Background A remarkable variability in the clinical course of Behçet's Syndrome (BS) seems to arise by comparing cohorts from different geographical areas. However, no data are currently available on the possible variability of organ damage burden, although it is currently recognized as a major outcome in BS. Objectives To evaluate and compare the extent, characteristics, and associated factors of organ damage in patients from different World areas. Methods We analyzed demographic and clinical data of a multicenter cohort of 935 consecutive BS patients from 11 Countries clustered in 5 geographic areas: Europe (EU, n 345), North Africa (NA, n 278), Middle East (ME, n 227), Central Asia (CA, n 44), America (AM, 41). Organ damage was assessed by the BS organ damage index (BODI) [1]. Uni- and multivariate analysis was performed to evaluate the association between the geographical region and organ damage using demographic and clinical data as covariates. Results Demographics and clinical features are reported in the Table 1. The prevalence of any damage (BODI≥1) in the EU, ME, NA, CA, and AM areas was 47.0%. 54.6%. 91.7%. 97.6% and 77.3%, respectively, whereas the mean (SD) total BODI score was 1.1 (1.7), 1.2 (1.7), 3.5 (2.4), 4.5 (2.6), and 1.9 (1.9). The prevalence of different BODI domains is reported in the Table 1. Significant differences were recorded in NA vs. EU and ME cohorts (Figure 1) (CA and AM not included in the statistical analysis for the small sample size). In multivariate analysis, the geographical area was independently associated (p < 0.001) with damage (NA vs. EU OR 11.3; ME vs. EU OR 1.5). Male gender (OR 1.5; p = 0.004), age (OR 1.03 per year; p = 0.002), disease duration (1.03 per year; p = 0.003), ocular (OR 2.8; p <0.001), vascular (OR 5.3, p <0.001), and neuropsychiatric (OR 3.8, P<0.001) involvement were also associated with BODI≥1. Conclusion A variable prevalence of organ damage was observed in BS patients from different World areas. Further research is needed to understand the cause underlying such geographic variability, as it may unveil biological, environmental, or health-system factors driving damage accrual in BS. The BODI effectively captures damage independently from the studied cohort's geographical origin. Reference [1]Piga M. Floris A. Espinosa G. et al. Development and preliminary validation of the Behçet's syndrome Overall Damage Index (BODI). RMD Open 2020;6:e001192. Acknowledgements: NIL. Disclosure of Interests None Declared.Table 1Demographic and clinical characteristic of the patients form different geographical area.EuropeMiddle EastNorth AfricaCentral AsiaAmericaMales37.1%59.5%80.2%41.5%40.9%Age, yrs46.3 (14.1)37.4 (10.0)37.7 (11.1)36.2 (17.6)44.1 (14.5)Disease duration, yrs14.6 (11.4)12.1 (8.7)8.6 (7.2)11.6 (9.6)14.3 (10.1)Diagnosis delay, yrs4.1 (7.2)6.5 (7.4)2.4 (4.8)5.2 (6.1)4.5 (6.5)BODI domainsMucocutaneous13.0%14.5%46.8%92.7%4.5%Musculoskeletal3.2%0.4%1.4%7.3%6.8%Ocular22.0%31.3%54.3%68.3%31.8%Vascular10.7%12.3%36.0%7.3%18.2%Cardiovascular11.9%12.3%37.4%12.2%18.2%Neuropsychiatric11.3%4.8%18.3%46.3%36.4%Gastrointestinal0.6%1.3%1.4%0.0%0.0%Miscellaneous10.4%5.3%4.0%9.8%9.1%BODI score1.1 (1.7)1.2 (1.7)3.5 (2.4)4.5 (2.6)1.9 (1.9)In males1.6 (2.1)1.5 (1.8)3.7 (2.3)5.0 (2.9)2.9 (2.2)In females0.8 (1.3)0.9 (1.4)2.6 (2.4)4.2 (2.5)1.7 (1.8)Europe included patients from Italy. Portugal. Spain. Greece; North Africa: Morocco. Egypt; Middle East: Turkey. Iran; Central Asia: Kazakhstan; America: USA. Brazil. Continuous variables are reported as mean (SD).

Background Preventing accrual of organ damage is a major goal in the treatment of Behçet’s Syndrome (BS). The BS Overall Damage Index (BODI) is the first damage assessment tool developed and preliminarily validated for BS. Objectives To assess the prevalence, extent, and determinants of organ damage accrual in the BODI validation cohort over 24 months of follow-up. Methods Overall, 189 patients from the multicenter BODI cohort underwent a 24 ±3 months follow-up (FU) visit. Demographics, ongoing medication, Behçet’s Disease Current Activity Form (BDCAF) score, Physician (PGA) and Patient Global Assessment (PtGA) of disease activity, disease relapsing (defined by any treatment change due to increased disease activity), and the BODI score were recorded. Damage accrual was defined as any increase ≥1 in the BODI score between baseline and follow-up visit (Δ-BODI). Logistic regression models were built to identify factors associated with BODI damage accrual. Results The mean age (standard deviation) at enrolment and the disease duration was 46.2 (12.1) and 10.8 (8.3) years, respectively, and 92/189 (48.7%) patients were males. During 24 months, 36 (19.0%) patients had an increase in the BODI score of at least 1 point (mean increase of 1.7 points). The BODI score increased from 1.6 (2.1) to 1.9 (2.1), with a mean Δ-BODI of 0.3 (0.8). Overall, 61 new BODI items of damage were recorded (Figure 1); 22 (34%) were steroid-related (diabetes, osteoporotic fractures, cataract). Factors independently associated with increased BODI score were longer glucocorticoids exposure (OR 1.01 per month, 95%CI 1.01-1.02, p<0.001), and occurrence of flares (OR 3.1, 95%CI 1.1-8.9, p = 0.035), whereas stable treatment with conventional and/or biologic immunosuppressants was negatively associated with an increase in the BODI score (OR 0.19, 95% 0.07-0.97, p <0.001) (Table 1). Table 1. Determinants of organ damage accrual over 2 years of follow-up. Univariate analysis Multivariate analysis Candidate determinants Δ-BODI ≥1 (n 36) Δ-BODI = 0 (n 153) p OR (95%CI) p Males 16 (44.4%) 76 (49.7%) 0.572 Age at enrolment 56.2 (42.9-62.0) 46.6 (35.4-53.1) 0.001 -- -- Disease duration 12.9 (7.1-22.0) 11.1 (5.4-21.2) 0.483 Major organ involv. 22 (61.1%) 72 (47.1%) 0,129 BDCAF at BL 3 (0-5) 2. (0-5) 0.365 BDCAF at FU visit 3.0 (3-5) 3 (0-7) 0.188 GC duration 112 (26.0-147.0) 24.0 (8.0-72.0) <0.001 1.012 (1.006-1.018 <0.001 cIS or TNFì ever 24 (66.7%) 133 (86.9%) 0.004 0.194 (0.073-0.972 ) <0.001 Relapse 9 (25.0%) 20 (13.1%) 0.070 3.093 (1.066-8.972 ) 0.038 BODI score at BL 1.0 (0-2.0) 1 (0-2) 0.579 Continuous variables are presented as median (IQR). Dichotomic variable are presented as n (%). BODI, Behçet’s Syndrome Overall Damage Index. FU, follow-up. cIS, conventional immunosuppressant. Δ-BODI increase of BODI score from baseline to the FU visit. Conclusion Despite the relatively high disease duration in the studied cohort, organ damage accrual was recorded in a relevant proportion of patients. BODI proved to capture the damage associated with major determinants such as inadequate control of disease activity and prolonged exposure to glucocorticoids. Disclosure of Interests None declared

BackgroundSystemic Sclerosis (SSc) is a complex autoimmune disease characterized by vascular damage, immune activation and fibrosis of skin and internal organs 1. Raynaud phenomenon (RP) is frequently the first symptom of the disease and growing evidences are supporting the hypothesis the SSc may be a vascular disease, with a pivotal role of endothelial cells, particularly in the very early phase2,3. Robust data support the use of vascular active drug to treat RP and to prevent vascular complication4–7.ObjectivesThe use of prostacyclin analog (PA) is evertything but standardized, with different regimen used all around the Country. We report data on the use of PA in a multicentric regional reality to understand which regimen are prevalent (and why) and if there is the opportunity to standardized them.MethodsWe collected data from an online survey exploring different items related to the use of PA.ResultsSurvey was fullfilled by 12 sites: 5 university hospital and 7 local hospitals, 7 driven by Rheumatologist and 5 from internal medicine specialists with/without concomitant rheumatologists. PA are ubiquitarly used for SSc-related digital ulcers (SSc-DU) and secondary RP but only a half of sites use it for primary RP. Seventy-five percent of sites (9/12) dispense PA at least once a month, but some other (1 each one respectively) on weekly basis, every other month or every 7 weeks. Drug administration may last from 2 to 5 consecutive days (mean 1.91+/- 1.5SD) with drug dose ranging from 0.5 to 2 ng/Kg/min with a minimum variability from site to site. Our regional hospitals may count on overall 68 spots, some available as beds (outpatient or inpatient), some as reclining chair or chair (outpatients only). University centers have usually more assigned personnel than local hospital (on average: 2 versus 1.5 physicians, 2 versus 1.2 nurse). Sites are able to offer meals (except one) and are able to accomodate from 1 to 12 patients at the same time (mean 3.45, +/- 3.2SD).ConclusionPA has known benefit in vascular involvement in SSc patients. Despite a multicenter palcebo-control study8 defining time and dose of this drugs and subsequent data based on the same regimen9, there is no homogeneity in treatment administration. The unequal treatment, based on our data, seems due to limited resources and personnel. High variability has been found in regimen duration and administration frequency.References[1]Ferri, C. et al. Systemic sclerosis evolution of disease pathomorphosis and survival. Our experience on Italian patients’ population and review of the literature. Autoimmunity Reviews vol. 13 1026–1034 (2014).[2]Mulligan-Kehoe, M. J. et al. Antiangiogenic plasma activity in patients with systemic sclerosis. Arthritis Rheum.56, 3448–58 (2007).[3]Wigley, F. M. Vascular disease in scleroderma. Clin. Rev. Allergy Immunol.36, 150–75 (2009).[4]Brueckner, C. S. et al. Effect of sildenafil on digital ulcers in systemic sclerosis: Analysis from a single centre pilot study. Ann. Rheum. Dis.69, 1475–1478 (2010).[5]Kowal-Bielecka, O. et al. EULAR recommendations for the treatment of systemic sclerosis: A report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann. Rheum. Dis.68, 620–628 (2009).[6]Matucci-Cerinic, M. et al. Bosentan treatment of digital ulcers related to systemic sclerosis: Results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. Ann. Rheum. Dis.70, 32–38 (2011).[7]Herrick, A. L. & Wigley, F. M. Raynaud’s phenomenon. Best Practice and Research: Clinical Rheumatology (2020) doi:10.1016/j.berh.2019.101474.[8]Wigley, F. M. et al. Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis: A multicenter, placebo-controlled, double- blind study. Ann. Intern. Med.120, 199–206 (1994).[9]Cappelli, L. & Wigley, F. M. Management of Raynaud Phenomenon and Digital Ulcers in Scleroderma. Rheumatic Disease Clinics of North America vol. 41 419–438 (2015).Disclosure of InterestsNone declared

Background Behçet’s Syndrome (BS) is a multisystem recurring inflammatory disorder characterised by a wide spectrum of clinical manifestations, which can vary from limited mucocutaneous lesions up to severe and even life-threatening events. Objectives To evaluate the impact of BS on the patients’ work activity and productivity. Methods A sub-cohort of 148 patients from the original Behçet’s syndrome Overall Damage Index (BODI) Project study was enrolled. The Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire was administered. Demographics, disease duration, comorbidity, major organ involvement, ongoing therapy, Behçet's Disease Current Activity Form (BDCAF), Physician Global Assessment (PGA), Patient Global Assessment (PtGA), and the BODI were recorded. Multiple regression models were built to investigate the independent effect of BS features on WPAI. Results Overall, 97 (65.6%) out of 148 patients who completed the WPAI:GH questionnaire resulted working for pay; 22 out of 97 (27.8%) patients reported missing work in the past week due to their health, accounting for a mean (SD) of 34.4% (17.8) of their working time (absenteeism). The only factor significantly associated with absenteeism in multivariate analysis was the presence of ocular damage, as assessed by the BODI (β 0.255, p = 0.027). Although 93 patients reported that they worked in the previous week, mean 27.3% (30.7) of their actual work productivity was impaired due to their health problem (presenteeism), with only 37 (38.5%) patients reporting no such loss. Factors associated with work impairment were female gender (β 0.319, p = 0.001), higher PtGA (β 0.298, p = 0.002), and an increased BODI score in the last 2 years follow-up (β 0.212 for one-point increased BODI score, p = 0.024). Finally, 99 (66.9%) of the total 148 patients complained of a daily activity impairment, reporting that a mean of 33.3% (30.6) of their regular daily activities had been prevented due to their health problems. Factors significantly associated with patients’ daily activity impairment were younger age at enrolment (β 0.187, p = 0.021), higher BDCAF disease activity (β 0.235, p = 0.002) and fibromyalgia (β 0.324, p = 0.033). Conclusion BS can lead to missing work time and significantly affect both the patient’s work productivity and daily activities. Active disease seems to be one of the major determinants together with a higher burden of damage and the association of some specific comorbidities, such as fibromyalgia. Table 1. WPAI:GH questionnaire results Variables n° Mean (SD) All patients 148 Patients working for pay 97 Percent work time missed due to health 97 7.9 (21.7) Percent work time missed due to health (patients with missed time >0) * 22 34.4 (17.8) Patients who actually worked in the past seven days** 93 Percent impairment while working due to health 93 27.3 (30.7) Percent impairment while working due to health (pts with % impairment while working > 0) *** 56 45.4 (27.2) Percent activity impairment due to health 148 33.3 (30.6) Percent activity impairment due to health (those with % activity impairment >0) 99 49.8 (23.9) * Patients working for pay who missed at least on hour of work, 22/97 = 22.7%. ** Patients working for pay, but who worked for > 0 hours in the last week = 93/97 *** Patients with impairment while working > 0 among patients who actually worked in the previous 7 day = 56/93. Disclosure of Interests None declared

Background Preventing accrual of organ damage represents a primary goal in the treatment of Behçet’s Syndrome (BS), as it may result in impairment of other outcomes, including the health-related quality of life (HR-QoL). Objectives The objective of this study was to investigate whether the recent accrual of organ damage, rather than its extent at a single time point, correlate with an impairment of the HR-QoL. Methods A sub-analysis of data from patients recruited in the longitudinal phase of the BODI Project validation cohort was performed. The HR-QoL and damage were measured by the Short-form 36 questionnaire (SF-36) and the BS Overall Damage Index (BODI), respectively, at the baseline visit and at a follow-up (FU) 24 ±3 months later. Then the possible increase of damage over FU was assessed by calculating the difference between the BODI score (Δ-BODI) in the two visits. Then, the relationship between the Δ-BODI and the individual and summary domains of the SF-36 was analysed by building multivariate regression models, including age, gender, concomitant fibromyalgia and/or depression, current disease activity as assessed by the BDCAF, as confounding variables. Results From the BODI validation cohort, 147 patients were recruitable for this sub-analysis;73 (49.8%) were males. The mean (SD) age and disease duration at enrolment were, respectively, 46.2 (12.4) and 13.4 (10.1) years. BODI score did not influence the SF-36 domains assessed at the baseline visit. In contrast, a significant correlation was recorded between the Δ-BODI and the following SF-36 domains: physical function (PF) (β -0.158 for 1 unit increase in BODI score, p 0.025), role physical (RP) (β -0.150, p 0.044), general health (GH) (β -0.199, p 0.004), role emotional (RE) (β -0.180, p 0.001), mental health (MH) (β -0.244, p 0.001), and the mental components summary (MCS) (-0.203, p 0.008)(Figure 1). Gender, age, fibromyalgia and disease activity were also confirmed to significantly influence HR-QoL (Table 1). Table 1. Multiple regression for the assessment of the relationship between Δ-BODI and SF-36 domains Δ-BODI Male Age FBM DPR BDCAF Physical function (PF) -0.158 (p 0.025 ) 0.180 (p 0.010) -0.299 (p<0.001) -0.358 (p<0.001) -- (p 0.552) -0.141 (p 0.044) Role-physical (RP) -0.150 (p 0.044 ) 0.154 (p 0.039) -0.212 (p 0.001) -0.278 (p<0.001) -- (0.086) -0.251 (p<0.001) Body-pain (BP) -- 0.868 0.266 (p<0.001) -0.286 (p<0.001) -0.276 (p<0.001) -- (p 0.799) -262 (p<0.001) General health (GH) -0.199 (p 0.004 ) 0.187 (p 0.010) -- (0.136) -0.296 (p<0.001) -- (0.861) -0.352 (p<0.001) Vitality (VT) -- (p 0.868) 0.238 (p 0.001) -0.178 (p 0.008) -0.213 (0.002) -- (p 0.855) -0.371 (p<0.001) Social function (SF) -- (p 0.239) 0.299 (p 0.004) -0.166 (p 0.024) -0.242 (p 0.001) -- (0.831) -0.202 (p 0.010) Role emotional (RE) -0.180 0.003 ) 0.158 (p 0.047) -0.157 (p 0.048) -0.233 (p 0.003) -- (0.531) -0.191 (p 0.016) Mental health (MH) -0.244 (p 0.001 ) -- (p 0.142) -- (p 0.142) -0.292 (p<0.001) -- (p 0.073) -0.254 (p 0.001) Physical Component Summary (PCS) -- 0.105 0.229 (p 0.001) -0.298 (p<0.001) -0.296 (p<0.001) -0.254 (p<0.001) Mental Component Summary (MCS) -0.203 (p 0.008 ) -- (p 0.068) -- (0.246) -0.255 (p 0.001) -- (0.122) -0.302 (p<0.001) FBM: fibromyalgia; DPR: depression Conclusion The recent accrual of organ damage, rather than its extent assessed in a single visit, is associated with impairment of different aspects of heath related quality of life, especially those mental related. Such phenomenon is similar to that observed in other systemic rheumatic disease, may be due to coping mechanisms. Disclosure of Interests None declared

Background Rheumatoid arthritis (RA) patients in a prolonged remission status represent a population whose future management has yet to be established. Treg cell function in patients with active RA is assumed to be impaired, a trend that seems to be reversed by TNFalpha antagonist therapy (aTNF). Theoretically a deeper remission may be represented by an immunological resetting of immune system, a condition which could enable to consider the possibility of a drug-free remission. Objectives To evaluate the incidence of disease flare after cessation of aTNF in pts in remission together with reconstitution of the CD4 +CD25highCD127low/- Tcell subset respect to those patients in the same remission status with persistent low CD4 +CD25highCD127low/-Tcell population, assuming the Treg populations as a markers of deep remission allowing a better selection of those patients at low-risk of flare after aTNF withdrawal. Methods inclusion criteria: patients with RA (>18 years) fulfilling the 1987 ACR classification criteria treated with aTNF and synthetic DMARDs for at least 12 months, in remission (DAS28 <2.6/DAS44 <1.6)>6 months, without glucocorticosteroid. Exclusion criteria:<18 years, glucocorticosteroids within the three months before; another inflammatory disease other than RA; ongoing infections. Intervention: aTNF drug withdrawal with continuation of DMARDs previously associated (MTX or LFN); a 24 months of follow up was performed. Serial clinical and instrumental evaluation, blood sampling and radiographs have been performed according to the scheduled protocol. Treg population and several cytokines/chemokines/growth factors were analysed (Human Cytokine/Chemokine Panel I, Millipore). Results 23 patients were included, mean age 53 years (SD 12.3), 68% RF +, 52% ACPA +, DAS28 medium 1.41 (SD 0.48); average duration of illness 9.62 years (SD ±5.73). During the 24 month post-suspension follow-up, for a total of 267 person-months, 11 patients presented a flare, for a flare rate of 3.74/100 person-months (CI95% 1.79–6.88). The average observed exacerbation time from aTNF withdrawal was 14.6 months (SD ±9.32). None statistical predictive value of Treg levels regarding disease outcome after aTNF withdrawal was observed IIR (95% CI) 1.38 (0.82–2.30). None significant correlation among cytokines concentrations and disease status/Treg levels was observed. A correlation was observed between the presence of a synovitis with PD1+* at the baseline and the loss of remission [HR 7.062 (1.64–30.41, p 0.009);*higher values were exclusion criteria]. All 3 patients with positive US (PD1) who had flare-up were asymptomatic at baseline. Conclusions 47.8% of pts maintained aTNF-induced remission at 24 months continuing only sDMARDs therapy (MTX). Only in 1 case reintroduction of Adalimumab did not allow to regain clinical remission, which was obtained using another therapeutic target (anti-CTL4). The presence of a residual synovitis, although mild (PD1), was correlated with the risk of exacerbation. Further results will be discussed. Reference [1] Kawashiri, et al. J Rheumatol2011;38(12):2517–21. Acknowledgements Study financed with funds from the Emilia-Romagna Region deriving from the ”Alessandro Liberati” young researchers in the framework of the. Region-University research program 2013 Disclosure of Interest None declared

Background The strategy for the choice of the second biologic agent after the failure of the first TNF inhibitor (TNFi) is still an unclear aspect in the treatment of both rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Switching between structurally different TNFis (from etanercept [ETN] to monoclonal antibody [mAb] or vice versa) has been proposed as a more effective procedure than switching among different mAbs, but to date no study has been specifically focused on exploring this topic. Objectives To evaluate the comparative 2-year retention rate and the 12-month efficacy of adalimumab (ADA) as second biologic agent in etanercept (ETN) non-responder RA and PsA patients in a multicentre retrospective study. Methods All RA and PsA patients from 11 Italian Rheumatology Units treated with ADA after a first-course ETN failure and with at least 12-month follow-up were retrospectively collected in a multicentre registry. Data analysis was limited to the period from January 2002 to May 2016. Two-year ADA retention rate was calculated by Kaplan-Meier method. 12-month ADA response was defined as achievement of disease activity score 28 calculated by using erythrosedimentation (DAS28-ESR) <2.6 (remission) or >2.6 and <3.2 (low disease activity, LDA). Sub-analyses according to reason for ETN discontinuation and concomitant methotrexate in RA and PsA patients have been performed. Results The study population (219 patients) included 117 RA (female 85.5%, mean [± standard deviation, SD] age 53.2±13.5 years, mean [±SD] disease duration 10.1±7.7; positive rheumatoid factor 70.2%; positive anti-citrullinated peptide antibodies [ACPA] 59.6%; mean [±SD] baseline DAS28-ESR 4.97±1.3; MTX users 64.9%) and 102 PsA (female 63.7%; mean [±SD] age 51.7±10.6; mean [±SD] disease duration 7.1±5.1; mean [±SD] baseline DAS28-ESR 4.4±1.1; MTX users 50%). The 2-year retention rate was 48.2% in RA and 56.5% in PsA patients, irrespective of reason for ETN discontinuation. Similarly, concomitant MTX was not associated with an increased drug survival in both RA (p=0.09) and PsA (p=0.969) subgroup. 12-month clinical remission and LDA were achieved respectively in 27.3% and 23.9% RA patients, and 27.4% and 23.5% PsA patients. Conclusions In our large real-life cohort, the use of ADA in primary and secondary ETN failures was highly effective in both RA and PsA patients, with more than 50% of ADA treated patients achieving remission or LDA. Reasons for ETN discontinuation were not associated with different ADA clinical response, as well as concomitant MTX. Disclosure of Interest None declared

Background Despite adavantages of biological combo therapy over biological mono for RA treatement and the limited approval of biologics as monotherapy (etanercept, adalimumab, certolizumab, tocilizumab), real life registries data revealed that approximately one-third of patients taking biologic agents are using them as monotherapy. Objectives To assess the prevalence of bDMARDs use as monotherapy (bDMARDs-mono) in a cohort of RA patients treated with bDMARDs attending a tertiary rheumatological center.To characterize the clinical profile of these patients, and to investigate factors related to monotherapy. Methods All patients with Rheumatoid Arthritis attending our center and receiving bDMARDs up to 31th january 2015 were retrospectively analyzed. Demographic, and clinical characteristics of each patient were recorded: age, gender, disease duration, drugs history and clinical disease activity (DAS28) at last visit. Results 341 RA patients receiving bDMARDS were included. F 160, M 123, mean age 59.98 ±12.54, disease duration 178.69±101.81 months. 197 patients were taking bDMARD as first line bio-therapy, 144 had been previously treated with one or more bDMARDs. 52% (n=179) of patients were receving bDMARD-mono with a mean disease duration 187.4±125.1 month; 48% (n=162) were bDMARDs-combo, 65% of them with MTX; mean disease duration 168.9±42.4 m. Biologic agents used as mono or combo are shown in table 1. 32% of bDMARDs-mono had discontinued csDMARDs before starting biological therapy, 68% after an average 50,4 months after starting bDMARDs (p<0.001). The most common reasons for discontinuing csDMARDs were toxicity (55% of cases), with significant difference between those who stopped before and after starting bDMARDs (66% vs 48% respectively, p<0,02). 11% of patients discontinue csDMARDs because of nonspecific bad tolerance, 9% for inefficacy, 11% for others unspecified reasons. 25 patients (14%) on bDMARDs-mono stopped csDMARDs for clinical remission. Overall, 57% of RA patients were in clinical remission (DAS28 PCR <2.6) at the time of the inclusion in the study, without significant differece between the two groups (bDMARDs-mono vs combo). The use of bDMARDs-mono was more frequently observed in those patients with disease duration longer than 10 years (p<0,0001). Conclusions Biologic monotherapy for managing RA is widely used in our clinical practice especially in patients with long term disease. The proportion of patients (1/3) who start bDMARD-mono is quite similar to that reported in literature. On the other hand, most of patients arrive to bDMARDs-mono after starting biologic agent as the result of csDMARD witdrawal due to AE or intollerance to DMARDs and to a lesser extent because achieving good control of the disease since patient9s preference is strongly oriented to csDMARD discontinuation rather than bDMARDs withdrawal or tapering. References Emery P, et al. Ann Rheum Dis 2013:Dec:72 (12):1897–904. Disclosure of Interest None declared

Background PM-Scl antibodies (abs) belong to the group of myositis-associated antibodies and typically determine a nucleolar or speckled pattern on immunofluorescence. These abs found in patients (pts) with Scleromyositis and, less frequently, in isolated forms of Systemic sclerosis (SSc), Polymyositis (PM) and Dermatomyositis (DM). In SSc pts PM-Scl +, pulmonary involvement seems less severe, while they show more frequent arthritis. Raynaud9s phenomenon (RP), digital ulcers (DU) and gastroesophageal involvement appear to be less frequently expressed. In myositis the association with esophageal and lung involvement is well known. Objectives To characterize demographic and clinical features of a single center series of PM-Scl positive patients. Methods Sera from 48 SSc and 60 idiopathic inflammatory myophaties (MII) attending local outpatient clinic, detected with EUROIMMUNE Myositis Profile 4 kit, were tested to search PM-ScL antibodies. Demographic, laboratory and clinical data (RP, arthritis, DU, muscular involvement, disphagia) were retrospectively retrieved from available clinical charts. The presence of interstitial lung disease (ILD), was evaluated by HRCT (measured by using score of Goh for the extension) and functional respiratory testing (FVC and DLCO). Severe ILD was defined by: Goh score of>20 and FVC and DLCO <75%. Results 23 Pts (18 F) resulted positive for PM-Scl. The mean age was 60.5±9.4 years and the mean disease duration was 145.9± 76.3 months. 1 patient had negative ANA, 1 showed ANA anticentromere and 1 dot pattern; the remaining 20 patients (86,9%) were ANA+ showing nucleolar pattern. By applying available formal classification criteria 5 (21.7%) pts were diagnosed as DM, 2 (8.7%) as DM amyopathic, 3 (13.05%) as overlap Scleromyositis, 3 (13.05%) as PM, 1 (4.4%) as cancer associated PM, 9 (39.1%) as SSc (2 diffuse, limited 6, intermediate 1). 13 (56.5%) pts had no evidence of cytopathic muscle involvement (defined as normal CPK, myoglobin and LDH). 5 pts (21.7%) presented a Goh score >20, 1 FVC <75%, and 7 (30.4%) DLCO <75%. 4 pts presented arthritis. 14 (60.8%) had RP, 6 (26%) DU, 8 (34.8%), dysphagia (see images 1). When compared with patients with SSc and MII negative for PM-Scl, MII PM-Scl + pts did not show significant greater risk of developing ILD (Goh>20)dysphagia or minor muscle involvement. SSc PM-Scl + pts seem to have a greater risk of developing arthritis and DU than their corresponding SSc PM-Scl negative pts (p<0.05) while no differences did emerged about ILD (Goh>20) and dysphagia. Conclusions The role of PM-Scl as a risk factor for ILD in MII pts is not confirmed, but should be considered the positivity in the control group of Jo1, representing per se a major risk factor for this complication (image 2). For patients with SSc is confirmed the role of PM-Scl as a risk factor for arthritis and digital ulcers but not for ILD. References Long-term out come of patients with polymiositis/dermatomyositis and anti PM/Scl antibody. Marie et al. Journal of Dermatology 2010; 162(2): 337–44 Disclosure of Interest None declared

Background the overlap syndrome Systemic sclerosis-rheumatoid arthritis (SSc-RA) is characterized by the presence in the same patient of clinical and laboratory features that meet the classification criteria for both diseases. The current literature shows how that lung involvement is more frequent and severe in SSc-RA than in SSc alone [1]. Objectives to describe the frequency of clinically significant interstitial lung disease (ILD), determining the reduction of the forced vital capacity (FVC) or the alveolar-capillary diffusion of carbon monoxide (DLCO) in a group of 25 patients with SSc-RA compared to a control group of 570 patients with SSc alone. Methods data were retrieved from a database and from medical records of patients followed at the outpatient clinic dedicated to SSc of the Rheumatology Unit of S. Anna Hospital, Ferrara. All patients fulfilled the classification criteria for SSc (ACR 1980 and LeRoy 2001) and RA (1987). For both groups (SSc and SSc-RA) the following seroimmunologic data were assessed: anticentromere antibodies (ACA), anti topoisomerase 1 (Scl 70), rheumatoid factor (RF) and anti-citrulline (ACPA). Pulmonary involvement was assessed by high-resolution chest CT scan using the score of Warrick, and spirometry including DLCO. A cut-off of Warrick9s score able to detect patients with ILD has been identified by the application of a regression curve between the total score at HRCT and spirometry data (FVC and/or DLCO <75% as predicted); the analysis identified a value>10 able to alter lung function. Results in the SSc control group FR was available in 38% of cases and ACPA only in 8.9% RF and ACPA were available in all 25 SSc-RA patients. Positivity for both FR and ACCP was detected in 23 SSc-RA patients whilst 2 were seronegative. ILD was more frequent in SSc-RA group compared to SSc (76% VS 33%, p<0.05, OR 6.43). The SSc-RA/ACA + group presented a higher frequency of ILD than in SSc/ACA + (54.5% VS 21.7%, p<0.05, OR 4:33) as if the known protective role of the ACA for the development of ILD was less relevant in SSc-RA. In the SSc group, the positivity of the RF seems to be associated with the risk of developing ILD only in patients ACA/Scl 70 negative (72% vs. 28%, p<0.05, OR 6.3). Due to missing data it was not possible to perform the analysis for the ACPA in SSc group. Conclusions an increased risk of ILD in SSc-RA compared to SSc was confirmed. In SSc-RA group, ACA seems to lose its role as a “protective” factor against the possible development of pulmonary fibrosis. If this information is confirmed, in SSc-RA patients, despite their ACA positivity, it could justify a more “tight” clinical-instrumental follow-up, to detect lung involvement early and to monitor its evolution. References Systemic sclerosis-rheumatoid arthritis overlap syndrome: a unique combination of features suggests a distinct genetic, serological and clinical entity. Szücs G, Szekanecz Z, Zilahi E et al. Rheumatology (Oxford). 2007 Jun;46(6):989-93 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5137

Background Adult onset Still9s disease (AOSD) is a rare rheumatic disease with an estimated prevalence of less than 1 case per 100,000 population. The diagnosis is difficult and is often delayed due to the lack of specific diagnostic tests and the need to rule out other pathological entities. Objectives To describe the clinical characteristics of a multicenter Italian case series of patients with AOSD. Methods 14 Italian University Hospital centers participated in the study. A standardized medical record containing clinical data, laboratory investigations, disease patterns and the different therapies has been sent to all participating centers. Each center collected data retrospectively. Results In the first wave of data collection, from March to May 2013, 233 patients were included with AOSD according to Yamaguchi criteria (125 males, 53.6%, mean age at onset: 40.2±16.2 years, time between onset and diagnosis: 242±650 days). The most frequent manifestations at onset were: arthralgia (93.0%), fever (92.6%), leukocytosis (89.0%), typical rash (67.7%), sore throat (61.8%), lymphadenopathy/splenomegaly (60.4%), increased liver enzymes (53.5%). In 56.4% of patients ferritin was increased more than 5 times the normal threshold. Fever intensity was recorded up to 41 ° C (mean 39.1±0.7), with a single daily peak in 27.3% of cases and 2 peaks in 51.9% of cases. The average duration of febrile episodes was 10.3 days with variable interval between episodes (average 3.2 days). Based on clinical evolution the disease was classified polycyclic systemic in 40.8%, chronic articular polycyclicin 30.7%, systemic monocyclic in 23.9% and chronic articular monocyclic in 4.6%. In 21.9% of cases, corticosteroids and traditional DMARDs have not been able to control the disease while biological drugs have been shown to be effective. 56 cycles of biological drugs were used in 51 patients: anakinra in 22 cases, etanercept in 15 cases, infliximab in 8 cases, adalimumab in 7 cases, rituximab in 3 cases, tocilizumab in 2 cases, abatacept and golimumab in 1 case each (anti- TNFalpha 52.5%, 37.3% anakinra, other 10.2%). Conclusions This study presents the largest Italian multicentre series of AOSD patients. The main clinical and laboratory characteristics are in line with those reported in the literature. In more than 20% of patients biologics are the only drugs that allow to control the disease. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5300

INTRODUCTIONDigital ulcers (DU) occur in about 50% of systemic sclerosis (SSc) patients. Scleroderma DU are responsible for chronic pain and disability with the need of systemic and local treatments. Recently, capillaroscopic skin ulcer risk index (CSURI) has been validated as useful tool in predicting the appearance of new scleroderma ulcers and/or persistence of non-healing lesions, within 3 months from capillaroscopy evaluation.OBJECTIVESSince the image length of 1.57 mm might represent a critical factor for CSURI calculation, the present study aimed to evaluate the reliability of CSURI using three different videocapillaroscopy devices with distinct image widths.METHODSOne hundred and seventy-six unselected SSc patients were consecutively enrolled for the study during a six-month period, using three different capillaroscopy devices (image widths of 1.33, 1.57, and 1.70 mm).RESULTSAfter a three month-follow-up new DU or persisting non-healing ulcers were observed in 46/176 patients (26.1%). The receiver operating characteristic curve analysis for CSURI showed an area under curve respectively of 0.705 for the image width of 1.33 mm, 0.786 for the image of 1.70 mm, and 0.888 for the image width of 1.57 mm.CONCLUSIONSThe good sensitivity, specificity and positive predictive value of CSURI was confirmed in the whole patients' series, as well as in the three subgroups on different image widths obtained with various available devices. In addition, the negative predictive value of the capillaroscopic index remained very high regardless of the picture length adopted.

OBJECTIVES:To estimate, using both the American College of Rheumatology-ACR 1980 classification criteria and revised LeRoy and Medsger 2001 criteria, the incidence and prevalence of systemic sclerosis (SSc) in an area in north-eastern Italy with a referral base population of about 346,000 inhabitants.METHODS:Retrospective examination of all patients 16 years and older of native Italian origin and resident in the Ferrara district who had either been admitted to hospital or referred to our outpatient clinic with a diagnosis of SSc between 1st January 1999 and 31st December 2007. SSc subjects were identified both by a search of hospital discharge code 710.1, as per the international classification of disease-9 codes, and using a computerised search for this pathology code in the national health care system. The subjects referred to our outpatient clinic were identified from a dedicated data base. Incidence and prevalence rates were calculated as the number of cases per 100,000 inhabitants (population data based on the October 2001 national census). The medical records of each potential case were accurately examined and reviewed by the same physician who determined whether those patients identified as having a diagnosis of SSc did indeed meet the ACR 1980 classification criteria for SSc and/or the LeRoy and Medsger 2001 criteria.RESULTS:After reviewing all cases, of the 118 patients meeting the LeRoy-Medsger 2001 criteria, only 88 patients had a definitive diagnosis of SSc according to the ACR 1980 criteria. Considering the ACR criteria, the prevalence rate was 25.4 cases per 100,000 (95% CI: 22.2-28.6), and the annual incidence rate over the study period was 3.2 per 100,000 (95% CI: 2.0-4.4). Considering the LeRoy and Medsger criteria epidemiological data were respectively 34.1 cases per 100,000 (95% CI: 30.4-37.8) and 4.3 cases per 100,000 (95% CI: 3.0-5.6). According to the LeRoy and Medsger criteria, the SSc subsets were broken down as follows: 20 limited-SSc (19.2%), 76 limited cutaneous-SSc (62.1%), 22 diffuse cutaneous-SSc (18.7%). The female/male ratio was 9.7:1.CONCLUSIONS:Incidence and prevalence of SSc observed in an area in north-eastern Italy were found to be higher than reported in the various geographical area (UK, US, Australia, etc.) but similar to another Italian study adopting, as here, the LeRoy-Medsger criteria. The different diagnostic criteria adopted may explain some of the differences found in comparison to the studies based only on the ACR criteria, however, regional discrepancies in disease occurrence cannot easily be dismissed only on the basis of methodological approaches to case definition or ascertainment; genetic, ethnic and environmental factors should also be considered. Currently the main challenge remains to determine the scientific basis for the observed differences, distinguishing between changes deriving from geographic/ethnic features and from the analytic methods.

To evaluate the prevalence of headache and its different patterns in patients with Behçet's disease (BD) with and without neurological involvement and to investigate clinical correlations.Patients fulfilling the International Study Group criteria for Behçet disease (ISGc) were studied. Patients were invited to fill a "headache questionnaire", which consisted of two sections: the first one included demographic and anamnestic data, family history for both headache and BD, disease duration and clinical manifestations of BD; the second section included items about headache, investigated accordingly to International Headache Society diagnostic criteria (IHS, 2004). Clinical history and current comorbidities-medications were collected. Each patient underwent a neurological examination to assess neurological involvement (Neuro-BD) and, if necessary, instrumental investigations. One hundred-fifty healthy subjects matched for age and gender were used as control group for comparison.Of the 55 patients diagnosed as BD (ISG criteria) 41 patients adhered and were enrolled into the study. Headache occurred in 29 of BD patients (70,7%) and in 13 of Neuro-BD patients (92,8%). Migraine without aura did prove the most frequent type of headache in BD patients (with and without neurological involvement) and there were no differences in the frequency of the different pattern of headache between BD patients and controls.Headache is a frequent manifestation in BD and primary headache like migraine emerged as the most frequent type of headache. A careful search for headache should be included in the diagnostic work-up of BD since this manifestation may be related to the underlying disease.

Objective: To evaluate the prevalence of headache and its different patterns in patients with Behcet's disease (BD) with and without neurological involvement and to investigate clinical correlations.Methods: Patients fulfilling the International Study Group criteria for Behcet disease (ISGc) were studied. Patients were invited to fill a "headache questionnaire", which consisted of two sections: the first one included demographic and anamnestic data, family history for both headache and BD, disease duration and clinical manifestations of BD; the second section included items about headache, investigated accordingly to International Headache Society diagnostic criteria (IHS, 2004). Clinical history and current comorbidities-medications were collected. Each patient underwent a neurological examination to assess neurological involvement (Neuro-BD) and, if necessary, instrumental investigations. One hundred-fifty healthy subjects matched for age and gender were used as control group for comparison.Results: Of the 55 patients diagnosed as BD (ISG criteria) 41 patients adhered and were enrolled into the study. Headache occurred in 29 of BD patients (70,7%) and in 13 of Neuro-BD patients (92,8%). Migraine without aura did prove the most frequent type of headache in BD patients (with and without neurological involvement) and there were no differences in the frequency of the different pattern of headache between BD patients and controls.Conclusions: Headache is a frequent manifestation in BD and primary headache like migraine emerged as the most frequent type of headache. A careful search for headache should be included in the diagnostic work-up of BD since this manifestation may be related to the underlying disease.

OBJECTIVES:Visceral leishmaniasis (VL) is an extremely rare example of opportunistic infection in patients treated with TNF-alpha antagonists and only a few cases have been described. In this paper risk factors, clinical features, diagnostic work-up and outcome of patients developing VL under biologic therapy are described.METHODS:Case report and review of the published cases of VL in patients under biologic treatment.RESULTS:We retrieved six patients, including ours, all of whom presented anarchic fever and pancytopenia. In 5 cases, splenomegaly was detected. The same number of patients came from endemic areas for VL. In the majority of the cases a bone marrow examination was not diagnostic, requiring the performance of a second one and/or the execution of other diagnostic tests. One fatal outcome was observed.CONCLUSION:Even if VL represents a sporadic complication of biologic treatments, its presence should always be suspected in patients developing a triad of signs and symptoms constituted by fluctuant fever, pancytopenia and splenomegaly, especially if coming from endemic areas. In these cases an extensive diagnostic work-up must be warranted. Atypical and confusing features may resemble autoimmune diseases at presentation and during the course of the illness.

Objectives: To describe an unusual case of Whipple disease (WD) with confusing clinical features at onset and to discuss the diagnostic challenges for the clinician.Methods: Description of a new case of this rare disease and thorough discussion of the atypical clinical manifestations at onset. A literature review, concerning the unusual onset, by means of a MEDLINE search from 1966 to 2007 was done.Results: A 39-year-old man with Sudden bilateral blurred vision due to retinal vasculitis and concomitant rapidly evolving symmetrical neurosensory bilateral hearing loss as initial features of WD is described. Due to the clinical manifestations resembling systemic vasculitis, high-dose corticosteroid and pulse cyclophosphamide therapy were started with Subsequent appearance of gastrointestinal symptoms (diarrhea and weight loss) and spiking fever, suggesting superimposed infection. After a complete evaluation, including gastroscopy, extensive duodenal-jejunal mucosal involvement was seen, while diffuse infiltration of the duodenal lamina propria with periodic acid-Schiff-positive foamy macrophages was observed on the histological sample. The diagnosis was confirmed by reverse transcriptase-polymerase chain reaction for the DNA of Tropheryma whippelii. To Our knowledge, no previous similar clinical onset of WD has been described.Conclusions: To avoid misdiagnosis and therapeutic mistakes, Clinicians Should be aware of unusual presentations of WD. Because this etiological agent is a difficult to Isolate bacterium, diagnosis may, be especially problematic in cases without intestinal involvement at onset. (C) 2009 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 38:403-406