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Primary systemic vasculitides are rare diseases affecting blood vessel walls. The type and patterns of distribution of the organs affected usually reflect the size of the vessels predominantly involved, and the patterns of clinical manifestations are generally useful to reach a specific diagnosis. However, presenting symptoms may lack adequate specificity for a prompt diagnosis, leading to a diagnostic (and therapeutic) delay, often causing irreversible damage to the affected organs. Due to their rarity and variable clinical presentation, the diagnosis of primary vasculitides could be challenging for physicians. Vasculitis mimickers, i.e. the clinical conditions that could be likely mistaken for vasculitides, need to be carefully ruled out, especially before starting the immunosuppressive therapy. We present here a practical approach to the diagnosis of primary systemic vasculitides involving large, medium and small size vessels, and reviewed most of the conditions that could mimic primary systemic vasculitides.

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.

We aimed to analyze rheumatic immune-related (ir) and nonimmune-related adverse events (AEs) due to immune-checkpoint inhibitors (ICIs) targeting programmed cell death-1 or its ligand PD-(L)1 in lung cancer patients from the available literature.We performed a systematic review and meta-analysis of phase III randomized clinical trials (RCTs) assessing PD-(L)1-ICIs in lung cancer patients, from inception until January 12th, 2021. We extracted data of each trial to estimate odds ratio (OR) for rheumatic ir or non-irAE as classified in RCTs safety data. Sensitivity analyses (by ICI, treatment group and histology) were performed.Eighteen RCTs met the inclusion criteria (n=12172 subjects). The OR [95%IC] for rheumatic irAE in ICIs versus controls (either placebo or chemotherapy) was 2.20 [0.85,5.72]. Among rheumatic non-irAEs, both overall and severe (grade≥3) back pain were significantly more frequent in ICIs versus controls, 2.01 [1.09;3.73] and 2.90 [1.18;7.08], respectively. The overall frequency of arthralgia was similar between ICIs and controls; by sensitivity analysis RCTs assessing ICIs in combination with chemotherapy showed a significant association with arthralgia (1.55 [1.15;2.10]). Similarly, the frequency of myalgia was significantly lower in RCTs assessing ICIs alone versus chemotherapy (OR 0.32 [0.24;0.42]). Muscular pain was not significantly increased with ICI.Rheumatic irAEs are not increased in RCTs assessing PD-(L)1 inhibitors, not reflecting the real-life incidence, therefore likely underreported or misclassified. Back pain is significantly associated with them regardless its severity, while arthralgia only when ICIs are added on conventional chemotherapy.

Background and objectiveSystemic small vessel vasculitides carry an increased risk of acute arterial and venous thromboembolic events (AVTE); however, this risk has not been systematically explored in Eosinophilic Granulomatosis with Polyangiitis (EGPA). This study assessed the occurrence and main risk factors of AVTE among EGPA patients as compared to the general community from the population-based Bruneck cohort.MethodsWe conducted a retrospective multicenter cohort study on 573 EGPA patients. Clinical and serological data were collected at diagnosis. Occurrence of AVTE and time to the first AVTE after EGPA diagnosis were recorded. Age-standardized event rate (SER) of AVTE as compared to the reference cohort was assessed. Cox regression was applied to identify AVTE predictors.Results129 EGPA patients (22.5%) had AVTE, considered as potentially life-threatening in 55.8%. Seventy patients experienced an AVTE prior to diagnosis (of whom 58.6% in the two years before diagnosis) and 75 following EGPA diagnosis, of whom 56% in the two subsequent years. The SER of AVTE as compared to the reference cohort was 2.10 (95% CI 1.67-2.63). This risk was particularly increased in patients with history of AVTE and with a Birmingham Vasculitis Activity Score ≥20 at diagnosis. Patients receiving immunosuppression within 2 months of diagnosis were at lower risk, while antiplatelet or anticoagulant treatment did not confer measurable benefit.ConclusionEGPA is associated with AVTE in approximately one quarter of patients, particularly around diagnosis. Immunosuppressants seemed to exert a protective effect, while anticoagulant and antiplatelet agents did not.

Up to 40% of patients treated with tumor necrosis factor alpha inhibitors (TNFi) do not respond to therapy. Testing drug bioavailability and/or anti-drug antibody (ADAb) levels may justify dosage adjustment or switch to different drugs, enabling a personalized medicine approach. We report a multicenter cross-sectional study on different methods [ELISA and a cell based functional assay (reporter gene assay – RGA)] for drug/ADAb detection, and on the relationship between drug bioavailability and ADAb. 163 patients with rheumatoid arthritis (RA) treated with infliximab (IFX; n = 67), adalimumab (ADL; n = 49) or etanercept (ETA; n = 47) were tested for drug and ADAb levels. Furthermore, we report prospective data from additional 70 patients (59 RA and 11 juvenile idiopathic arthritis - JIA) tested for drug and ADAb levels at baseline (T0) and after 3 (T3) and 6 months (T6) of treatment with ADL or ETA only. IFX-treated patients were not included because of the increasing use of IFX biosimilars. Stringent inclusion criteria were used in order to avoid unwanted variables in both studies; none of the patients used TNFi before the study, and TNFi was used only in combination with methotrexate. Clinical response was defined according to EULAR response criteria. The two assays performed comparably in the comparison study. Accordingly, ELISA was selected for the prospective study because of its feasibility in the clinical setting. The cross-sectional study found ADAb in IFX and ADL treated groups only, that were associated with a decrease in pharmacological drug availability in the blood. Comparable results were found for the ADL-treated group in the prospective study which also showed a relationship between drug/ADAb levels and the loss of clinical response. Altogether our findings support drug and anti-drug Ab monitoring in the real-world clinical setting thus enabling individualized treatment and reducing disability in chronic inflammatory arthritis.

Introduction Alveolar haemorrhage (AH) is considered an important cause of morbidity and early mortality in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV). Objectives The aim of this study was to identify predictors of outcome in patients with AH-AAV and to evaluate outcome and causes of death in this subset. Materials and methods A multicenter retrospective study was conducted in 29 Italian Centers. Clinicians were asked to recruit all patients diagnosed with AAV-associated AH during the last 10 years, from 2007 to 2016. Univariate and multivariable analysis were performed. Results One-hundred and six patients were included (median age at onset of 55 years [IQR 42–67]). The majority were ANCA-positive (PR3 57.1%, MPO 33.7%) and 72.6% had also renal involvement. At presentation, anaemia was shown in 97 (92.4%) patients, hemoptysis in 54 (51.9%), respiratory failure in 68 (66.7%), of whom 48 (70.6%), requiring respiratory support. At the end of the 37 months [IQR 13–77] follow-up, 19/106 (17.9%) patients were dead. The main causes of death were active disease and infections. By stepwise regression analysis, age >65 years (HR 3.66 [95% CI 1.4–9.51], p = 0.008) and the need for respiratory support (HR 4.58 [95% CI 1.51–13.87], p = 0.007) at AH onset were confirmed to be predictive of mortality. Conclusions Predictors of outcome in AAV-AH were determined. Factors related to the patient's performance status and the severity of the lung involvement strongly influenced the outcome. Balancing harms and benefits for the individual patient in induction and maintenance treatment strategies is crucial.

Objective To establish clinical consensus for the optimal placement of TNF inhibitor (TNFi) in DMARDs-naive RA patients. Methods The steering group was composed of 15 Italian rheumatologists expert in the field of RA, who proposed and selected by consensus the clinically relevant questions on the role of TNFi treatment in DMARDs-naive RA patients. The question was rephrased according to the population, intervention, comparison and outcome statement. The available scientific evidence on this topic were collected by updating the systematic literature reviews used for the EULAR 2013 recommendations up to January 2016. The aspects evaluated in the studies concerned clinical efficacy, radiographic structural damage and safety. After the systematic literature review the expert panel formulated a consensus statement, and a modified Delphi panel evaluated the level of agreement between panellists (strength of recommendation). Results From a total of 1080 records we have included 6 studies, 2 randomized clinical trials and 4 open-label extension trials. Evidence from publications generated three statements for the final consensus document. The systematic literature review and the consensus statements developed showed that, for patients with early RA and in the presence of a treat-to-target strategy, the immediate use of anti-TNFi compared with an early (within 12 weeks) step-up to anti-TNF therapy did not confer a significant advantage regarding clinical, functional and radiographic outcomes. Conclusion The most appropriate placement of the TNFi therapy in the treatment algorithm of early RA still remains a challenging clinical question that needs to be further addressed.

The aim of this study was to assess the efficacy and tolerability of balneotherapy (BT) in patients with primary fibromyalgia syndrome (FS). In a prospective, randomized, controlled, double-blind trial with a 6-month follow-up, 100 FS patients were randomized to receive a cycle of BT with highly mineralized sulfate water (BT group) or with tap water (control group). Clinical assessments were performed at screening visit, at basal time, and after treatment (2 weeks, 3 and 6 months). The primary outcome measures were the change of global pain on the Visual Analogue Scale (VAS) and Fibromyalgia Impact Questionnaire total score (FIQ-Total) from baseline to 15 days. Secondary outcomes included Widespread Pain Index, Symptom Severity Scale Score, Short Form Health Survey, State-Trait Anxiety Inventory (STAI), and Center for Epidemiologic Studies Depression Scale. We performed an intent-to-treat analysis. The Kolmogorov-Smirnov test was applied to verify the normality distribution of all quantitative variables and the Student’s t test to compare sample data. In the BT group, we observed a significant improvement of VAS and FIQ-Total at the end of the treatment that persisted until 6 months, while no significant differences were found in the control group. The differences between groups were significant for primary parameters at each time point. Similar results were obtained for the other secondary outcomes except for the STAI outcome. Adverse events were reported by 10 patients in the BT group and by 22 patients in the control group. Our results support the short- and long-term therapeutic efficacy of BT in FS. Trial registration: NCT02548065

Ear, nose and throat (ENT) manifestations in granulomatosis with polyangiitis (GPA) represent the most frequent symptoms at disease onset. The aim of the study was to analyse ENT involvement at diagnosis, as well as how it could influence relapse rate, mortality and disease severity. A retrospective non-controlled cohort study was performed including all consecutive diagnosed GPA from 1996 to 2016 in two rheumatology centres of Northern Italy, focusing particularly on ENT presenting signs and symptoms at baseline. Eighty-nine patients (48.3% females) with new onset GPA were evaluated. They were mostly Caucasian (97.7%), middle aged (mean 54.5 years) and more frequently anti-neutrophil cytoplasmic antibodies (ANCA) positive (78.6%) with PR3 specificity (81.4%). At diagnosis, ENT involvement was reported in 71.9% patients, second only to systemic symptoms. These patients were significantly younger at disease onset (0.013), with less frequent renal involvement (0.014) irrespectively to ANCA status, but with significantly higher Vasculitis Damage Index (VDI) (0.001). The most frequent ENT manifestation was sinonasal involvement (58.4%, 73% of which with nasal inflammation/chronic sinusitis and 48% with nasal crusting), while otologic involvement (mainly otitis media/otomastoiditis) was observed in 34.8%. ENT-GPA patients presented a higher survival rate at 5 years (98.1 vs 77.7%, 0.049), and ENT involvement resulted to be an independent predictor of better outcome (OR 0.37, 95% CI 0.2-0.8, 0.019). Our data confirms that ENT involvement is not only one of the key clinical features of GPA, but also could point out a milder GPA subset with lower renal involvement and lower mortality rate, irrespectively to ANCA status.

Introduction The introduction in clinical practice of the immune checkpoint inhibitors (ICIs) radically changed the treatment algorithm of lung cancers. To characterize the toxicity of ICIs (atezolizumab, durvalumab, nivolumab, pembrolizumab) is important for personalizing treatment. Patients and Methods We performed a systematic review and meta-analysis of phase III randomized controlled trials assessing ICIs, from inception until April 23rd, 2020. We extracted the data from the ICI arm of each trial for indirect comparisons to estimate relative risk for immune-related adverse events (irAEs), severe (grade ≥3) irAEs, drug discontinuation due to irAEs or toxic death. Results Sixteen trials included a total of 6226 subjects randomized to the experimental immunotherapy arm. Immunotherapy was administered in monotherapy (8 trials), in combination with chemotherapy (6 trials) or other ICI (2 trials). Any grade irAEs and severe irAEs for ICI were 37.1% and 18.5%, respectively. Discontinuations due to any grade irAEs and severe irAEs were 13.8% and 9.2%, respectively; toxic deaths were 2.9% in the immunotherapy arm. Pooled data on any, severe and organ-specific irAEs showed that immunotherapy has a significantly lower risk of irAEs compared to immuno-chemotherapy, especially when analysis was restricted to monoimmunotherapy, like drug discontinuation and toxic death (all p Conclusions Our findings contribute to clarifying frequency and features of immune-related toxicities between different ICIs in lung cancer patients, including any grade irAEs, severe irAEs, drug discontinuation and toxic deaths, and may be useful to inform the selection of treatment.

Resume Objectifs Le virus Epstein-Barr (EBV) joue un role dans la pathogenese d’environ 40 % des syndromes lymphoproliferatifs (SLP) qui surviennent chez des patients sous traitement immunosuppresseur (TIS) pour une maladie rhumatismale, mais il n’y a pas encore de donnees issues de grandes cohortes. Nous avons souhaite identifier les caracteristiques clinicopathologiques, la prise en charge et les resultats de cette affection. Methodes Nous avons passe en revue tous les cas publies de SLP positifs pour l’ARN encode de l’EBV (EBER), incluant dans notre analyse un patient dont le cas n’avait pas ete publie mais dont le diagnostic avait ete etabli dans notre hopital. Nous avons exclu les cas ne presentant pas d’affection rhumatismale sous-jacente, sans TIS specifique ou pour lesquels il n’existait pas de donnees univoques. Resultats La majorite des 159 patients cumules de notre cohorte presentaient une polyarthrite rhumatoide (83 %) et recevaient du methotrexate (75,4 %). Chez 68,5 % des patients, le SLP est apparu entre 40 et 70 ans, apres une periode de 13,3 ± 9,6 ans depuis l’apparition de la maladie rhumatismale et apres 58,7 ± 47 mois de TIS. Les SLP etaient majoritairement derives de la lignee B (39 %), de stade I dans la classification d’Ann Arbor (38,3 %) et presentaient dans 63,1 % des cas une atteinte extranodale touchant principalement le systeme nerveux central (17,6 %). L’approche la plus frequemment adoptee a ete l’arret du TIS (93,3 %) associe, dans 38,3 % des cas, a une radiotherapie (RT) ou une chimiotherapie (CT). Au total, une remission complete a ete obtenue chez 61,7 % des patients (RC ; 30,2 ± 24,0 mois). Parmi les cas publies de patients pour lesquels l’approche de premiere instance a consiste en l’arret seul du TIS, une RC a ete obtenue dans 67,2 % des cas. Aucune difference demographique, clinique ou histologique significative n’a ete observee entre les patients ayant obtenu une RC et les autres, ni entre ceux ayant atteint la RC par arret seul du TIS et les autres (p > 0,05 pour toutes les comparaisons). Conclusions Cette etude examine toutes les preuves publiees relatives a des SLP induits par l’EBV chez des patients recevant un TIS pour une affection rhumatismale.

Objective Arthritis, myositis and interstitial lung disease (ILD) constitute the classic clinical triad of anti-synthetase syndrome (ASSD). These patients experience other accompanying features, such as Raynaud's phenomenon, fever or mechanic's hands. Most ASSD patients develop the complete triad during the follow-up. In the present study we aimed to determine whether the subsequent appearance of accompanying features may suggest the development of triad findings lacking at the onset in anti-Jo1 positive ASSD patients. Methods Anti-Jo1 positive patients presenting with incomplete ASSD (no >2 classic triad features) were assessed. Clinical characteristics and clusters of disease manifestations were retrospectively collected and analyzed in a large international multicenter cohort of ASSD patients. Results 165 patients (123 women) with incomplete ASSD were identified. Ninety-five patients (57.5%) developed new classic triad manifestations after 15months median (IQR 9–51) and 40 (24%) developed new accompanying features after 19months median (IQR 6–56) from disease onset. During the follow-up, the ex-novo occurrence of triad features was observed in 32 out of 40 patients (80%) with new accompanying findings and in 63 out of 125 patients (50.5%) without new accompanying findings (p=0.002). In patients with at least one new accompanying feature the odds ratio for the occurrence of new triad manifestations was 3.94 with respect to patients not developing ex-novo accompanying findings (95% CI 1.68–9.21, p=0.002). Conclusion Anti-Jo1 ASSD patients with incomplete forms at disease onset are at high risk for the subsequent occurrence of lacking classic triad findings. Although all ASSD patients should be carefully assessed for the occurrence of new triad features, a closer follow-up should be considered in the subgroup of patients developing ex novo accompanying findings. These patients, indeed, have near four-fold increased risk for new classic triad manifestation occurrence with respect to patients not presenting ex novo accompanying findings.

Resume Objectifs Evaluer la pertinence des anti-anticorps, (Ac) anti-adalimumab (ADA) et leur relation avec les caracteristiques cliniques et biologiques dans la polyarthrite rhumatoide (PR), la spondylarthrite ankylosante (SpA) et le rhumatisme psoriasique (RP). Methodes Cinquante-huit patients atteints de PR, SpA et RP ont ete inclus de facon prospective. Les caracteristiques cliniques et biologiques, l’activite de la maladie, les anticorps anti-ADA, anti-nucleaires (ANA), anti-ADN double-brin (db), anti-antigenes nucleaires solubles (anti-ENA) et anti-phospholipides (aPL) ont ete evalues a l’inclusion et apres 4, 12 et 24 semaines de traitement par l’adalimumab. Resultats Des Ac anti-ADA ont ete observes chez 11/58 (19 %) des patients. Ils ont ete detectes a partir de la quatrieme semaine de traitement chez 90,9 % des sujets positifs. Une reponse anti-ADA positive a ete associee de maniere significative a des niveaux seriques moyens d’adalimumab plus faibles (p = 0,028). L’echec du traitement a ete observe chez 20/58 (34,5 %) des patients et a ete associe de maniere significative a des Ac anti-ADA (p = 0,035). Les taux seriques moyens d’adalimumab etaient significativement plus faibles chez les patients presentant un echec de traitement que chez les repondeurs, a la fois dans l’ensemble de la cohorte (p = 0,005) et dans le groupe de patients positifs pour les anti-ADA (p = 0,006). Des evenements indesirables sont survenus plus souvent chez les patients ayant des anti-ADA que chez les patients qui n’en n’avaient pas (27,3 vs. 14,9 %). Conclusions Les Ac anti-ADA pourraient etre consideres comme un marqueur precoce d’une mauvaise reponse clinique au traitement par l’adalimumab. Le suivi des ANA/anti-ENA/aPL en routine ne s’est pas revele comme un outil utile pour predire le developpement des Ac anti-ADA.

Background:Few studies have examined the correlation between clinical demographic and laboratory parameters with peripherical radiological erosive disease in PsA pts.Objectives:To examine the association between clinical, demographical and laboratory data and the presence of radiographic erosions (RE) in the peripheral joints of psoriatic arthritis (PsA) pts.Methods:A cross-sectional study was conducted in consecutive patients with PsA afferring 7 rheumatological italian tertiary care centers. Demographical, clinical, laboratory and imaging data were collected according to a standardized protocol. A patient was considered as affected by erosive disease (ED) if at least one joint presented radiographic erosions at hand and/or feet rx examination. Patients with ED at early rx examination (before 5 y from disease diagnosis) were considered as early ED (EED) pts and pts without ED at 6 y or more rx examination from disease diagnosis were considered as not EED (NEED).The association between the presence of joint erosions and demographical, clinical and laboratory data was assessed using logistic regression analysis. The results were expressed in terms odds ratios (OR), and 95% confidence intervals (CI).Results:Rx hand and feet examination were available for analysis in 492/794 (39.9 % females, mean age 53.3 ± 13.2 y, mean PsA duration 16.9 ± 16.8 y, ED 171 pts). 48 pts had EED and 133 pts had NEED. At univariate analyses factors significantly associated with EED (p < 0.20) were PsA duration (OR=0.979,95%CI 0.953-1.006, p = 0.119), diagnostic delay (OR=1.077, 95%CI 1.018-1.138, p = 0.009), history of peripheral enthesitis (OR=2.308,95%CI 0.904-5.888, p= 0.080), hypertrigliceridemia (OR=2.756,95%CI 0.997-7.618, p = 0.0.051), hypercholesterolemia (OR=1.687, 95%CI 0.777-3.661, p = 0.186), hyperuricemia (OR=0.450, 95%CI 0.174-1.166, p = 0.10), use of biological agents (OR=1.712, 95%CI 0.873-3.355, p=0.118). Factors significantly associated with EED at multivariate regression analyses were diagnostic delay (OR = 1.11, 95% CI: 1.01, 1.22), history of enthesitis (OR = 3.15, 95% CI: 1.23, 8.22), use of therapy with biological agents (OR = 3.60, 95% CI: 1.31, 9.85) with protective effect of hyperuricemia (OR = 0.25, 95% CI: 0.07, 0.90).Conclusion:The presence of EED in a group of consecutive PsA patients is correlated to diagnostic delay and history of enthesitis. Longitudinal study may confirm these associations.Disclosure of Interests:Maria Grazia Catanoso: None declared, Pierluigi Macchioni: None declared, Antonio Marchesoni Speakers bureau: Abbvie, Pfizer, UCB, Novartis, Celgene, Eli Lilly, Salvatore D’Angelo Speakers bureau: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sanofi, and UCB, Roberta Ramonda Speakers bureau: Novartis, Celgene, Janssen, Pfizer, Abbvie, Lilly, Alberto Cauli: None declared, fabio perrotta: None declared, Roberto Bortolotti: None declared, mariana lofrano: None declared, laura rotunno: None declared, maria grazia lorenzin: None declared, Guido Valesini: None declared, giovanni mathieu: None declared, Giuseppe Paolazzi: None declared, Carlo Salvarani Grant/research support from: consulting and investigator fees from Abbvie, Pfizer, MSD, Roche, Celgene, Novartis, Consultant of: consulting and investigator fees from Abbvie, Pfizer, MSD, Roche, Celgene, Novartis

Objective Aging may be a risk factor for morbidity in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We compared the rate and better characterized the type of disease- and treatment-related complications affecting young and elderly patients with AAV. Methods All new cases of granulomatosis with polyangiitis or microscopic polyangiitis diagnosed in three referral centers between 2000–2016 were included. Patients were stratified by age into young or elderly ( Results Of 141 patients included, 42 were elderly and 99 were young at the time of AAV diagnosis. Median follow-up was 58.0 [25–75% IQR, 31.0–60.0] months in young and 48.0 [23.25–60.0] months in elderly patients (p>0.05). Overall, the elderly group was associated to higher damage accrual assessed by Vasculitis Damage Index during follow-up (β=0.28, p Sixty-three (44.7%) patients had acute kidney injury due to AAV-glomerulonephritis at diagnosis. In contrast to elderly, young patients showed significant improvement in renal function over time, particularly in the first 6 months while on induction treatment (ΔeGFR, median [25–75%IQR], 5.3 [0.4–14] versus 22.8 [5.9–52.1] ml/min/1.73m2, p=0.008), without significant changes after ANCA type stratification. Despite similar immunosuppressive therapy approaches and relapse rates, elderly patients had a higher rate of severe infections compared to younger patients (HR 2.1, 95% CIs: 1.1–4.4, p=0.043). Conclusions Elderly patients with AAV had higher susceptibility to disease- and treatment-related morbidity than younger patients, particularly to renal and infective morbidity.

Background: Advancing age may be a risk factor for morbidity in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Objectives: We aimed to compare the rates and better characterize the type of disease- and treatment-related complications affecting young and elderly patients with AAV. Methods: All new cases of granulomatosis with polyangiits or microscopic polyangiitis diagnosed between 2000 and 2016 in three referral centers in Northern Italy were included. Patients were stratified by age into young or elderly ( Results: Of 141 patients included, 99 were young and 42 elderly at the time of AAV diagnosis. Median follow-up was 58.0 months (25-75% IQR, 31.0-60.0) in young and 48.0 months (25-75% IQR, 23.25-60.0) in elderly patients (p>0.05). Overall, total chronic damage assessed by Vasculitis Damage Index (VDI) significantly increased in elderly patients compared to young ones during follow-up (ρ=0.28, p 0.05). Sixty-three (44.7%) patients had acute kidney injury due to AAV-glomerulonephritis at diagnosis, 37 were young and 26 were elderly. In these patients, renal function recovery in the first 6 months was significantly lower for elderly (median ΔeGFR (25-75%IQR), 5.3 (0.4-14) ml/min/1.73m2) compared to young patients (22.8 (5.9-52.1) ml/min/1.73m2, p=0.008) while on induction treatment. Stratification for ANCA status (MPO-ANCA+ versus PR3-ANCA+), did not change these results. Despite similar immunosuppressive therapy approaches and relapse rates, elderly patients had a higher rate of severe infections compared to younger patients (OR 2.1, 95% CIs: 1.1-4.4, p=0.043; Figure below). Conclusion: Our findings indicate that elderly patients had higher susceptibility to morbidity related to vasculitis or its treatment than younger patients, particularly to worst renal function recovery and higher infection rate. References: [1] Harper L, et al. ANCA-associated renal vasculitis at the end of the twentieth century-a disease of older patients. Rheumatology (Oxford, England). 2005;44(4):495-501. [2] Pagnoux C, et al. Treatment of systemic necrotizing vasculitides in patients aged sixty-five years or older: results of a multicenter, open-label, randomized controlled trial of corticosteroid and cyclophosphamide-based induction therapy. Arthritis & rheumatology (Hoboken, NJ). 2015;67(4):1117-27. [3] Yates M, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Annals of the rheumatic diseases. 2016;75(9):1583-94. Disclosure of Interests: Alvise Berti: None declared, Mara Felicetti: None declared, Sara Monti: None declared, Augusta Ortolan: None declared, Roberto Padoan: None declared, Giuliano Brunori: None declared, Roberto Bortolotti: None declared, Roberto Caporali Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Roche, Genzyme, Lilly, MSD, Pfizer, UCB, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB, Franco Schiavon: None declared, Giuseppe Paolazzi: None declared

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.

ObjectivesThis multicentre study aimed to investigate the overall mortality of combined pulmonary fibrosis and emphysema (CPFE) in systemic sclerosis (SSc) and to compare CPFE-SSc characteristics with those of other SSc subtypes (with interstitial lung disease—ILD, emphysema or neither).MethodsChest CTs, anamnestic data, immunological profile and pulmonary function tests of patients with SSc were retrospectively collected. Each chest CT underwent a semiquantitative assessment blindly performed by three radiologists. Patients were clustered in four groups: SSc-CPFE, SSc-ILD, SSc-emphysema and other-SSc (without ILD nor emphysema). The overall mortality of these groups was calculated by Kaplan-Meier method and compared with the stratified log-rank test; Kruskal-Wallis test, t-Student test and χ² test assessed the differences between groups. PResultsWe enrolled 470 patients (1959 patient-year); 15.5 % (73/470) died during the follow-up. Compared with the SSc-ILD and other-SSc, in SSc-CPFE there was a higher prevalence of males, lower anticentromere antibodies prevalence and a more reduced pulmonary function (pConclusionsCPFE increases the mortality risk in SSc along with a highly impaired lung function. These findings strengthen the importance to take into account emphysema in patients with SSc with ILD.

Background:Observational data on the use of secukinumab for the treatment of spondyloarthritides are still lacking. Large population-based registries that allow long-term follow-up have been increasingly used to investigate the performance of biologic drugs in a real life setting.Objectives:The aim of this study is to evaluate the effectiveness and the retention rate of secukinumab in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients in a real-life setting over a 3-year follow-up period.Methods:Data of all PsA and axSpA patients (diagnosed according to CASPAR and ASAS criteria, respectively) treated with secukinumab were prospectively collected in the Italian multicentric LORHEN registry. Effectiveness was measured as the mean change from baseline of Disease Activity in PSoriatic Arthritis score (DAPSA) in PsA and Ankylosing Spondylitis Disease Activity Score (ASDAS) in axSpA patients. Rates of DAPSA remission and ASDAS inactive disease were also computed. The 3-year retention rate was calculated by the Kaplan-Meier method and compared between PsA and axSpA by a log-rank test. A descriptive analysis of reasons for discontinuation was performed.Results:The study population included 195 PsA (55.4% females, mean age 50.7 [±11.8] years, mean disease duration 10 [±7.8] years, mean baseline DAPSA 23.12 [±12.3]) and 94 axSpA (61.7% males, mean age 49.1 [±12.7] years, mean disease duration 10.4 [±9.4] years, mean baseline ASDAS 3.41 [±1.1]) patients who received secukinumab as first (26.5 and 33%, respectively) or subsequent biologic agent. Compared with baseline, the 3-, 6- and 12-month mean values of both DAPSA (12.6 [±9], 11.2 [±10.5] and 9.3 [±7.5], respectively) and ASDAS (2.23 [±0.9], 2.15 [±0.9], and 1.84 [±0.9], respectively) were significantly decreased (pConclusion:Our data confirmed in a real-life setting the 1-year clinical efficacy and the 3-year survival of secukinumab in both PsA and axSpA. The safety profile of secukinumab was very favorable for both the indications. No significant differences were observed in the performance of secukinumab between ax-SpA and PsA.References:[1]Deodhar A, et al. Arthritis Research & Therapy; 2019.[2]Mease PJ, et al. RMD Open. BMJ Specialist Journals; 2018;4(2):e000723.[3]Baraliakos X, et al. Clin Exp Rheumatol. 2018 Jan;36(1):50–5.Disclosure of Interests:Ennio Giulio Favalli Consultant of: Consultant and/or speaker for BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis, and Abbvie, Speakers bureau: Consultant and/or speaker for BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis, and Abbvie, Antonio Marchesoni Speakers bureau: Abbvie, Pfizer, UCB, Novartis, Celgene, Eli Lilly, Silvia Balduzzi: None declared, Carlomaurizio Montecucco: None declared, Claudia Lomater Consultant of: Advisory board for Sanofi, Novartis, Abbvie, Gloria Crepaldi Consultant of: Advisory board for Sanofi and Celgene, Speakers bureau: BMS, MSD, Silvia Talamini: None declared, Chiara Bazzani: None declared, Enrico Fusaro: None declared, Marta Priora: None declared, Aurora Iannello: None declared, Giuseppe Paolazzi: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB

Acquired hemophilia (AH) is a rare bleeding disorder caused by the spontaneous development of autoantibodies against coagulation factors, most commonly factor (F) VIII (acquired hemophilia A, AHA). The clinical manifestation of AHA includes mostly spontaneous hemorrhages into skin, mucous membranes, muscles, soft tissues, or joints. AHA should be suspected when a patient with no history of hemorrhages presents with bleeding and an unexplained prolonged activated partial thromboplastin time. The diagnosis is based on the clinical picture, the presence of low FVIII activity and evidence of FVIII inhibitor. In around half of patients, an underlying disorder (rheumatic diseases, malignancy, infections) or taking some drugs are associated with AHA; the remaining cases are idiopathic. Rheumatoid arthritis is a chronic inflammatory condition, marked by swelling and tenderness of small joints; it is usually treated with steroid and immunosuppressive drugs such as methotrexate, TNF-alpha inhibitors, and other biologic therapies (abatacept, tocilizumab, rituximab).We presented a patient with rheumatoid arthritis who developed acquired hemophilia A with hemarthroses; starting from this case, we focused on the literature about AHA in rheumatic diseases. We found 35 cases, 15 in systemic lupus erythematosus and 12 in rheumatoid arthritis, while the remaining cases were reported in Sjögren’s syndrome, polymyalgia rheumatica, systemic sclerosis, and psoriatic arthritis. Ecchymosis and cutaneous hematomas were the main clinical features while hemarthroses was quite a rare condition, shown in just three patients.

Background Diffuse alveolar haemorrhage (DAH) is a rare and severe manifestation of ANCA-associated vasculitides (AAV). Objectives To identify predictors of survival in patients with AAV-DAH. Methods A retrospective study of 102 consecutive patients (50% females; mean age 59±17 years) from 27 Italian Centres diagnosed with AAV-DAH was planned. Cox regression unadjusted analyses were performed. Results Among AAV patients, 47% had Granulomatosis with Polyangiitis (GPA), 47% Microscopic Polyangiitis (MPA) and 6% Eosinophilic Granulomatosis with Polyangiitis (EGPA). At DAH onset, mean BVAS was 20±8 and most patients had renal involvement (RI). Admission to Intensive Care Unit was needed in 27% of patients, while ventilatory support (VS) was required in 46%. At least one cardiovascular risk factor (CVRF) was recorded in 48%. Over a median follow-up of 39 months (25%–75% IQR 66 months), 19/102 patients (18.6%) died (figure 1). All patients received high-dose glucocorticoids in association with Cyclophosphamide (CYC 78%, mean cumulative dose 8±7 g) or Rituximab (37%). Plasma exchange was performed in 46%. Infections occurred in 38%. Age>65 years (HR 3.05 [95% CI 1.18–7.9], p=0.04), CVRF ≥2 (HR 8.85 [95% CI [AG7] 2.34–33.50], p=0.01), BVAS (v.3) (HR 1.07 [95% CI 1.01–1.13], p=0.01) were associated with mortality, whereas FFS was not. The need for VS (HR 4.54 [95% CI 1.48–13.85], p=0.008) and infections (HR 3.98 [95% CI 1.48–10.69] were also associated with mortality. Conclusions Older age, VS, CVRF and infections affect the survival in AAV. There is a need for specific outcome measeures. Disclosure of Interest None declared

Background The optimal duration of remission-maintenance treatment in ANCA-associated vasculitis (AAV) is still unknown, 1 with International recommendations suggesting to maintain it for at least 24 months. Data supporting the correct balance between relapse risk, treatment-related adverse events and damage are highly needed. Objectives To analyse the frequency and predictors of withdrawal of remission-maintenance immunosuppressive drugs (IS) in a large real-life cohort of AAV patients. Methods Clinical records of patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were retrospectively analysed from a multicentric cohort. We divided the cohort into group A (withdrawal) and group B (ongoing). Results We included 185 patients. Forty-one patients (22%) had withdrawn IS at the end of follow-up (median 73.5 months, IQR 54–115). Concomitant glucocorticoids were stopped in 33%. There were no significant differences in AAV subtype, ANCA pattern, age at diagnosis, diagnostic delay or comorbidities rates between group A and group B (table 1). Disease onset with pulmonary involvement was significantly more frequent in patients in whom IS was maintained (69.7% vs 45%; p=0.004). Figure 1. Disease activity at onset, but not during follow-up, was significantly higher in patients from group B (ongoing): median BVAS 18 (12–24) vs 15; (8–20) p=0.02. The type of IS used for remission induction did not differ between the two groups. Maintenance treatment with Rituximab (RTX) was associated with higher probability of discontinuing IS by the end of follow-up (21% vs 7.6%; p=0.02). There was no difference in the number of major relapses between the two groups. Safety profile was equally good in both groups, except for a higher number of infections over the course of disease in patients who withdrew IS (5% vs 0). Vasculitis damage index (VDI) was comparable between the two groups. Conclusions IS withdrawal was observed in a minority of real-life patients with AAV. Drug-free remission was negatively associated with pulmonary involvement and higher BVAS at disease onset. Remission maintenance with RTX was associated with a higher frequency of drug withdrawal at the end of follow-up. Reference [1] Karras, et al. Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis. Ann Rheum Dis2017;76:1662–68 Disclosure of Interest None declared

Background Rheumatic Diseases (RD) frequently affect women during reproductive age, therefore counselling on family planning is crucial for their quality of life. Children’s outcome is a major topic, but no large studies are available. Objectives To assess the long-term health conditions of children born to women with RD in a large multicentre cohort. Methods 24 Rheumatology Centres distributed the questionnaire (65 multiple-choice and 12 open-answer questions) to consecutive patients (18–55 years) in September 2015. Data were analysed dividing children upon maternal diagnosis: Chronic Arthritides (CA) and Connective Tissue Diseases (CTD). Results Data were collected for 320 children (166 males, 52%) born to 184 mothers (63 CA and 121 CTD). At the time of interview, children had a mean age of 17.1±9.6 years. Preterm delivery ( Conclusions In this long-term follow-up of children born to mothers with RD in this large, multicenter study of randomly interviewed women each AIID did not display a significantly increased frequency as compared to the literature; only coeliac showed a mild increased frequency. Children with LD had a tendency to cluster in the group of mothers with CTD, especially after maternal diagnosis (4/63, 6.3%), with a higher frequency as compared to general paediatric population. No significant relationships between ND/LD and prematurity, intrauterine drug exposure or maternal autoantibodies were identified. Acknowledgements Statistical analysis supported by an unrestricted grant by UCB Pharma. The authors wish to thank Patients Associations and Participants to the survey. Disclosure of Interest None declared

Background: Interstitial Lung Disease (ILD) is the main cause of death in Systemic Sclerosis (SSc). Serious lung involvement increase the hospitalization rate and sometimes oxygen therapy is required. An prompt treatment in ILD-SSc patients is essential, but nowadays there is not a feasible method to identify patients with poor prognosis. Although chest Computed Tomography (CT) is the gold standard to detect ILD, there is no standardized assessment of its severity. Quantitative CT (QCT) is an innovative and operator independent method to assess ILD-SSc extent and severity. An increasing number of evidences confirm that QCT is extremely useful for detecting SSc-ILD with the worst prognosis. However is not well established if QCT can predict death or comorbidity associated to ILD. Objectives: The main aim of this study is to verify if QCT predict 8-years mortality or clinical worsening (i.e. hospitalization for respiratory complications or chronic oxygen therapy) in SSc. Methods: Consecutive SSc patients (according to ACR/EULAR classification criteria) from ten different centers underwent a chest CT. Their clinical history was carefully recorded in the following 96 months. A rheumatologist post-analyzed every CT with an open source DICOM viewer in order to obtain QCT indexes. Patients were clustered in two subgroups: according to QCT indexes’ cutoff previously found (see Ariani et al., 2017). The survival time of each patient was considered the time interval between the CT date and death, hospitalization related to lung worsening, beginning of chronic oxygen therapy or last medical examination Results: We enrolled 342 patients; during the 8-years follow-up 15.5% (53/342) died and 4,4% (15/342) had a clinical worsening. The Kaplan-Meier survival analysis demonstrates a worse survival in patients with QCT indexes above or below the previously observed cutoffs. (p References: The QCT indexes’ cutoffs previously found (see Ariani, et al., 2017) identify the SSc-ILD subjects with an high risk of 8-years mortality and comorbidity. These findings suggest that QCT could became a pivotal assessment in SSc management because its role in identifying patients with poor prognosis and who deserve an early aggressive treatment. Disclosure of Interest: None declared

Background Patients affected by ANCA associated vasculitides (AAV) show lower survival than general population, even if the mortality decreased significantly in the last decade. Objectives Aim of our study is to analyse the early mortality (within 6 months) and the long-term survival in a multicentric Italian cohort of AAV patients. Methods we identified all patients affected by AAV, diagnosed from 1995 until 2017, followed routinely in four vasculitis referral centres in Norther Italy. We enrolled patients with diagnosis of granulomatosis with polyangiitis (GPA) and micro polyangiitis (MPA), fulfilling EMA algorithm or CHCC 2012 definitions, with complete survival data at last follow up. The analysis focused on early mortality, long-term survival and their predictors. Results We enrolled 200 AAV patients (F/M 110/90, Caucasian 98%) with a median age at diagnosis of 54.6±15.2 years. 157 (78.5%) were affected by GPA and 43 (21.5%) by MPA. Data about ANCA antibodies were available in 181 patients and 157 (87%) resulted ANCA positive: 100 c-ANCA/PR3, 56 p-ANCA/MPO and one with double specificity PR3-MPO-ANCA. During the follow up period [5328–100 months], we registered 21 (10.5%) deaths, 6 (28.5% of all mortality) within 6 months after diagnosis: 9 patients died due to infectious complications, 1 due to hepatic cancer, 1 due to end stage heart failure, 1 due to massive cholestasis and 9 due to unknown causes. Early mortality was significantly associated with a higher frequency of alveolar haemorrhage (p=0.01; OR 11.1 IC95% 2.1–60.1) and respiratory failure (p The long-term survival, analysed with Kaplan-Maier method, did not show significant differences between GPA and MPA patients, while a significant poorer survival was observed in p-ANCA/MPO patients than c-ANCA-PR3 and ANCA negative patients (Log rank test: p=0.04). At univariate analysis of baseline data, deceased patients resulted older at disease onset (p=0.001) with more comorbidities (p Conclusions In this large cohort of Italian patients we confirm a higher short and long-term survival in AAV patient than reported in literature. Nevertheless, up to one third of deaths occurred within 6 months after diagnosis and infection diseases resulted the most frequent cause of death. Moreover, our data confirm the prognostic importance of ANCA pattern and the poor outcome of patient with severe lung and renal involvement. Disclosure of Interest None declared

Background Rheumatic diseases (RD) predominantly affect young women during reproductive age. Pregnancy, contraception and family planning (FP) are crucial for the quality of life of these patients. Objectives We aimed to investigate 9women9s health9 through a self-reported questionnaire. Answers from patients with connective tissue diseases (CTD) vs chronic arthritis (CA) were compared. Methods 24 centres distributed the questionnaire (65 multiple-choice and 12 open-answer questions) to women with RD (18–45years) regularly attending their outpatient clinics. Results Answers were collected from 249 CTD vs 149 CA patients. Their desire to have children was influenced by RD in 40% of cases: half of them reduced the number of children they wanted (Table 1). 39% CA vs 29% CTD were afraid of being mother because of disability. 24% CTD vs. 18% CA had at least one miscarriage; 21% CTD vs. 2% CA had more than one. 31% CTD and 34% CA were never asked about their desire to have children. 61% CTD vs 70% CA received counselling about contraception, given by a gynaecologist (G) (58% vs 64%), rheumatologist (R) (22% vs 14%) or both (7% vs 9%). 60% in both groups received a counselling before pregnancy: 34% vs 39% from R and G, 14% vs 22% by R. This positively changed family planning in 64% vs 59%. We created a Knowledge Index (based on the average of the normalized performed scores on 6 key questions for different sections): 55% CTD patients vs 44% CA had a medium-high score. A higher score directly correlated with the desire to became pregnant and with a multidisciplinary counselling. Conclusions This survey suggested that CTD have a major impact on FP and family size, possibly mediated by the increased rate of miscarriages as compared to CA. Concerns about reproductive issues could be positively overcome by adequate counselling. Rheumatologists should implement the discussion about FP and the compatibility of drugs with pregnancy in the management of young women with RD, especially those with CTD for whom contraception and pregnancy have particular implications. Acknowledgements Statistical analysis supported by an unrestricted grant by UCB Pharma Thanks to Patients9 Associations and Participants Disclosure of Interest None declared

Background Rheumatic diseases (RD) affect women during reproductive age. Children9s outcome is a major topic for counselling on family planning, but no large studies are available. Objectives We aimed at assessing the long-term health conditions of children born to mothers with RD through a self-reported questionnaire. Methods 24 Rheumatology Centers distributed the questionnaire (65 multiple choice and 12 open-answer questions) to consecutive women with RD attending their outpatient clinic during September 2015. Data were compared according to maternal diagnosis (MD) -chronic arthritis (CA) or connective tissue disease (CTD)- and to the timing of pregnancy (before or after MD of RD). Results The survey yielded data about 269 children born to 184 mothers (63 CA, 121 CTD). According to MD, children had a mean age of 17.1 (±9.6 SD) and 14.4 (±9.0 SD) years at the time of interview, and male children were 52/93 (56%) and 91/176 (52%), respectively. Twenty-nine children in the CA group (31.2%) and 64 in the CTDs group (36.4%) were born after MD of RD. Pre-term delivery (before 37 weeks) was observed in 48 cases (17.8%), mostly children born to mothers with CTD (37/48, 77%). Regarding school performance, 12 children (4.5%) repeated one year of school, in 7 cases for indolence, in 3 for learning disabilities (LD)/health problems (HP), in 2 for family problems. Eleven of these children were born before MD. Overall, 9 children (3.3%) were diagnosed with a LD and 53 children were affected by HP requiring either hospitalization or evaluation by a Specialist (Table). Three children (1%) were affected by autoimmune disease. Conclusions The long-term follow-up of children born to women with RD is reassuring of an outcome similar to that of the general pediatric population (GPP). Autoimmune diseases are not frequent. Problems seem to cluster in children born to CTD, especially after MD, with a higher frequency of LD (6.3% vs 2.5–3.5% of GPP), but no particular pattern of exposure to maternal autoantibodies nor drugs was observed. Acknowledgements Statistical analysis supported by an unrestricted grant by UCB Pharma Thanks to Patients Associations and Participants to the survey Disclosure of Interest None declared

Background ANCA specificity, rather than clinical diagnosis, has been suggested to influence the phenotype and clinical course of ANCA associated vasculitis (AAV) (1,2). Objectives To investigate differences in clinical presentation at disease onset between MPO-ANCA-positive granulomatosis with polyangiitis patients (MPO-GPA), PR3-ANCA-positive-GPA (PR3-GPA), and MPO-ANCA-positive microscopic polyangiitis (MPO-MPA). Methods Clinical records of AAV patients from three third level rheumatologic centers in Northern Italy were retrospectively analyzed. Results Of the 133 AAV patients included, 84 were PR3-GPA, 24 MPO-GPA, and 25 MPO-MPA. Patients with MPO-MPA were significantly older at diagnosis compared to both PR3-GPA and MPO-GPA (average age 63±10, 49±15, 55±29, respectively) (Table 1). Patients with MPO-GPA experienced a significant diagnostic delay compared to PR3-GPA (17±30 vs 7±14, p=0.02). ENT involvement was equally frequent in both GPA groups despite ANCA specificity, and significantly more represented than the MPO-MPA group (68%, 71% and 17% respectively; p Conclusions Clinical phenotype of GPA at disease onset did not seem to be influenced by ANCA specificity. Despite ANCA positivity (PR3 or MPO), GPA patients were significantly different from MPA. References Schirmer JH, Wright MN, Herrmann K, et al. Myeloperoxidase-Antineutrophil Cytoplasmic Antibody (ANCA)-Positive Granulomatosis With Polyangiitis (Wegener9s) Is a Clinically Distinct Subset of ANCA-Associated Vasculitis: A Retrospective Analysis of 315 Patients From a German Vasculitis Referral Center. Arthritis Rheumatol Hoboken NJ 2016;68:2953–63. Miloslavsky EM, Lu N, Unizony S, et al. Myeloperoxidase-Antineutrophil Cytoplasmic Antibody (ANCA)-Positive and ANCA-Negative Patients With Granulomatosis With Polyangiitis (Wegener9s): Distinct Patient Subsets. Arthritis Rheumatol 2016;68:2945–2952. Disclosure of Interest None declared

Background Advancing age is a risk factor for complications and mortality in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). 1,2 Objectives To analyze differences in infectious, metabolic and cardiovascular complications, renal function, and mortality in patients diagnosed with AAV before or after 65 years of age, and followed for up to 5 years. Methods We retrospectively collected long-term clinical and laboratory data of AAV patients of two referral centers in Northern Italy from 2000, and grouped patients in young (YP, Results Of the 114 patients included, 83 had a follow-up of at least 2 years (58 YP vs 25 EP). Median follow-up was 55 [32–100] months in YP and 44 [18–59] months in EP (p 0.05). At 2 year, creatinine levels (YP 1.0 mg/dL [0.85–1.31], EP 1.2 mg/dL [1.1–2.2]) and renal insufficiency rate decreased within each group (p Within the first 5 years of follow-up, severe infection (requiring hospitalization) and mortality rates were significantly higher in EP group when compared with YP group (p=0.024 and p=0.010 by Kaplan-Meier analysis, respectively, Figure 1), mirrored by a higher annual severe infection rate (p=0.041; 0.22±0.69 versus 0.05±0.17) and annual mortality rate (p=0.001; 0.33±1.02 versus 0.01±0.08) in EP group. Relapse rate was similar in YP and EP within 5 years (Figure 1). Lymphopenia rate (at least 1 event, 9 /L) was significantly higher in EP only at 6 month (p 9 /L), leukopenia ( 9 /L) or hypogammaglobinemia (Ig 9 /L) was detected in 3 patients after cyclophosphamide treatment (2 YP and 1 EP). Only relapse before 2 years of follow-up was associated with infections in YP (p Conclusions Heart failure is more frequent in older patients, which have higher infection and mortality rates. Transient lymphopenia is significantly higher in EP after induction treatment, but is not associated with their increase in infectious events. Despite a similar incidence of relapse in YP and EP, relapsing disease associates with infectious events in YP, but not in EP. References Flossmann O et al. Ann Rheum Dis. 2011 Mar;70(3):488–94. Timlin H et al. Semin Arthritis Rheum. 2015 Aug;45(1):67–9. Disclosure of Interest None declared

According to international recommendations, the selection of the biologic disease modifying anti-rheumatic drug (bDMARD) for rheumatoid arthritis (RA) is mainly left to the clinician’s preference. We analyzed the real-life factors influencing the first-line choice or the switching strategy, focusing on the prescription of abatacept (ABA) or tocilizumab (TCZ) compared to TNFα inhibitors (TNFi). Patients enrolled in the Lombardy Rheumatology Network (LORHEN) Registry after January 1, 2010, when all considered bDMARD agents were available, were included. The population was divided into “first-” and “second-line” bDMARD. We included 1910 patients (first line n = 1264, second line n = 646). Age was higher in ABA or TCZ vs TNFi treated patients (p

Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) are chronic immune-mediated rheumatic diseases that cause joint destruction and/or ankylosis, with resulting disability and diminished quality of life. Golimumab is the first human monoclonal antibody to tumor necrosis factor (TNF) administered monthly by subcutaneous injection. It is approved by the US Food and Drug Administration and by the European Medicines Agency for the treatment of RA, PsA, and AS. It is produced by a murine hybridoma cell line with innovative recombinant DNA technology, which minimizes immunogenicity of the antibody after injection. This paper reviews the main studies on the efficacy and safety of golimumab in these disease settings, illustrates the latest clinical updates, and analyzes the pharmacoeconomic aspects. Golimumab is effective in improving the physical function of patients in both the short and long term, and its safety profile is in keeping with that of other anti-TNF agents; the use of golimumab is cost-effective, simple, and convenient for the patient. Electronic supplementary material The online version of this article (doi:10.1007/s13554-013-0012-y) contains supplementary material, which is available to authorized users.

Objectives Epstein-Barr virus (EBV) is involved in the pathogenesis of approximately 40% of lymphoproliferative disorders (LPDs) arising in patients receiving immunosuppressive treatment (IST) for rheumatic diseases, but data from large cohorts are still not available. We aimed to identify clinicopathological features, management and outcome of this condition. Methods We reviewed all published cases of EBV-encoded RNA (EBER)-positive LPDs and included in our analysis one unpublished patient diagnosed in our Hospital. We excluded those cases without an underling rheumatic condition, a specific IST or not reporting univocal data. Results In the cumulative cohort of 159 patients, most were affected by rheumatoid arthritis (83.0%) and treated with methotrexate (75.4%). 68.5% of LPDs developed between the age of 40 and 70 years, after 13.3 ± 9.6 years from rheumatic disease onset and 58.7 ± 47.0 months of IST. LPDs were mostly B-cell lineage derived (39.0%), Ann Arbor disease's stage I (38.3%) and presented with extra-nodal involvement in 63.1%, which was most frequently represented by central nervous system (17.6%). The most common approach was IST withdrawal (93.3%), variably associated with radiotherapy(RT)/chemotherapy(CT) in 38.3% of cases. Overall, 61.7% of patients achieved a complete remission (CR; 30.2 ± 24.0 months). Among published cases of patients that only suspended IS as first line treatment approach, 67.2% achieved CR. No significant demographic, clinical and histological differences between patients who achieved CR and who did not, and between who achieved CR by IST withdrawal alone and who did not were observed ( P > 0.05 in all comparison). Conclusions The current study reviews all the published evidences of EBV-induced LPDs in patients receiving IST treatment for rheumatic conditions.

Background: Interleukin (IL)-1 inhibitors have been suggested as possible therapeutic options in a large number of old and new clinical entities characterized by an IL-1 driven pathogenesis. Objectives: To perform a nationwide snapshot of the on-label and off-label use of anakinra (ANA) and canakinumab (CAN) for different conditions both in children and adults. Methods: We retrospectively collected demographic, clinical, and therapeutic data from both adult and pediatric patients treated with IL-1 inhibitors from January 2008 to July 2016. Results: Five hundred and twenty-six treatment courses given to 475 patients (195 males, 280 females; 111 children and 364 adults) were evaluated. ANA was administered in 421 (80.04%) courses, CAN in 105 (19.96%). Sixty-two (32.1%) patients had been treated with both agents. IL-1 inhibitors were employed in 38 different indications (37 with ANA, 16 with CAN). Off-label use was more frequent for ANA than CAN (p < 0.0001). ANA was employed as first-line biologic approach in 323 (76.7%) cases, while CAN in 37 cases (35.2%). IL-1 inhibitors were associated with corticosteroids in 285 (54.18%) courses and disease modifying anti-rheumatic drugs (DMARDs) in 156 (29.65%). ANA dosage ranged from 30 to 200 mg/day (or 1.0-2.0 mg/kg/day) among adults and 2-4 mg/kg/day among children; regarding CAN, the most frequently used posologies were 150mg every 8 weeks, 150mg every 4 weeks and 150mg every 6 weeks. The frequency of failure was higher among patients treated with ANA at a dosage of 100 mg/day than those treated with 2 mg/kg/day (p = 0.03). Seventy-six patients (14.4%) reported an adverse event (AE) and 10 (1.9%) a severe AE. AEs occurred more frequently after the age of 65 compared to both children and patients aged between 16 and 65 (p = 0.003 and p = 0.03, respectively). Conclusions: IL-1 inhibitors are mostly used off-label, especially ANA, during adulthood. The high frequency of good clinical responses suggests that IL-1 inhibitors are used with awareness of pathogenetic mechanisms; adult healthcare physicians generally employ standard dosages, while pediatricians are more prone in using a weight-based posology. Dose adjustments and switching between different agents showed to be effective treatment strategies. Our data confirm the good safety profile of IL-1 inhibitors.

Objective To evaluate the frequency and type of vascular lesions and to study the association of factor V gene G1691A (Leiden) and prothrombin gene G20210A polymorphisms with venous thrombosis in Italian patients with Behcet's disease (BD). Methods Included were 118 consecutive Italian BD patients followed over a 3-year period (1997–1999) who satisfied the International Study Group criteria for BD. The control group consisted of 132 healthy Italian blood donors. All BD patients and controls were genotyped by polymerase chain reaction and allele-specific restriction enzyme techniques for factor V Leiden and prothrombin gene G20210A polymorphisms. Results Vascular lesions were observed in 37 (31.4%) patients. The 2 most common lesions were subcutaneous thrombophlebitis (10.2%) and deep vein thrombosis (DVT) of the legs (22.8%). No significant demographic and clinical differences between patients with and without DVT were present. The distribution of allele and genotype frequencies of prothrombin gene G20210A and factor V Leiden polymorphisms did not differ significantly between BD patients and healthy controls. The frequencies of carriage rates of prothrombin gene G20210A and factor V Leiden polymorphisms in BD patients with and without DVT were similar. However, the frequency of 20210A allele was significantly higher in BD patients with ocular disease than in those without, particularly in the patients with posterior uveitis/retinal vasculitis. Conclusions The frequency and types of vascular lesions in Italian BD patients were similar to those reported in studies from other countries. No association between factor V Leiden mutation and G20210A mutation in the 3′-untranslated region of the prothrombin gene with DVT was found. However, a prothrombin gene G20210A mutation may influence the development and severity of ocular involvement in BD.

To evaluate the relevance of anti-adalimumab (anti-ADA) antibodies (Abs) and their relationship with clinical/laboratory features in rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA).Fifty-eight patients affected with RA, AS and PsA were prospectively enrolled. Clinical/laboratory characteristics, disease activity, anti-ADA, anti-nuclear (ANA), anti-double strand (ds)DNA, anti-extractable nuclear antigens (anti-ENA) and anti-phospholipid Abs (aPL) were evaluated at baseline, 4, 12 and 24 weeks of adalimumab treatment.Anti-ADA Abs were observed in 11/58 (19%) patients; they were detected within the 4th week of therapy in 90.9% of the positive subjects. Anti-ADA positivity was associated with significantly lower mean adalimumab serum levels (P0.05). Treatment failure was observed in 20/58 (34.5%) patients and was significantly associated with anti-ADA Abs (P0.05). Mean adalimumab serum levels were significantly lower in patients with treatment failure than in the responders one, both in the whole cohort (P0.01) and in the group of anti-ADA positive patients (P0.01). Adverse events happened more often in anti-ADA positive then in anti-ADA negative patients (27.3% vs 14.9%).Anti-ADA abs could be considered an early marker associated to a poor clinical response to adalimumab treatment. Routine ANA/anti-ENA/aPL monitoring did not reveal as useful tools to predict the development of anti-ADA abs.

OBJECTIVE: The polymorphism 158V/F of Fc fragment of IgG (FCGR) type 3A may influence the response to rituximab (RTX) in rheumatoid arthritis (RA). We investigated the FCG3A polymorphism in a large cohort of RA patients treated with RTX, also by considering the possible loss of response from month +4 to +6 after RTX and the presence of established predictors of response. METHODS: The study analysed 212 RA patients. European League Against Rheumatism (EULAR) response was evaluated at months +4 and +6 after the first RTX infusion. The FCGR3A polymorphism was analysed by PCR followed by Sanger sequencing. RESULTS: The FCGR3A genotypes were associated with EULAR response (good or moderate) at month +6 (response in 34/38 (89.5%) VV vs 70/106 (66%) VF and in 51/77 (66.2%) FF patients; p=0.01), but not at month +4 (response in 32/37 (86.5%) VV vs 69/102 (67.6%) VF and 53/73 (72.6%) FF patients; p=0.09). Loss of response was observed only in VF and FF carriers ((VV vs VF vs FF: 0/37 (0%) vs 11/102 (10.8%) vs 12/73 (16.4%); p=0.02)). Probability of response at month +6 was very high when at least two of the three following items selected by multivariate analysis were present: positive rheumatoid factor and/or anticyclic citrullinated peptide antibodies, previous treatment with ≤1 anti-tumor necrosis factor (TNF) agent, and 158VV FCGR3A genotype (p

Background The therapeutic armamentarium for the treatment of rheumatoid arthritis (RA) has been significantly implemented with the use of biologic-disease modifying anti-rheumatic drugs (bDMARDs). TNF inhibitors (TNFi), abatacept (ABA) or tocilizumab (TCZ) are all approved as first-line biologic agents. International Recommendations (1) do not provide a preference on the mechanism of action (MoA) to be chosen first or after the failure of bDMARD therapy. Objectives To analyse the factors influencing the choice of the first-line bDMARD or the switching strategy in RA, focusing on the prescription of ABA or TCZ compared to TNFi. Methods Patients were selected from the Lombardy Rheumatology Network (LORHEN) Registry. The analysis was limited to patients enrolled after 2008, when all three different MoA were available. The study population was divided into “first-line” and “second-line” bDMARD. Results A total of 1910 patients were included. First line n=1264, second line n=646 patients. Both age at diagnosis and at bDMARD initiation were significantly lower in patients treated with first-line TNFi compared to ABA and TCZ (p Conclusions According to International Guidelines, the selection of the first and second-line bDMARD is left to the clinician9s preference. However, real-life data suggest that higher age and comorbidities influence the choice towards ABA and TCZ compared to TNFi. After failing a first-line TNFi, a strategy of swapping to a different MoA is more common. References Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014;73(3):492–509. Disclosure of Interest None declared

Background Lyme disease (LD) is a multisystemic infection caused by Borrelia burgdorferi ( Bb ) sensu lato complex, involving skin, joints, nervous system and heart. Objectives To assess clinical and serological data of patients with LD at presentation in an endemic area of Northeast Italy (Trentino), with a special focus on rheumatic manifestation. Methods We retrospectively collected clinical data of Bb seropositive patients from 2014 to 2015, tested with ELISA (Enzyme-Linked Immunosorbent Assay) IgM/IgG and Western blot (WB; IgM/IgG immunoblots). Only patients with a LD9 diagnosis confirmed by a trained physician of our center were selected. Other laboratory and instrumental tests ( Bb -PCR on synovial fluid, anti- Bb antibodies research on cerebrospinal fluid, etc.) were performed if deemed necessary by clinical judgment. Results Seventynine patients resulted seropositive for Bb , but only 54 met the inclusion criteria. Among patients with confirmed LD, 27 (50%) were female, mean age at presentation was 48±21years; children were 12.9%. The main presenting symptom was erythema migrans in 72% of cases (39/54), arthritis in 17% (9/54), flu-like symptoms in 7% (4/54), chronic atrophic acrodermatitis and cognitive dysfunction in 2% of cases (1 patient each). Among arthritis, 89% (8/9) presented with acute knee monoarthritis and one patient with hand PIP arthritis. Other concomitant or further developed manifestations were CNS involvement (2/54), cranial neuropathy (1/54), pleuropericarditis (1/54), I°grade atrioventricular block (1/54), transitory leucopenia (2/54), flu-like symptoms (12/54). All patients received antibiotic treatment: 58% doxycycline, 25% amoxicillin, 5% ceftriaxone (12% not reported). Twentysix (48%) patients remember tickborne bite, with a mean latency of 10.4±16.9 weeks. When compared to the rest of the cohort, patients presenting with arthritis were younger (48y±12 vs 56y±12; p=.04), remember tickborne bite in 22% of cases (2/9; p=ns), and had increased ESR (mm/h, 51.1±36.6 vs 24.3±20.3; p=.03) and CRP levels (mm/L, 19.6±23.3 vs 5.6±10.2; p=.01). Arthritis-presenting LD-patients had higher serum IgG antibody levels if compared to overall non-arthritis presenting LD-patients (124.0 vs 25.5; p Bb antibodies presence after the 4th week from bite (124.0 vs 29.0, p Conclusions Arthritis is the second most frequent presenting symptoms of LD (17%). Knee monoarthritis is typical, patients affected are younger and only 20% recall a tick bite. We first demonstrated higher levels of serum anti- Bb IgG antibodies in patients presenting with arthritis. This seems not directly related to a longer time from bite to disease development, since anti- Bb IgG levels of patients with arthritis remain significantly higher if selectively compared to patients without arthritis tested for antibodies after the decline of the primary immune response, after 4th week. References Guellec D et al. RMD Open. 2016 Jan 11;2(1):e000120 Stinco G et al. ScientificWorldJournal. 2014 Jan 16;2014:414505 Disclosure of Interest None declared

Background To date four subcoutaneus TNF inhibitors (TNFis) have been licensed for the treatment of rheumatoid arthritis (RA). Although data from real-life registries have largely confirmed the favourable long term retention rates of adalimumab (ADA) and etanercept (ETN), data on golimumab (GOL) and certolizumab pegol (CZP) drug survival are still lacking. Objectives The aim of the study is to evaluate the 2-year retention rate of TNFis used as 1st or 2nd line biotherapy in RA patients in a multicentric observational cohort (the LORHEN registry). Methods Data of all RA patients treated with a TNFi were retrospectively extracted from the LORHEN registry, including a cohort of more than 3000 RA subjects who received at least one biologic agent since 1999. The analysis was limited to patients who received ADA, ETN, CZP, or GOL as first- or second-line biotherapy in the period when all the considered TNFis were available in Italy (from January 2010 to November 2015). The 2-year retention rate was calculated by Kaplan-Meier method and the comparative risk for discontinuation among individual TNFi was compared by a stratified log-rank test. Sub-analyses according to first or second line treatment have been performed. Results The study population included 677 RA patients (79.7% female, mean age [±SD] 54.3 [±13.5] years, mean disease duration 8.9 [±8.8] years, mean baseline disease activity score 28 4.9 [±1.3]), treated with a first (n=444) or a second line (n=233) TNFi. In the biologic naive group, 141 patients received ADA, 88 CZP, 130 ETN, and 85 GOL, whereas in the switcher group 68 patients have been treated with ADA, 38 with CZP, 76 with ETN, and 51 with GOL. The overall 2-year retention rate was 58.5% (63.3 and 49.4% in first- and second-line group, respectively; p Conclusions In the real-life scenario of the Lorhen registry, overall 2-year retention rate of TNFis was about 60% with a significantly higher persistence in biologic naive patients compared with switchers. In the comparison among individual TNFis, no significant differences were found with the exception of a lower drug survival of ADA compared with CZP in biologic naive subjects and with GOL in switchers. Disclosure of Interest None declared

Background The efficacy of Golimumab (GLM) treatment in rheumatoid arthritis (RA) has been widely documented in clinical trials. Data are still needed to assess its efficacy and tolerability in everyday clinical practice. Objectives To assess the efficacy of the treatment with GLM in RA previously treated with conventional synthetic disease modifying antirheumatic drugs (csDMARDs) or biological DMARDs (bDMARDs) from a multicentric observational cohort (the LORHEN Registry). Methods All patients with a diagnosis of RA in the LORHEN database who started GLM from october 2010 up to september 2015, with at least one reported visit, were included. We reviewed the data regarding the first 24 months of treatment, focusing on clinical efficacy. The efficacy of GLM was assessed with DAS28, DAS28(CRP), SDAI and EULAR response criteria. We executed intention-to-treat (ITT) and per-protocol analysis (PP). We repeated the analysis for the subgroups of patients who received GLM as first or second bDMARD. Results We retrieved the data regarding 180 patients, with a mean (sd) age of 54,57 (13,62) years and a mean (sd) disease duration of 9,52 (9,32) years. Methotrexate was the concomitant csDMARD for 123 (68,3%) patients, while leflunomide, sulfasalazine and cyclosporine were given to 13 (7,2%), 5 (2,8%) and 4 (2,2%) patients respectively. 35 (19,4%) patients were treated with GLM monotherapy. 137 (76,1%) and 5 (2,8%) patients were given low dose (≤10mg prednisone equivalent a day) and medium dose (≥10 and ≤25) corticosteroid at baseline, with following tapering. A total of 79 patients stopped the treatment with GLM due to inefficacy or adverse events before 24 months of treatment. With the ITT design 55 (30,6%) and 44 (24,4%) patients achieved good or moderate EULAR response respectively at 6 months. The mean (sd) DAS28, DAS28(CRP) and SDAI progressively reduced, reaching 2,61 (1,11), 2,41 (0,72) and 4,62 (3,80) respectively at 24 months. Within the PP scenario, 32 (66,7%) and 9 (18,8%) patients reached and maintained good or moderate EULAR response respectively to the end of the follow-up. The clinical response to GLM therapy resulted slightly reduced when given as a second line bDMARD treatment, but the data did not met statistical significance. Conclusions GLM is effective in treating RA in everyday clinical practice. The efficacy increases significantly over the first 6 months and slightly during the following 18 months. Interestingly enough, patients treated with GLM after a first bDMARD can still achieve low disease activity and clinical remission, with an overall efficacy of the treatment not statistically different to the first line. Disclosure of Interest None declared