Diagnostic delay, months12 (7-77)27 (15-50)0.73Age at IFX start, years42 (38-61)34 (27-44)0.040Delay before IFX start, months33 (14-90)24 (11-53)0.48Daily PDN at IFX start, mg8.75 (5-10)11.25 (8.5-16.25)0.051CRP at IFX start, mg/L6.5 (2.1-9.3)10.7 (5.2-20.9)0.07Class V Numano, n (%)3 (30)16 (57)0.133PETVAS score8 (6-12)12 (9-16)0.056Figure 1.Infliximab dose escalation regimens (the cross (x) indicates treatment suspension)Conclusion:In TAK, dose escalation can be a safe strategy to optimize IFX durability in refractory patients. Younger patients seem to be more refractory to standard dosages.References:[1]Mekinian A, Néel A, Sibilia J, et al. Efficacy and tolerance of infliximab in refractory Takayasu arteritis: French multicentre study. Rheumatology. 2012; 51:882–6[2]Ollendorf DA, Massarotti E, Birbara C, et al. Frequency, predictors, and economic impact of upward dose adjustment of infliximab in managed care patients with rheumatoid arthritis. J Manag Care Pharm. 2005;11(5):383-93[3]Taxonera C, Olivares D, Mendoza JL, et al. Need for infliximab dose intensification in Crohn’s disease and ulcerative colitis. World J Gastroenterol. 2014;20(27):9170-7Disclosure of Interests:Alessandro Tomelleri: None declared, Corrado Campochiaro: None declared, Silvia Sartorelli: None declared, Francesco Baldassi: None declared, Federico Fallanca: None declared, Maria Picchio: None declared, Elena Baldissera Speakers bureau: Pfizer, Roche, Sanofi-Genzyme, Consultant of: Novartis, Lorenzo Dagna Consultant of: Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Galapagos, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline,Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi Genzyme, and SOBI

Background:Adult-onset still’s disease (AOSD) is a rare systemic inflammatory disease. Interleukin-1 (IL1) blockade has shown to be crucial for the management of refractory AOSD patients. The IL1 inhibitors anakinra and canakinumab are both effectively used in clinical practice for the management of AOSD. No data are available on the impact of these therapies on patient-reported outcomes (PROs).Objectives:To assess the impact of ANK and CNK therapies on PROs of AOSD patients.Methods:Medical records of AOSD patients followed up at our Institution who had been treated with both ANK and CNK were identified. Disease features were retrospectively collected. All patients were initially treated with ANK and subsequently with CNK. At the moment of CNK introduction and at their latest visit while on CNK, patients were asked to fill a questionnaire investigating their experience with either ANK or CNK. The questionnaire included 4 different domains that were assessed through means of Visual Analogue Scales (VAS) ranging from 0 to 10. The following domains were considered: injection-related pain, satisfaction with the frequency of administration, concern for drug-related adverse events including infections, and overall drug tolerability. VAS values for each of the domains were compared between ANK and CNK with Mann-Whitney U test.Results:Ten AOSD patients treated with both ANK and CNK were included in the analysis. Disease characteristics are shown in Table 1 below. ANK was discontinued due to inefficacy in 6 patients and due to adverse reactions in 4. As shown in Figure 1, CNK overall tolerability significantly exceeded ANK one (p=0.021). Only 1 AOSD patient reported a greater tolerability with ANK compared to CNK because she felt more comfortable with pre-filled syringes. The reasons for higher CNK tolerability were the lower pain at injection site (median 1, IQR 1-1 vs median 4.5, IQR 1.25-7; p=0.015) and the greater level of satisfaction with the frequency of administration (median 10, IQR 9.25-10 vs median 3.5, IQR 2.25-4.75, pp=0.549) and overall low among AOSD patients. CNK led to a satisfying control of systemic inflammation and steroid-sparing effect in most of patients and it was discontinued in only one case (Patient 5), due to ineffective disease control.Figure 1.Comparative tolerability of anakinra (blue line) and canakinumab (orange line) in our study population, expressed as Visual Analogue Scale values (range from 1 to 10). Reported p-values refer to the comparative analysis between the two drugs.Conclusion:In our cohort of AOSD patients, CNK proved not only to be effective in controlling systemic inflammation in ANK refractory cases, but its use was associated with greater patients’ satisfaction and tolerability.References:[1]Kluetz et al, Value Health, 2018;21(6):742-747.Table 1.Clinical and treatment characteristics of study population.Sex and age (years)Disease duration (months)Disease manifestationsSequential biologic therapiesSteroid dosage variation (mg/day)*ESR variation (mm/hour)*CRP variation (mg/L)*Patient 1Male, 7022Arthritis, FeverRashTCZ, ANK, CNK25 → 5120 → 1355 → 1Patient 2Female, 7211Arthritis, FeverRashTCZ, ANK, CNK5 → 060 → 24265 → 6Patient 3Male, 3248Fever, RashANK, CNK15 → 029 → 1127 → 1Patient 4Male, 7112FeverANK, CNK20 → 5120 → 2180 → 1Patient 5Female, 5872FeverANK, CNK0 → 527 → 365 → 83Patient 6Female, 485Arthritis, FeverRashANK, CNK10 → 08 → 102 → 1Patient 7Female, 74180Arthritis, Fever, Rash, MASETN, ANK, CNK5 → 533 → 11 → 25Patient 8Male, 78180Arthritis, FeverRash, MyocarditisPleuropericarditisANK, CNK40 → 2046 → 1058 → 40Patient 9Male, 22144Arthritis, FeverETN, TCZ, ANK, CNK20 → 1086 → 94135 → 1Patient 10Male, 4324Arthritis, FeverRashANK, CNK15 → 515 → 104 → 1* Before and after canakinumab start.ANK, anakinra; CNK, canakinumab; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; ETN, etanercept; MAS, macrophage activation syndrome; MTX, methotrexate; PDN, prednisone; TCZ, tocilizumab.Disclosure of Interests:Nicola Farina: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Alessandro Tomelleri: None declared, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, MSD, Pfizer, Giulio Cavalli Speakers bureau: SOBI, Elena Baldissera Speakers bureau: Novartis, Pfizer, Roche, Alpha Sigma, Sanofi, Lorenzo Dagna Speakers bureau: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, SOBI, Celgene Janssen, MSD, MP

Background:Rituximab (RTX), an anti-CD20 monoclonal antibody, represents a valuable treatment for anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). RTX biosimilar CT-P10 (RTX-B) has been approved in Europe in all indications held by RTX originator (RTX-O). As stated by recent international consensus-based recommendations, 1 there is evidence regarding safety and efficacy of biosimilars in the context of rheumatic diseases, but it is encouraged to gather additional data. 2,3Objectives:To report the experience of a single Italian center with RTX-B in AAV in terms of safety and efficacy.Methods:We retrospectively reviewed the charts of all AAV patients followed up in our Small Vessel Vasculitis Clinic and we selected those who received RTX-B between October 2017 and May 2020, both naïve to RTX (RTX-Bn) or already treated with ≥1 course of RTX-O and switched to RTX-B (RTX-Bs). Baseline features, disease outcome, concomitant therapy and adverse events 6 (T6), 12 (T12) and 24 (T24) months after RTX-B introduction, when available, were collected. Non-parametric statistic tests were used.Results:Fifty-six AAV patients (44 [78.6%] granulomatosis with polyangiitis (GPA), 12 [21.4%)] microscopic polyangiitis (MPA)) received RTX-B with a median follow up of 20 (IQR 10-24) months. ANCA were positive in 49 (87.5%) patients. Ten (17.9%) patients were newly diagnosed with AAV, while 23 (41.1%) had refractory disease and another 23 had relapsing disease.Thirty-three (58.9%) patients were RTX-Bs, whereas 23 (41.1%) RTX-Bn. In 29 (51.8%) patients RTX was decided because of remission induction, while in 27 (48.2%) as maintenance regimen. Median cumulative RTX-B dose was 2.5 (2-3.875) grams with 3 (IQR 2-4) median courses. AAV activity, adverse events and concomitant therapy at T6, T12 and T24 are shown in Table 1. One GPA patient died of severe infection 3 months after a single infusion of RTX-B 500 mg as maintenance therapy.Table 1.AAV activity, concomitant therapy and adverse events at T0, T6, T12 and T24.T0T6T12T24n (%)56 (100)52 (92.6)40 (71.4)18 (32.1)Dose RTX-B, median (IQR) grams1.75 (0.5-2)0.5 (0.5-1)0.5 (0.5-1)0.5 (0.5-1)Concomitant prednisone therapy, n (%)42 (75)27 (48.2)13 (32.5)4 (22.2)Dose prednisone, median (IQR) milligrams/day5 (5-15.625)2.5 (2.5-5)3.75 (2.75-7.5)2.75 (1.56-4.5)Concomitant bDMARDs, n (%)10 (17.9)5 (9.6)3 (7.5)1 (5.6)RefractorinessNA4 (7.7)2 (5)1 (5.6)RelapseNA0 (0)3 (7.5)2 (11.1)RemissionNA48 (92.3)35 (87.5)15 (83.3)SuspensionNA10 (19.2)9 (22.5)4 (22.2)Infusion reaction, n (%)1 (1.8)1 (1.9)0 (0)0 (0)Infectious adverse events, n (%)NA10 (19.2)6 (15)3 (16.7)Severe infectious adverse events, n (%)NA2 (3.8)1 (2.5)0 (0)Considering the 52 (92.6%) patients who reached a 6 months-follow up, we marked a significant decrease of number of patients on steroid therapy (39 [75%] vs 27 [51.9%]; p=0.003), of median prednisone daily dose (5 [IQR 5-25] vs 2.5 [IQR 1.25-5 mg; p=0.001) and of number of patient on concomitant bDMARDs (10 [19.2%] vs 5 [9.6%]; p=0.003).Analysing the 40 (71.4%) patients who reached a 12 months-follow up, we confirmed the tendency with a decrease of number of patients on steroid therapy (29 [72.5%] vs 13 [32.5%]; p=0.007), of median prednisone daily dose (5 [IQR 5-12.5] vs 3.75 [IQR 2.75-7.5]; p=0.008) and of number of patient on concomitant bDMARDs (9 [22.5%] vs 3 [7.5%]; p=0.009).No statistically significant difference was found for the same variables comparing T0 versus T24.Conclusion:Our experience with RTX-B is limited; however, it represents an extensive report about the use of RTX-B in AAV patients and confirmed that it may be a well-tolerated and effective therapy in AAV setting, in agreement with previous evidence on RTX-O. Prospective and larger studies are needed to confirm this preliminary evidence.References:[1]Kay J, et al. Ann Rheum Dis 2018;77:165–74.[2]Kwon HC, et al. Yonsei Med J 2020;61:712-9.[3]Mittal S, et al. Clin Rheumatol 2021;40:645-51.Disclosure of Interests:Silvia Sartorelli: None declared, adriana cariddi: None declared, Luca Moroni: None declared, Elena Baldissera Speakers bureau: Pfizer, Roche, Sanofi-Genzyme, Consultant of: Novartis, Enrica Bozzolo: None declared, Lorenzo Dagna Consultant of: Abbvie, Amgen, Biogen, BristolMyers Squibb, Celltrion, Galapagos, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unrestricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.

We read with interest the correspondence by Comarmond et al 1 on our study about the impact of novel COVID-19 on Italian patients with large-vessels vasculitis (LVV).2 COVID-19 has been declared a global pandemic by WHO in March 2020. Since then, the number of patients diagnosed with SARS-CoV-2 infection has rapidly grown and today more than 46 million cases worldwide have been identified.3 International and National surveys on different groups of patients with chronic inflammatory diseases have been performed to evaluate the impact of COVID-19 pandemic among frail patients.4 5 After a first study by our group, based in Milan, Italy,2 Comarmond et al reported the results of a survey conducted among patients affected by LVV, followed up at Pitie-Salpetriere Hospital (Paris, France).1 Both studies were performed during the so-called ‘first wave’ of the pandemic, in areas characterised by a high rate of infection, and among patients followed up in tertiary referral centres. In addition, the number of patients included and the ratio between patients affected by the two …

Background:biologic drugs (bDMARD), especially anti-TNFα (TNFi), are used in refractory TA patients. Up to 60% of patients are eventually switched to a different bDMARD because of inefficacy. No data are available on which strategy (switch or swap) is more efficient in this setting.Objectives:to evaluate whether switch or swap strategy can be more effective in TA patients failing TNFis.Methods:TA patients treated with bDMARDs after TNFi failure were identified from 3 referral centres. Patients were classified as “switch” if treated with a different TNFi (infliximab, IFX, etanercept, ETN, golimumab, GOL, adalimumab, ADA) or “swap” if treated with a non-TNFi bDMARD (tocilizumab, TCZ, ustekinumab, USK). Baseline features and disease outcome (number of patients with NIH score ndbDMARD introduction were analyzed. Non parametric tests were used.Results:24 TA patients were identified. TNFi (IFX= 13; ADA= 8; ETN= 1; GOL= 2) was withheld after a median of 19 (8.5; 38) months (in 9 patients ndbDMARD start are summarized in Table 1. 2ndbDMARD retention at month 6 was comparable between switch (8, 73%) and swap (10, 77%) patients, p=1. Reasons for discontinuation were: inefficacy in 5 patients, allergic reaction in 1 switch patient. 5 (45%) switch and 6 (46%) swap patients had a NIHndbDMARD retention was comparable: 7 (64%) switch vs 7 (54%) swap, p=0.210. Discontinuation reason was inefficacy in all cases. 6 (54%) switch and 4 (30%) swap patients had a NIHTable 1.Disease features of switch and swap TA patients at 2nd bDMARD start.Switch (11 patients)Swap (13 patients)p valueAge (years)39 (31-54)37 (32-46)0.613Sex (female,%)821000.199Numano -I21 -IIa22 -IIb11 -III11 -IV02 -V56Disease duration (years)4 (2 -6)3 (2 – 8)0.743Previous csDMARD (%)911000.458TNFi duration (months)25 (9 – 27)16 (9 – 44)0.813Steroid dose (mg daily)15 (8.75 – 22.5)15 (10 – 25)0.726Current csDMARD, n(%)10 (91)9 (70)0.327 - Methotrexate66 - Azathioprine12 - Sirolimus10 - Salazopyrin01 - Cyclophosphamide10 - Mycofenolate10NIH ≥2 (%)73610.679CRP (mg/L)34 (14 – 73)24 (10 – 45)0.604ESR (mm/1h)43 (35 – 56)51 (35 – 68)0.729Conclusion:our retrospective study suggests that in first-line TNFi failure TA patients both switch and swap strategies are seemingly effective.Disclosure of Interests:Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Elena Galli: None declared, Emanuele Cocchiara: None declared, Alessandro Tomelleri: None declared, Silvia Sartorelli: None declared, Francesco Muratore: None declared, Maria Grazia Catanoso: None declared, Elena Baldissera Speakers bureau: Novartis, Pfizer, Roche, Alpha Sigma, Sanofi, Angelo Ravelli: None declared, Carlo Salvarani: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI