Search

Objectives The frequency and consequences of anti-drug antibodies to rituximab (RTX-ADA) are not well known in RA and even less in other systemic auto-immune diseases (sAID). We aimed to evaluate the frequency, consequences and predictive factors of RTX-ADA in RA and sAID. Methods All patients presenting with RA or other sAID treated with RTX from 2012 to 2017 in our tertiary reference centre for sAID were retrospectively studied. Patients who were tested for RTX-ADA were identified. Results One hundred and ninety-nine patients were treated with RTX (RA: 124, other sAID: 75). Among 62/199 (31.1%) tested for RTX-ADA, 14 were positive: 3/35 RA (8.6%) and 11/27 (40.7%) other sAID, (P = 0.0047). Among the whole RTX-treated populations, the frequency of RTX-ADA was 2.4% and 14.7% (P = 0.0026) in RA and sAID, respectively. Most of the immunized patients had infusion reactions to second or subsequent RTX cycles (11/14) and loss of efficacy (2/14). Predictive factors of immunization were sAID vs RA (78.6% vs 21.4%, P = 0.026, adjusted odds ratio (OR) = 5.35[1.43—54.75]) and African ethnicity (57.1% vs 4.2%, P < 0.001, adjusted OR = 9.25 [5.08—302.12]). Associated immunosuppressive therapy did not protect against immunization. Three patients with pSS immunized against RTX were treated with ofatumumab with complete remission of their disease. Conclusion Immunization against RTX is more frequent in other sAID than in RA. Testing for RTX-ADA must be performed in patients with infusion reactions or loss of efficacy especially if they are of African origin. Immunized patients might be treated efficiently and safely with ofatumumab. This alternative should be further evaluated for sAID.

Summary Background Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases. Methods In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609. Findings Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66–6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46–0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55–3·19, p=0·53). Interpretation Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases. Funding None.

ObjectiveTo evaluate the relevance of salivary gland ultrasound (SGUS) and its place in the diagnostic algorithm in patients referred with dry syndrome (DS) for a suspicion of Sjögren’s syndrome (SS).MethodsWe included all patients assessed at our dedicated DS clinic from June 2015 to September 2019 for which a SGUS has been carried out. Images were read blindly and the worst salivary gland was scored according to OMERACT classification. Clinical features, disease activity and treatments were collected.Results337 patients were seen from June 2015 to September 2019. 269 patients underwent SGUS. 77 patients were diagnosed with SS and 192 did not meet the ACR/EULAR criteria for SS: non-Sjögren’s DS (NSDS). Of these 192 patients, 60 had another possible cause of DS, and 132 patients were diagnosed with SAPS (sicca, asthenia, polyalgia syndrome).SGUS abnormalities were significantly higher in patients with SS versus NSDS: 51% vs 8% for a score ≥2 (pConclusionSGUS is useful for SS diagnosis. If anti-SSA antibodies are negative and SGUS score

Objective.Spondyloarthritis (SpA) and Takayasu arteritis (TA) are 2 chronic inflammatory diseases; their coexistence in a single patient is uncommon. The aims of our study were to describe clinical features of patients having SpA associated with TA and to identify some characteristics of the types of patients with SpA associated with TA. We also analyzed treatments used in this context.Methods.This French multicenter retrospective survey called for observations on behalf of the Club Rhumatismes et Inflammations, with a standardized questionnaire established by the investigators.Results.We included 14 patients (women: 10/14; median age at SpA diagnosis: 43.5 yrs, ranging from 19 to 63). Subtypes of SpA were ankylosing spondylitis (n = 11), psoriatic arthritis (n = 2), and synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome (n = 1). HLA-B27 was positive in 3 cases, negative in 9, and unknown in 2. SpA was diagnosed before TA in 13 cases. Imaging findings compatible with the diagnosis of TA were found with computed tomography (11/14) and/or Doppler ultrasound (10/14). Laboratory tests showed increased acute-phase reactants in all cases (C-reactive protein ≥ 25 mg/l in 71% of the cases). All patients except 1 received corticosteroids and 7 were treated with anti–tumor necrosis factor (anti-TNF).Conclusion.Association of SpA and TA is rare but probably not coincidental. Peripheral pulse palpation and vascular auscultation should be systematic and are the first indicators of TA in patients with SpA. Moreover, increased acute-phase reactants during SpA followup should lead to search for TA. Finally, there are therapeutic implications because anti-TNF are efficient in SpA and might be efficient in TA.

Introduction La pseudopolyarthrite rhizomelique (PPR) est un rhumatisme inflammatoire survenant apres 50 ans avec un pic de frequence entre 70 et 80 ans. La TEP-TDM au 18F-FDG n’est pas recommandee en cas de PPR isolee mais est utile pour rechercher une arterite a cellules geantes associee ou en cas de doute sur l’existence d’une forme paraneoplasique. Les spondylarthropathies (SPA) touchent classiquement le sujet jeune, avant l’âge de 45 ans. La TEP-TDM n’a pas d’indication dans la SPA de presentation classique. Neanmoins, on estime que 3,5 % des SPA surviennent apres l’âge de 50 ans. Ces SPA de debut tardif constituent un challenge pour le clinicien, car elles ont une presentation clinique atypique. L’objectif de cette etude est d’evaluer l’interet de la TEP-TDM pour discriminer PPR et SPA a debut tardif en pratique clinique. Patients et methodes Afin d’identifier les patients atteints de PPR et SPA, nous avons conduit une recherche dans la base de donnees de 2 services de rhumatologie. Le diagnostic de PPR ou de SPA etait pose par des cliniciens experimentes. La lecture de la TEP-TDM etait effectuee par 2 medecins nucleaires en aveugle des donnees cliniques. Resultats Nous avons inclus 62 patients entre septembre 2012 et aout 2018. Trente-cinq patients avaient une PPR (56,5 %) et 27 une SPA (43,5 %). Les caracteristiques des patients sont presentees dans le Tableau 1 . L’hypermetabolisme en TEP-sur les entheses etait environ 2 fois plus frequent chez les patients PPR, particulierement au niveau rachidien (processus epineux 88,6 vs 40,7 %, p Tableau 1 ). L’intensite de l’hypermetabolisme des entheses ne permettait pas de discriminer PPR et SPA. Un score cumulatif d’hyperfixation enthesitique est en cours de construction pour permettre de differencier PPR et SPA a debut tardif. Nous n’avons pas observe de difference de frequence d’hypermetabolisme sur les articulations, les vaisseaux ni les muscles. Conclusion Cette etude montre que l’hypermetabolisme des entheses se rencontre aussi bien au cours de la SPA que de la PPR mais est plus frequente dans cette derniere population, essentiellement au niveau du rachis, des hanches et des epaules. Des analyses complementaires sont en cours pour la recherche d’un score musculosquelettique permettant de discriminer les 2 pathologies en cas de presentation atypique comme c’est le cas chez les SPA a debut tardif.

Objective To investigate maintenance of rituximab (RTX) in RA patients re-treated with reduced doses compared with standard dose in a real life setting. Methods The Autoimmunity and Rituximab (AIR) registry is a nationwide prospective observational cohort investigating the long-term safety and efficacy of RTX in RA. The present study included patients from the AIR registry that have been re-treated with RTX after a first course of RTX standard dose (1000 mg × 2). Two groups were defined according to dose of RTX of the first retreatment course (i.e. second course): standard dose group and reduced dose group. Five years' maintenance and rate of serious infections of the retreatment period were compared between standard dose and reduced dose groups. Analyses used the inverse probability of treatment weighting propensity score adjusted method. Results Among the 1986 patients from the AIR registry, 1278 were included, 1093 (85.5%) treated with standard dose and 185 (14.5%) with reduced doses. Maintenance of RTX at 5 years in the standard and reduced groups was 55.5 and 53.8%, respectively, and did not significantly differ between groups in adjusted analyses (hazard ratio = 1.03; 95% CI: 0.81, 1.30), but the cumulative RTX dose received for retreatment [1.4 (0.6) vs 2.3 (1.0) g/year, P < 0.001] and the rate of serious infections were significantly lower in the reduced dose group (adjusted hazard ratio = 0.50; 95% CI: 0.27, 0.92; P = 0.02). Conclusion Use of reduced doses of RTX for retreatment did not alter the maintenance of RTX at 5 years in RA patients, but allowed a 39% total dose reduction and a lower rate of serious infections.

Resume Objectifs Chez les patients souffrant de polyarthrite debutante, naifs de traitement de fond, nous avons evalue la prevalence de la lymphopenie initiale et persistante, le diagnostic sous-jacent, les risques d’infection et de neoplasie ou d’hemopathie maligne. Methodes Huit cent treize patients souffrant de polyarthrite debutante inclus dans la cohorte Espoir ont eu un examen clinique, des examens de laboratoire (serologies virales, examens immunologiques et profil cytokinique), et des radiographies. Nous avons determine la prevalence de la lymphopenie a l’inclusion et a 3 ans, les facteurs associes, les diagnostics, et les risques d’infection, de neoplasie ou d’hemopathie maligne. Resultats A l’inclusion, 50/813 patients (6,2 %) avaient une lymphopenie. La lymphopenie etait associee a la presence de facteur rhumatoide positif ( p = 0,02), une cytopenie ( p ≤0,05) une hepatite C ( p = 0,05), une C-reactive proteine ( p ≤0,05) et un DAS 28 augmentes ( p ≤ 0,05). Le profil cytokinique et la progression radiologique n’etaient pas significativement differents entre les patients avec ou sans lymphopenie. Les diagnostics suspectes a l’inclusion etaient : une polyarthrite rhumatoide (PR, n = 27), une arthrite indifferenciee ( n = 15), un lupus erythemateux systemique (LES, n = 3), une spondyloarthrite ( n = 2), un syndrome de Gougerot-Sjogren ( n = 1), une hemopathie ( n = 1), et une fibromyalgie ( n = 1). Sur un total de 42 patients, 15 (35,7 %) ayant une lymphopenie initiale, avaient une lymphopenie persistante apres 3 ans, dont 5 avec des causes documentees (LES, hepatite C, denutrition, traitement par azathioprine et tamoxifene) ; aucun n’avait d’infection a PVB19, VIH ou VHB et aucun n’avait d’infection, de tumeur ou hemopathie maligne pendant le suivi. Le diagnostic final chez ces 15 patients etait : PR ( n = 6), arthrite indifferenciee ( n = 6), LES ( n = 1), spondyloarthrite ( n = 1), et fibromyalgie ( n = 1). Conclusion La lymphopenie est rare dans la polyarthrite debutante. La cause la plus courante est la PR, avec une inflammation marquee et d’autres cytopenies frequentes. La lymphopenie dans la polyarthrite debutante est souvent de courte duree, meme lorsque le methotrexate est prescrit.

Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatic condition over the world. RA is potentially disabling because chronic inflammation of the joints leads to joint destruction. To date, the best predictor of radiographic progression for patients with early RA is the presence of radiographic erosions at baseline, but a limited number of predictive biomarkers of structural progression are currently used in daily practice. Here, we investigated Dickkopf-1 (DKK-1) and sclerostin (SOST) serum levels in patients with recent inflammatory arthritis from the ESPOIR cohort. This cohort is a prospective, multicenter French cohort of 813 patients with early arthritis. We observed that mean baseline DKK-1 level was higher among RA patients with than without radiological progression within the first 2 years of evolution. DKK-1 level was still associated with radiographic progression in a model including other main predictors of severity (erosions at baseline and anti-CCP antibody positivity). This study demonstrates that increased DKK-1 level at baseline predicted structural progression after 2-year follow-up and suggests that DKK-1 might be a new structural biomarker for early RA.

Objective To assess the link between monoclonal gammopathy (MG), disease activity, and incidence of malignant hematologic disorders (MHDs), including lymphoma and multiple myeloma (MM), in patients with primary Sjogren's syndrome (SS). Methods Screening for the presence of MG was performed in 352 primary SS patients. Each patient with MG was paired with 2 age- and sex-matched primary SS controls without MG. Their characteristics were compared for the presence of risk factors for MG and for the relationship between MG and MHD. Results Twenty-six of the 352 primary SS patients (7.4%) had MG; 88% were women, with a median age of 62.7 years (interquartile range [IQR] 50.3–69.1 years) and a median disease duration of 7.8 years (IQR 3.6–12.8 years). The parameters associated with MG on multivariate analysis were higher disease activity, as measured by either the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI; adjusted odds ratio [OR] 9.7, P = 0.0002) or the Clinical ESSDAI (adjusted OR 6.7, P = 0.001), and low C4 level (adjusted OR 3.4, P = 0.04). After a median follow-up of 6.3 years (IQR 3.1–9.5 years), 10 patients with MG had developed an MHD (38.5%; 4 had lymphomas and 6 had MM), as compared with 4 patients in the control group (7.7%; all had lymphomas) (OR 7.5, P = 0.002). The only factor associated with the risk of MHDs was the presence of MG (adjusted OR 5.5, P = 0.02), which was principally associated with an increased risk of MM (23% versus 0%; P = 0.0009), but not lymphoma (15% versus 8%; P = 0.3). Conclusion The presence of MG was associated with higher disease activity and an increased risk of MHD in primary SS. In the presence of MG, the risk of MM was even higher than the risk of lymphoma. These results suggest that regular monitoring of primary SS patients with MG for the emergence of both lymphoma and MM is necessary.

International audience; Objectives : To investigate DKK-1 and SOST serum levels among patients with recent inflammatory back pain (IBP) fulfilling ASAS criteria for SpA and associated factors.Methods : The DESIR cohort is a prospective, multicenter French cohort of 708 patients with early IBP (duration >3 months and

To assess the link between monoclonal gammopathy (MG), disease activity, and incidence of malignant hematologic disorders (MHDs), including lymphoma and multiple myeloma (MM), in patients with primary Sjögren's syndrome (SS).Screening for the presence of MG was performed in 352 primary SS patients. Each patient with MG was paired with 2 age- and sex-matched primary SS controls without MG. Their characteristics were compared for the presence of risk factors for MG and for the relationship between MG and MHD.Twenty-six of the 352 primary SS patients (7.4%) had MG; 88% were women, with a median age of 62.7 years (interquartile range [IQR] 50.3-69.1 years) and a median disease duration of 7.8 years (IQR 3.6-12.8 years). The parameters associated with MG on multivariate analysis were higher disease activity, as measured by either the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI; adjusted odds ratio [OR] 9.7, P = 0.0002) or the Clinical ESSDAI (adjusted OR 6.7, P = 0.001), and low C4 level (adjusted OR 3.4, P = 0.04). After a median follow-up of 6.3 years (IQR 3.1-9.5 years), 10 patients with MG had developed an MHD (38.5%; 4 had lymphomas and 6 had MM), as compared with 4 patients in the control group (7.7%; all had lymphomas) (OR 7.5, P = 0.002). The only factor associated with the risk of MHDs was the presence of MG (adjusted OR 5.5, P = 0.02), which was principally associated with an increased risk of MM (23% versus 0%; P = 0.0009), but not lymphoma (15% versus 8%; P = 0.3).The presence of MG was associated with higher disease activity and an increased risk of MHD in primary SS. In the presence of MG, the risk of MM was even higher than the risk of lymphoma. These results suggest that regular monitoring of primary SS patients with MG for the emergence of both lymphoma and MM is necessary.

Background: Cardiac involvement in idiopathic inflammatory myopathy has been recognised as an important prognostic factor, but treatment remains empirical. Objective: To investigate the effects of corticosteroids and immunosuppressors on myocarditis in patients with inflammatory myopathies. Methods: Patients with inflammatory myositis of recent onset who had not received treatment were evaluated for associated myocarditis by magnetic resonance imaging (MRI) and reinvestigated after treatment with high dose corticosteroids and immunosuppressors. Results: Four patients with histologically proven myositis were included. Two patients with polymyositis had cardiac clinical symptoms. Two other patients with dermatomyositis and diffuse cutaneous systemic sclerosis-polymyositis overlap syndrome were asymptomatic. In three cases the usual conventional screening tests were normal. For all patients an area of contrast enhancement and hypokinesia detected by cardiac MRI was markedly reduced after treatment with corticosteroids and immunosuppressors for 6 months. Conclusion: Treatment with intravenous methylprednisolone followed by prednisone and immunosuppressive therapy seems to be effective for treating myocardial involvement in patients with idiopathic inflammatory myopathies, either alone or presenting as overlap syndromes. Cardiovascular MRI is a non-invasive technique that may be a powerful tool for diagnosis and monitoring of myocardial inflammation in this setting.

Case-report. – A 76-year-old woman was admitted for evaluation of esophagitis complicating limited cutaneous systemic sclerosis. Endoscopy showed persistent grade III esophagitis and an erythematous antral lesion found upon biopsy to be a lymphoma of mucosa-associated lymphoid tissue (MALT). Tests were positive for Helicobacter pylori . Moderate mucosal infiltration by endoscopic ultrasonography was the only finding from staging investigations. Six months after treatment to eradicate H. pylori , a repeat endoscopy showed no evidence of the lesion. Discussion. – MALT lymphomas are usually confined to the gastric wall. Gastric MALT lymphomas have a well-established association with H. pylori infection. The clinical manifestations are nonspecific. Endoscopy usually shows a focus of erythema or, less often, erosion. The diagnosis rests on histological examination of a biopsy, which shows infiltration by monoclonal cells whose immunophenotype is characteristic of marginal-zone B cells. Eradication of H. pylori is the mainstay of treatment.

Resume Observation. – Une patiente de 76 ans a ete hospitalisee pour evaluation d'une œsophagite compliquant une sclerodermie systemique de forme cutanee limitee. Une gastroscopie a montre la persistance de l'œsophagite grade III associee a une lesion erythemateuse antrale se revelant etre un lymphome du MALT (mucosa-associated lymphoid tissue) a la biopsie. La recherche d'Helicobacter pylori etait positive. Le bilan d'extension n'a montre qu'un infiltrat muqueux modere a l'echoendoscopie. La patiente a ete traitee pour eradication d'H. pylori et un controle gastroscopique six mois plus tard montrait la disparition de cette lesion. Discussion. – Les lymphomes du MALT sont le plus souvent localises a l'estomac et il existe un lien etabli entre infection a H. pylori et ce type de tumeur. Il n'existe pas de manifestation clinique specifique et les principaux aspects endoscopiques sont l'existence d'une plage erythemateuse ou parfois d'une erosion. Le diagnostic est anatomopathologique, avec presence d'un infiltrat lymphocytaire B monoclonal et immunophenotypage caracteristique. Le traitement passe par l'eradication d'H. pylori.

Resume Propos. – Les spondylarthropathies constituent un groupe heterogene de maladies, incluant la spondylarthrite ankylosante, le rhumatisme psoriasique, les arthrites reactionnelles, les arthrites associees aux enterocolopathies inflammatoires, et les spondylarthropathies indifferenciees. Ces maladies sont caracterisees par une inflammation du rachis, des articulations sacro-iliaques, des entheses, des articulations peripheriques, et une forte association au gene HLA-B27 ; elles peuvent entrainer une destruction ou ankylose severe chez une minorite de patients. Les traitements conventionnels comprennent les anti-inflammatoires non steroidiens, les injections articulaires de corticoides et les traitements dits de fond comme la sulfasalazine chez les patients avec arthrites peripheriques. Le TNFα pourrait jouer un role important dans la pathogenie des spondylarthropathies. Methode et resultats. – Parmi les medicaments anti-TNFα, l'etanercept et l'infliximab ont demontre leur efficacite dans le traitement symptomatique de la spondylarthrite ankylosante et du rhumatisme psoriasique. Une rechute clinique est observee quelques semaines apres l'arret du traitement chez une majorite de patients. L'effet benefique potentiel sur les lesions destructrices ou ankylosantes necessite confirmation. Conclusions. – Les patients avec spondylarthropathies actives, severes et refractaires au traitement conventionnel sont des candidats potentiels au traitement par medicaments anti-TNFα. Des criteres pour l'initiation, la surveillance et l'arret de ces medicaments ont ete proposes, tenant compte non seulement de leur efficacite mais egalement de leurs effets secondaires, rares mais potentiellement graves comme les tuberculoses ou autres infections opportunistes, ainsi que de leur cout relativement eleve. Un suivi a long terme de grandes populations de malades souffrant de spondylarthropathies est necessaire pour mieux definir les rapports benefice/risque/cout des medicaments anti-TNFα.

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 9 avril 2016

Objectives In patients with early arthritis naive to disease-modifying antirheumatic drugs, we evaluated the prevalence of initial and persistent lymphopenia, underlying diagnoses, and risk of infection or malignancy. Methods Eight hundred and thirteen patients with early arthritis included in the ESPOIR cohort had a clinical examination, laboratory tests (viral serology, immunological tests, and cytokine profile), and radiographs. We determined the prevalence of lymphopenia at baseline and after 3 years, associated factors, diagnoses, and risk of infection or malignancy. Results At baseline, 50/813 (6.2%) patients had lymphopenia. Lymphopenia was associated with positive rheumatoid factor (P = 0.02), cytopenia (P ≤ 0.05), hepatitis C (P = 0.05), higher C-reactive protein and DAS28 (P ≤ 0.05 for both). Cytokine profile and radiological progression were not significantly different between patients with and without lymphopenia. Suspected diagnoses at inclusion were rheumatoid arthritis (RA, n = 27), unclassified arthritis (n = 15), systemic lupus erythematosus (SLE, n = 3), spondyloarthritis (n = 2), Sjogren's syndrome (n = 1), hematologic disease (n = 1), and fibromyalgia (n = 1). Fifteen patients out of 42 (35.7%) with initial lymphopenia had persistent lymphopenia after 3 years, including 5 with documented causes (lupus, hepatitis C, undernutrition, azathioprine, and tamoxifen); none had PVB19, HIV, or HBV infection and none experienced infections, solid or hematologic malignancies during follow-up. Final diagnoses in these 15 patients were RA (n = 6), unclassified arthritis (n = 6), SLE (n = 1), spondyloarthritis (n = 1), and fibromyalgia (n = 1). Conclusions Lymphopenia is rare in early arthritis. The most common rheumatic cause is RA, in which marked inflammation and other cytopenias are common. Lymphopenia in early arthritis is often short-lived, even when methotrexate is prescribed.

International audience; Objective: In rheumatoid arthritis (RA), nurses are now increasingly involved in joint count assessment but training is not standardized. The aim was to evaluate and describe the learning curve of nurses for the assessment of swollen and tender joints in RA. Method: Twenty nurses from university rheumatology centres inexperienced with joint counts were allocated to a rheumatologist from their centre (teacher). Acquisition of skills consisted of Phase 1: (training), a centralized 4 hour training session, with (a) lecture and demonstration, and (b) practical sessions on patients with their teachers, followed by Phase 2: (practice) involving further practice on 20 patients in their own hospitals. Primary outcome was achievement of adequate swollen joint agreement between nurse and their teacher (''gold standard'') at the ``joint'' level defined by prevalence adjusted biased adjusted kappa (PABAK) > 0.60. Agreement at the ``patient'' level of swollen joint count (SJC), tender joint count (TJC) as well as DAS28 between nurse and their teacher were assessed with intra-class correlation coefficients (ICC). Results: During the training phase, 75% of nurses achieved a swollen joint PABAK > 0.60 when compared with their teachers, which further improved to 89% after the 20 practice patients (Phase 2). Median swollen joint PABAK improved from 0.64 (Q1 :Q3 0.55,0.86) to 0.83 (Q1 :Q3 0.77,1) by the end of Phase 2. At the ``patient'' level, SJC agreement remained globally stable (ICC, 0.52 to 0.66), while TJC and DAS28 agreement remained excellent throughout. Conclusion: Nurses inexperienced in joint counts were able to achieve excellent agreement with their teachers in assessment of tender and swollen joints through a short training session; practice further enhanced this agreement. Larger longitudinal studies are required to assess skills retention. (C) 2013 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.

International audience; Synovitis assessment through evaluation of swollen joints is integral in steering treatment decisions in rheumatoid arthritis (RA). However, there is high inter-observer variation. The objective was to assess if a short collegiate consensus would improve swollen joint agreement between rheumatologists and whether this was affected by experience.; Eighteen rheumatologists from French university rheumatology units participated in three 30 minutes rounds over a half day meeting evaluating joint counts of RA patients in small groups, followed by short consensus discussions. Agreement was evaluated at the end of each round as follows: (i) global agreement of swollen joints (ii) swollen joint agreement according to level of experience of the rheumatologist (iii) swollen joint count and (iv) agreement of disease activity state according to the Disease Activity Score (DAS28). Agreement was calculated using percentage agreement and kappa.; Global agreement of swollen joints failed to improve (kappa 0.50 to 0.52) at the joint level. Agreement between seniors did not improve but agreement between newly qualified rheumatologists and their senior peer, which was initially poor (kappa 0.28), improved significantly (to 0.54) at the end of the consensus exercises. Concordance of DAS28 activity states improved from 71% to 87%.; Consensus exercises for swollen joint assessment is worthwhile and may potentially improve agreement between clinicians in clinical synovitis and disease activity state, benefit was mostly observed in newly qualified rheumatologists.

The functional consequences of TNF-α promoter SNPs are still controversial and, to date, the functional consequences of TNF-α haplotype combinations in healthy subjects have not been assessed. In order to assess functional consequences of each TNF-α polymorphism and of their haplotype combination, TNF-α expression and secretion by LPS-stimulated monocytes from 50 healthy subjects were assessed. Monocytes were isolated and cultured for four hours, after 100 ng/mL LPS stimulation. mRNA expression was quantified using the real-time polymerase chain reaction, and TNF-α levels were measured by enzyme-linked immunosorbent assay. Each subject was genotyped for TNF-α -857 C/T, -238 G/A, -308 G/A polymorphisms. In order to confirm definitively the functional consequences of these TNF-α polymorphisms, we then performed a systematic review of the literature for TNF-α SNPs, and then a meta-analysis of the functional studies of the TNF-α -308 G/A SNP. No association between TNF-α mRNA or protein level expression, and TNF-α -238G/A, -308G/A, -857C/T polymorphisms, studied either independently or in haplotype combinations, was revealed. Using a meta-analysis for the TNF-α -308 G/A polymorphism, we confirmed the absence of any association between TNF-α mRNA and protein levels, and TNF-α -308 G/A genotypes. This study and meta-analysis of the literature confirmed the absence of any functional consequences of the TNF-α -308G/A promoter polymorphism, either alone, or in various haplotype combinations in healthy subjects.

International audience; OBJECTIVES: To develop recommendations about pharmacotherapy (excluding biotherapeutic agents) in patients with axial forms of ankylosing spondylitis (AS) seen in everyday clinical practice. METHODS: The recommendations were based on evidence from the literature. First, a scientific committee used a Delphi procedure to select five focal points about which recommendations were needed. Then, a literature task force looked for relevant publications in the following: Cochrane, PubMed, and Ovid databases; and abstracts from the French Society for Rheumatology, European League against Rheumatism, and American College of Rheumatology. Based on the data in these publications, recommendations were drafted then validated by a group of experts. The strength of each recommendation was determined, as well as the extent of agreement among the experts. RESULTS: The four focal points were the best strategy for using nonsteroidal anti-inflammatory drugs, role for systemic glucocorticoid therapy, role for glucocorticoid injections into the sacroiliac joints and entheses, and role for slow-acting drugs (e.g., methotrexate, sulfasalazine, leflunomide, thalidomide, and pamidronate). Of the 661 promising publications identified by the literature search, 173 were found to be relevant. The evidence in these 173 papers was reported to experts during interactive workshops. At the end of the workshops, the experts drafted recommendations, which were then validated by having all panel participants vote during a final meeting. There were seven recommendations, whose strength ranged from A to D. CONCLUSION: Seven recommendations about pharmacotherapy in patients with AS were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with AS in France.

International audience; OBJECTIVE: To develop recommendations regarding imaging studies for the diagnosis and follow-up of patients with axial forms of ankylosing spondylitis (AS) seen in everyday practice. METHODS: Evidence from the literature and expert opinion were used to develop the recommendations. Using the Delphi consensus procedure, a scientific committee selected five areas of interest, about which scientific evidence was sought by searching Medline and the databases maintained by the French Society for Rheumatology, European League against Rheumatism, and American College of Rheumatology. Based on this evidence, a panel of experienced rheumatologists drafted recommendations, using expert opinion if needed to supplement gaps in evidence. For each recommendation, the level of evidence and the extent of agreement among the experts were specified. RESULTS: The five areas of interest dealt with the usefulness of imaging studies for the diagnosis, follow-up, prognostic evaluation, and assessment of treatment responses in patients with AS. The literature search retrieved 144 articles based on titles and abstracts. After elimination of articles that did not include an analysis of the radiological evaluation of AS, 73 articles were left for review. Eight recommendations were drafted then validated by having all panel participants vote during a final meeting. CONCLUSION: Eight recommendations about the use of imaging studies in patients with AS were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with AS.

International audience; OBJECTIVE: To develop French recommendations about the clinical and laboratory follow-up of patients with axial ankylosing spondylitis (AS) seen in everyday practice. METHODS: The recommendations were developed based on evidence from the literature and on expert opinion. A Delphi consensus procedure was used by a scientific committee to select five focal points, about which evidence was obtained by searching Medline and the databases maintained by the French Society for Rheumatology, European League against Rheumatism, and American College of Rheumatology. The results of the literature review were used by a panel of experienced rheumatologists to draft and to validate the recommendations, using expert opinion if needed to supplement gaps in published knowledge. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: The three focal points selected using the Delphi procedure dealt with choosing the best clinical and laboratory parameters for monitoring patients with AS; whether follow-up benefits from the use of composite indices (e.g., the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], the BAS Functional Index [BASFI] and the BAS Metrology Index [BASMI]); and the clinical and laboratory parameters that predict functional or structural outcomes in patients with AS. The literature search retrieved 1510 relevant articles based on titles and abstracts, of which 322 were selected for in-depth review. Five recommendations about the clinical and laboratory follow-up of patients with AS were developed then validated by having all panel participants vote during a final meeting. CONCLUSION: Recommendations about the clinical and laboratory follow-up of patients with AS were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with AS.

Background Spondyloarthritis (SpA) and Takayasu arteritis (TA) are two chronic inflammatory diseases; their association is rare but has already been described in the literature. Objectives The aim of this study was to describe the clinical features of patients suffering from SpA associated with TA and to identify some characteristics of SpA patients that could be suggestive of TA. Finally, we analyzed treatments that were generally used in this clinical context and their efficacy in TA. Methods This retrospective study collected patients9 cases from 10 medical centers in France. Data collection relied on a call for observations on behalf of the Club Rhumatismes et Inflammation. A standardized questionnaire was established and validated by the investigators. Results We included 14 patients, 10 of them were women. The median age at SpA diagnosis was 43.5 years (ranging from 19 to 63). Subtypes of SpA were: ankylosing spondylitis (n=11), psoriatic arthritis (n=2) and SAPHO syndrome (n=1). HLA-B27 was positive in 3 cases, negative in 9 cases and unknown in 2 cases. SpA was diagnosed before TA in 13 cases (median time of 4.5 years). During SpA patients9 follow-up, TA revealing symptoms were: clinical detection of a pulse diminution/abolition (3/14), superior limb claudication (2/14), and vascular sound (2/14). Other TA diagnoses were made by the exploration of inflammatory cervical pain (1/14), or the radiological detection of radial artery thrombosis (1/14). TA was confirmed by CT (11/14) and/or PET (6/14) or anatomopathology (1/14). Laboratory tests shown increased acute phase reactants in all cases, C-reactive protein being ≥25mg/L in 71% of the cases; systemic inflammation was the revealing factor for TA in 6 cases. Seven patients were treated with anti-TNF: 2 with adalimumab, 4 with etanercept (among whom one required a switch to infliximab and another required a switch to adalimumab, and then to golimumab) and 1 with infliximab. Anti-TNF treatment was introduced in 5/7 cases after TA diagnosis. Vascular surgery was necessary for 4 patients. Conclusions Association of SpA and TA is probably not coincidental. The recent findings of double negative T cells expressing IL-23 receptor in the aorta of mice presenting with a model of SpA supports this association [1] . The careful peripheral pulse palpation and vessels auscultation should be systematic and stay the first alert to TA diagnosis in SpA patients. Moreover, increased acute phase reactants during SpA follow-up, without alternative explanation, should alert physicians and lead to screen patients for TA, as well as for an inflammatory bowel disease. Finally, the identification of this association has therapeutic implications since anti-TNF alpha have already demonstrated their efficacy in both diseases as observed in our study. References Sherlock et al., IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+CD4−CD8− entheseal resident T cells. Acknowledgements Club Rhumatisme et Inflammation Disclosure of Interest None declared

To investigate the safety of infliximab (INF) combination therapy with leflunomide (LEF) or azathioprine (AZA) in patients with rheumatoid arthritis (RA).A standardized questionnaire on the use of INF in combination with LEF or AZA was mailed to hospital physicians and collected over a 2 month period. Adverse events (AE) and the reasons for withdrawal of combination therapy were analyzed.Data on 225 patients with RA were collected retrospectively. INF was used in combination with LEF in 171 patients and with AZA in 54. The duration of INF exposure was similar in both groups (mean 8.8 mo). AE were reported in 75 patients (33.3%), 60 LEF/INF (35%) and 15 AZA/INF combinations (27.8%) (p=nonsignificant). No unexpected AE were observed. The main AE were infections (6.2%), cytopenia (5.8%), hepatotoxicity (5.8%), reactions to infusion (5.3%), and skin reactions (4%). At the time the questionnaires were sent out, 161 patients were continuing combination therapies. The main reasons for drug withdrawal were AE (53 patients, 23.5%), inefficacy (10 patients, 4%), and one temporary discontinuation for surgery.Our study suggests that INF used in combination with LEF or AZA could be an alternative to methotrexate/INF combinations.

International audience; OBJECTIVES: To develop clinical practice guidelines for the use of methotrexate in rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing recommendations. Evidence providing answers to the five questions was sought in the Cochrane databases, PubMed, and proceedings of meetings of the French Society for Rheumatology, European League Against Rheumatism, and American College of Rheumatology. Using this evidence, a group of rheumatologists developed and validated the recommendations. For each recommendation, the level of evidence and the extent of agreement among experts were specified. RESULTS: The recommendations were as follows: 1: The starting dosage for methotrexate in patients with RA should not be less than 10 mg/week and should be determined based on disease severity and patient-related factors; 2: When a patient with RA shows an inadequate response to methotrexate, the dosage should be increased at intervals of 6 weeks, up to 20 mg/week, according to tolerance and patient-related factors; 3: When starting methotrexate treatment in a patient with RA, preference should be given to the oral route. A switch to the intramuscular or subcutaneous route should be considered in patients with poor compliance, inadequate effectiveness, or gastrointestinal side effects; 4: At present, there is no evidence indicating that a change in methotrexate dosage is in order when a TNF antagonist is given concomitantly; 5: The investigations that are mandatory before starting methotrexate therapy in a patient with RA consist of a full blood cell count, serum transaminase levels, serum creatinine with computation of creatinine clearance, and a chest radiograph. In addition, serological tests for the hepatitis viruses B and C and a serum albumin assay are recommended. In patients with a history of respiratory disease or current respiratory symptoms, lung function tests with determination of the diffusing capacity for carbon monoxide are recommended; 6: Investigations that are mandatory for monitoring methotrexate therapy in patients with RA consist of full blood cell counts and serum transaminase and creatinine assays. These tests should be obtained at least once a month for the first 3 months then every 4-12 weeks; 7: Folate supplementation can be given routinely to patients treated with methotrexate for RA. In practice, a minimal dosage of 5 mg of folic acid once a week, at a distance from the methotrexate dose, is appropriate; 8: In the event of respiratory symptoms possibly related to methotrexate toxicity, the drug must be stopped and symptom severity evaluated. Should evidence of serious disease be found, the patient should be admitted immediately or advice from a pulmonologist should be obtained immediately. CONCLUSION: Recommendations about methotrexate therapy for RA were developed. These recommendations should help to improve practice uniformity and, ultimately, to improve the management of RA.

The minimum clinically important difference (MCID) is the minimum level of change of an outcome measure that is considered to be clinically relevant. This prospective study was conducted to establish the minimum level of change in the Bath Ankylosing Spondylitis (BAS) indices that is meaningful for both the patient and the clinician.The BAS questionnaires [i.e., Bath Ankylosing Spondylitis Functional Index (BASFI); Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); and Bath Ankylosing Spondylitis patient Global score (BAS-G)] were administered to 125 patients with ankylosing spondylitis (AS) at baseline and at the end of a 2-week intensive physiotherapy program. Together with the final assessment, a global validated rating scale was used to examine each domain. Receiver operating characteristic (ROC) curves were plotted to determine the BAS change score that most accurately classified patients with respect to a clinically meaningful change. This analysis was repeated to investigate whether the estimate of change was dependent upon the patients' baseline scores.According to analyses of ROC curves, the MCID are 7 mm or 17.5% for BASFI: sensitivity = 0.60/specificity = 0.85; 10 mm or 22.5% for BASDAI: sensitivity = 0.65/specificity = 0.82; and 15 mm or 27.5% for BAS-G: sensitivity = 0.61/specificity = 0.74. MCID values were independent of the patients' baseline scores (p = 0.09 to 0.72) by regression analysis.This prospective study gives MCID values for BASFI, BASDAI, and BAS-G that allow translation from the BAS indices to readily understood values for both patients and clinicians.

In 1888, Mikulicz-Radecki reported a case exhibiting bilateral, painless and symmetrical swellings of the lacrimal, parotid and submandibular glands. In 1953, Morgan and Castleman suggested that Mikulicz disease (MD) should be reconsidered as one of the manifestations of primary Sjogren's syndrome (pSS) as they shared many histopathological characteristics. But recently, several groups demonstrated that MD may differ from pSS. Actually, MD may partly be an IgG4-related systemic disease, the other components of which are still undelineated and include autoimmune pancreatitis, chronic sclerosing sialoadenitis, Riedel's thyroiditis, some cases of cholangitis, retroperitoneal fibrosis.1 Masaki defined a new clinical entity, the IgG4 multiorgan lymphoproliferative syndrome (MOLPS), which includes these manifestations.2 It is characterised by hyper-IgG4 γ-globulinaemia and IgG4 plasma cell infiltration. There are a number of differences with …

Background In early arthritis, detection of lymphopenia may help clinician for diagnosis (connective tissue diseases, viral infections, hemopathies) or prognosis (systemic manifestations). An increased risk of infection should be anticipated when immunosuppressive treatment is prescribed. Objectives The aim of this study was to determine the prevalence of lymphopenia during early arthritis, to assess the risk of its persistence, its diagnostic and prognostic value. Methods The French Society for Rheumatology established a nationwide, longitudinal, prospective cohort, the ESPOIR cohort, to enable investigations of the diagnosis, outcome markers, epidemiology, pathogenesis, and medico-economics of early arthritis and RA. Patients were included if they were older than 18 years and younger than 70 years, had swelling of at least two joints for 6 weeks with a symptom duration no longer than 6 months, and had no prior treatment with DMARDs or glucocorticoids; however, the use of glucocorticoids for ≤2 weeks, in a mean dosage ≤20 mg/day and with discontinuation for at least the past 2 weeks, did not prevent study inclusion. Patients who were included were evaluated every 6 months for 2 years then once a year for at least 10 years. 813 patients with recent arthritis were included in the cohort ESPOIR. Patients had a clinical examination, laboratory tests (viral serology, immunological tests, cytokine profile), and radiographs. To determine the prevalence, associated factors, diagnosis and prognostic impact of persistent lymphopenia in early inflammatory joint disease, naive of lymphopenic treatment, we analyzed patients with lymphopenia at baseline and those with persistent lymphopenia at 3 years. Lymphopenia was defined by the rate of blood lymphocytes Results At baseline, 50/813 (6.2%) patients had lymphopenia. They had more often positive rheumatoid factor (p=0.02), cytopenias (p≤0.05), a higher CRP and DAS28 (p≤0.05), and hepatitis C (p=0.05) than the remainders. There were no difference in the cytokine profile and radiological progression. Diagnostics after 3 years were 27 RA, 15 unclassified arthritis, 3 SLE, 2 spondyloarthritis, one Sjogren9s syndrome, hematologic disease and fibromyalgia. Only 15/609 patients (2.5%) had persistent lymphopenia at 3 years. In 5 of these 15 patients, a cause of lymphopenia was found (SLE, hepatitis C, under nutrition, azathioprine and tamoxifen treatments). None had PVB19, HIV or HBV infection. None developed any infection, solid or hematologic neoplasia during the follow-up. Diagnostics were 6 RA, 6 unclassified arthritis, one SLE, spondyloarthritis and fibromyalgia. Conclusions Lymphopenia in early arthritis was rare and require to search another disease than RA. However, the majority of patients have active RA and cytopenias. The majority of our lymphopenic patients do not present lymphopenia during the disease course, even when they received methotrexate. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3228

Objectif. - Proposer des recommandations concernant l'utilisation d'examens d'imagerie pour le diagnostic et le suivi de la Spondylarthrite Ankylosante (SA), forme axiale en pratique quotidienne, selon la methodologie de la medecine fondee sur les preuves (Evidence Based Medicine - EBM) et l'opinion d'experts. Methodes. - Elaboration de recommandations en suivant une double approche fondee sur les preuves et sur l'avis d'experts. Choix de 5 questions, base de la redaction des recommandations, par un comite scientifique selon la methode Delphi Revue de la litterature realisee a partir des bases de donnees Medline, congres de la SFR, de l'EULAR et de l'ACR. Determination puis validation des recommandations par un comite d'experts rhumatologues a partir de ces elements, en precisant le niveau de preuve et le degre d'accord des experts pour chacune des recommandations. Resultats. - Les cinq questions selectionnees portaient sur l'interet des examens d'imagerie pour le diagnostic, le suivi, l'evaluation pronostique et l'evaluation de la reponse au traitement de la SA. La revue de la litterature a permis de selectionner 144 articles sur le titre et le resume. Les publications dont l'analyse ne concernait pas l'evaluation radiologique de la SA ont ete eliminees. Au final, 73 articles originaux ont ete inclus dans l'analyse globale. Huit recommandations relatives a l'utilisation d'examens d'imagerie au cours de la SA ont ete elaborees a partir des resultats de la revue de la litterature et de l'opinion d'experts. Ces recommandations ont ete validees par un vote final de l'ensemble des participants. Conclusion. - Des recommandations relatives a l'utilisation d'examens d'imagerie au cours de la SA ont ete elaborees. Ces recommandations devraient pouvoir contribuer a une plus grande homogeneite des pratiques et a terme, a une optimisation de la prise en charge des patients atteints de SA.

Background The BAFF (or BLyS) cytokine plays a key role in pathogenesis of primary Sjogren’s syndrome (pSS). The level of BAFF is increased in the serum and BAFF may be expressed by salivary epithelial cells and the lymphoid infiltrate of salivary glands. Moreover, BAFF is induced by innate immunity stimulation, the later playing a role in pSS pathogenesis. Belimumab, the first biological treatment inhibiting soluble BAFF/BLyS has proved its effectiveness in systemic lupus and has been recently approved for this indication. Lupus and pSS share a lot of pathogenic mechanism including interferon signature and BAFF involvement. Thus we run the first open label study of belimumab in pSS patients and recently showed that 19/30 patients (63%) achieved the primary end-point which was a composite clinico-biological outcome. Objectives To address the change in labial salivary gland (LSG) inflammation after Belimumab therapy Methods Patients were included in 2 parallel and identical studies in 2 European Centres. Patients had to fulfill AECG criteria, to be anti-SSA/SSB positive and had to have at the time of inclusion either systemic complications or early disease ( Minor labial salivary gland (LSG) biopsies of the 15 patients (all female, mean age=50 yrs, mean disease duration= 5 yrs) from the French center, performed at W0 and W28, were analyzed for estimating the focus score, the B-cell/T-cell ratio (CD20 and CD3 staining), BAFF expression (BAFF (Buffy-2) staining) and NK infiltrate (NKp46 staining). Results Before treatment, significant lymphocytic sialadenitis (focus score >1) was observed in 11 (78.6%) patients before treatment, five of whom became negative (focus score B-cell /T cell ratio decreased after treatment in 5 patients and remained stable in all other patients (median ratio decreased from 0.58 to 0.50, p=0.055). Before treatment, a BAFF staining was detected in 11/14 (78.6%) patients, and in only 7/14 (50.0%) after belimumab (p=0.07). The median percentage of BAFF positive cells in foci significantly decreased from 27.5% to 5% after belimumab therapy (p=0.03). NKp46 staining revealed that NK cells infiltrate was predominantly located in interstitium rather than in foci (median number of NK cell: 24.7 vs. 8.2/mm², p=0.0003), and did not change after belimumab. Conclusions There was a clear tendency in favour of a decrease in foci number, B cells and BAFF-expressing cells within LSG after belimumab therapy. It is tempting to interpret the decrease in BAFF staining as an effect of the drug on membrane BAFF-expressing cells, but it could be also only due to the decrease in B cells expressing BAFF receptors linked to soluble BAFF passively stained by the anti-BAFF antibody. After belimumab therapy, we observed regression of lymphocytic infiltration of LSG in one third of the patients. Also the percentage of BAFF positive cells significantly decreased with a trend to a decrease of B-cell/T-cell ratio. Disclosure of Interest None Declared

Background Dickkopf-1 (DKK-1) is an inhibitory protein of the Wnt signalling pathway that could rationally be involved either in AS osteoporosis or in the osteoblastogenesis associated with syndesmophyte construction. Objectives To investigate DKK-1 serum levels among patients with recent inflammatory back pain (IBP) fulfilling ASAS criteria for spondyloarthritis (SpA) and to investigate the parameters associated or correlated with DKK-1 increase. Methods The DESIR cohort is a prospective, multicenter French cohort of patients with early IBP (Calin or Berlin criteria) (>3 months and Results Serum DKK-1 levels were available for 695 patients with IBP (472 of them fulfilling ASAS criteria for axial SpA) and were significantly increased in SpA patients (mean ± SEM 30.7±0.7 pmol/L) compared with controls (10.8±1.1 pmol/L) ( p 0; N=131) (mean ± SEM 35.4±1.6 pmol/L) compared with patients with normal X-Rays (N=334) (mean ± SEM 28.6±1.1 pmol/L) (P Conclusions This study conducted in a large cohort of patients presenting with early axial SpA clearly showed an increase in DKK-1 serum levels, such increase being even more important in the subgroup of patients with syndesmophytes. Such latter results might be the consequence of DKK-1 dysfunction (1,2), e.g through an impaired fixation of DKK-1 on its receptor LRP5/6. References [1]Diarra D, et al. Nat Med. 2007 Feb;13(2):156-63. [2]Daoussis D, et al. Arthritis Rheum. 2010 Jan;62(1):150-8. Disclosure of Interest None Declared

Background “Tight control” of rheumatoid arthritis (RA) necessitates regular disease activity assessment using clinical joint counts. However, joint counts take time, and are not always performed in busy clinics [1]. Nurses are now increasingly involved in joint count assessment but training for joint counts is not standardised. Objectives Evaluate an effective method of teaching nurses to perform 28-joint counts (tender and swollen). Methods This was the first phase of a national study (COMEDRA).Twenty nurses from university rheumatology centers without any joint count experience were allocated to a rheumatologist from their center (trainer). Training program consisted of 2 phases: Phase 1 was a centralized 4 hour training session, with (a) a one-hour lecture and demonstration, and (b) practical sessions on patients with the trainers. Phase 2 involved further practice on 20 patients in their own hospitals; with 10 nurses randomized to (i) one additional comparative assessment with the trainer for patient 10, and 10 nurses to (ii) no further training (but a separate assessment by the trainer at patient 10). Strength of agreement was measured between each nurse and his/her trainer, through prevalence adjusted biased adjusted kappa (PABAK); poor agreement Results Mean pooled PABAK for swollen joint agreement at baseline was 0.67 (95%CI 0.57, 0.77). By the end of the training program, this increased to 0.82 (95%CI 0.80, 0.93). There were successive improvements in swollen joint PABAK at each assessment point and by the end of training; everyone had achieved a swollen joint PABAK >0.60 with their trainer except 2 nurses. Most of the improvement was seen during Phase 2. In Phase 2, swollen joint agreement improved for those who had the additional training; from PABAK 0.71 (95%CI 0.57, 0.84) to 0.83 (95%CI 0.70, 0.96), but not for those who had no further training; PABAK 0.79 (95%CI 0.53, 1.0) to 0.80 (95%CI 0.62, 0.99). The agreement for tender joints remained very good throughout Phase 1 and 2 with PABAK >0.80 at each assessment point. Conclusions Nurses can effectively learn how to perform swollen and tender joint counts with this teaching method. Swollen joint agreement improved significantly. This method can be practically applied in the clinical setting. References Pincus T, Segurado OG. Ann Rheum Dis 2006; 65: 820-2. Disclosure of Interest None Declared

Introduction There is a suspicion of increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferations in patients with inflammatory arthritides receiving immunosuppressive drugs. We investigated the EBV load and EBV-specific T-cell response in patients treated with methotrexate (MTX) or anti-TNF therapy. Methods Data for patients with rheumatoid arthritis (RA) (n = 58) or spondylarthropathy (SpA) (n = 28) were analyzed at baseline in comparison with controls (n = 22) and after 3 months of MTX or anti-TNF therapy for EBV load and EBV-specific IFNγ-producing T cells in response to EBV latent-cycle and lytic-cycle peptides. Results The EBV load and the number of IFNγ-producing T-cells after peptide stimulation were not significantly different between groups at baseline (P = 0.61 and P = 0.89, respectively). The EBV load was not significantly modified by treatment, for RA with MTX (P = 0.74) or anti-TNF therapy (P = 0.94) or for SpA with anti-TNF therapy (P = 1.00). The number of EBV-specific T cells was not significantly modified by treatment, for RA with MTX (P = 0.58) or anti-TNF drugs (P = 0.19) or for SpA with anti-TNF therapy (P = 0.39). For all patients, the EBV load and EBV-specific T cells were significantly correlated (P = 0.017; R = 0.21). For most patients, short-term exposure (3 months) to MTX or anti-TNF did not alter the EBV load or EBV-specific T-cell response but two patients had discordant evolution. Conclusions These data are reassuring and suggest there is no short-term defect in EBV-immune surveillance in patients receiving MTX or anti-TNF drugs. However, in these patients, long term follow-up of EBV-specific T-cell response is necessary and the role of non-EBV-related mechanisms of lymphomagenesis is not excluded.