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Non-cancer pain of the locomotor apparatus is the main symptom justifying referral to a rheumatologist with potential introduction of opioids, leading to addiction if misused. The objective was to evaluate the impact of a personalized pharmaceutical plan on patients' knowledge of their opioid treatment and its duration. This prospective non-randomized pilot study was conducted during 7 months with standardized data collected in a French rheumatology department. Patients with rheumatic diseases and non-cancer pain requiring opioid treatment were included. The intervention group had a 30-min opioid-targeted pharmaceutical interview and received a full medication plan and the control group received usual care. A total of 17 patients were included in the intervention group and 18 in the control group. Among patients in the intervention group, only 6 (35%) knew that immediate-release opioids have a rapid and short action, 9 (53%) were worried about taking opioids, and 13 (76%) reported that they would refer to the information document provided if side effects occurred. A trend toward a shorter duration of treatment was observed in the study group (HR = 1.87, 95% CI 0.93 to 3.76, p = 0.08), but this trend was attenuated when adjusting on hospital duration (HR = 1.53, 95% CI 0.74 to 3.15, p = 0.25). This pilot study provides preliminary evidence on the role of the clinical pharmacist in the management of non-cancer pain with strong opioids. Clinical benefits will be assessed in a randomized study. Key Points • Knowledge of opioids is insufficient in rheumatology patients with non-cancer pain. • Pharmaceutical interviews may improve patients' knowledge of opioids.

This study aims to evaluate in patients hospitalized for vertebral osteomyelitis (VO) the effectiveness of bacteriological diagnosis and the yield of percutaneous needle biopsy (PNB) and to identify factors associated with the result of PNB. This retrospective, two-centre study was conducted between 2000 and 2009. Data on patients with VO were retrieved from the diagnosis database and confirmed by checking medical records. A total of 300 patients with VO were identified; 31 received antibiotics without bacteriological diagnosis, and 269 patients with spondylodiscitis imaging were included. Eighty-three (30.9%) and 18 (6.7%) infections were documented by blood cultures and by bacteriological samples other than PNB, respectively; 168 patients with no bacteriological diagnosis had PNB. Of these, 92 (54.8%) were positive and identified the pathogen and 76 (45.2%) were negative. The most common bacteria were Staphylococcus aureus (34.3%), Streptococcus spp. (20.6%) and coagulase-negative staphylococcus (14.8%). After multivariate analysis, the only factor associated with negative PNB was previous antibiotic intake (OR: 2.31 [1.07-5.00]). When VO was suspected on imaging, bacteriological investigation identified the microorganism in 209/300 (70%) of the cases. The yield of PNB was 54.8%. The only predictor of PNB negativity was previous antibiotic intake. Therefore, we believe that a second PNB should be done after a sufficient delay withdrawal of antibiotics if the first sample was negative. The study was retrospectively registered by the local ethics committee (N°E2019-61).

Rhupus syndrome is better characterized, but uncertainties remain, and therapeutic management must be defined. The objective was to analyze therapeutic procedures with a focus on biologic disease-modifying antirheumatic drugs (bDMARDs).This 10-year medical records review was based on diagnosis codes (rheumatoid arthritis [RA] and systemic lupus erythematosus [SLE]) and biological data (anti-CCP testing, anti-dsDNA, and anti-RNP antibodies). Patients fulfilling 2010 ACR/EULAR and 2012 SLICC and/or 2019 ACR/EULAR classification criteria for RA and SLE, respectively, were included.Sixteen patients were identified. Rheumatoid arthritis most often preceded rhupus, with predominant articular pattern; 11 of them had erosive arthropathy. Skin involvement was the most frequent associated manifestation (n = 12). Serious events were reported, including active glomerulonephritis (n = 3), ischemic stroke (n = 1), and myocardial infarction (n = 1). Immunological profiles showed positivity for antinuclear (n = 16), anti-dsDNA (n = 9), and anti-CCP (n = 9). Ten patients required bDMARDs. All types of RA-approved bDMARDs were used. Abatacept was considered effective in 3 of the 4 patients, with 1 primary failure, 1 secondary escape, and 2 therapeutic maintenances, whereas primary or secondary failure was observed under tocilizimub and TNF-blocking agents. Rituximab was the most prescribed (n = 9) and the most effective with a sustained response in 6 patients.In rhupus refractory to conventional treatment, T or B lymphocytes targeted therapies, and particularly rituximab, seem to be a relevant therapeutic option unlike anticytokine biologics.

Objective Cryopyrin-associated periodic syndrome (CAPS) is a rare but treatable inherited autoinflammatory condition including familial cold autoinflammatory syndrome (FCAS), Muckle–Wells syndrome (MWS) and chronic infantile neurologic cutaneous articular syndrome (CINCA). Our objective was to describe the main features of CAPS AA amyloidosis (AA-CAPS) associated and the efficacy of IL-1 inhibitors in this indication. Methods Retrospective study in France associated with a systematic literature review. Results Eighty-six patients were identified: 23 new French cases and 63 from the literature, with a median age at amyloidosis diagnosis of 39 years old. CAPS subtypes were MWS (n = 62), FCAS (n = 9), frontier forms between MWS and FCAS (n = 12) and between CINCA and MWS (n = 3). NLRP3 had been sequenced in 60 patients (70%) and the most frequent mutation was R260W (60%). Three AA-CAPS patients displayed somatic NLRP3 mutations. Death occurred in 35 patients (41%), none of whom having ever received IL-1 inhibitors. Twenty-eight patients (33%) received IL-1 inhibitors, with a >50% decrease in proteinuria in 89% of cases. Conclusion AA amyloidosis can occur in nearly all CAPS subtypes. IL-1 inhibitors are effective, underlining the necessity of an early diagnosis of CAPS in order to start this treatment as soon as possible among AA-CAPS patients.

International audience; An association between sarcoidosis and spondyloarthritis (SpA) has already been reported. The prevalence of sacroiliitis in sarcoidosis was estimated between 6.6% and 23.4%. All patients with sacroiliitis were diagnosed with SpA according to the Assessment of SpondyloArthritis International Society (ASAS) classification criteria. However, sacroiliac joint involvement has been described in sarcoidosis without associated SpA.This association led us to determine a clinical form of sarcoidosis predictive of SpA development and to evaluate their respective management.We conducted a retrospective, single-center, multiparameter, case-control study that enrolled patients with a sarcoidosis/SpA sequence, followed up between 1992 and 2018, who were randomly matched to patients with sarcoidosis without SpA development during the same period. Identification of patients was performed via a semantic query in the database of the Normandy Clinical Data Warehouse (NCDW). The diagnoses of sarcoidosis and SpA were based on ATS/ERS/WASOG and ASAS diagnostic and classification criteria, respectively. The number of events was gathered under one entity based on sarcoidosis organ involvement. The predictive effect of different variables, collected at the time of sarcoidosis diagnosis, on SpA occurrence was studied using conditional logistic regression models (PROC PHREG). This study has been approved by the local Institutional Review Board (E2020-91). Twenty-two patients with a sarcoidosis/SpA sequence were identified; 66 controls were selected. The proportion of organ involvement related to sarcoidosis was similar between the two groups except for rheumatologic manifestations. In cases, the mean (SD) delay to SpA diagnosis was 7.7 years [range 0–25]. The occurrence of SpA was significantly associated with the rheumatologic involvement of sarcoidosis (OR 6.42 95%CI [2.30–19.59] P < 0.01 after Bonferroni's correction). This association remained significant in our age- and sex-adjusted model (OR 5.36 95%CI [1.80–17.19] P < 0.05). No specific rheumatologic clinical picture could be identified, but axial involvement, corresponding to inflammatory back pain and alternating buttock pain, was more frequently observed in cases, resulting in a higher proportion of patients presenting a combined pattern of axial and peripheral involvement. SpA characteristics of patients with sarcoidosis developing SpA are summarized in Appendix A.

International audience; Le syndrome de chevauchement polyarthrite rhumatoïde (PR)/sclérodermie systémique (ScS) est une association rare et peu étudiée. Elle concerne 5 % des patients atteints de ScS. Seules des études ouvertes ayant évalué les biomédicaments (bDMARDs) ont rapporté des résultats encourageants, notamment sur l’atteinte articulaire. La prise en charge de ces patients n’est donc pas codifiée. L’objectif était d’analyser en conditions réelles la stratégie thérapeutique et la réponse aux bDMARDS, avec un focus sur l’atteinte articulaire

Resume La maladie de Castleman est une pathologie lymphoproliferative rare regroupant plusieurs tableaux cliniques et histologiques. Nous rapportons deux cas de maladie de Castleman chez des patientes atteintes de spondyloarthrite (avec et sans psoriasis) traitees par anti- Tumor Necrosis Factor-alpha. Au cours d’examens morphologiques realises pour le bilan de la maladie, ont ete decouvertes fortuitement une masse pelvienne accolee au psoas ou une adenopathie atypique. Les deux lesions fixaient moderement a la tomographie par emission de positon couplee au TDM. Apres exerese chirurgicale et analyse histologique, la maladie de Castleman est diagnostiquee sans mise en evidence de signes de malignite. A notre connaissance, il s’agit des premiers cas de maladie de Castleman diagnostiques dans un contexte de spondyloarthrite traitee par anti- Tumor Necrosis Factor-alpha. La relation entre ces deux pathologies et le lien avec l’anti- Tumor Necrosis Factor-alpha n’ont pas ete explores dans la litterature jusqu’a maintenant.

This work aimed to assess treatment adherence in rheumatoid arthritis patients with several tools and to identify factors associated with poor adherence.Between February and December 2015, 183 patients were included in this cross-sectional study. A homemade 23-item self-questionnaire was filled by patients during an outpatient consultation or a day hospitalization stay. Morisky Medication Adherence Scale (MMAS)-4, MMAS-8 and Girerd scores were extracted from this homemade questionnaire. Medication possession ratio (MPR) was then calculated. For identification of factors associated with nonadherence, patients were divided in two groups according to MMAS-8 results differentiating patients with good or bad adherence to treatments.Of the 183 patients, 59% received a combination of biologic and conventional synthetic disease-modifying drugs, 22% a biological treatment alone, and 19% a conventional DMARD alone. Respectively, 3%, 10%, and 7% were considered as low adherent according to MMAS-4, MMAS-8, and Girerd scores. MPR was calculated for 84/183 patients; 23% were low adherent. The need for a help in preparing the drugs (p = 0.05; OR = 6.12; 95% CI: 0.86 to 268.90) and concomitant diabetes (p0.001; OR = 0.045, 95% CI: 0.001 to 0.299) was higher in patients with good adherence. Presence of a patient's relative reminding to take medications was associated with low adherence (p = 0.002; OR = 4.32, 95% CI: 1.41 to 13.11).This study highlighted the difficulty of assessing treatment adherence in rheumatoid arthritis patients despite four different tools. Objective measures by MPR indicated a higher proportion of poor adherent patients than self-questionnaires.Key Points• Proportion of patients considered as low adherent ranged from 3 to 27% according to the method of evaluation.• The use of a pillbox and/or the preparation of drugs by a patient's relative was associated with good adherence.• The presence of a patient's relative reminding to take medication was associated with low adherence.

International audience

Resume L’accroissement du nombre de molecules disponibles pour le traitement de la polyarthrite rhumatoide incite les rhumatologues a identifier et valider des biomarqueurs de reponse ou biomarqueurs theranostiques, capables de predire la reponse aux traitements, prealablement a toute exposition. Cette demarche s’inscrit dans le contexte de medecine personnalisee afin de traiter efficacement un patient donne et a un instant donne. Les anticorps anti-peptides citrullines, les facteurs rhumatoides et la signature interferon sont les biomarqueurs les plus robustes et valides parmi tous ceux identifies. Les matrices utilisant des parametres cliniques ou biologiques, diagnostiques ou pronostiques, semblent pertinentes pour definir un traitement a l’echelon individuel. Par ailleurs, le developpement des approches a grande echelle sans a priori, comme la genomique fonctionnelle ou la metabolomique, representent une voie de recherche tout a fait prometteuse, bien que la replication des resultats reste difficile. La complexite de la reponse therapeutique chez un meme patient et la variabilite interindividuelle incitent a identifier des combinaisons de biomarqueurs plutot qu’un seul biomarqueur. L’objectif de cette revue est de faire le point sur les differentes approches utilisees pour identifier des biomarqueurs theranostiques et de recenser l’ensemble des biomarqueurs disponibles en discutant de leur performance en pratique clinique. Cependant, le nombre de biomarqueurs actuellement utilisables en pratique quotidienne reste tres limite.

International audience

International audience

Background Native joint and bone infections (NJBI) are associated with infective endocarditis (IE) in 15% of cases. There are no studies analyzing the use of cardiac imaging in cases of NJBI. The objective of this study was to identify factors associated with echocardiography suggestive of IE in patients with NJBI. Methods This medical records review was conducted in patients hospitalized for NJBI between 2007 and 2017 in Rheumatology and Infectious Diseases departments of 2 university hospitals. Patients included had a microbiologically proven NJBI during their hospitalization. Results In this cohort of 546 patients, median age 66 years, echocardiography was suggestive of IE in 66 (12%). In multivariate analysis, factors associated with echocardiography suggestive of IE were 2 or more positive blood cultures (OR 11.55 (CI95% 3.24–74.20)), cardiac conditions with a high risk of IE (OR 7.34 (CI95% 2.95–18.61)), unknown heart murmur (OR 4.59 (CI95% 1.79–11.74)), multifocal infection (OR 2.26 (CI95% 1.21–4.23)) and an infection due to S. bovis (OR 3.52 (CI95% 1.26–9.79)). The factor associated with the absence of an echocardiography evocative of IE was infection due to unconventional bacteria for IE (OR 0.13 (CI95% 0.01–0.76)). According to the factors associated with echocardiography evocative of IE, we propose the Normandy score based on three kinds of data: cardiac condition, bacterial strain and NJBI mechanism. Echocardiography should be realized when this score, whose negative predictive value is 100% CI95% (98–100%) for prescription of echocardiography, is more than zero. Conclusions A score based on valvular condition, bacterial strain and NJBI mechanism could guide clinicians in prescribing echocardiography during NJBI with an excellent negative predictive value.

Castleman's disease is a rare lymphoproliferative syndrome involving several anatomical and clinical entities. We report two cases of Castleman's disease in patients with spondyloarthritis (with and without psoriasis) treated with Tumor Necrosis Factor-alpha blockers. During follow-up, imaging examinations, carried out for disease assessment, fortuitously revealed a pelvic mass close to the psoas or an atypical cervical adenopathy. Both lesions were in moderate hypermetabolism on Positron emission tomography-computed tomography. After surgical excision and histological analysis, Castleman's disease was diagnosed without signs of malignancy. To the best of our knowledge, these are the first cases of Castleman's disease diagnosed in a context of spondyloarthritis treated with Tumor Necrosis Factor-alpha blockers. The relationship between these two pathologies and the link with Tumor Necrosis Factor-alpha blockers agents has not been explored in the literature until now.

International audience; Objectives: Abatacept acts as a competitive inhibitor of the CD28/(CD80/86) costimulation signal required for T cell activation. Mechanisms of action of abatacept have not been fully investigated. The objective of this study was to provide detailed insight into the mode of action of Abatacept based on gene expression data. Methods: In this ancillary study from the APPRAISE trial, we investigated the global molecular effects of Abatacept in whole blood samples collected prospectively in biologic naive rheumatoid arthritis patients (n = 19) at baseline and 6 months after the initiation of Abatacept therapy concomitant with methotrexate. Whole human genome microarrays (4x44K) were performed on both baseline and 6-month samples from responders and non-responders patients categorized according to EULAR criteria. T-test with Benjamini-Hochberg correction was performed to identify significant gene expression changes. Gene Ontology and Single Experiment Analysis tools allowed us to highlight specific biological mechanisms involved in methotrexate/Abatacept. Results: In methotrexate/Abatacept responders, 672 genes were significantly (q

Debido a la abundancia y la complejidad de sus elementos anatomicos, asi como a las exigencias biomecanicas a las que se ve sometida, la rodilla es una de las articulaciones que mas frecuentemente se ven afectadas por diversos procesos patologicos. El enfoque es ante todo clinico. En ausencia de un contexto traumatico, la actitud dependera de la presencia o no de derrame articular. En caso de inflamacion de la rodilla, una vez descartada la bursitis prerrotuliana y el sindrome de dolor regional complejo de tipo I, se debe investigar una posible monoartritis. Aparte de las etiologias bacteriana, por microcristales e inflamatoria, el derrame articular en personas jovenes puede ser revelador de osteocondromatosis o de un tumor sinovial. Cuando no hay inflamacion, lo primero es descartar una lesion a distancia de la rodilla, como una coxopatia o un problema de la columna vertebral. Si la causa esta en la rodilla, los trastornos mecanicos pasan al primer plano. La orientacion etiologica se basa en la edad del paciente, las caracteristicas del dolor, los mecanismos de aparicion, la localizacion del dolor y la presencia o ausencia de signos acompanantes, como la sensacion de inestabilidad, los bloqueos verdaderos y los seudobloqueos. En una persona de 50 anos, el dolor difuso de instauracion progresiva sugiere la existencia de una gonartrosis, mientras que un dolor en la cara interna de aparicion brusca debe hacer pensar en una osteonecrosis del condilo interno, una fractura por sobrecarga o una ruptura meniscal (casi siempre en una rodilla artrosica).

Ante un dolor de cadera, la primera cuestion es saber si la articulacion coxofemoral esta implicada, ya que puede corresponder a la irradiacion de una patologia raquidea como un sindrome de la charnela toracolumbar. La anamnesis y la exploracion fisica son etapas fundamentales. El manejo diagnostico debe tener en cuenta la localizacion del dolor, su modo de aparicion, su ritmo, la limitacion o no de ciertos movimientos de la articulacion asi como los signos asociados. El dolor puede localizarse en el hueco inguinal o en el gluteo y/o en la region peritrocanterea y/o en el muslo. De topografia inguinal, el dolor puede ser agudo, de tipo inflamatorio (coxitis infecciosa que debe sugerirse en primer lugar, coxitis inflamatoria en el marco de una espondiloartritis en el paciente joven o de una condrocalcinosis en el anciano, coxartrosis rapidamente destructiva) o de tipo mecanico, que traduce un acceso congestivo de artrosis o una osteonecrosis aseptica de la cabeza femoral, incluso una fractura de estres de la cabeza femoral. Para estas dos ultimas etiologias, la resonancia magnetica (RM) ocupa un lugar destacado, asi como en la algoneurodistrofia de cadera. Cuando evoluciona de forma cronica, la primera hipotesis que hay que tener en cuenta es la de una coxartrosis; en el paciente joven deportista, se debe pensar en un compromiso anterior femoroacetabular. Cuando la localizacion del dolor no es inguinal, la etiologia puede orientarse gracias a los datos obtenidos por la movilizacion activa y/o pasiva de la cadera. En ausencia de limitacion de las amplitudes de movimiento, se puede sugerir una ciatalgia o una cruralgia. En caso de movilizacion activa dolorosa y de desencadenamiento del dolor en una sola maniobra, se sugiere una patologia periarticular, en particular tendinosa. La mas frecuente es la tendinobursitis trocanterea. Por ultimo, se dedica un paragrafo especifico al manejo del caso de una cadera protesica dolorosa.

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 10 janvier 2018

Resume Le tabac, qui est un facteur de risque reconnu de developpement d’une polyarthrite rhumatoide (PR), peut egalement avoir un impact sur le devenir de la maladie. Les donnees sont assez bien documentees sur le tabagisme actif. En termes d’activite du rhumatisme, les resultats sont plutot contradictoires. Il semble associe a une activite articulaire et systemique plus marquee au debut de la maladie mais il n’apparait pas predictif d’une activite persistante de la maladie. S’agissant de la severite de la PR, le tabagisme actif n’est pas predictif d’une progression structurale plus importante et aurait plutot des effets « protecteurs ». En revanche, il contribue a la survenue de manifestations extra-articulaires (nodules rhumatoides, pneumopathie interstitielle infraclinique et symptomatique, parodontopathie, vascularite) et majore le risque d’infections severes, d’infection periprothetique, de cancer pulmonaire et de deces. Quel que soit le statut immunologique, le tabagisme est associe a une moindre reponse au methotrexate et aux 3 antagonistes du TNF (infliximab, etanercept et adalimumab) qui ont ete evalues. Nous ne disposons pas d’informations de son impact sur les autres agents biologiques. En outre, les taux de remission et de maintien therapeutique sont moindres en cas d’exposition au tabac. Neanmoins, il n’a pas d’effet pejoratif en cas d’allegement ou d’arret du traitement. Alors que l’arret du tabac, qui reste un objectif difficile a atteindre en raison de plusieurs freins identifies, ne semble pas modifier l’activite de la maladie, son interet demeure pour limiter l’apparition de manifestations extra-articulaires, de complications infectieuses et d’une surmortalite d’origine cardiorespiratoire ou tumorale.

Background:Tofacitinib is an oral JAK inhibitor indicated for moderate to severe active rheumatoid arthritis (RA).Objectives:To present baseline patients characteristics and effectiveness data at 6 months of DeFacTo real life study (“IDentification of Factors predictive of Tofacitinib’s survival”).Methods:DeFacTo is an observational, open-label, prospective, multi-center, national study designed to evaluate the predictive factors of tofacitinib’s survival in patients with moderate-to-severe active rheumatoid arthritis according to the SmPC[1]. Here we present the 1st interim results involving a descriptive analysis of the 221 patients included between January 2019 and March 2020 (POP1). Effectiveness results at 6 months of 145 patients having ≥ 6 months follow-up (POP2) are also described.Results:The baseline characteristics of the POP1 patients (n = 221) were: 78.3% women with a mean age (± SD) of 60.4 ± 11.1 years, disease duration of 12.0 ± 9.8 years, TJC: 7.3 ± 5.7 and SJC: 5.1 ± 4.7; 44.0% of patients had erosions, 79.5% were RF+ and 75.9% were ACPA+. The mean CRP was 15.3 ± 21.8 mg/l, the ESR at one hour was 28.7 ± 23.6 mm, DAS28-4 CRP was 4.6 ± 1.0, DAS28-4 ESR was 4.9 ± 1.1 and the FACIT-Fatigue score was 27.6 ± 11.3. A total of 97.3% of patients had been previously treated by ≥1 csDMARD (mean number 1.9 ± 1.0) and 66.1% by b/tsDMARDs (mean number 2.9 ± 2.5), tofacitinib was prescribed as monotherapy (without csDMARD) in 49.3% of patients. The characteristics of the POP2 patients were similar to those of POP1. At 6 months in POP2, 29 patients have discontinued their treatment with tofacitinib. The results showed a decrease from baseline in inflammatory markers (CRP from 14.2±17.1 to 4.7±4.2 mg/l), pain (Pain VAS from 58.3±23.4 to 27.6±22.1) and DAS28 activity scores with 23% of patients in DAS28-CRP remission and 36% of patients in DAS28-CRP LDA (figure 1). This interim analysis didn’t identifyany new safety findings (Table 1).Conclusion:Preliminary results from this prospective observational study on the use of tofacitinib in patients suffering with RA in France indicate that its effectiveness and safety are similar to those found in the clinical studies[1-3]. In this study, tofacitinib was prescribed as monotherapy (without csDMARD) in more than 49% of cases.References:[1]European Medicines Agency, Tofacitnibi SmPc (summary of product characteristics).[2]Burmester G et al. Lancet. 2013; 381: 451-460.[3]Fleischman R et al. Lancet 2017; 390: 457-6.[4]Wollenhaupt et al. Arthritis Research & Therapy (2019) 21:89Figure 1.Patients with LDA or remission at baseline and 6 monthsTable 1.Safety dataTolerability, n patients (%)≥ 65 years, n = 86Total n = 218AE56 (42.4)33 (38.4)89 (40.8)Serious AE8 (6.1)5 (5.8)13 (6.0)Herpes Zoster4 (3.0)2 (2.3)6 (2.8)Infection27 (20.5)15 (17.4)42 (19.3)Severe infection2 (1.5)2 (2.3)4 (1.8)Acknowledgements:To all investigators involved in this study.Disclosure of Interests:Cécile Gaujoux-Viala Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB, Consultant of: AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB, Andre BASCH Speakers bureau: Janssen, Novartis, Amgen, BMS, Abbvie, Lilly, Pfizer, MSD, UCB, Consultant of: Janssen, Novartis, Amgen, BMS, Abbvie, Lilly, Pfizer, MSD, UCB, Slim Lassoued: None declared, Fabienne COURY-LUCAS Consultant of: AbbVie, Bristol-Myers Squibb, Janssen, Lilly, MSD, Novartis and Pfizer, Grant/research support from: AbbVie, Biogen, Roche Chugai, Pfizer, and UCB, Meriem Kessouri Shareholder of: Pfizer, Employee of: Pfizer, Nadir Mammar Shareholder of: Pfizer, Employee of: Pfizer, Thierry Lequerre Consultant of: Abbvie, BMS, Boeringher, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Roche – Chugai, Sanofi, UCB, Carine Salliot Consultant of: Biogen, Lilly, Novartis, Roche Chugai, Pfizer

Les anticorps anti-peptides-cycliques-citrullinees (anti-CCP) sont des biomarqueurs fiables pour caracteriser les patients atteints de polyarthrite rhumatoide (PR). Des etudes ont montre que leur positivite pouvait influencer la reponse aux biomedicaments. L’objectif de notre etude etait de determiner si le titre des anti-CCP a l’introduction du traitement est predictif de remission chez les patients traites par abatacept, inhibiteurs du facteur de necrose tumorale alpha (anti-TNF-α) ou tocilizumab. Materiels et methodes : Dans cette etude observationnelle, retrospective, ont ete inclus des patients atteints de PR suivis au C.H.U. de Rouen, traites par abatacept, anti-TNF-α ou par tocilizumab entre octobre 2009 et mai 2021. Les patients ont ete separes en 3 groupes : anti-CCP negatifs, anti-CCP positifs 340 UI/mL, et cela pour chaque biomedicament. Pour savoir s’il existe un lien entre le titre des anti-CCP et l’obtention d’une remission ou d’une faible activite (definies par le DAS28) a 12 mois de traitement, des analyses univariees et multivariees avec ajustement sur les caracteristiques initiales ont ete realisees. Une analyse en sous groupe a egalement ete effectuee en distinguant parmi les patients traites par anti-TNF-α ceux traites par etanercept de ceux traites par un anti-TNF-α monoclonal. Resultats : Parmi les 329 patients inclus, 99 etaient traites par abatacept (28 anti-CCP negatifs, 40 anti-CCP positifs 340 UI/mL), 180 par anti-TNF-α (38 anti-CCP negatifs, 93 anti-CCP positifs 340 UI/mL) et 50 par tocilizumab (11 anti-CCP negatifs, 23 anti-CCP positifs 340 UI/mL). L’âge median des patients a l’introduction du traitement etait de 57 [47 - 67] ans. Le sex-ratio etait de 2,96 femmes pour 1 homme. La duree d’evolution mediane de la PR avant l’initiation du biomedicament etait de 7 [2 - 12] ans ; 73,6% des patients presentaient une atteinte structurale. Pour chacune des molecules, les caracteristiques des patients a l’introduction du biomedicament etaient comparables, quel que soit le titre des anti-CCP, sauf pour les facteurs rhumatoides (FR) dont la positivite etait moins frequente dans les groupes anti-CCP negatifs. Apres analyse univariee puis ajustement sur les caracteristiques initiales, aucune association significative n’a ete montree entre le titre des anti-CCP et la proportion de remission ou de faible activite chez les patients traites par abatacept, anti-TNF-α ou tocilizumab. Dans l’analyse en sous groupe, le titre des anti-CCP semblait influencer la remission avec l’etanercept, mais pas avec les anti-TNF-α monoclonaux. Cette association n’etait pas retrouvee en analyse multivariee. Conclusion : Le titre des anti-CCP a l’introduction du biomedicament n’a pas d’impact sur l’obtention d’une remission selon le DAS28 apres un delai de 12 mois de traitement par abatacept, anti-TNF-α ou tocilizumab.

Objectives To study the characteristics of B-cell non-Hodgkin’s lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence. Methods A multicentre case–control study was performed in France. Cases were patients with RA fulfilling ACR-EULAR 2010 criteria in whom B-cell NHL or Hodgkin lymphoma developed after the diagnosis of RA. For each case, 2 controls were assigned at random from the ESPOIR cohort and were matched on age at lymphoma diagnosis (cases)/age at the 10-year follow-up visit in the cohort (controls). Case and control characteristics were compared to identify parameters associated with the occurrence of lymphoma. Results 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphoma (DLBCL, n=27, 50.0%). On immunochemistry, 4 of 27 (14.8%) lymphoma cases were positive for Epstein-Barr virus. On univariate analysis, factors associated with the occurrence of lymphoma were male sex (OR 3.3, 95% CI 1.7 to 6.7), positivity for ACPA (OR 5.1, 95% CI 2.0 to 15.7) and rheumatoid factor (OR 3.9, 95% CI 1.6 to 12.2), and erosions on radiographs (OR 3.8, 95% CI 1.7 to 8.3) and DAS28 (OR 2.0, 95% CI 1.5 to 2.7), both at the time of matching. Methotrexate, TNF blockers and a number of previous biologics were not associated with the occurrence of lymphoma. On multivariable analysis, erosions and DAS28 remained significantly associated with increased risk of lymphoma. Conclusion Lymphomas complicating RA are mostly DLBCL. Risk of lymphoma in patients with RA was increased with markers of disease activity and severity, which supports the paradigm of a continuum between autoimmunity and lymphomagenesis in RA.

Objectives The aim of this study was to investigate the clinical value of sVE and anti-vascular endothelial-cadherin antibodies (AAVE) in RA treated with etanercept or adalimumab combined with methotrexate. Methods This was an 18-month prospective multicenter study in which patients had active RA, requiring TNF antagonist. sVE rates and AAVE titers were measured respectively by dot blot and ELISA. The relationship of these biomarkers with parameters reflecting articular or systemic disease activity, progression of structural damage, and response or remission to treatment was analyzed. Results Forty-eight patients received TNF blocking agents. Variation of sVE rates were significantly correlated with that of C-reactive protein (CRP) levels at weeks 6, 12, 26 and 52. A significant decrease in sVE levels was observed in the group of patients exhibiting a decrease in CRP levels as compared to the patient group with unmodified CRP. AAVE at baseline were correlated with rheumatoid factor. Kinetics analysis of sVE levels and AAVE titers showed that their level were not associated with disease activity score and to methotrexate/adalimumab or etanercept response. Conclusions sVE is a biomarker associated with systemic RA activity under anti-TNF. AAVE are related to autoantibodies usually associated to RA.

Resume L’amelioration de la prise en charge de la polyarthrite rhumatoide conduit le rhumatologue a se preoccuper davantage des comorbidites dont le diabete. L’objectif de cette revue est de mieux comprendre les relations entre polyarthrite rhumatoide et diabete, d’une part, et d’etudier l’impact des traitements de fond de la polyarthrite rhumatoide sur le diabete, d’autre part. L’augmentation de l’insulino-resistance observee dans la polyarthrite rhumatoide est etroitement liee a l’inflammation systemique induite par certaines cytokines pro-inflammatoires tels que le tumor necrosis factor α ou l’interleukine-6. La prevalence du diabete de type 2 est egalement augmentee dans la polyarthrite rhumatoide. De plus, certains traitements de fond, comme l’hydroxychloroquine, le methotrexate, les inhibiteurs du tumor necrosis factor α, de l’interleukine-1β ou de l’interleukine-6, semblent ameliorer les parametres glucidiques. A l’inverse, les corticoides, surtout utilises au long cours, ont plutot des effets deleteres sur l’index glycemique. Le depistage et le traitement des facteurs de risque cardiovasculaire, encore insuffisamment realises, sont donc indispensables chez ces patients d’autant plus que le choix du traitement de fond peut impacter directement le metabolisme glucidique.

Introduction L’atteinte pulmonaire dans la polyarthrite rhumatoide (PR-PID) represente la deuxieme cause de mortalite apres l’atteinte cardiovasculaire. Un titre eleve des facteurs rhumatoides de classe IgA (FR IgA) est associe a l’activite du rhumatisme, a une progression radiologique plus importante et aux manifestations extra-articulaires. L’objectif de notre etude etait donc d’etudier le lien entre la presence/les titres des FR IgA, consideres seuls ou en combinaison avec d’autres autoanticorps et l’atteinte bronchopulmonaire de la PR. Materiels et methodes Etude observationnelle, retrospective et monocentrique portant sur l’ensemble des dosages consecutifs des FR IgA realises sur les 10 dernieres annees a partir d’un ELISA maison. Etaient inclus les patients atteints de PR repondant aux criteres diagnostiques de l’ACR/EULAR 2010 et classes en deux groupes : FR IgA positif et FR IgA negatif ou douteux. Les donnees cliniques, biologiques et therapeutiques etaient recueillies grâce a un suivi standardise dans notre centre. Le diagnostic de PR-PID etait etabli apres analyse des scanners thoraciques de haute resolution qui faisaient l’objet d’une double lecture par des radiologues specialises permettant de classer les lesions en atteinte parenchymateuse et/ou bronchique. Les discordances d’interpretation faisaient l’objet d’une adjudication par un pneumologue expert. L’analyse principale a utilise un modele de regression logistique ajuste sur l’âge, le sexe, le tabagisme, l’activite de la maladie, la presence de manifestations extra-articulaires et les FR/anti-CCP. Resultats Etude observationnelle, retrospective et monocentrique portant sur l’ensemble des dosages consecutifs des FR IgA realises sur les 10 dernieres annees a partir d’un ELISA maison. Etaient inclus les patients atteints de PR repondant aux criteres diagnostiques de l’ACR/EULAR 2010 et classes en deux groupes : FR IgA positif et FR IgA negatif ou douteux. Les donnees cliniques, biologiques et therapeutiques etaient recueillies grâce a un suivi standardise dans notre centre. Le diagnostic de PR-PID etait etabli apres analyse des scanners thoraciques de haute resolution qui faisaient l’objet d’une double lecture par des radiologues specialises permettant de classer les lesions en atteinte parenchymateuse et/ou bronchique. Les discordances d’interpretation faisaient l’objet d’une adjudication par un pneumologue expert. L’analyse principale a utilise un modele de regression logistique ajuste sur l’âge, le sexe, le tabagisme, l’activite de la maladie, la presence de manifestations extra-articulaires et les FR/anti-CCP. Conclusion Notre etude n’a pas permis de mettre en evidence d’association entre la positivite/les titres des FR IgA et l’atteinte bronchopulmonaire de la PR. Contrairement a d’autres etudes, en analyse ajustee sur les principaux facteurs de risque, aucun autoanticorps ne semble associe a ce type d’atteinte, ce qui corrobore les donnees d’une etude recente mettant en exergue la place des anti-proteines carbamylees.

Introduction Une association entre la sarcoidose et la spondyloarthrite (SPA) ou une coexistence fortuite de ces deux pathologies fait debat depuis plus de 70 ans. Certaines manifestations cliniques qu’elles soient articulaires (sacro-iliite, oligoarthrite, dactylite …) ou extra-articulaires (MICI, uveite …) sont communes entre les deux pathologies et peuvent preter a confusion. La prevalence non negligeable des SPA au cours de la sarcoidose nous amene a nous interroger sur les facteurs associes au risque de developpement d’une SPA en cas de sarcoidose et de leur prise en charge respective. L’objectif principal de cette etude etait donc d’identifier une forme clinique de sarcoidose predictive de survenue d’une spondyloarthrite. Patients et methodes Nous avons realise une etude cas temoins, retrospective, monocentrique sur une duree de 26 ans (entre 1992-2018) au CHU de Rouen. Les patients repondant aux criteres diagnostiques de la ATS/ERS/WASOG et de classification de l’ASAS pour la sarcoidose et la SPA respectivement ont ete inclus (“cas”) et apparies a des patients presentant une sarcoidose sans SPA (“temoins”) sur l’annee de diagnostic de la sarcoidose. Apres identification des patients grâce a l’entrepot de donnees de sante normand, les donnees cliniques, biologiques, radiologiques et therapeutiques ont ete colligees pour chacun des patients. L’effet predictif des differentes variables a ete etudie grâce a un modele de regression logistique, ainsi qu’un modele ajuste sur l’âge et le sexe. Resultats 22 patients ayant une sequence sarcoidose/SPA ont ete identifies ; 66 temoins ont ete selectionnes. La proportion d’atteinte des differents organes au cours de la sarcoidose etait similaire entre les deux groupes a l’exception de l’atteinte rhumatologique. Elle est presente chez 68,2 % des cas et 27,3 % des temoins avec une association statistique significative (OR a 6,42 (95 % IC [2,30–19,59] p = 0,0005). Aucun tableau clinique rhumatologique specifique n’a pu etre identifie du fait d’effectifs faibles. Cependant, une symptomatologie axiale semble plus frequemment observee chez les cas, engendrant une proportion plus importante de patients presentant un tableau combine d’atteintes axiale et peripherique. Le nombre d’organes touches par la sarcoidose, ne semble pas influencer la survenue d’une SPA. La prise en charge des patients presentant une sequence sarcoidose/SPA est singuliere conduisant souvent a une escalade therapeutique avec 81,8 % et 63,6 % des cas traites par DMARD synthetiques et biologiques respectivement versus 27,3 % et 3,0 % chez les temoins. Conclusion L’association sarcoidose/SPA bien que rare est possiblement sous diagnostiquee. Une atteinte rhumatologique axiale et peripherique initiale ou apparaissant dans les formes en remission doit etre un facteur d’alerte motivant la recherche d’une SPA associee.

Background:Rheumatoid arthritis (RA) is associated with an increased risk of non-Hodgkin B-cell lymphoma (B-cell NHL).Objectives:1)To study the characteristics of B-cell NHL complicating RA2)To identify the factors associated with their occurrence.Methods:A multi-centre case-control study was performed in France. Cases were patients with RA fulfilling the ACR-EULAR 2010 criteria, who developed a B-cell NHL after the diagnosis of RA. Cases were reported following a call for observations by the “Club Rhumatismes et Inflammation” network, registries from the French society of Rheumatology (AIR, ORA and REGATE) and the ESPOIR cohort. For each case, 2 control patients were drawn at random from patients in the ESPOIR cohort with RA fulfilling the ACR-EULAR 2010 criteria; cases and controls were matched on age (age at lymphoma diagnosis for cases and age at the 10-year ESPOIR visit for controls). Patients with associated Sjögren’s syndrome were excluded. Cases and controls characteristics were compared for parameters associated with the occurrence of lymphoma.Results:A total of 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphomas (n=26, 48.2%)(Figure 1). EBV positivity was found in 4 cases among 27 tested (14.8%). Cases had a mean age of 63.5 years (SD=10.9), and had a mean RA duration of 12.4 years (SD=10.5) at the time of diagnosis of lymphoma; there was no significant difference with controls (p=0.47 and p=0.40 respectively). The mean duration of follow-up after the diagnosis of lymphoma was 5.2 years (SD=5.8). In univariate analysis, factors associated with occurrence of B-cell NHL were: male gender (OR=3.3, 95%CI: 1.7-6.7), positive ACPA (OR=5.1, 95%CI: 2.0-15.7), positive Rheumatoid Factor (RF) (OR=3.9, 95%CI=1.6-12.2), erosions on X-rays (OR=15.4, 95%CI: 6.9-37.7) and DAS28 (OR=2.0, 95%CI: 1.5-2.7). Methotrexate, TNF-blockers and the number of previous biologics were not associated with the occurrence of B-cell NHL. Hydroxychloroquine and sulfasalazine were more frequent in cases versus control, which could be linked to a date bias. Erosions and DAS28 remained significant in multivariate analysis(Table 1).Conclusion:This study revealed an association between markers of activity (DAS28), severity (erosions) and autoimmune B-cell activation (RF and ACPA) and the risk of B-cell NHL in patients with RA, supporting the continuum between autoimmunity and lymphomagenesis in RA.Figure 1.lymphomas histologyTable 1.association between RA characteristics and B-cell NHL in univariate and multivariate analysisVariablesCases (N=54)Controls (N=108)Univariate analysisMultivariate analysisOR (95%CI)p-valueOR (95%CI)p-valueMale gender, N (%)27 (50.0)25 (23.2)3.3(1.7-6.7)0.00062.2(0.8-6.1)0.13Positive ACPA, N (%)49 (90.7)71 (65.7)5.1(2.0-15.7)0.0006--Positive RF, N (%)49 (90.7)77 (71.3)3.9(1.6-12.2)0.005--Positive RF or ACPA, N (%)49 (90.7)80 (74.1)3.4(1.3-10.6)0.012.9(0.7-15.0)0.16Erosions on X-rays, N (%)44 (81.5)26 (24.1)15.4(6.9-37.7)< 0.00019.8(3.8-28.2)< 0.0001DAS28 at B-cell NHL diagnosis/at the 10th year visit*, mean(SD)4.1 (1.6)2.6 (1.4)2.0(1.5-2.7)< 0.00011.9(1.3-2.8)0.0007*B-cell NHL diagnosis for cases, 10thyear visit for controlsDisclosure of Interests:Joanna KEDRA: None declared, Raphaèle Seror Consultant of: BMS UCB Pfizer Roche, Philippe Dieudé: None declared, Arnaud Constantin: None declared, ERIC TOUSSIROT: None declared, Elias Kfoury: None declared, Charles Masson: None declared, Divi Cornec: None declared, Jean-Jacques Dubost: None declared, Laurent Marguerie: None declared, Sebastien Ottaviani: None declared, Franck Grados: None declared, Rakiba Belkhir: None declared, olivier fain: None declared, Philippe Goupille Grant/research support from: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Christelle Sordet: None declared, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Peggy Philippe: None declared, Muriel PIPERNO: None declared, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, Olivier Lambotte Consultant of: BMS France, MSD, Astra Zeneca, Incyte, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Jérémie SELLAM: None declared, Thomas Sene: None declared, Guillaume Denis: None declared, Thierry Lequerre: None declared, Xavier Mariette Consultant of: BMS, Gilead, Medimmune, Novartis, Pfizer, Servier, UCB, Gaetane Nocturne: None declared