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Dear Editor, A potential association between rituximab and more severe COVID-19 outcomes has been previously raised, based on case reports, retrospective studies and mostly declarative registries.1–4 To further investigate this association, we focused on patients with inflammatory arthritides (IA) receiving intravenous biological agents at day hospitals to limit selection and recall bias, as well as missing data. All patients with IA treated in day hospitals with intravenous biological agents (rituximab, abatacept, infliximab or tocilizumab) in seven clinical centres in France (Strasbourg, Colmar, Mulhouse, Nancy, Reims, Clermont-Ferrand and Saint-Antoine hospitals in Paris) were enrolled in the study. Data were collected from 1 September 2019 (5 months before the outbreak of the epidemic in France, so that all enrolled patients had been exposed to a biologic prior to the start of the epidemic) to 1 January 2021.3 In each centre, we obtained the list of all patients receiving intravenous biological agents from the hospital pharmacist. Therefore, all patients receiving one of the four drugs within the time frame of the study were enrolled in each centre. The occurrence of hospitalised COVID-19 was the primary outcome criterion, that is, SARS-CoV-2 presence confirmed by PCR and resulting in hospitalisation or death. Data were analysed with Bayesian methods in univariate and multivariate analyses …

ObjectiveTo investigate outcome and course of pregnancies in women with axial spondyloarthritis (axSpA) in a pooled data analysis of pregnancy registries in rheumatology.MethodsProspectively followed women with axSpA, fulfilling ASAS classification criteria and for whom a pregnancy outcome was reported, were eligible for the analysis. Anonymised data of four registries was pooled. Rates of adverse pregnancy outcomes were calculated. Systemic inflammation, disease activity and treatment patterns with tumour necrosis factor inhibitor (TNFi) before, during and after pregnancy were analysed.ResultsIn a total of 332 pregnancies from 304 axSpA women, 98.8% of the pregnancies resulted in live birth. Mean maternal age was 31 years and disease duration 5 years. Most of these patients received pre-conception counselling (78.4%). Before pregnancy, 53% received TNFi treatment, 27.5% in first and 21.4% in third trimester. Pregnancy and neonatal outcomes were favourable with rates of 2.2% for pre-eclampsia, 4.9% for preterm birth, 3.1% for low birth weight and 9.5% for small for gestational age. Neonates were delivered by caesarean section in 27.7% of pregnancies, of which 47.4% were emergencies. Pooled mean CRP was 4 mg/L before conception peaking in the second trimester at 9.4 mg/L. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was below 4 at all time-points.ConclusionsPooled rates of most outcomes were better than what had been reported in the literature and within expected rates of those reported for the general population. Pre-conception counselling, planned pregnancies and a tight management in expert centres applying a tailored treatment approach may have contributed to the favourable pregnancy outcomes.

ObjectivesTo describe current management and outcome of native joint septic arthritis (NJSA) in French rheumatology departments.MethodsFor this retrospective, nationwide multicentric study, 127 French rheumatology departments were contacted to report up to 12 cases of NJSA that occurred between 1 January 2016 and 31 December 2017. Characteristics, diagnosis procedures, therapeutic management and outcome were recorded.ResultsOverall, 362 patients were included (mean age 64.0±18.6 years, median Charlson comorbidity index 3.5 (0–14)). Knee was the most frequent site (n=160 (38.9%)), andStaphylococcussp (n=185 (51.4%)), the most frequent pathogen. All patients received antibiotics for a mean duration of 46.8 (±22.0) days, including intravenous route for a mean of 17.2 (±15.4) days. Management was heterogeneous. Surgical procedure was performed in 171 (48.3%), joint immobilisation in 128 (43.8%). During follow-up, 91 (28.3%) patients have had serious complications and 28 (9.2%) of them died. Factors associated with 1-year mortality were age (OR 1.08, 95% CI 1.04 to 1.13; pStaphylococcus aureusNJSA compared withStreptococcussp. NJSA (OR 7.24, 95% CI 1.26 to 41.68, p=0.027). The complete recovery with no adverse joint outcome at 1 year was observed in n=125/278 patients (55.0%).ConclusionPrognosis of NJSA remained severe with a high rate of morbimortality. Its management was very heterogeneous. This study highlights the importance of the new French recommendations, published after the completion of the study, in order to facilitate NJSA management.

We would like to thank Coiffier and colleagues for their attention to our paper.1 2 Dryness in systemic sclerosis (SSc) may …

Background:Ultrasonography (US) can detect more erosions than radiography (RX) at the joint level in rheumatoid arthritis (RA), especially at an early stage of the disease.Objectives:The aim of the study is to determine the ability of ultrasonography to detect erosion progression by the US Score for erosions (USSe), in early (less than 2 years disease duration (DD)) and late stage (more than 2 years DD) RA over two years of follow-up.Methods:Patients fulfilling ACR 1987 and/or ACR/EULAR 2010 criteria for RA were prospectively included. Clinical and demographic informations were recorded at baseline and hands and feet RX were scored according to the Sharp erosion score (SHSe). Erosive RA on RX was defined by the presence of at least three eroded joints (1). US examinations were performed at baseline and during the two years of follow-up. Erosions were scored by US on six bilateral joints (MCP 2, 3, 5 and MTP 2, 3, 5) with a four grade-scale to calculate total USSe. Erosive RA on US was defined by presence of one erosion ≥ 2mm (2). Inter-examiner reproducibility was performed on 14 patients in order to calculate the smallest detectable change (SDC), which was 2.3. Ultrasonographic progression was defined as a change in USSe > 2 (erosion change > SDC).Results:A total of 71 patients were included, 22 patients (31.0%) had early RA and 49 (69.0%) patients had late RA diseases. On RX, 30 (42.3%) patients were erosive at baseline with a mean SHSe at 29.4 (SD at 24.7). On US, 63 patients (88.7%) were classified as eroded. On US, erosions prevailed at baseline in MTP5 joints, then MCP2 and MCP5 joints on their lateral facets. During follow-up, 28 patients (39.4%) were classified as US progressors, 30 (42.3%) were stable and 13 (18.3%) considered as regressors (figure 1). In early RA disease, three of the four non eroded patients became eroded. USSe progressed in 11 patients (50%) while regression was observed in only one patient. In late RA disease, 17 patients (34.7%) progressed and 12 patients (24.5%) decreased significantly their USSe. Erosion progression prevailed on MTP 5 joints followed by MCP2 and finally MCP5 joints (figure 2).Figure 1.USSe progression plots (n=71)Figure 2.Differences of USSe by joints during follow-up in early and late RAConclusion:US structural examination is a highly reproducible method to assess erosion in RA disease. The USSe is able to detect structural changes (progression, stabilization and regression) in RA patients during a follow-up of two years especially in RA patients with short disease duration.References:[1]Van der Heijde D, van der Helm-van Mil AHM, Aletaha D, Bingham CO, Burmester GR, Dougados M, et al. EULAR definition of erosive disease in light of the 2010 ACR/EULAR rheumatoid arthritis classification criteria. Ann Rheum Dis. avr 2013;72(4):479‑81.[2]Roux C, Gandjbakhch F, Pierreisnard A, Couderc M, Lukas C, Masri R, et al. Optimization of ultrasonographic examination for the diagnosis of erosive Rheumatoid Arthritis in comparison to erosive hand Osteoarthritis. Eur J Radiol. sept 2019;118:10‑8.Disclosure of Interests:None declared

Background:Objectives:To describe current management and outcome of septic arthritis on native joint in French rheumatology departments.Methods:Retrospective, nation-wide multicentric study. 127 French rheumatology departments were contacted to report 10 successive cases of septic arthritis on native joint that occurred between the 01/01/16 to 31/12/17 (excluding mycobacteria). Characteristics, diagnosis procedure, therapeutic management and outcome were recorded.Results:52 centers included 363 patients (mean age 64± 18.7 years, mean Charlson comorbidity index 4±3). 28.3% patients had a preexisting arthropathy on affected joint. Monoarthritis was observed in 89.6% patients, knee was the most frequent site (38.9%). The most frequent pathogens wereStaphylococcus sp(50.7%) andStreptococcus sp.(23.3%). Bacteremia was found in 156 (45.1%) patients and endocarditis in only 12 (3.0%). Management was heterogeneous. All patients received antibiotics for a mean duration of 46.7±22 days (including intravenous route: 17.3±15.4 d). An initial monotherapy was administered in 42.3% of patients. Surgical procedure (mostly lavage 70.6%) was performed in 171 (48.3%), joint immobilization in 128 (35.3%) (median duration of 21.7±14.1 days). 94 (29.2%) patients have had serious complications including 29 (9.5%) death. Factors associated with death are reported in the table.Conclusion:This study shows that management of septic arthritis is very heterogenous with a still high rate of morbidity and mortality. We identified age, comorbidities, bacteremia and recent antibiotherapy were associated with mortality. Of note, duration of antibiotics was not. Thus, new guidelines are needed in order to facilitate septic arthritis management.Table:FactorsSurvivor(N=276)Dead(N=29)Univariate analysispAdjusted Odds ratio (95%IC)Multivariate analysispAge65 (16-97)82 (32-98)1,07 (1,03-1,12)< 0.001Charlson’s index1 (0-12)2 (0-9)0,00011,3 (1,05-1,63)0,018Delay before antibiotic initiation8,5 (0-310)5 (0-75)0,04840,99 (0,96-1,02)0,562Corticosteroid in the previous 3 months13,9%33,3%0,01842,56 (0,75-8,74)0,133Bacteriemia42,4%71,4%0,00615,07 (1,4-18,370,013Antibiotics in the previous 3 months26,6%56,6%0,00566,7 (2,04-22,01)0,002Disclosure of Interests:Pauline Richebé: None declared, Sophie Godot: None declared, Guillaume Coiffier: None declared, Pascal GUGGENBUHL: None declared, Denis Mulleman: None declared, Marion Couderc: None declared, Emmanuelle Dernis Speakers bureau: Lilly, Novartis, Valentine Deprez: None declared, Carine Salliot: None declared, Saik Urien: None declared, Rachel Brault: None declared, Adeline Ruyssen-Witrand Grant/research support from: Abbvie, Pfizer, Consultant of: Abbvie, BMS, Lilly, Mylan, Novartis, Pfizer, Sandoz, Sanofi-Genzyme, Emmanuel Hoppe: None declared, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Christian Roux: None declared, Sebastien Ottaviani: None declared, Maxime Breban: None declared, Marie Beaufrere: None declared, Alexia Michaut: None declared, Loic Pauvele: None declared, Christelle Darrieutort: None declared, Daniel Wendling: None declared, Pascal COQUERELLE: None declared, Géraldine Bart: None declared, Elisabeth Gervais: None declared, Vincent Goeb: None declared, Marc Ardizzone: None declared, Edouard Pertuiset: None declared, Sophie Derolez: None declared, Jean Marc Ziza: None declared, René-Marc Flipo Consultant of: Johnson and Johnson, MSD France, Novartis, Sanofi, Speakers bureau: Johnson and Johnson, MSD France, Novartis, Sanofi, Raphaèle Seror Consultant of: BMS UCB Pfizer Roche

Gjika et al 1 recently reported the non-inferiority of 2-week versus 4-week antibiotic therapy after systematic surgical washing (with or without synovectomy) in the management of septic arthritis. Although this randomised, controlled trial adds important new insights to the management of patients with infectious arthritis, it has several drawbacks that limit generalisation of the results. First, the patients included in this study were not representative of a usual population of native joint septic arthritis patients. These patients had mainly septic arthritis affecting the small joints (metatarsophalangeal, metacarpophalangeal and proximal interphalangeal joints in 85% of cases). Moreover, in most cases, contamination occurred after direct inoculation following skin invasion (bite/scratch or post-traumatic), with only 4% of patients with systemic signs of infection. Finally, patients were included on the basis of having been treated with surgical drainage, the indications for which are largely centre dependent. These characteristics are probably explained by the monocentric design of the study. Native joint septic arthritis affects mainly …

Background Renal impairement in spondyloarthritis (SpA), although uncommon, may include secondary renal amyloidosis (AA type), non-steroidal anti-inflammatory drug (NSAID) nephropathy, and glomerulonephritis. Data on the prevalence of renal impairement in SpA are relatively rare and usually come from small or retrospective studies. Objectives To assess the prevalence and associations of renal dysfunction in patients with SpA. Methods COMOSPA was an international (22 participating countries from four continents) multicentric study on comorbidities in SpA. Renal function was assessed from the estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation. SpA characteristics, risk factors for renal impairment were collected. NSAID use was assessed by the currently (last 3 months) intake. Logistic regression models were constructed from variables which were significantly associated with an eGFR of 2 or clinically relevant. Results Of the 3984 recruited patients, after excluding of outliers and patients for whom eGFR was not available, 2098 (52.6%) were analysed (male gender: 63.5%; age: 45.3 years; disease duration: 8.6 years; HLAB27+: 53.7%; BASDAI: 3.6/10). A total of 153 patients (5.2%, mean age 53.6 years) had an eGFR 2 . In univariate analysis, renal impairment was associated with age (p Conclusions Renal impairment is not rare in SpA and is associated with age, disease severity and inflammation but not with cardiovascular risk factors or NSAID currently use. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) is a risk factor for septic arthritis (SA), and anti-TNF therapy doubles the risk of SA. Objectives The purpose of this study was to see whether the frequency and features of SA complicating RA have changed over the last 35 years. Methods This retrospective single-center study included the full register of all patients hospitalized at the rheumatology department of Clermont-Ferrand – CHU between 1979 and 2013 for septic arthritis bacteriologically documented by synovial fluid and/or blood culture samples. The periods 1979–2002 (period before biotherapies) and 2003–2013 (last decade in the era of biotherapies) were compared. Results Between 1979 and 2013, 64/514 (12.5%) SA presented with a RA – 21/153 (13.7%) in the 2003–2013 period and 43/361 (11.9%) in the 1979–2002 period. Over the past decade, median age of SA–RA patients increased (61 vs 68 years; p vs 40%). The features of the RA remained unchanged: history (18 years (8–29) vs 16 (8–25)), rheumatoid factor (95% vs 87%), and corticosteroids (91% vs 81%) at the same mean dose (10 mg/d). 71% in the period before biotherapies and 63% in the last decade received a DMARD. Over the last decade 24% ( vs 0; p vs 37%; p S. aureus infections had stabilized (62% vs 74%) in SA-RA patients but was higher than SA-non-RA (47% and 53%). MRSA infections became more frequent in SA-RA (31% vs 6%; p vs 16%; ns). Gram-negative bacilli infections have tended to become more frequent (19% vs 5%; p =0.08). Blood cultures less often tested positive (29% vs 47%; ns). Mortality rates has fallen slightly (5% vs 9%; ns), in contrast to SA-non-RA cases (7% vs 6%; ns). Conclusions This study brings reassuring findings – in the era of biotherapies, the frequency of septic arthritis complicating rheumatoid arthritis has stabilized, and the most severe septic polyarticular forms are on the decline. Disclosure of Interest None declared

Background Fibromyalgia (FM) is a prevalent syndrome in patients with inflammatory rheumatic disease. Objectives The purpose of this study was to evaluate and compare the prevalence of FM in various inflammatory rheumatic diseases. Methods This single-center cross-sectional study was conducted between September 2014 and April 2015. We screened for clinical signs of fibromyalgia in all patients presenting for rheumatoid arthritis (RA), spondyloarthritis (SpA), and connective tissue disease (Sjogren9s syndrome (SS), systemic lupus erythematosus (SLE), scleroderma (Scl), myositis). Diagnosis of FM was based on ACR–90 classification criteria (to minimize interfering overlap between rheumatic disease-related pain and FM-related pain) and expert opinion. Results In total, 691 patients were included in the study: 325 RA, 298 SpA (59 psoriatic arthritis, 137 radiographic axial SpA, 64 non-radiographic axial SpA, 38 peripheral SpA), 28 SLE, 27 SS, 14 Scl, and 6 myositis. The population counted 451 women (65.3%) and 240 men (34.7%). Mean all-population age was 55.8±15.5 years. Median disease duration was 11 years [IQR 5–20]. In the total population, 55 patients (8%) met the ACR–90 criteria, and 97 patients (14%) were given a diagnosis of FM by the expert doctor. Prevalence of FM meeting ACR–90 criteria was 4.9% in RA, 11.1% in SpA, and 11.3% in connective tissue disease, and was significantly higher in the SpA group than in the RA group (p=0.05). The expert settled on a diagnosis of FM for 7.7% of patients with RA, 17.5% of patients with SpA, and 28.2% of patients with connective tissue disease. The expert diagnosed significantly more FM in SpA (p=0.003) and connective tissue disease (p=0.001) than in RA. Conclusions Concomitant fibromyalgia is prevalent in inflammatory rheumatic disease, especially in spondyloarthritis and connective tissue disease. The expert doctor makes the diagnosis of fibromyalgia more often than ACR–90 criteria. Disclosure of Interest None declared

Background While several registries have already evaluated the retention of first-line anti-TNF therapy in RA, divergent conclusions have at times been reported. Following treatment failure with a first-line anti-TNF agent, a non-TNF-targeted biologic is recommended rather than a second anti-TNF drug. Objectives This study sought to compare the retention rate (RR) of a first-line anti-TNF treatment in routine care and in patients with inadequate or insufficient response the RR of either a second-line anti-TNF drug or a non-TNF-targeted biologic, in a monocenter cohort from Auvergne. Methods All RA patients treated with anti-TNF between 2008 and 2015 were enrolled. Results In total, 200 RA patients were analyzed, including 37 men and 163 women (81.5%). The mean age was 55.1 ± 13.1 years and disease duration was 8 years [3–15]. 89 (70.1%) patients had RF and 75 (72.8%) anti-CCP antibodies; 96 cases were erosive (69.6%). DAS-ESR was 4.87 ± 1.30. The first-line anti-TNF drugs were etanercept (ETA) (61%), adalimumab (ADA) (24%) or infliximab (IFM) (15%), either as monotherapy (14.6%) or associated with a DMARD (85.4%) (MTX: 64.5%). 131 patients had corticosteroids (mean dose: 7.5 mg/day). At 6 months, 73.8% were EULAR responders (27.8%: moderate; 46%: good). The overall median retention time (RT) was 55.1 months (ADA: 73.9 [19.3 -136.2], ETA 59.3 [17.1 –NA], IFM: 31.1 [7.1 -65.1] months). The RR of the first anti-TNF drug 2 years after initiation was 67.4% for ETA, 67.8% for ADA, and 55% for IFM. The hazard ratios (HR) for treatment cessation did not significantly differ between ETA and monoclonal antibodies. Inefficiencies were observed for 78 patients (70%), including 26 primary inefficiencies (33%) and 30% treatment discontinuations due to side-effects. Reasons for discontinuation did not significantly differ between the anti-TNF groups. IFM exhibited lower safety. Predictors of treatment discontinuation were older age, high activity disease, CRP, and rheumatoid nodules. In contrast, association with a DMARD significantly improved the median RT (17.5 vs. 60 months, 76 vs 29 months for MTX) for all anti-TNF drugs. Following treatment failure with the first anti-TNF therapy, a second anti-TNF was administered in 61 patients, while 44 were switched to a non-TNF-targeted biologic (22: rituximab; 8: abatacept; 10: tocilizumab; 4: anakinra). A second treatment failure was more common when using a second anti-TNF agent than with non-TNF-targeted biologics (77.1% vs. 9.1%, p Conclusions Our results showed near-identical retention levels recorded for anti-TNF, lower safety for infliximab, improvement of retention when anti-TNF were associated with a DMARD and better efficacy achieved with a non-TNF-targeted biologic following the failure of a first-line anti-TNF treatment. Disclosure of Interest None declared

Background Biotherapies prescribed in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) are associated with risks that patients must be aware of. Patient education offers them to learn how to manage such treatments on a day-to-day basis. In our department, patients can benefit from 3 different educational models: individual informational consultation (Model 1), individual consultations including the 4 recommended steps (educational diagnosis, objectives, education and assessment) (Model 2) and individual consultations with group workshops (Model 3). Objectives To assess which educational model appears the most appropriate for maintaining optimal safety in the self-management of biotherapy. Methods This is an observational, monocentric, retrospective study on routine care. All patients on biotherapy with at least one educational consultation between 2009 and 2013 were subsequently divided up according to the undergone educational model (Models 1, 2, or 3). During normal management, patients filled out the BIOSECURE questionnaire, meant to assess their theoretical and practical knowledge (clinical cases), prior to consultation with an education nurse. The overall BIOSECURE score, its theoretical and practical subsections, the different dimensions of the questionnaire and the behaviors in risk situations were compared based on the 3 models. Results In total, 222 patients were included (67% women, age 53.9 years, disease duration: 10 years, RA n=137, SpA n=77 and uncategorized rheumatism n=8, anti-TNF 89.6%, rituximab 3.2%, abatacept 3.6%, and tocilizumab 3.6%. As regards the educational model, 106 patients (47.8%) benefited from Model 1, 88 (39.6%) from Model 2, and 28 (12.6%) from Model 3. The overall BIOSECURE score was 76.6/100 without any significant difference depending upon the educational model (Model 1: 75.1, Model 2: 76.7, Model 3: 81.8; p=0.07). The BIOSECURE score was significantly higher amongst women (p=0.007), young people (p Conclusions The educational model involving group workshops showed no significant variation from the overall BIOSECURE score amongst patients treated with a biotherapy for RA or SpA when compared to the models based solely on individual consultations. However, patients having participated in group workshops exhibited improvement in practical scores and certain skill areas. Disclosure of Interest None declared

Background Diagnosing infectious spondylodiscitis is greatly facilitated by improved access to MRI testing. However, MRI testing increases the possibility of false positives. The efficiency of bacteriological testing is highly variable depending on the series performed, and this efficiency is not improving. Objectives The objective of this study is to evaluate the efficiency of such testing in the last decade and to compare it with the efficiency determined in the preceding decade by the same department. Methods This is a retrospective monocentre study of records of patients hospitalised in the rheumatology department of the CHU de Clermont Ferrand university hospital from 2003 to 2012 for infectious spondylodiscitis. These patients were compared with a historical cohort of 90 patients from the department, including all spondylodiscitis cases from 1992 to 2002 selected using the same criteria. Results From 2003 to 2013, 99 patients were hospitalised for infectious spondylodiscitis and were compared with the cohort of 90 patients hospitalised from 1992 to 2002. A pathogen was identified in 78% (77/99) of the cases, which is not significantly different from the preceding decade: 68% (61/90). Blood cultures were positive respectively in 37% (37/99, 37/95 excluding tuberculosis) and 39% (35/90, 35/88 excluding tuberculosis) (NS). In the last decade, pathogens were more often isolated through fine needle aspiration biopsy (FNAB) of the vertebral disc: 47/99 (47%) vs. 28/90 (31%) p=0.02. In the last decade, the efficiency of vertebral disc FNAB was 66% (47/71); eight patients underwent two vertebral disc FNAB and the second biopsy was only positive once. The efficiency was 77% (72/93) for primitive non-tubercular spondylodiscitis in the last decade. Over both periods, the proportion of staphylococci (49%), streptococci and enterococci (23% and 26%), gram negative bacilli (13 and 20%) and tuberculosis (5 and 3%) were not significantly different. However, amongst staphylococci, there was an observed decrease in the proportion of S. aureus in the last decade (47% vs. 70%, p=0.03) and increase in the proportion of coagulase negative staphylococci. Patients of the last decade were older (66 vs. 61 years of age; p=0.01) and more often had infection risk factors (51% vs. 33%; p=0.03), and diabetes in particular (27% vs. 9%; p=0.001). Conclusions In our recruitment, the efficiency of bacteriological testing for spondylodiscitis has not declined in 20 years, and has even slightly improved. However, for one quarter of spondylodiscitis cases presumed to be infectious, the pathogen remains unknown. Disclosure of Interest None declared

Background Tocilizumab (TCZ) is an interleukin 6 (IL-6) inhibitor that is used in Rheumatoid Arthritis (RA) treatment (1). Although, IL-6 plays a role in viral immunosurveillance Objectives We studied the effect of TCZ on the evolution in viral load for the Epstein Barr Virus (EBV), Cytomegalovirus (CMV) and Varicella Zoster Virus (VZV) in patients with RA. Methods This was a prospective monocenter study of RA patients taking TCZ. Demographic, clinical and laboratory data were collected on each patient. Viral loads (VL) were determined in whole blood (using the EBV R-gene quantification kit, Abbott Real Time CMV kit, and Biomerieux VZV R-Gene kit) at TCZ initiation and during treatment follow-up. A difference between two viral loads of 0.5log10 copies/ml of whole blood was considered significant. Results 22 patients were evaluated. There were 20 (89%) women of a mean age of 57.8±11.2 with seropositive (68%) and erosive (74%) RA that had been progressing for a mean of 11.3±9.7 years. TCZ was administered alone (36.7%) or in combination with methotrexate (MTX) (50%). When TCZ was introduced, the EBV VL was positive in eight patients with a mean VL value of 1777.2±3518.3 (3.5±0.4 log10) copies/ml. Only one patient had a positive CMV VL. The VZV VL was negative in all patients. After 9.2±4.8 months had lapsed, EBV VL and CMV VL became negative in six of eight patients (p=0.02) and did not significantly vary in the remaining two patients. No VL (EBV, CMV, VZV) became positive. A positive EBV VL did not correlate with RA activity (DAS28ESR, DAS28CRP) or with inflammatory biomarkers (ESR and CRP). RA activity significantly declined after six months of TCZ treatment (DAS28ESR after six months 2.8±1.1 vs. 5.14±0.9 [p Conclusions EBV, CMV and VZV viral loads do not seem to significantly increase with the introduction of TCZ treatment. Studies involving larger patient populations are necessary. References Smolen JS. Ann Rheum Dis 2014 Mar;73(3):492-509. Kawada J. Mod Rheumatol 2012 Aug;22(4):565-70. Balandraud N. Arthritis Rheum 2007 Jun 15;57(5):762-7. Couderc M. Joint Bone Spine 2010 Oct;77(5):414-7. Van Duin D. Emerg Infect Dis 2011 Apr;17(4):754-6. Ogawa J. Ann Rheum Dis 2006 Dec;65(12):1667-9. Kubandova Z. Joint Bone Spine 2010 Dec;77(6):623. Disclosure of Interest None declared

Background Rheumatoid artritis (RA) is characterized by increased cardiovascular (CV) mortality and by a metabolic profile including obesity, cachexia, insulin resistance, dyslipidaemia. Traditional DMARDs as well as biologics decreases inflammation and could thus improve CV risk. However, the effects of such therapies on lipids and body composition are still unclear. Objectives To investigate the effects of tocilizumab, an inhibitor of the IL6 pathway on markers of subclinical atherosclerosis and body composition in active RA. Methods We conducted an open 1-year follow-up study of patients with active RA treated with tocilizumab. Waist circumference (WC), body mass index (BMI), total and regional body fat and lean mass assessed with dual-energy x-ray absorptiometry, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides (TG), fasting glucose, blood pressure, and arterial stiffness (pulse wave velocity PWV, augmentation index AIx) were measured at baseline when started first treatment with tocilizumab, 6 months and 1 year of treatment. The longitudinal data were explored in univariate analysis using a random-effects model. To assess the issue of missing data, the estimation methods developed by Verbeke and Molenberg were considered in this study. Results 21 RA patients, including 16 women with a mean age of 57.8±10.5 years were included. RA duration was 8.5 years [IQR 1.7–21.5]. 14 had positive rheumatoid factors, 17 anti-CCP antibodies, 13 were erosive. At baseline, 19 patients received a DMARD, 14 steroids, 11 cholesterol-lowering drug therapy, 1 anti-diabetic drug, 6 antihypertensive medication. 18 patients have previously received at least one biologic. The mean DAS 28 at baseline was 4.7±1 and decreased significantly at 6 and 12 months (2.92±0.8 and 2.8±1.5 respectively, p Conclusions Despite weight gain during efficacious treatment with IL6 inhibitor, no increase in fat, metabolic syndrome or CV risk markers have been observed. In contrast, muscle gain with increase of lean mass was detected at 1 year suggesting that blocking IL6 might be efficient in rheumatoid cachexia and sarcopenia. Acknowledgements This work was supported by a grant from Chugai and Roche Disclosure of Interest None declared

Background Methotrexate is the reference treatment for rheumatoid arthritis (RA). It has potentially serious side effects which can be prevented by an improvement in patient9s information. Objectives To assess the knowledge of patients suffering from RA about their methotrexate treatment with a questionnaire. Methods A questionnaire containing 21 closed questions and 2 situation studies about the medication (mechanism of action, method of administration, therapeutic interactions, side effects, monitoring and implications on lifestyle) was given to all RA patients treated with methotrexate who consulted between March and September 2013 in the rheumatology department of Clermont-Ferrand Hospital. Results 183 patients were recruited, including 143 women (79%), with a mean age of 60 years ±13.5 and a median RA duration of 12 years (IQR: 7-20). Methotrexate has been initiated for a mean of 8 years (IQR: 5-13). Methotrexate was identified as a DMARD by 78% of participants. The weekly administration method was well known (97%) and 67% said that the folic acid was to reduce the toxicity of treatment. Only 21% knew that trimethoprim was contraindicated. Half of the patients knew about the haematological risks and 36% about the risks of hypersensitivity pneumonia. The frequency of laboratory assessments was known (80%) but 54% thought that the only purpose of these tests was to assess the RA activity. Only 13% of men (n=38) knew that contraception was essential compared to 90% of women of child-bearing age (n=20), 75% reported that alcohol consumption should be reduced. In multivariate analysis, a low knowledge score correlated significantly, with age and low educational status. Scores were independent of sex, duration of treatment or of the RA. Conclusions Patients9 knowledge about methotrexate, particularly about the interaction with trimethoprim, risk of hypersensitive pneumonia and need for men to use a couple contraception should be increased by the treatment education programme instruments, especially in the elderly and the lower socio-educational status population. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4930

Background Structural progression in rheumatoid arthritis (RA) is a major outcome. Radiographic scoring should be performed by one or two readers, blinded to clinical data. This method may be limited in terms of feasibility in large observational longitudinal research including large number of patients and multiple timepoints. Objectives To compare a new method for radiographic scoring involving multi-reader evaluation to a mono-reader evaluation taken as reference. Methods 11 rheumatologists were trained for radiographic reading according to Sharp-van der Heijde Score (SHS) (objective: ICC≥0.8 for intra and inter-reliabilities). ESPOIR cohort is a longitudinal observational study of early arthritis (ie; at least 2 swollen joints, symptom duration:6 weeks-6 months, no DMARDs). Xrays of hands and feet were performed each year. All patients with complete radiographic data at M0 and M60 were included in this study. Xrays were scored (SHS) according to 2 different methods (monoreader or multireader evaluations).The “mono-reader evaluation” was taken as reference and consisted in scoring all the patients by one reader (M0 and M60). A “multi-reader evaluation” was compared to the monoreader evaluation. For this multireader evaluation, patients were randomly divided in equal subgroups which were randomly allocated to the readers. Each reader had to read all available Xrays (M0 to M60) of the patients allocated to him. Xrays were scored according to SHS, blindly from clinical data, in chronological order. Statistical analysis was performed using R.2 software. Intraclass correlation coefficients (ICC) for SHS scores and kappa coefficients for rapid radiographic progression (RRP: change (M60-M0) of SHS≥5) between multireader and monoreader evaluations were calculated. Results Patients characteristics in the ESPOIR cohort have already been published (1). 524 patients had complete radiographic data at M0 and M60 and were included in this study. 144 patients (34.6%) had RRP. While correlations between the multireader and monoreader readings were moderate at M0, good correlations of the change of SHS scores between M0 and M60 were observed. Moderate agreements for the evaluation of structural progression were observed between the 2 methods, with good agreement for erosion progression. Conclusions Multireader evaluation for radiographic structural progression could be an alternative to Monoreader evaluation in large observational longitudinal cohort. References Tobon et al. Arthritis Care & Research Vol. 65, No. 12, December 2013, pp 1907–1915. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4659

Background Subclinical atherosclerosis and an increased incidence of cardiovascular diseases have been observed in rheumatoid arthritis (RA). Inflammation and traditional risk factors could be involved in the pathogenesis. Tocilizumab, an inhibitor of the IL6 pathway, decreases inflammation and could thus improve cardiovascular risk. However, this positive effect can be counterbalanced by tocilizumab-induced dyslipidemia. Objectives To investigate the effects of tocilizumab on markers of subclinical atherosclerosis in active RA. Methods Subclinical atherosclerosis was assessed by flow mediated dilatation (FMD) and arterial stiffness (i.e. augmentation index AIx and pulse wave velocity PWV), at baseline and after 24 weeks of tocilizumab therapy. Results 22 RA patients, including 18 women (81%), with a mean age of 58.2±11.6 years were included. 18 (81%) had positive rheumatoid factors, 16 (72%) had positive anti-CCP antibodies, 20 (90%) were erosive. 18 patients (81%) were refractory to TNF alpha inhibitor treatment, 2 (9%) to rituximab, and 4 (18%) to abatacept, 14 patients received glucocorticoids (7.8 ± 6.4 mg/day). No changes in FMD (N=9 patients) (6.63±4.68 at 6 months vs. 5.21±2.54 at baseline, p=0.59) or arterial stiffness (N=22) (PWV: 7.95±3.59 vs. 7.96±2.98, p=0.93; Alx: 29.57±11.7 vs. 29.89±12.83, p=0.92) were detected after 6 months of treatment with tocilizumab. DAS28ESR and DAS28CRP were significantly improved (2.67±1.1 vs. 5.03±0.84, p Conclusions Our results are consistent with those of McInnes 1 who did not find any improvement in arterial compliance after 24 weeks of tocilizumab therapy, but our findings disagree with data reported by Protegorou 2 and Kume 3 describing an improvement in endothelial function and arterial compliance References Ann Rheum Dis 2013, doi:10.1136annrheumdis-2013-204345 Atherosclerosis. 2011;219:734-6. J Rheumatol. 2011;38:2169-71. Acknowledgements This study was conducted with a grant from the French National Clinical Research Program (PHRC) and and a grant from Roche Ltd France. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4911

Background Patients with rheumatoid arthritis (RA) are at increased risk of renal dysfunction. Objectives To assess the prevalence and associations of renal dysfunction in patients with RA. Methods COMEDRA is a French nation-wide cross-sectional multicentric study on comorbidities in RA patients. Renal function was assessed by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation in patients from the COMEDRA study. Demographics and RA characteristics, risk factors for renal dysfunction (cardiovascular risks, medications) were collected in all participants. Results Of the 970 recruited patients, 931 were analyzed (female gender: 79.6%, age: 57.8 years, disease duration: 11.1 years, DAS28-erythrocyte sedimentation rate: 3.1). 8.8% of patients had eGFR

In an article published in Annals of the Rheumatic Diseases , Chowalloor et al 1 suggested, based on a literature review, that ultrasonography (US) is a promising tool that could be used in the diagnosis and management of gout. In this letter, we wish to add further data to Chowalloor et al's conclusion. We have performed a meta-analysis (up to July 2012) to investigate the frequency of ultrasonographic signs, that is, joint effusion, synovitis, bone erosion, tophi and double contour (DC), in gout and asymptomatic hyperuricaemia compared with controls (figure 1). Figure 1 Prevalence of double contour signs in …

Objectives To study the sensibility (Se) and specificity (Sp) of clinical and biological signs for the diagnosis of septic arthritis (SA). Methods This prospective study included all adult patients with a suspicion of SA seen in the emergency department or rheumatology service at the University Hospital of Clermont-Ferrand during a period of 18 months. The sensibility and specificity of the clinical and biological signs for the diagnosis of SA were calculated. A univariate analysis followed by a logistic regression analysis for SA diagnosis was conducted. Results In total, 105 patients with a suspected SA were included, 38 (36%) presenting with SA (29 with a bacteriologically documented SA). In univariate analysis, chills (Se 39%; Sp 82%, p=0.015) but not fever (Se 53%; Sp 53%, p=0.6), a slow onset duration (Se 54%; Sp 72%, p=0.04), local redness (Se 53%, Sp 72%, p=0.01), as well as an infection entry-site (Se 7%; Sp 54%, p=0.01) were found most often in the SA cases. Microcrystalline antecedents (Se 5%, Sp 72%, 95% CI 0-0.6) and involvement of the knee were more frequent in non-septic arthritis (non-SA) cases. An erythrocyte sedimentation rate (ESR) >50 mm (Se 72%; Sp 60%, p=0.005), a C-reactive protein level >100mg/L (Se 58%; Sp 66%, p=0.019) and, above all, suggestive radiological signs (Se 30%; Sp 95%, p=0.001) were more frequent in the SA cases. The clear (Se 0; Sp 81%, p=0.007) and purulent (Se 57%, Sp 88, p 50000/μL (Se 57%; Sp 82%, p 90% (Se 42%; Sp 82%, p=0.02), but not the presence of microcrystals (Se 24%, Sp 58% p=0.09). In multivariate analysis, only chills (OR=4.1, 95% CI: 1.4-12.2), microcrystalline antecedents (OR=0.08, 95% CI: 0.01-0.5), and radiological signs (OR=11, 95% CI: 2.4-50.1) remained significant. The parameters chills, microcrystalline antecedents, infection entry-site, risk factors for SA, the aspect and cellularity of synovial fluid, and radiological signs permitted the elaboration of two logistic regression models for the diagnosis of SA (AUC: 0.85 and 0.87). Conclusions No clinical or biological (excluding bacteriological) sign, taken alone, is conclusive for the differentiation between SA and non-SA pathology, but the association of several signs, notably chills, microcrystalline antecedents, radiological signs of SA, and the aspect and cellularity of joint liquid may be conclusive. Disclosure of Interest None Declared

Background Positivity for rheumatoid factor (RF), anti–cyclic citrullinated peptide antibodies (anti-CCP) and high gamma globulin levels are predictive of better response to rituximab forrheumatoid arthritis (RA) [1]. Magnusson et al. showed a better response to RTX in patients with positive initial EBV load [2]. Objectives To study the influence of several factors (FR, Anti-CCP, serum gamma globulin level, EBV load) on response to RTX. Methods Patients treated by RTX for active RA in the rheumatology department of the university hospital of Clermont-Ferrand (France) between April 2006 and May 2011 were prospectively included. RF, anti-CCP, gamma globulin level and EBV load were measured before the first RTX cycle. Clinical response were analysed 6 months after RTX according to the criteria the European league against rheumatism (EULAR). Univariate and multivariate analyses were performed to identify factors associated with response to RTX at 6 months. Results Sixty-four patients (51 women (79.7%), mean age =61.2 years) were included. Mean disease duration was 16.4 years and 46 patients (71.8%) had already received one or more anti-TNF treatments. At 6 months, 46 patients (71.8%) had moderate-to-good response to RTX. Thirty-seven patients, of whom 6 were positive, had EBV-load measure before RTX. After 6 months, all were negative. Positivity for RF (odds ratio 0,53 [95% confidence interval O,1-2,8]), or positive initial EBV load (odds ratio 0,2 [95% confidence interval 0,03 – 1,3])were not associated with good-to-moderate response. Positivity for anti-CCP was associated with good-to-moderate response (odds ration 4,3 [95% confidence interval 1,2 – 15,7]). High level of gammaglobulin (>12g/L) was correlated with non-response to RTX (odds ratio 0,05 [95% confidence interval 0,03-0,66]). Conclusions In contrast with precedent studies, high level of gamma globulins was predictive of worth response to RTX and only anti-CCP antibodies were correlated to a better response. References Sellam J, Hendel-Chavez H, Rouanet S, Abbed K, et al. B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study. Arthritis Rheum. 2011;63:933-8. Magnusson M, Brisslert, Zendjanchi K, Lindh M, Bokarewa MI. Epstein-Barr virus in bone marrow of rheumatoid arthritis patients predicts response to rituximab treatment. Rheumatology (Oxford). 2010;49:1911-9. Disclosure of Interest None Declared

Background Anakinra has shown modest efficacy in rheumatoid arthritis and there is proof of principle for its efficacy in gout. Several case reports have suggested it is effective in pseudogout [1-2]. Methods We report a small study of 3 patients treated with anakinra for pseudogout. Results Three patients, two men and one woman aged 49, 68 and 68 years, respectively, were treated with subcutaneous anakinra 100mg/day for pseudogout. Diagnosis was based on the association of polyarthralgia and typical X-ray features of pseudogout. In two patients, pseudogout was secondary to haemochromatosis. All three patients had previously received non-steroidal anti-inflammatory drugs and colchicine. Two had been treated unsuccessfully with methotrexate. The first patient did not respond to anakinra (delta DAS +0.3) and treatment was discontinued after 3 months. Anakinra was also stopped in the second patient after 2 months, because of lack of response (delta DAS -0.72) and adverse event. In the last patient, after 3 months of treatment, DAS 28 decreased from 4.83 to 2.31 (delta DAS -2.5) and HAQ from 1.5 to 0.875 and anakinra was continued. Significant side-effects occurred with moderate reaction at the site of injection in two patients and interstitial lung disease in one that could have been due to anakinra. Conclusions In contrast with previous case-reports, this study showed low efficacy of anakinra in pseudogout. The efficacy of Il-1 blockade treatment in pseudogout needs to be confirmed by randomised controlled studies. References McGonagle D, Tan AL, Madden J, Emery P, McDermott MF. Successful treatment of resistant pseudogout with anakinra. Arthritis Rheum. 2008;58:631-3. Announ N, Palmer G, Guerne PA, Gabay C. Anakinra is a possible alternative in the treatment and prevention of acute attacks of pseudogout in end-stage renal failure.Joint Bone Spine. 2009;76:424-6. Disclosure of Interest None Declared