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Objective To report the 10-year outcome of an inception cohort of patients with early rheumatoid arthritis (RA), the ESPOIR cohort, and predictors of outcome. Methods From 2003 to 2005, 813 patients were included if they had early arthritis ( Results In total, 521 (64.1%) RA patients were followed up for 10 years; 35 (4.3%) died, which appears to be similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174 (33.4%) received at least one biologic DMARD, 13.6% within 2 years. At year 10, 273 (52.4%) patients were in DAS28 remission, 40.1% in sustained remission, 14.1% in drug-free remission, 39.7% in CDAI remission. Half of the patients achieved a health assessment questionnaire-disability index (HAQ-DI) < 0.5. SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 (17.9). Only 34 (6.5%) patients required major joint surgery. A substantial number of patients showed new comorbidities over 10 years. Positivity for anti-citrullinated peptides antibodies (ACPA) was confirmed as a robust predictor of long-term outcome. Conclusions We report a very mild 10-year outcome of a large cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients.

Resume Le traitement du melanome metastatique a connu recemment des innovations therapeutiques majeures grâce au developpement des therapies ciblees anti-BRAF et anti-MEK chez les patients porteurs d’une mutation BRAF V600. Les associations vemurafenib + cobimetinib, dabrafenib + trametinib, et encorafenib + binimetinib, evaluees respectivement dans les etudes de phase III coBRIM, COMBI-d/COMBI-v et COLUMBUS, sont actuellement approuvees dans cette indication. Les toxicites associees aux combinaisons sont differentes de celles deja connues avec les monotherapies, en termes de frequence et de severite. Les medecins qui prennent en charge les patients atteints de melanome sont donc confrontes a de nouvelles problematiques concernant la prevention, la detection et le traitement de ces effets indesirables. Cet article fait le point sur les donnees de tolerance issues des trois etudes pivotales (coBRIM, COMBI-v et COLUMBUS) et propose des recommandations de prise en charge specifiques basees sur des avis d’experts. Les toxicites dermatologiques, ophtalmologiques, cardiovasculaires, digestives, musculosquelettiques, renales et generales sont discutees et un calendrier de realisation des examens complementaires avant l’instauration et pendant le traitement anticancereux est propose.

This study was conducted in order to compare the prevalence of inflammatory posterior arch abnormalities on lumbar spine MRI between axial spondyloarthritis (axSpA) patients and low back pain (LBP) patients. Patients—axSpA patients meeting the 2009 ASAS criteria and chronic LBP patients who had a lumbar spine MRI were selected. MRI—STIR and T1 sagittal images up to T8–T9 were reviewed by two experienced rheumatologists blinded to the diagnosis and clinical data to identify inflammatory posterior arch abnormalities. Analyses—The prevalence of inflammatory posterior arch abnormalities between axSpA and LBP patients was compared. Clinical data were compared in the axSpA group depending on whether or not inflammatory posterior arch abnormalities were present. Ninety-five patients were enrolled in each group. The prevalence of all inflammatory posterior arch abnormalities was the same in the axSpA and LBP groups (58% in the SpA group versus 70% in the LBP group, p = 0.1). However, differences in terms of the prevalence of costotransverse joint arthritis, pedicle oedema above L3 and transverse and spinous process oedema were observed between the two groups (axSpA 27% versus LBP 6%, p = 0.0004). Patients with inflammatory posterior arch abnormalities in the axSpA group had a longer disease duration (11 versus 8 years, p = 0.02), higher CRP levels (median 11 versus 3 mg/l, p = 0.0002) and higher prevalence of radiographic sacroiliitis (84 versus 47%, p = 0.001) compared to patients without inflammatory posterior arch abnormalities. Costotransverse arthritis, pedicle oedema and transverse process oedema are more frequent in axSpA patients than LBP patients, on lumbar spine MRI depicting TH9-S1. • MRI pedicle oedema above L3, transverse process oedema, spinous process oedema or costotransverse arthritis is more frequently observed in axial spondyloarthritis (SpA). • SpA patients with at least one MRI inflammatory lesion on the posterior arch had higher clinical activity scores and biological inflammation. • Facet joint arthritis was more common in patients with chronic low back pain.

International audience; The 2014 French Society for Rheumatology (Société Française de Rheumatologie, SFR) recommendations about the management of rheumatoid arthritis (RA) have been updated by a task force composed of 12 expert rheumatologists, 2 patient self-help group representatives, and an occupational therapist. The material used by the task force included recent EULAR recommendations, a systematic literature review, and expert opinion. Four general principles and 15 recommendations were developed. The general principles emphasize the need for shared decision-making between the rheumatologist and the patient and for a global management program including both pharmacological and non-pharmacological treatments. The recommendations deal with the diagnostic strategy for RA, treatment targets, management organization, drug selection based on the treatment line and prognostic factors, management of remissions, and global patient management. Disease-modifying anti-rheumatic drug (DMARD) therapy should be started as early as possible. Validated composite scores should be determined at regular intervals to assess disease activity - according to the tight disease control concept - to achieve the treatment target, i.e., a remission. Methotrexate is the recommended first-line DMARD. The treatment should be optimized when methotrexate is poorly tolerated or inadequately effective. While waiting for conventional synthetic DMARDs to take effect, glucocorticoid therapy can be used, for a brief period to keep the cumulative dose low. When a sustained remission without structural progression is achieved in a patient who is not taking glucocorticoid therapy, targeted therapy de-escalation according to tight disease control principles should be considered. Patients should be periodically screened for comorbidities and their risk factors, which should be evaluated and treated.

Background To investigate the association between 12 single nucleotide polymorphisms (SNPs) located on ERAP1 and IL23R with the presence of inflammation on the sacroiliac joint (SIJ) or spinal magnetic resonance imagery (MRI) in an early onset spondyloarthritis (SpA) cohort. Methods All the patients included in the DESIR cohort with an axial SpA and available DNA at baseline were enrolled in this study (n = 645 patients) and underwent a clinical examination, CRP assay, SIJ and spinal MRI scans. Six SNPs located on ERAP1 (rs30187, rs27044, rs27434, rs17482078, rs10050860, rs2287987) and six SNPs located on IL23R (rs1004819, rs10489629, rs1343151, rs2201841, rs10889677, rs11209032) were genotyped. Univariable analyses were performed to test the association between the genotypes and SIJ and spinal MRI inflammation, as well as disease activity based on Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP) and CRP. Results One SNP located on ERAP1 (rs27434) and haplotype CCT of ERAP1 were associated with SIJ inflammation detected by MRI, but these associations were below the Bonferroni corrected threshold of significance. However, one SNP (rs1004819) located on IL23R was associated with SIJ MRI inflammation (rs1004819: TT 42.3%, CT 40.5%, CC 26.5%, p = 0.0005). This locus was also significantly associated with Spondyloarthritis Research Consortium of Canada scores while no association with another inflammatory parameter such as BASDAI, ASDAS-CRP, CRP or Berlin MRI score was identified in this population. Conclusion One locus of the IL23R gene was associated with SIJ MRI inflammation and might be a marker of more active disease in recent onset SpA. Trial registration clinicaltrials.gov, NCTO 164 8907

Summary In order to ascertain the significance of transmembrane tumor necrosis factor (tmTNF) reverse signaling in vivo, we generated a triple transgenic mouse model (3TG, TNFR1−/−, TNFR2−/−, and tmTNFKI/KI) in which all canonical tumor necrosis factor (TNF) signaling was abolished. In bone-marrow-derived macrophages harvested from these mice, various anti-TNF biologics induced the expression of genes characteristic of alternative macrophages and also inhibited the expression of pro-inflammatory cytokines mainly through the upregulation of arginase-1. Injections of TNF inhibitors during arthritis increased pro-resolutive markers in bone marrow precursors and joint cells leading to a decrease in arthritis score. These results demonstrate that the binding of anti-TNF biologics to tmTNF results in decreased arthritis severity. Collectively, our data provide evidence for the significance of tmTNF reverse signaling in the modulation of arthritis. They suggest a complementary interpretation of anti-TNF biologics effects in the treatment of inflammatory diseases and pave the way to studies focused on new arginase-1-dependent therapeutic targets.

Highlights • La SFR a sélectionné les questions les plus critiques auxquelles sont confrontés les rhumatologues dans la prise en charge de leurs patients atteints de maladies rhumatismales pendant la pandémie de COVID-19. • Un groupe de 10 experts composé de membres du conseil de la SFR et du Club Rhumatismes et Inflammations (CRI) a proposé des réponses basées sur l’état des connaissances au mois de mai 2020. • La plupart du temps, il n’y a aucune contre-indication à la mise en place ou à la poursuite d’un traitement par anti-inflammatoires ou DMARD. • En cas de signes suggérant une infection (par le coronavirus ou autre), les traitements doivent être arrêtés, puis rétablis si nécessaire après une période de deux semaines sans aucun symptôme., Contexte Les rhumatologues doivent composer avec la pandémie de COVID-19 dans la prise en charge de leurs patients, ce qui a soulevé de nombreuses interrogations sur l’utilisation des anti-inflammatoires et des traitements de fond antirhumatismaux (DMARD). La Société française de rhumatologie (SFR) a sélectionné les questions les plus critiques pour la pratique quotidienne d’un rhumatologue et un groupe de 10 experts composé de membres du conseil de la SFR et du Club Rhumatismes et Inflammations (CRI) a proposé des réponses basées sur l’état des connaissances au mois de mai 2020. Procédure fondamentale Lorsque les 18 premières questions et déclarations ont été mises à disposition, 1 400 personnes ont consulté la liste des questions fréquemment posées entre le 31 mars et le 12 avril 2020. Seize questions supplémentaires ont ainsi été transmises à la SFR et le conseil y a répondu. Une revue complémentaire a été organisée par e-mail et visioconférence, notamment pour actualiser les déclarations. Cinq des questions, jugées scientifiquement pertinentes, ont été ajoutées à ce document. Chaque réponse a reçu une note finale de 0 à 10, 0 correspondant à l’absence totale d’accord et 10, à un accord sans réserve. La valeur moyenne des votes obtenus par chaque question est présentée comme le degré d’accord (DA) à la suite de chaque réponse. Date de la dernière mise à jour de ce document : 17 avril 2020. Principales observations Selon la littérature scientifique publiée, il n’y a la plupart du temps aucune contre-indication à la mise en place ou à la poursuite d’un traitement par anti-inflammatoires ou DMARD. En cas de signes suggérant une infection (par le coronavirus ou autre), les traitements doivent être arrêtés, puis rétablis si nécessaire après une période de deux semaines sans aucun symptôme. Quelques indices suggèrent que les personnes prenant une dose immunosuppressive de corticoïdes présentent un risque accru de développer une forme sévère de COVID-19. Les infiltrations intra-articulaires de glucocorticoïdes sont autorisées lorsqu’il n’existe pas d’alternative thérapeutique raisonnable et sous réserve de précautions protégeant le patient et le praticien d’une contamination virale, ce qui inclut une information appropriée du patient. Principales conclusions Les données disponibles sur la prise en charge des patients atteints de maladies rhumatismales pendant la pandémie de COVID-19 sont rassurantes et favorables à la poursuite ou à l’instauration de traitements symptomatiques et spécifiques, l’objectif principal demeurant le contrôle de ces maladies même en temps de pandémie.

Background Human cytomegalovirus (HCMV) seropositivity has been associated with higher inflammation during rheumatoid arthritis (RA). However, no data are available on the impact of HCMV seropositivity on bone erosion progression during RA. Methods We selected 487 individuals of ESPOIR cohort who fulfilled the 2010 ACR/EULAR criteria for RA. HCMV serology for these patients was determined using Architect CMV IgG assay. Baseline and 1-year central X-ray reading using modified Total Sharp Score (mTSS), Erosion Sharp Score, and joint space narrowing Sharp score were used to quantify structural damage progression. We performed univariate and multivariate analyses to investigate the association between HCMV status and bone erosion progression. Results We analyzed 273 HCMV seropositive (HCMV+) and 214 HCMV seronegative (HCMV−) RA patients. At inclusion, HCMV+ patients were less frequently ACPA+ (49.8% versus 58.9%, p p 1 point) was lower in HCMV+ patients (16.1% versus 25.2%, p = 0.0128) in comparison with HCMV−. HCMV+ status remained independently associated with lower bone erosion progression in multivariate analysis. Conclusions Our findings suggest that, independently of other confounding factors, HCMV seropositivity is associated with a lower progression of bone erosion during RA.

Introduction L’epidemie a COVID-19 a bouleverse le systeme sanitaire francais au mois de mars 2020. La meconnaissance de cette nouvelle maladie et la difficulte d’acces aux professionnels de sante pendant le confinement ont potentiellement abouti a des modifications, parfois inadaptees, de la prise en charge des patients suivis pour des pathologies chroniques. L’objectif de cette etude etait d’evaluer l’impact de l’epidemie COVID-19 sur la prise charge de la polyarthrite rhumatoide (PR) par une enquete transversale realisee au mois de juin 2020 chez les patients suivis dans la e-cohorte du registre ART-SFR. Patients et methodes Le registre national multicentrique francais ART-SFR inclut des PR initiant un traitement par anti-TNF depuis septembre 2016 avec un suivi prospectif prevu sur 5 ans. Lors de l’inclusion dans le registre, il est systematiquement propose au patient de participer a la e-cohorte qui consiste a recevoir des questionnaires mensuels en ligne portant sur leurs comorbidites, les traitements pris, la tolerance des traitements, le handicap fonctionnel, les vaccins. En juin 2020 un questionnaire supplementaire a ete envoye a tous les patients participant a la e-cohorte portant sur leurs traitements en cours et sur l’impact de l’epidemie COVID-19 sur la prise en charge habituelle de leur PR. Resultats En juin 2020, sur les 1155 patients inclus dans le registre ART, 455 avaient accepte de participer a la e-cohorte. Parmi eux, 169 (37 %), (72 % de femmes, âge moyen 54 ans, 86 % sous bDMARD ou anti-JAK) ont repondu au questionnaire portant sur l’impact du COVID-19 sur la prise en charge de leur maladie. Parmi ces patients, 16 (2,7 %) d’entre eux ont eu des symptomes compatibles avec une COVID-19, mais aucun d’entre eux n’a ete teste positif (test non fait, n = 11, ou negatif, n = 5). Aucun de ces patients n’a ete hospitalise pour une forme severe de COVID-19. Parmi les 145 patients sous bDMARD ou anti-JAK en mars 2020, 27 (18,6 %) d’entre eux ont eu un changement therapeutique entre mars et juin, dont la majorite (n = 18, 78 %) a la demande du rhumatologue pour une raison sans lien avec l’epidemie, 6 pour une suspicion d’infection a COVID-19. Seuls 6 patients ont interrompu d‘eux meme leur traitement par crainte d’une infection a COVID-19. Par ailleurs, 79 patients (47 %) ont declare avoir eu des poussees pendant la periode de confinement motivant un changement therapeutique pour 23 d’entre eux (29 %). Sur les 110 patients qui devaient avoir un rendez-vous pour le suivi de leur PR pendant la periode de confinement, 66 (60 %) ont note des modifications avec un report de la consultation ou une teleconsultation. Pendant la periode de confinement, 40 patients (24 %) ont ete mis en arret de travail ou chomage partiel, 32 (19 %) ont poursuivi leur activite en teletravail et 94 (57 %) ont poursuivi leur activite a la fois en teletravail et en presentiel, 12 patients (7 %) ont uniquement travailles en presentiel, parmi eux seuls 2 patients n’ont pas eu les moyens de respecter les gestes barriere pendant l’exercice de leur travail. Enfin, 3 patients (2 %) ont perdu leur travail. Conclusion Ces resultats rassurants sur le suivi pendant le confinement des patients PR majoritairement sous bDMARD ou anti-JAK doivent etre pris avec precautions. En effet, les patients inclus dans la e-cohorte du registre ART-SFR ne sont probablement pas representatifs des tous les patients suivis pour une PR sous traitement cible en France.

Objectives The aims of the Oral Status And Rheumatoid Arthritis (OSARA) cross-sectional study were to study the oral health-related quality of life and to assess the associated factors in a population of outpatients with rheumatoid arthritis in France. Methods The data were collected by five trained and standardised dentists who asked each subject the questions of a socio-demographic, behavioural and medical questionnaire, which was completed with the medical records, and performed the dental examination. Each subject filled out two self-assessment questionnaires: the Health Assessment Questionnaire and the General Oral Health Assessment Index. Results Seventy-three subjects were included. The mean age of the participants was 60.2 ± 11.9 years and 75.3% were women. For 58.3% of the subjects, their self-perceived oral health-related quality of life was described as poor. The logistic regression analysis found that a small number of teeth and marked difficulties in dressing and grooming were associated with bad oral health-related quality of life [ORa = 10.5 (1.96–56.19) and ORa = 4.3 (1.15–15.77), respectively]. Conclusions More care should be given to the prevention of dental diseases in order to improve the oral health-related quality of life of patients with rheumatoid arthritis and their self-esteem, which will already be heavily affected.

Background:ESPOIR is a longitudinal prospective cohort of adults with possible early RA (ClinicalTrials.gov: NCT03666091). Patients were referred by rheumatologists and general practitioners to one of the 14 regional centers in France. The objective and design of the cohort are described elsewhere (1). Patients received standard of care by their rheumatologists and were followed without predefined therapeutic strategiesObjectives:To report the current 10-year outcome of patients with early rheumatoid arthritis (RA) in the ESPOIR cohort, and predictors of outcome.Methods:From 2003 to 2005, 813 patients were included if they had early arthritis (< 6 months) with a high probability of RA developing and had never been prescribed disease modifying anti-rheumatic drugs (DMARDs). Multivariate logistic regression analysis was used to evaluate predictors of outcome.Results:In total, 521 (64.1%) RA patients were followed up for 10 years and 35 (4.3%) died, which appears similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174/521 (33.4%) received at least one biologic DMARD, 13.6 and 23.4% within 2 and 5 years. At year 10 (Table), mean DAS28 ESR was 2.5 ± 1.3; 273 (52.4%) patients were in DAS28 remission, 39.7% in CDAI remission, 40.1% in DAS28 sustained remission, and 14.1% in drug-free remission. Disability was well controlled overtime (Figure) and half of the patients achieved a HAQ Disability Index < 0.5; the SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 ± 17.9. A total of 82 (16.5%) patients required joint surgery including arthroplasty or arthrodesis in only 6.5% of the cases. A substantial number of patients showed new comorbidities, mainly cardiovascular or metabolic diseases over 10 years. Finally, positivity for anti-citrullinated protein antibodies was confirmed as a robust predictor of long-term outcome in patients with early RA.Table 1.Outcome in ESPOIR cohort and 1993 cohort at 10 yearsESPOIR cohort n=5211993 cohort n=112DAS28 ESR2.5 ± 1.3DAS44-2.2 ± 0.9SDAI7.5 ± 8.7CDAI6.8 ±8.3DAS28 ESR remission (n (%)273 (52.4)CDAI remission207 (39.7)DAS28 sustained remission, n (%)209 (40.1)DAS28 drug-free remission, n (%)75 (14.1)DAS28 ESR LDA336 (64.5)Rheumatoid nodules39 (7.5)Sicca syndrome314 (60.3)Patient global assessment24.0 ± 24.0HAQ DI score0.5 ± 0.60.75 ± 0.71HAQ DI < 0.5, n (%)280 (54.5)SF36 MCS46.7 ± 10.5SF36 PCS44.6 ± 9.2Pain (mm, VAS)16.6 ± 20.6Fatigue (mm, VAS)31.4 ± 27.023.2 ± 23.0ESR (mm/hr)14.4 ± 13.818.4 ± 16.5CRP level (mg/l)6.4 ± 16.59.3 ± 11.7Normal CRP (< 5 mg/l), n (%)336 (67.6)Total mSharp score*13.8 ± 19.635.4 ± 46.1Erosion score4.9 ± 9.418.4 ± 26.5)Joint narrowing score8.9 ± 12.132.1 ±23.2Joint surgery82 (16.5)26 (23.2)Joint arthroplasty/arthrodesis34 (6.5)20 (17.9)Data are mean (SD)DAS28, disease activity in 28 joints; HAQ DI, Health Assessment Questionnaire Disability Index; SF36 MCS, Medial Outcomes Study 36-item Short Form mental component summary; SF36 PCS, Medical Outcomes Study 36-item Short Form physical component summary; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; VAS, visual analog scale; CDAI, Clinical Disease Activity Index; SDAI, Simple Disease Activity Index; *van der Heijde-modified Total Sharp scoreFigure 1.Health Assessment Questionnaire Disability Index (HAQ-DI) over 10 years Data are mean (SD).Conclusion:We report a very mild 10-year outcome of a large inception cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of early RA patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients than previously.References:[1]Combe B et al. Jt Bone Spine Rev Rhum. 2007;74:440–5Acknowledgements:We thank MC Boissier, G Falgaronne and F. Lioté for help in patient recruitment. An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years of the cohort study. Two additional grants from INSERM supported part of the biological database. The French Society of Rheumatology, Abbvie, Pfizer, Lilly and more recently Fresenius and Biogen supported the ESPOIR cohort.Disclosure of Interests:Bernard Combe Speakers bureau: AbbVie; BMS; Gilead; Lilly; Merck; Pfizer; Roche-Chugai;, Consultant of: AbbVie; BMS; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Grant/research support from: Fresenius, Novartis, Pfizer, and Roche-Chugai., Nathalie Rincheval: None declared, Francis Berenbaum Speakers bureau: Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4Moving Biotech, 4P Pharma, Consultant of: Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4Moving Biotech, 4P Pharma, Patrick BOUMIER: None declared, Alain Cantagrel Speakers bureau: AbbVie; Amgen, Bristol-Myers Squibb; Grunenthal; Lilly; Medac; MSD France; Novartis; Pfizer; Roche-Chugai; Sanofi;, Consultant of: AbbVie; Amgen, Bristol-Myers Squibb; Grunenthal; Lilly; Medac; MSD France; Novartis; Pfizer; Roche-Chugai; Sanofi;, Grant/research support from: Abbvie, Fresenius, MSD France, Novartis, Pfizer, and UCB, Philippe Dieudé Speakers bureau: Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Lilly, Medac, Novartis Roche-Genentech, Sanofi, Consultant of: Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Lilly, Medac, Novartis Roche-Genentech, Sanofi, Grant/research support from: Bristol-Myers Squibb, GlaxoSmithKline, Pfizer., Maxime Dougados Speakers bureau: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Consultant of: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Grant/research support from: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Bruno Fautrel Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Grant/research support from: AbbVie, Lilly, MSD and Pfizer, René-Marc Flipo Speakers bureau: Abbvie, Biogen, BMS, Janssen, MSD, Nordic, Novartis, Pfizer, Roche-Chugai and Sanofi-Genzyme, Consultant of: Abbvie, Biogen, BMS, Janssen, MSD, Nordic, Novartis, Pfizer, Roche-Chugai and Sanofi-Genzyme, Grant/research support from: Abbvie, Janssen, Novartis, Pfizer and Roche-Chugai, Philippe Goupille Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB., Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB., Grant/research support from: Abbvie, Biogen, MSD, Pfizer, Xavier Mariette Speakers bureau: BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Servier, and UCB., Consultant of: BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Servier, and UCB., Grant/research support from: Servier, Alain Saraux Speakers bureau: AbbVie, Bristol-Myers Squibb, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB, Grant/research support from: Roche-Chugai, Thierry Schaeverbeke Speakers bureau: AbbVie, BMS, Lilly, Novartis, Nordic Pharma, Pfizer, Roche, UCB, Consultant of: AbbVie, BMS, Lilly, Novartis, Nordic Pharma, Pfizer, Roche, UCB, Grant/research support from: Pfizer, AbbVie, BMS, Roche, UCB, Astra, MSD, Rigel, AB-sciences, Jean Sibilia Speakers bureau: AbbVie, Lilly, MSD, Amgen, Pfizer, BMS, Janssen, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Novartis., Consultant of: AbbVie, Lilly, MSD, Amgen, Pfizer, BMS, Janssen, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Novartis., Grant/research support from: AbbVie, Lilly, Pfizer, Roche, Olivier VITTECOQ Speakers bureau: AbbVie, Bristol-Myers Squibb, Gilead, Lilly, Merck, Novartis, Pfizer; Roche-Chugai, Mylan and Sanofi, Consultant of: AbbVie, Bristol-Myers Squibb, Gilead, Lilly, Merck, Novartis, Pfizer; Roche-Chugai, Mylan and Sanofi, Grant/research support from: Novartis, Pfizer, Merck, and Bristol-Myers Squibb, Jean-Pierre Daures: None declared

Major therapeutic advances have been made recently in the treatment of metastatic melanoma, due to the development of targeted therapies, namely BRAF and MEK inhibitors, in patients with BRAF V600 mutation. Combinations of vemurafenib+cobimetinib, dabrafenib+trametinib, et encorafenib+binimetinib, evaluated in coBRIM, COMBI-d/COMBI-v and COLUMBUS trials respectively have been approved in this indication. Toxicities induced by combination therapies are different from those reported with monotherapies, in terms of frequency and intensity. Physicians who treat melanoma patients thus face news issues relating to prevention, detection and treatment of these adverse events. This paper summarizes tolerance data from the three pivotal trials (coBRIM, COMBI-v and COLUMBUS) and issues recommendations for the specific management of main toxicities, based on experts' opinion. We discuss dermatological, ophthalmological, cardiovascular, digestive, musculoskeletal, renal and general toxicities and propose a timetable for examinations to be performed before and during treatment.

Highlights • The SFR selected the most critical questions Rheumatologists must contend in the management of their patients with rheumatic diseases during COVID-19 pandemic • A group of 10 experts from SFR and CRI boards proposed responses based on the current knowledge of May 2020. • In most circumstances, there is no contraindication to the initiation or continuation of anti-inflammatory drugs as well as DMARDs. • If signs suggestive of infection (coronavirus or other) occurs, treatments should be discontinued and resumed, if necessary, after 2 weeks without any symptoms., Background: Rheumatologists must contend with COVID-19 pandemic in the management of their patients and many questions have been raised on the use of both anti-inflammatory drugs and disease-modifying anti-rheumatic drugs (DMARD). The French Society of Rheumatology (SFR) selected the most critical ones to the daily practice of a rheumatologist and a group of 10 experts from SFR and Club Rheumatism and Inflammation (CRI) boards proposed responses based on the current knowledge of May 2020. Basic procedure: Following the availability of the first 18 questions and statements, 1400 individuals consulted the frequently asked questions between the March 31, 2020 and April 12, 2020. As a result, 16 additional questions were forwarded to the SFR, and answered by the board. An additional round of review by email and video conference was organized, which included updates of the previous statements. The scientific relevance of 5 of the questions led to their inclusion in this document. Each response received a final assessment on a scale of 0–10 with 0 meaning no agreement whatsoever and 10 being in complete agreement. The mean values of these votes for each question are presented as the levels of agreement (LoA) at the end of each response. This document was last updated on April 17, 2020. Main findings: Based on current scientific literature already published, in most circumstances, there is no contraindication to the initiation or continuation of anti-inflammatory drugs as well as DMARDs. If signs suggestive of infection (coronavirus or other) occurs, treatments should be discontinued and resumed, if necessary, after 2 weeks without any symptoms. Only, some signals suggest that people taking an immunosuppressive dose of corticosteroid therapy are at greater risk of developing severe COVID-19. Intra-articular injections of glucocorticoids are allowed when there is no reasonable therapeutic alternative, and providing that precautions to protect the patient and the practitioner from viral contamination are adopted, included appropriate information to the patient. Principal conclusions: Currently available data on managing patients with rheumatic diseases during the COVID-19 pandemic are reassuring and support continuing or initiating symptomatic as well as specific treatments of these diseases, the main target of their management remaining their appropriate control, even during this pandemic.

International audience; Pain in rheumatic diseases is primarily due to mechanical or inflammatory mechanism, but neuropathic pain (NP) component is also occurring in many conditions and is probably underdiagnosed. The purpose of this article is to provide an overview of prevalence, pathophysiological and currently available treatment of NP in rheumatic diseases. When associated with clinical evaluation assessing neurological clinical signs and neuroanatomical distribution, Douleur Neuropathique 4 Questions, painDETECT, Leeds assessment of neuropathic symptoms and signs and Neuropathic Pain Questionnaire can detect NP component. Inflammatory or connective diseases, osteoarthritis, back pain or persistent pain after surgery are aetiologies that all may have a neuropathic component. Unlike nociceptive pain, NP does not respond to usual analgesics such as paracetamol and non-steroidal anti-inflammatory drugs. Entrapment neuropathy, peripheral neuropathy or smallfibre neuropathy are different aetiologies that can lead to NP. A part of the pain labelled neuropathic is rather nociplastic, secondary to a central sensitisation mechanism. Identifying the right component of pain (nociceptive vs neuropathic or nociplastic) could help to better manage pain in rheumatic diseases with pharmacological and nonpharmacological treatments.

Summary In order to ascertain the significance of transmembrane tumor necrosis factor (tmTNF) reverse signaling in vivo, we generated a triple transgenic mouse model (3TG, TNFR1−/−, TNFR2−/−, and tmTNFKI/KI) in which all canonical tumor necrosis factor (TNF) signaling was abolished. In bone-marrow-derived macrophages harvested from these mice, various anti-TNF biologics induced the expression of genes characteristic of alternative macrophages and also inhibited the expression of pro-inflammatory cytokines mainly through the upregulation of arginase-1. Injections of TNF inhibitors during arthritis increased pro-resolutive markers in bone marrow precursors and joint cells leading to a decrease in arthritis score. These results demonstrate that the binding of anti-TNF biologics to tmTNF results in decreased arthritis severity. Collectively, our data provide evidence for the significance of tmTNF reverse signaling in the modulation of arthritis. They suggest a complementary interpretation of anti-TNF biologics effects in the treatment of inflammatory diseases and pave the way to studies focused on new arginase-1-dependent therapeutic targets., Graphical abstract, Highlights • In vivo demonstration of tmTNF reverses signaling existence • tmTNF reverse signaling induces anti-oxidative stress response • tmTNF reverse signaling induces an arginase-1-mediated anti-inflammatory response • Reverse signaling is a complementary mechanism to TNF neutralization by anti-TNF, Immunology; Cell Biology

Objective.Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in rheumatoid arthritis (RA). There is limited knowledge regarding the factors that impede implementation of T2T, particularly in a setting where adherence to T2T is protocol-specified. We aimed to assess clinical factors that associate with failure to adhere to T2T.Methods.Patients with RA from 10 countries who were starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required per protocol to adhere to the T2T strategy. Factors influencing adherence to T2T low disease activity (T2T-LDA; 44-joint count Disease Activity Score ≤ 2.4) were analyzed in 2 types of binomial generalized estimating equations models: (1) including only baseline features (baseline model); and (2) modeling variables that inherently vary over time as such (longitudinal model).Results.A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. Failure of adherence to T2T-LDA was noted in 1765 visits (40.5%). In the baseline multivariable model, a high number of comorbidities (OR 1.10, 95% CI 1.02–1.19), smoking (OR 1.32, 95% CI 1.08–1.63) and high number of tender joints (OR 1.03, 95% CI 1.02–1.04) were independently associated with failure to implement T2T, while anticitrullinated protein antibody/rheumatoid factor positivity (OR 0.63, 95% CI 0.50–0.80) was a significant facilitator of T2T. Results were similar in the longitudinal model.Conclusion.Lack of adherence to T2T in the RA BIODAM cohort was evident in a substantial proportion despite being a protocol requirement, and this could be predicted by clinical features. [Rheumatoid Arthritis (RA) BIODAM cohort; ClinicalTrials.gov: NCT01476956].

International audience; Increased osteoclastogenesis is a common feature of bone erosion, notably in osteoporosis but also in inflammatory diseases such as rheumatoid arthritis (RA) and osteoarticular infections. Human cytomegalovirus (HCMV) infection has been described to impair monocyte differentiation into macrophages and dendritic cells. However, its effect on monocyte-derived osteoclasts is yet to be determined. We showed here that in vitro HCMV infection is associated with an inhibition of osteoclastogenesis through decreased expression of colony stimulating factor 1 receptor (CSF-1R) and RANK in monocytes, which was mediated by an upregulation of quaking I-5 protein (QKI-5), a cellular RNA-interacting protein. We found that deliberate QKI5 overexpression in the absence of HCMV infection is able to decrease CSF-1R and RANK expression, leading to osteoclastogenesis inhibition. Finally, by using lentiviral vectors in a calvarial bone erosion mouse model, we showed that QKI5 inhibits bone degradation. This work identifies QKI5 as a strong inhibitor of bone resorption. Future research will point out whether QKI5 could be a target for bone pathologies. © 2019 American Society for Bone and Mineral Research

Resume Objectifs Evaluer l’effet du traitement parodontal sur les parametres cliniques et biochimiques de la polyarthrite rhumatoide (PR) et la qualite de vie chez des patients atteints d’une PR moderement active et d’une parodontite. Methodes Dans cet essai ouvert, randomise et controle, des sujets atteints de PR (n = 22) ont ete affectes a un traitement parodontal « immediat » ou « differe » (detartrage et debridement radiculaire non chirurgical complet, antibiotherapie par voie systemique et instructions d’hygiene orale). Le critere de jugement principal a ete le changement du DAS28 (avec vitesse de sedimentation) a 3 mois. La qualite de vie generale et la qualite de vie relative a la sante bucco-dentaire ont ete evaluees. Resultats La sante parodontale s’est considerablement amelioree apres le traitement parodontal (surface enflammee de la gencive, p = 0,03). Le traitement parodontal n’a entraine ni evenement indesirable ni amelioration de DAS28 (difference moyenne ajustee avec un intervalle de confiance a 95 % de −0,03[−0,98 ; 0,92]). Aucune amelioration de la qualite de vie generale n’a ete constatee apres le traitement parodontal ni aucun effet significatif sur la qualite de vie bucco-dentaire, malgre une tendance positive dans le domaine « impacts psychologiques » (0,13[− 0,07 ; 0,33], p = 0,20). Conclusions Bien qu’aucun effet du traitement parodontal sur les parametres de la PR n’ait ete identifie, cet essai fournit des donnees importantes pour recommander les soins parodontaux chez les patients atteints de PR. Le traitement parodontal est sur et reduit l’inflammation orale avec un effet possible sur la qualite de vie bucco-dentaire. Comme la parodontite et la PR sont des maladies chroniques complexes et multifactorielles, il est probable que les approches centrees sur le patient impliquant a la fois les professionnels de la sante bucco-dentaire et les rhumatologues contribueront a optimiser les soins aux patients.

ObjectivesTo investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target.MethodsRA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44 ResultsIn total 4356 visits of 571 patients (mean (SD) age: 56 (13) years, 78% female) were included. Appropriate application of T2T was found in 59% of the visits. T2T (vs no T2T) did not yield a higher likelihood of DAS44 remission 3 months later (OR (95% CI): 1.03 (0.92 to 1.16)), but sustained T2T resulted in an increased likelihood of achieving DAS44 remission (OR: 1.19 (1.03 to 1.39)). Similar results were seen with DAS28-ESR remission. For more stringent definitions (CDAI, SDAI and ACR/EULAR Boolean remission), T2T was consistently positively associated with remission (OR range: 1.16 to 1.29), and sustained T2T had a more pronounced effect on remission (OR range: 1.49 to 1.52).ConclusionIn daily clinical practice, the correct application of a T2T-strategy (especially sustained T2T) in patients with RA leads to higher rates of remission.

Objective.The Outcome Measures in Rheumatology Soluble Biomarker Working Group initiated an international, multicenter, prospective study, the Rheumatoid Arthritis (RA) BIODAM cohort, to generate resources for the clinical validation of candidate biomarkers predictive of radiographic progression. This first report describes the cohort, clinical outcomes, and radiographic findings.Methods.Patients with RA from 38 sites in 10 countries starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required to adhere to a treat-to-target strategy. Biosamples (serum, urine) were acquired every 3 months, radiography of hands and feet every 6 months, and ultrasound of hands and feet every 3 months in a subset. Primary endpoint was radiographic progression by the Sharp/van der Heijde score.Results.A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. At baseline, the majority was female (76%), mean age 55.7 years, and mean disease duration 6.5 years. Patients had a mean of 8.4 swollen and 13.6 tender joints, 44-joint count Disease Activity Score (DAS44) 3.8, 77.7% rheumatoid factor–positive or anticitrullinated protein antibody–positive. Percentage of patients in DAS and American College of Rheumatology remission at 2 years was 52.2% and 27.1%, respectively. Percentage of patients with radiographic progression (> 0.5) at 1 and 2 years was 38.2% and 59.9%, respectively.Conclusion.The RA BIODAM prospective study succeeded in generating an extensive list of clinical, imaging (2343 radiographs), and biosample (4638 sera) resources that will be made available to expedite the identification and validation of biomarkers for radiographic damage endpoints. (Clinicaltrials.gov: NCT01476956, clinicaltrials.gov/ct2/show/NCT01476956)

Abatacept retention rates were evaluated in the French cohort in the prospective ACTION study (2010-2013), which included patients with moderate-to-severe rheumatoid arthritis managed in everyday clinical practice and started on intravenous abatacept therapy.Two-year abatacept retention rates were evaluated in 455 patients classified according to treatment line, body mass index (BMI), and status for rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA).After 2 years, the overall abatacept retention rate was 44%. The retention rate was non-significantly higher in the patients with vs. without a history of unresponsiveness to at least one biologic (48.1% vs. 41.8%, respectively). No significant retention rate differences were found across BMI categories (444 patients;25, 45.5%; ≥25 to30, 48.9%; and ≥30, 36.6%). Neither were any significant differences demonstrated according to RF and ACPA status (RF+ and ACPA+, 45.7%; RF+ or ACPA+, 43.8%; and FR- and ACPA-, 39.1%).The 44% 2-year retention rate in the French ACTION cohort supports the usefulness of abatacept therapy. In this study, retention was not associated with treatment line, BMI, or antibody status.

Background and objective Early seronegative rheumatoid arthritis (RA) is considered a specific entity, especially regarding diagnostic issues and prognosis. Little is known about its potentially different initial clinical presentation and outcome. We aimed to determine predictors of good response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in seronegative RA patients with early inflammatory arthritis. Patients and methods Patients from the ESPOIR cohort with early inflammatory arthritis fulfilling the 2010 ACR/EULAR classification criteria for RA despite negativity for both rheumatoid factor and anti-CCP antibodies. The primary endpoint was a good or moderate EULAR response assessed after 1 year of follow-up, given at least 3 months of treatment with a csDMARD. Secondary objectives were to compare the early therapeutic response to methotrexate (MTX) and leflunomide (LEF) versus other csDMARDs (hydroxychloroquine, sulfasalazine) and to identify factors associated with functional disability (Health Assessment Questionnaire-Disability Index [HAQ-DI] > 0.5 at 1 year) and structural progression (van der Heijde-modified total Sharp score > 1 and > 5 points at 1 year). Logistic regression analysis was used to determine independent predictors of outcomes. Results One hundred seventy-two patients were analyzed. Overall, 98/172 (57%) patients received MTX during the first year of follow-up. A good or moderate EULAR response at 1 year was associated with early use of csDMARDs (i.e., within 3 months after the first joint swelling) on univariate and multivariable analysis (odds ratio = 2.41 [95% confidence interval 1.07–5.42], p = 0.03). Response rates were not affected by other classical prognostic factors (i.e., baseline DAS28). Presence of erosions at baseline was associated with Sharp score progression > 1 point and > 5 points (both p = 0.03) at 1 year. HAQ-DI ≥ 1 at inclusion and active smoking were significantly associated with HAQ-DI > 0.5 at 1 year. Conclusion Our results suggest that delay in initiation of csDMARD more than baseline clinical, biological, or imaging features predominantly affects the outcome in early seronegative RA. These findings confirm that the usual therapeutic concepts in RA (early treatment, tight control, and treat-to-target) should be applied similarly to both seropositive and seronegative disease forms. Trial registration ClinicalTrials.gov: NCT03666091. Registered September 11, 2018.

Resume Introduction Bien que les biotherapies aient nettement ameliore le pronostic des polyarthrites rhumatoides, les patients peuvent encore avoir recours a une chirurgie orthopedique. La recommandation actuelle, en cas d’intervention programmee, est d’interrompre l’agent biologique 2 a 6 semaines avant l’acte chirurgical. La reprise de l’anti-TNFα est proposee apres obtention de la cicatrisation. Nous avons voulu savoir si les patients traites par anti-TNF sont exposes a un sur-risque infectieux au decours d’un acte chirurgical et si l’interruption du traitement anti-TNF modifie le risque infectieux chirurgical. Methodes Nous avons mene une analyse systematique de la litterature a partir de Pubmed, Embase et Cochrane, jusqu’en mars 2014. Nous avons selectionne les etudes qui rapportaient les infections postoperatoires en comparant des patients sous anti-TNFα a des patients sous csDMARD sans traitement biologique, ou des patients ayant poursuivi l’anti-TNFα a des patients l’ayant interrompu avant la chirurgie. Resultats Une premiere meta-analyse portant sur 12 etudes evaluant le risque infectieux postoperatoire chez les patients traites par anti-TNFα montre un risque d’infection postoperatoire 2 fois plus eleve (RR = 1,81 [1,31–2,50]). Sept etudes ont pu etre groupees en une seconde meta-analyse pour evaluer le benefice de l’arret preventif de l’anti-TNFα. L’interruption du traitement ne modifie pas le risque infectieux postoperatoire de facon significative : RR = 0,69 [0,39–1,21]. Conclusion Ce travail montre que les patients traites par anti-TNFα sont plus exposes au risque d’infection postoperatoire au decours d’une intervention orthopedique. L’arret preventif des anti-TNFα ne semble pas modifier ce sur-risque.

Resume Objectifs Rechercher si l’âge d’apparition de la maladie conditionne l’evolution clinique, radiographique ou fonctionnelle dans une cohorte de PR debutantes. Methodes La cohorte ESPOIR est une cohorte multicentrique des patients atteints de polyarthrites debutantes. Ont ete selectionnes dans notre etude les patients qui remplissaient les criteres ACR/EULAR 2010 pour la PR pendant les 3 premieres annees du suivi. Ces patients ont ete repartis dans 3 groupes en fonction de l’âge d’apparition de la PR : 60 ans (PR d’apparition tardive [LORA]). Les resultats suivants ont ete compares a l’inclusion puis au cours des 3 premieres annees de suivi : La remission selon le score SDAI (Simple Disease Activity Index), la presence d’une erosion radiologique supplementaire, le questionnaire HAQ-DI (Health Assessment Questionnaire Disability Index) Resultats Un total de 698 patients a ete inclus (d’âge moyen [ecart interquartile] 50,3 [39,8–57,2] ans), 266 YORA, 314 IORA, et 118 LORA. 1 an, on notait une remission SDAI plus importante pour les patients YORA que pour ceux des groupes IORA et LORA ( p p = 0,009) puis a 3 ans ( p = 0,017) de suivi. La proportion de patients ayant un score HAQ p = 0,007), 2 et 3 ans de suivi. Le taux de maintien therapeutique du premier DMARD etait plus faible dans le groupe YORA que dans les autres groupes au cours des 3 ans ( p = 0,005) de suivi. Conclusions Dans une cohorte de PR debutantes, l’apparition precoce de la maladie est associee a un taux eleve de remission a 1 an, une progression radiologique nulle a 3 ans et un faible score fonctionnel au cours des 3 ans de suivi.

Key Points Question Is receipt of tumor necrosis factor (TNF) inhibitor monotherapy at the time of COVID-19 diagnosis associated with adverse COVID-19 outcomes compared with other treatment regimens among patients with immune-mediated inflammatory diseases (IMIDs)? Findings In this cohort study of 6077 patients with IMIDs and COVID-19, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, or Janus kinase inhibitor monotherapy were each associated with significantly higher odds of hospitalization or death compared with TNF inhibitor monotherapy. Meaning This study’s findings support the continued use of TNF inhibitor monotherapy among individuals with IMIDs during the pandemic., Importance Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. Objective To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19–associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs. Design, Setting, and Participants This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age ≥18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included. Exposures Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy. Main Outcomes and Measures The main outcome was COVID-19–associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations. Results A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P, This cohort study uses data from 3 international registries to examine the association between the receipt of tumor necrosis factor monotherapy and the risk of COVID-19–associated hospitalization or death among adult patients with immune-mediated inflammatory diseases.

Resume Certains patients consultant pour des arthralgies ont un risque eleve d’apparition d’arthrites cliniques et/ou de PR. L’evaluation du risque individuel repose sur l’interrogatoire et l’examen physique : PR chez un apparente au premier degre, localisation aux metacarpophalangiennes, raideur matinale articulaire ≥ 60 minutes, notion de gonflements articulaires rapportes par le patient, difficulte a serrer le poing, positivite du squeeze test des metacarpophalangiennes. Elle repose aussi sur la recherche de biomarqueurs : elevation de la CRP, presence d’ACPA et/ou de FR. Elle repose enfin sur les donnees issues de l’imagerie : signes d’inflammation articulaire a l’echographie ou a l’IRM. A l’issue de l’evaluation du risque individuel, le rhumatologue peut intervenir sur les facteurs de risque modifiables pouvant potentiellement favoriser le developpement d’arthrites, tels le tabac et le surpoids. Chez les sujets a haut risque, il peut envisager d’initier un traitement immunomodulateur visant a prevenir l’apparition d’arthrites cliniques et/ou de PR, bien que le niveau de preuve d’une telle strategie a ce stade soit actuellement faible.

Resume La production de cytokines par les cellules de l’inflammation et de l’immunite joue un role essentiel dans les mecanismes lesionnels de l’articulation rhumatoide. Inhiber ces cytokines par des biomedicaments permet de reduire l’inflammation et de proteger l’articulation. Parmi toutes les cytokines presentes dans une synovite rhumatoide, le TNF-α, l’IL-6 et l’IL-1 exercent une action preponderante. Cette revue est principalement axee sur ces 3 cytokines, en retracant successivement leur role physiologique et leur role pathogene au cours de la PR. Ces 3 cytokines sont la cible d’importantes biotherapies actuellement disponibles pour traiter les patients atteints de PR.

Introduction Although biotherapy has greatly improved the prognosis of RA many patients have still recourse to an orthopaedic surgery. The current recommendation for scheduled surgery is to discontinue administration of the biological agent two to six weeks before surgery. Reinitiating anti-TNF therapy is proposed when the patient has healed. We wanted to know whether patients treated with anti-TNFα were exposed to an infectious risk undergoing a surgical procedure and if discontinuation of anti-TNFα therapy altered the risk of surgical infection. Methods We conducted a systematic review of the literature in PubMed, Embase and Cochrane until March 2014. We selected studies that reported post-operative infections by comparing patients treated with anti-TNFα to patients treated with csDMARD without biological treatment, or patients who continued anti-TNFα therapy to the patients who discontinued treatment prior to surgery. Results A first meta-analysis of 12 studies evaluating postoperative infection risk in patients treated with anti-TNFα showed that the postoperative infection risk doubled (RR = 1.81 [1.31–2.50]). Seven studies were grouped into a second meta-analysis to evaluate the benefit of the preventive discontinuation of anti-TNFα. Discontinuation of treatment did not alter the post-operative infection risk significantly: RR = 0.69 [0.39–1.21]. Conclusion This study showed that patients treated with anti-TNFα were more at risk of post-operative infection undergoing orthopaedic surgery. Preventive discontinuation of anti-TNFα does not seem to change this risk.

Resume Objectifs La cohorte des patients francais inclus dans l’etude ACTION (2010–2013) a ete analysee. Cette etude en vie reelle, prospective, portait sur des patients atteints de polyarthrite rhumatoide moderee a severe, ayant initie un traitement par abatacept intraveineux. Methodes Le maintien therapeutique de l’abatacept a 2 ans a ete analyse chez 455 patients selon : la ligne de traitement, l’IMC et le statut serologique du facteur rhumatoide (FR) et des anticorps antipeptides citrullines (ACPA). Resultats A 2 ans, le taux global de maintien therapeutique (IC 95 %) etait de 44 % et plus eleve chez les patients naifs de traitement biologique comparativement aux patients en echec a au moins un agent biologique, mais non significatif (48,1 % vs 41,8 %). Ce taux a ete evalue en fonction de l’IMC chez 444 patients, il est de 45,5 % sans surpoids, 48,9 % avec surpoids, 36,6 % avec obesite ; sans difference significative entre sous-groupes. Ce taux a ete evalue chez 390 patients en fonction du statut FR et ACPA, il est de 45,7 % pour les FR+ et ACPA+, 43,8 % pour les FR+ ou ACPA+ et de 39,1 % pour les FR− et ACPA− ; sans difference significative entre sous-groupes. Conclusion Les donnees de la cohorte francaise d’ACTION ont confirme l’interet de l’abatacept, avec un maintien therapeutique a 2 ans de 44 %. Dans cette analyse, le maintien therapeutique n’a pas ete influence par la ligne de traitement, l’IMC et le statut serologique.

The objective of this non-interventional study was to evaluate the effectiveness and safety of the etanercept biosimilar SB4 (BenepaliTM) following transition from reference etanercept in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA).Data were collected from clinical records of adult patients with stable RA or axSpA, in France, Germany, Italy and Spain. Key outcomes included the change from transition to 3 and 6 months in Disease Activity Score 28 (DAS28) for RA or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for axSpA.In total, 358 patients with RA and 199 patients with axSpA were enrolled. The mean individual change in disease score from transition was -0.02 (95% confidence interval [CI] -0.11, 0.08) at 3 months and 0.01 (95% CI -0.09, 0.11) at 6 months for DAS28, and -0.01 (95% CI -0.24, 0.21) at 3 months and -0.11 (95% CI -0.31, 0.10) at 6 months for BASDAI. In the RA cohort, 19 (5.3%) and 5 patients (1.4%) reported adverse events and serious adverse events (SAEs), respectively. In the axSpA cohort, 12 (6.0%) and 2 patients (1.0%) reported adverse events and SAEs, respectively. One SAE of pneumonia (RA cohort) was considered to be related to SB4 administration. At 6 months post-transition, the SB4 retention rate was 90.8% (95% CI 87.2%, 93.4%) in the RA cohort and 92.4% (95% CI 87.5%, 95.4%) in the axSpA cohort.Transition from reference etanercept to SB4 is effective and safe in patients with stable RA and axSpA.

Background: Dietary long-chain polyunsaturated fatty acids (PUFAs) of the n3 and n6 families are involved in immune homeostasis and can contribute to modulate inflammatory processes. Dietary intake of n3PUFA (by either supplementation or fish consumption) has been inversely associated with RA incidence in different populations. Some evidence suggests that, in subject at high risk of developing rheumatoid arthritis (RA), high erythrocyte membrane content in long-chain n3-PUFA is associated with lower ACPA prevalence and progression to RA. While long-chain n6PUFA are considered mainly proinflammatory, some, like gamma-linolenic acid (GLA), are endowed with anti-inflammatory activity, and the erythrocyte content in n6 linoleic acid was inversely associated with the development of RA in a nested-case control study. No study hitherto evaluated the longitudinal association between individual PUFA profile and disease activity in early RA. Objectives: To characterize serum profiles of PUFA and to determine their association with baseline variables and with 6-month disease activity in a cohort of patients with early RA. Methods: Serum PUFAs were quantified by gas chromatography-mass spectrometry (GC/MS) in 594 patients with early RA at the time of recruitment in the French Etude et Suivi des POlyarthrites Indifferenciees Recentes (ESPOIR) cohort. Principal component analysis on 19 serum fatty acids with 14 to 22 carbon atoms allowed to determine 3 orthogonal patterns of baseline serum PUFA. Pattern 1 included high proportions of short-chain fatty acids, pattern 2 was high in n3 long-chain PUFA (EPA et DHA), pattern 3 was rich in n6 long-chain fatty acids (among which, GLA had the highest concentration). Patients were stratified in tertiles according to how much the fitted into each pattern, with tertile 1 meaning lowest and tertile 3 highest fitting into the pattern. The association of PUFA patterns with baseline variables was tested in univariate analysis. The association with 6-month disease activity (with high disease activity defined as DAS28>5.1) was tested in multivariable analysis after adjustment on baseline CRP, corticosteroid and/or NSAIDs use, socioeconomic status, ACPA and RF positivity, traditional and biologic DMARDs treatment between 0 and 6 months after inclusion. Results: In baseline univariate analysis, pattern 1 was associated with high BMI, active smoking and with non-Caucasian origin. Profile 2 was associated with higher socioeconomic status and inversely associated with DAS28 and CRP. Profile 3 was associated with ACPA positivity and higher baseline CRP. In multivariate analysis, fitting into pattern 2 and 3 was associated with lower odds of having active disease after 6 months (OR for tertile 3 vs. tertile 1: 0.49 (95% CI 0.25 to 0.97, p Conclusion: In a cohort of early RA patients, we could identify a high serum long-chain n3PUFA profile associated with low disease activity between 0 and 6 months of follow-up in the cohort. This is consistent with a presumed immunomodulatory action of n3PUFA. Despite the baseline association with disease severity features, like ACPA positivity and high CRP, a high serum long-chain n6PUFA profile is also associated with 6-month lower disease activity, possibly due to the presence of high concentrations of GLA in this profile. Disclosure of Interests: Johanna Sigaux Speakers bureau: celgene, Camille de Brauer Buscail: None declared, Chantal Julia: None declared, Rene Marc Flipo: None declared, Alain Cantagrel: None declared, Bernard Bannwarth: None declared, Francois Laporte: None declared, marie-Christophe Boissier Grant/research support from: Pfizer MSD, Speakers bureau: Pfizer Lilly Biogen, Luca Semerano Grant/research support from: pfizer, Speakers bureau: pfizer, roche, msd.

To describe the clinical and microbiological characteristics and outcomes after antibiotic treatment of a national cohort of patients with Lyme arthritis confirmed by PCR testing on synovial fluid and by serology, when available. Objectives To describe the clinical and microbiological characteristics and outcomes after antibiotic treatment of a national cohort of patients with Lyme arthritis confirmed by PCR testing on synovial fluid and by serology, when available. Methods Using the French National Reference Center for Borrelia database, patients with a positive PCR on synovial fluid for Borrelia were identified. Patient clinical and biological characteristics were reviewed from patient records. Long-term outcomes after treatment were studied through a questionnaire and with follow-up data. Results Among 357 synovial fluid testing by PCR between 2010 and 2016, 37 (10.4%) were positive for Borrelia. Patients’ median age was 36 years (range 6–78) with 61% of men and 28% patients under 18. The presentation was monoarticular in 92% and the knee was involved in 97%. Contrary to the Borrelia species repartition in European ticks, B. burgdorferi sensu stricto was the most prevalent species found in synovial fluid (54%) followed by B. azfelii (29%) and B. garinii (17%). Antibiotic treatments were mainly composed of doxycycline (n = 24), ceftriaxone (n = 10) and amoxicillin (n = 6), for a median duration of 4 weeks (range 3–12). Despite a properly conducted treatment, 34% of patients (n = 12) developed persistent synovitis for at least 2 months (median duration 3 months, range 2–16). Among those, 3 developed systemic inflammatory oligo- or polyarthritis in previously unaffected joints with no signs of persistent infection (repeated PCR testing negative), which mandated Disease-Modifying Antirheumatic Drugs (DMARD) introduction, leading to remission. Conclusion In France and contrary to ticks ecology, Lyme arthritis is mainly caused by B. burgdorferi sensu stricto. Despite proper antibiotic therapy, roughly one third of patients may present persistent inflammatory synovitis and a small proportion may develop systemic arthritis. In such cases, complete remission can be reached using DMARD. journal article 2019 06 2018 09 28 imported