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Objective To study the impact of hyperuricemia on clinical presentation, severity, and associated comorbidities of psoriatic arthritis (PsA). Methods Retrospective bicentric case–control study performed in Strasbourg and Colmar, France, from 2009 to 2019. Patients with PsA (according to ICD-10 coding) and at least one available serum urate (SU) measurement were included. Demographic, comorbidities, clinical, and radiographic data were collected. Hyperuricemia was defined as SU level ≥ 360 µmol/L. Results We included 242 patients: 73 (30.2%) had hyperuricemia and 15 (6.2%) met 2015 ACR/EULAR criteria for gout. On univariate analysis, as compared with normo-uricemic patients, hyperuricemic patients were more frequently male (72.6% vs 39.1%, p = 1.6 × 10−6) with higher body mass index (30.9 vs 28.7 kg/m2, p = 0.015) and more comorbidities (Charlson comorbidity index: 2.6 vs 1.8, p = 0.005). PsA started at an older age (47.5 vs 43 years, p = 0.016) was more polyarticular (56.2% vs 41.9%, p = 0.049) than axial (9.6% vs 22.8%, p = 0.019) and more destructive (52.8% vs 37.4%, p = 0.032). PsA patients with joint destruction more frequently had hyperuricemia than did others (37.6% vs 25.8%, p = 0.047). Multivariable analysis confirmed the association of hyperuricemic PsA with peripheral joint involvement (odds ratio 2.98; 95% confidence interval 1.15–7.75; p = 0.025) and less good response to treatment (0.35; 0.15–0.87; p = 0.024). Conclusion Patients with hyperuricemic PsA show poorer response to PsA treatment and have more peripheral and destructive joint damage than normo-uricemic patients. Key Points• Gout and psoriatic arthritis (PsA) can co-exist in the same patient.• Monosodium urate crystals might have a deleterious impact on PsA.• Hyperuricemic PsA is more polyarticular, less frequently axial, and more destructive than normo-uricemic PsA.• PsA with hyperuricemia should lead to more personalized medicine.

Resumen Los progresos de la inmunopatologia han dado lugar al auge de los tratamientos «dirigidos» que se utilizan en muchas especialidades medicas para las enfermedades inflamatorias inmunomediadas (IMID, immune-mediated inflammatory diseases). Estos tratamientos engloban los biofarmacos (anticuerpos monoclonales y proteinas de fusion) o de inmunoterapias dirigidas quimicas, como los inhibidores de JAK, que actuan sobre la via de senalizacion intracelular. Los biofarmacos son anticitocinas (factor de necrosis tumoral [TNF]-α; IL-6; IL-1; IL-17; IL-12/23), anti-linfocitos B o inhibidores de la coestimulacion del linfocito T. El objetivo de esta actualizacion es presentar estos nuevos inmunosupresores disponibles en el mercado en distintas enfermedades sistemicas, como la artritis reumatoide, las espondiloartritis, el lupus sistemico, etcetera. Para cada tratamiento dirigido, la descripcion del mecanismo de accion, de las indicaciones, de los efectos adversos y de las contraindicaciones graves permite disponer de informacion sobre una utilizacion adecuada. La descripcion de la evaluacion preterapeutica, asi como los consejos sobre las situaciones particulares, como la sospecha de una tuberculosis, la aparicion de una alergia, de una hemopatia, de una patologia neoplasica o de una reaccion paradojica, un deseo de gestacion, la preparacion de un viaje, asi como la realizacion de una vacunacion o de cuidados dentales constituyen una ayuda practica en el tratamiento de nuestros pacientes.

BackgroundNo immunomodulatory drug has ever demonstrated its efficacy in primary Sjögren’s Syndrome (pSS). Drug repurposing, or drug repositioning, refers to the use in another disease of an existing drug, originally approved or evaluated in a different disease.ObjectivesThe objective of our study was to repurpose existing therapeutic drugs in pSS using a transcriptomic approach.MethodsWe generated pSS transcriptomic signatures from peripheral blood samples of patients with pSS compared to healthy controls in two cohorts (ASSESS and a Norwegian cohort) and data mined available pSS transcriptomic signatures in public databases. We compared each disease signature to transcriptomic signatures, obtained from the biological action of 2837 drugs, 2160 knock-in and 3799 knock-down genes, available in the Connectivity Map database. A median similarity score with regard to disease signatures was computed for each candidate drug/gene. Drugs and genes were selected if p│80│. If this score is sufficiently high and statistically significant (>80, pFigure 1.Methods of drug-repurposing transcriptomic analysis (adapted from Toro-Dominguez et al, Arthritis Res Ther 2017;19:54)Results1091 peripheral blood transcriptomes were analyzed from 6 independent studies (906 patients with pSS and 185 healthy controls). Our analysis identified 11 transcriptomic drug signatures significantly associated with pSS signature. We identified 72 transcriptomic knock-in (11) or knock-down (61) gene signatures significantly associated with that of pSS, including 21 with a negative similarity score (Table 1).Table 1.Knock-down and knock-in genes significantly associated with the pSS transcriptomic signaturesType ofexperimentSimilarity scoreGenesNumber of genesKnock-in+IFNG, DUSP28, IFNB1, LYN, BCL2L2, TNFRSF1A, CD40, BCL10, NLK, ZNF39810-SLC52A2111Knock-down+SLC25A14, GOLIM4, DTYMK, DCXR, RRM2, IMPA1, CLTB, F12, CAB39, ID1, ISOC1, UBAP1, HIGD2A, UFD1L, SOD2, BTG1, PRKCI, HIST2H2BE, NISCH, TEAD4, MTX2, TYK2, GTF2B, NDUFS7, NNT, ACADSB, GSTP1, HOMER2, SORBS3, PCK2, PHB2, PDXK, TES, TM9SF2, TBX2, HOXA6, KIF2C, MED1, NR2F6, CD14, BECN141-TM9SF3, E2F3, PRMT3, KD, PKN2, SUCLA2, CD44, GRN, SP3, ATP5S, MYCBP2, TRAF7, POLA2, ADRB2, PSMG1, PPP2R3C, PMAIP1, ETFA, ANKRD37, SPECC1L2061Type I and II interferons were highly ranked (similarity score >99), and their overexpression mimicked the disease signature. CD40 appeared also as a very relevant target (similarity score = 98.8). Three drugs had a significant negative similarity score: ampicillin (-88.69, p=0.0019), amylocaine (-88.28, p=0.0026), and droxinostat (-85.42, p=0.0027). Droxinostat is a HDAC inhibitor. HDAC activity has been shown to be an essential element of the coactivation system for IFN-induced gene regulation and the IFN-induced innate immune response.ConclusionThis first drug repositioning transcriptomic approach in Sjögren’s syndrome confirms the interest of targeting interferons and identifies histone deacetylases as potential therapeutic targets.AcknowledgementsInvestigators of the ASSESS cohort: Emmanuelle Dernis, Valerie Devauchelle-Pensec, Philippe Dieude, Jean-Jacques Dubost, Anne-Laure Fauchais, Vincent Goeb, Eric Hachulla, Pierre Yves Hatron, Claire Larroche, Véronique Le Guern, Jacques Morel, Aleth Perdriger, Carinne Salliot, Stephanie Rist, Alain Saraux, Jean Sibilia, Olivier Vittecoq, Gaétane Nocturne, Philippe Ravaud, Raphaèle SerorCentre de Ressources Biologiques de l’Hôpital Bichat: Sarah TubianaJohan G. Brun for contributing to the Norwegian cohort.Funding SourcesThis work was supported by the Innovative Medicines Initiative 2 Joint Undertaking (IMI 2 JU) (NECESSITY grant 806975). The Joint Undertaking received support from the European Union’s Horizon 2020 Research and Innovation Program and from the European Federation of Pharmaceutical Industries and Associations. This work was also supported by R01 AR065953 Beth the NIH, United States. The contents are the sole responsibility of the authors and do not necessarily the official views of the NIH.JEG received an unrestricted grant from Bristol-Myer-Squibbs to do the transcriptomic analysis of the ASSESS and Norwegian cohorts. JEG received a grant from Geneviève Garnier (Association Française du Syndrome de Gougerot-Sjögren et des syndromes secs).The ASSESS cohort is promoted by the French Society of Rheumatology and received two research grants from the French Society of Rheumatology.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Disclosure of InterestsRenaud FELTEN: None declared, Tao Ye: None declared, Cédric Schleiss: None declared, Benno Schwikowski: None declared, Jean Sibilia: None declared, Fanny Monneaux: None declared, Hélène Dumortier: None declared, Roland Jonsson: None declared, Christopher Lessard: None declared, Wan Fai Ng: None declared, Tsutomu Takeuchi: None declared, Xavier Mariette: None declared, Jacques-Eric Gottenberg Grant/research support from: JEG received an unrestricted grant from Bristol-Myer-Squibbs to do the transcriptomic analysis of the ASSESS and Norwegian cohorts.

To study the impact of hyperuricemia on clinical presentation, severity, and associated comorbidities of psoriatic arthritis (PsA).Retrospective bicentric case-control study performed in Strasbourg and Colmar, France, from 2009 to 2019. Patients with PsA (according to ICD-10 coding) and at least one available serum urate (SU) measurement were included. Demographic, comorbidities, clinical, and radiographic data were collected. Hyperuricemia was defined as SU level ≥ 360 µmol/L.We included 242 patients: 73 (30.2%) had hyperuricemia and 15 (6.2%) met 2015 ACR/EULAR criteria for gout. On univariate analysis, as compared with normo-uricemic patients, hyperuricemic patients were more frequently male (72.6% vs 39.1%, p = 1.6 × 10Patients with hyperuricemic PsA show poorer response to PsA treatment and have more peripheral and destructive joint damage than normo-uricemic patients. Key Points • Gout and psoriatic arthritis (PsA) can co-exist in the same patient. • Monosodium urate crystals might have a deleterious impact on PsA. • Hyperuricemic PsA is more polyarticular, less frequently axial, and more destructive than normo-uricemic PsA. • PsA with hyperuricemia should lead to more personalized medicine.

BackgroundTherapeutic inertia (TI), or clinical inertia, is the medical behavior of not initiating or intensifying treatment when recommended by clinical recommendations (1). TI was established in diabetes and then studied in hypertension, multiple sclerosis and psoriasis, and is estimated to affect 30 to 70% of physicians managing patients with chronic diseases (2-4). To our knowledge, no data have reported TI in the setting of psoriatic arthritis (PsA).ObjectivesThe OPTI PSA survey was conducted to assess therapeutic inertia around PsA in France.Methods825 French rheumatologists were contacted by e-mail between January and March 2021 and asked to complete an online questionnaire, consisting of 7 clinical vignettes illustrating common situations and reflecting the polymorphic character of PsA: five clinical cases (oligoarthritis, enthesitis, polyarthritis, neoplastic history, cardiovascular risk) requiring treatment optimization in accordance with the latest SFR/EULAR recommendations (5, 6,7) and two “control” clinical cases (DIP arthritis, atypical axial) not requiring any change of treatment. The rheumatologists were also questioned about their routine practice and perception of PsA.Results101 (12%) of the rheumatologists contacted completed the questionnaire. Sixty percent of respondents were men, and 45% of rheumatologists were aged between 46 and 60 years; most practiced exclusively in hospitals (34%), private practice (33%) or in both (34%); the mean duration of clinical practice was 23 years. Almost all of the respondents stated that they were comfortable with the management of PsA (99%) and familiar with French and EULAR recommendations (90%). There was general consensus regarding the difficulties inherent in PsA: therapeutic objectives difficult to achieve (74% of respondents); polymorphism making it difficult to evaluate the effectiveness of a treatment (72%). Almost half the respondents (47%) demonstrated TI on at least one of the 5 vignettes that warranted treatment optimization. The clinical cases that induced the most TI were “oligoarthritis” and “enthesitis” with 20% and 19% of respondents not modifying treatment, respectively. Conversely, the vignettes “polyarthritis in relapse”, “neoplastic history” and “cardiovascular risk” generated fewer TIs with 11%, 8% and 6% of respondents, respectively, choosing not to change the current treatment.ConclusionDespite a good knowledge of PsA and associated clinical recommendations, almost half of the rheumatologists we surveyed demonstrated at least one TI. The rate of TI we observed for PsA is similar to published data for other chronic diseases (1-4). The clinical profiles for which there was the least uncertainty (comorbidities and polyarticular involvement) generated the least inertia; the more complex profiles oligoarthritis and enthesitis generated more inertia. Our study is the first to show the existence of clinical inertia in PsA and further research is warranted to ascertain the reasons behind this inertia.References[1]Phillips LS, et al. Clinical inertia. Ann Intern Med 2001; 135:825-834.[2]Saposnik G, et al. Therapeutic Inertia in Multiple Sclerosis Care: A Study of Canadian Neurologists. Front Neurol 2018; 9:781.[3]Paul SK, et al. Delay in treatment intensification increases the risks of cardiovascular events in patients with type 2 diabetes. Cardiovasc Diabetol 2015; 14:100.[4]Halioua B, et al. Therapeutic inertia in the management of moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol 2020; 34:e30-e32.[5]Peabody JW, et al. Comparison of vignettes, standardized patients, and chart abstraction: a prospective validation study of 3 methods for measuring quality. JAMA 2000; 283:1715-22.[6]Gossec L, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis 2020; 79:700-712.[7]Wendling D, et al. 2018 update of French Society for Rheumatology (SFR) recommendations about the everyday management of patients with spondyloarthritis. Joint Bone Spine 2018; 85:275-284.AcknowledgementsThis survey was funded by Amgen S.A.S. Writing support was funded by Amgen S.A.S. and provided by Medical Education Corpus, FranceDisclosure of InterestsFrederic Lioté Paid instructor for: Amgen, Biogen, Celgene, Fresenius Kabi, Lilly, Nordic, Sandoz, Etienne Dahan Consultant of: Amgen, Celgene, Lilly, Janssen, Abbvie, Arthrex, Arnaud Constantin Consultant of: Abbvie, Amgen, Biogen, BMS, Boehringer, Fresenius Kabi, Galapagos, Janssen, Lilly, Medac, MSD, Mylan, Novartis, Pfizer, Roche, Sanofi, UCB, Viatris, Hanane LAOUAR BOUAZIZ Employee of: Amgen, Aline Frazier-Mironer Paid instructor for: Abbvie, Amgen, BMS, Celgene, Chugai, Fresenius Kabi, UCB, Roche, Pfizer, Novartis, Lilly, Janssen, Galapagos, Jean Sibilia Speakers bureau: Amgen, Consultant of: Amgen

BackgroundThe COVID-19 pandemic has taken a toll on the mental health of the general population. Patients with systemic lupus erythematosus (SLE) were particularly exposed due to many uncertainties linked to the virus and their immunosuppression as well as difficulties to access medical care and their treatment (eg, hydroxychloroquine) during the early pandemic.ObjectivesTo evaluate the difficulties encountered by SLE patients during the early COVID-19 pandemic, and evaluate their impact on patient mental health.MethodsWe conducted a nationwide survey including SLE patients from France metropolitan and overseas territories, recruited by their treating specialist or through a patient association (AFL+). The survey was administered online or in paper form between November 2020 and April 2021, and included questions aiming at evaluating the difficulties encountered during the early COVID-19 pandemic (March to August 2020). The impact on mental health was evaluated using Hospital Anxiety and depression scale (HADS) and post-traumatic stress disorder (PTSD) Checklist for DSM-5 (PCL-5).Results536 SLE patients (91.9% women) of mean age 50 (±14.1) years responded to the survey. The main reported difficulties were issues to access medical care (n = 136, 25.4%) or to obtain hydroxychloroquine treatment (n = 98/389, 25.2%), the loss of employment (n = 85/349, 24.4%) and financial difficulties (n = 75/536, 11%). Hydroxychloroquine shortage was responsible for difficulties in obtaining the drug for 25.2% (98/389) of HCQ-treated patients, and 57 had to interrupt HCQ treatment for a median of 7 days (IQR: 3-17). In the 342 patients with complete assessment, 161 (47.2%) screened positive for anxiety, 141 (41.2%) for depressive syndrome and 128 (38.7%) for PTSD. Multivariate analysis showed that female sex (OR=4.29 [95%CI: 1.39-13.24]), financial issues (OR=2.57 [1.27-5.22]), difficulties to access medical care (OR=2.15 [1.26-3.69]), or to obtain hydroxychloroquine treatment (OR=1.90 [1.06-3.40]) were independently associated with a positive screening for PTSD.ConclusionThe COVID-19 pandemic resulted in a severe burden in SLE patients, including difficulties in access to care and treatment along with high psychological distress. Better understanding these difficulties will allow better prevention and care in times of crisis.Table 1.Factors associated with the development of anxiety, depression or PTSD. Odds ratio (CI95%) using multivariate logistic regression are shown.Patient and pandemic-associated factorsOdds ratio (95%CI) for anxietyOdds ratio (95%CI) for depressionOdds ratio (95%CI) for PTSDFemale sex2.25 (0.97-5.25), p = 0.058ns4.29 (1.39-13.24)p = 0.01Financial difficultiesns2.59 (1.31-5.11)p = 0.0062.57 (1.27-5.22)p = 0.009Difficulties to obtain HCQ1.70 (0.97-2.98)p = 0.065ns1.90 (1.06-3.40)p = 0.03Difficulties to access medical care1.94 (1.15 3.25)p = 0.0122.57 (1.53-4.33)p < 0.00012.15 (1.26-3.69)p = 0.005AcknowledgementsAntonin Folliasson for his help.Disclosure of InterestsMarc SCHERLINGER: None declared, naimah zein: None declared, Jacques-Eric Gottenberg: None declared, Marianne Riviere: None declared, Jean François Kleinmann: None declared, Jean Sibilia: None declared, Laurent Arnaud Speakers bureau: Alexion, Amgen, Astra-Zeneca, Abbvie, Biogen, BMS, Boehringer-Ingelheim, Cêmka, Kezar, GSK, Grifols, Janssen, LFB, Lilly, Menarini France, Medac, Novartis, Oséus, Pfizer, Roche-Chugaï, Sêmeia, UCB., Consultant of: consultant for Alexion, Amgen, Astra-Zeneca, Abbvie, Biogen, BMS, Boehringer-Ingelheim, Cêmka, Kezar, GSK, Grifols, Janssen, LFB, Lilly, Menarini France, Medac, Novartis, Oséus, Pfizer, Roche-Chugaï, Sêmeia, UCB.

BackgroundThe low prevalence of systemic autoimmune diseases and the diversity of their clinical manifestations make complex to conduct randomised clinical trials to assess the potential efficacy of targeted treatments.ObjectivesTo assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory autoimmune diseases.MethodsThe TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age > 18 years; rare systemic autoimmune disease (systemic lupus erythematosus, Sjögren’s syndrome, systemic scleroderma, inflammatory myopathy, vasculitis) or other refractory rheumatism treated with off-label drugs started after 1st January 2019.ResultsHundred (100) patients (79 females) were enrolled. The median age was 52.5 years [49;56], the median disease duration before enrolment was 5 years [3;7]. The targeted therapies at enrolment were as follows: JAK/STAT inhibitors (44%), anti-IL6R (22%), anti-IL12/23, anti-IL23 and anti-IL17 (9%), anti-BAFF (5%), abatacept (5%), other targeted treatments (9%), and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months [8;10].Safety: 11 serious infections (incidence rate of 14.8 /100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: The targeted treatment was considered effective by the clinician in 56% of patients and allowed in responders a median reduction of oral corticosteroids of 15 [9-21] mg/day.ConclusionThese initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.References[1]B. Terrier et al., Safety and efficacy of rituximab in systemic lupus erythematosus: results from 136 patients from the French AutoImmunity and Rituximab registry. Arthritis Rheum 62, 2458-2466 (2010).[2]J. E. Gottenberg et al., Efficacy of rituximab in systemic manifestations of primary Sjogren’s syndrome: results in 78 patients of the AutoImmune and Rituximab registry. Ann Rheum Dis 72, 1026-1031 (2013).[3]J. E. Gottenberg et al., Risk factors for severe infections in patients with rheumatoid arthritis treated with rituximab in the autoimmunity and rituximab registry. Arthritis Rheum 62, 2625-2632 (2010).[4]F. R. S. S. S. C. I. consortium, contributors, Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients. Ann Rheum Dis, (2020).[5]R. Felten et al., B-cell targeted therapy is associated with severe COVID-19 among patients with inflammatory arthritides: a 1-year multicentre study in 1116 successive patients receiving intravenous biologics. Ann Rheum Dis 81, 143-145 (2022).[6]D. J. Wallace et al., Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet 392, 222-231 (2018).[7]J. J. Paik et al., Study of Tofacitinib in Refractory Dermatomyositis: An Open-Label Pilot Study of Ten Patients. Arthritis Rheumatol 73, 858-865 (2021).[8]S. Cole et al., Integrative analysis reveals CD38 as a therapeutic target for plasma cell-rich pre-disease and established rheumatoid arthritis and systemic lupus erythematosus. Arthritis Res Ther 20, 85 (2018).[9]S. J. Bowman et al., Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjogren’s syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial. Lancet 399, 161-171 (2022).AcknowledgementsFrench networks (FAI2R, CRI, IMIDIATE, SFR, SNFMI) focused on rare systemic autoimmune diseases contributed this work by the contribution of network-affiliated physicians.Disclosure of InterestsJacques-Eric Gottenberg Consultant of: Abbvie, BMS, Gilead, Galapagos, Novartis, Lilly Roche Chugai, Sanofi, Janssen, Pfizer, Grant/research support from: BMS.Lilly and Pfizer for this register (with no access to data)., Aurore Chaudier: None declared, Yves Allenbach: None declared, Arsene Mekinian: None declared, Zahir Amoura: None declared, Patrice cacoub: None declared, Divi Cornec: None declared, Eric Hachulla: None declared, Pierre Quartier: None declared, isabelle melki: None declared, Christophe Richez: None declared, Raphaèle Seror: None declared, Benjamin Terrier: None declared, Valerie Devauchelle-Pensec: None declared, Julien Henry: None declared, MARC GATFOSSE: None declared, LAURENCE BOUILLET: None declared, Emeline GAIGNEUX: None declared, Vincent ANDRE: None declared, Gildas BAULIER: None declared, Aurélie SAUNIER: None declared, Marie Desmurs: None declared, Antoine POULET: None declared, Mathieu ETE: None declared, Marie-Elise Truchetet: None declared, Martin Michaud: None declared, Claire Larroche: None declared, AZEDDINE DELLAL: None declared, Amelie LEURS: None declared, Sebastien Ottaviani: None declared, Hubert NIELLY: None declared, Guillaume VIAL: None declared, Roland JAUSSAUD: None declared, Benedicte ROUVIERE: None declared, Pierre-Yves JEANDEL: None declared, Aurelien GUFFROY: None declared, Anne-Sophie Korganow: None declared, Mathieu JOUVRAY: None declared, alain meyer: None declared, Emmanuel Chatelus: None declared, Christelle Sordet: None declared, Renaud FELTEN: None declared, Jean Sibilia: None declared, Samira AHMED YAHIA: None declared, Jean François Kleinmann: None declared, Xavier Mariette Consultant of: BMS, Galapagos, GSK, Janssen, Novartis, Pfizer, Sanofi, UCB

BackgroundVaccination against SARS-CoV-2 is effective in preventing severe forms of COVID-19, but there remain concerns about a reduced vaccine response in patients suffering from inflammatory arthritides who are treated by immunosuppressive therapies.ObjectivesWe analysed the impact of bDMARDs on the humoral anti-SARS-CoV-2 vaccine response of patients followed in day hospitals.MethodsWe studied the vaccine response after a complete vaccine regimen followed in day hospital in 5 French hospitals and treated with an intravenous bDMARD between September 2019 and August 2021. After obtaining their informed consent, we included patients with an anti-SARS-CoV-2 serology. They were considered non-responders if the antibody level detected was inferior to the threshold of positivity of the kit used.Results205 patients were included (148 females/57 males). The median age was 64 years (Interquartile Range [IQR] 56-71). 25 were treated with tocilizumab (TCZ), 36 with abatacept (ABA), 53 with infliximab (IFX) and 91 with rituximab (RTX). When considering both patients after a complete vaccination schema (2 doses, or 1 dose in case of prior COVID-19) and those with 1 booster dose, 34 patients (16.6%) were non-responders (2 [5.9%] treated by IFX, none treated by TCZ, 9 [26.5%] treated by ABA and 23 [67.7%] treated by RTX). In multivariate analysis, the only characteristics that significantly and independently differed between responders and non-responders were last bDMARD and corticosteroid therapy at the time of 1st vaccination (Table 1). In RTX-treated patients, the delay from last infusion to 1st vaccine dose was significantly shorter in non-responders (median 4.3 IQR [2.9-6.1] months in non-responders versus 8.4 IQR [5.7-14.5] in responders, p=0.0007). Median survival, i.e. achieving a vaccine response in 50% of RTX-treated subjects, was achieved after 277 days (95CI [209-310]) in patients vaccinated with 2 or 3 doses (Figure 1). In ABA-treated patients, the delay from last infusion to 1st vaccine dose was not different between non-responders and responders.Table 1.Patients’ characteristics and comparisons between responders and non-responders.All patients (n=205)Responders (n=171)Non responders (n=34)Univariate p valueMultivariatep valueAge (median [IQR]), in years64 [56-71]64 [54-70]69 [57-75.5]0.070.40Female sex, n (%)148 (72.2)125 [73.1)23 (67.7)0.53Inflammatory arthritides, n (%)0.16**0.24 Rheumatoid Arthritis156 (78.0)128 (74.9)28 (82.4)0.51 Spondyloarthritis33 (16.1)31 (18.1)2 (5.9)0.12 Others*16 (7.8)12 (5.9)4 (1.9)0.31Last bDMARDs at time of 1st vaccination, n (%)0.0004ABA/RTX versus IFX/TCZ < 0.00010.00024 Infliximab53 (25.9)51 (29.8)2 (5.9) Tocilizumab25 (12.2)25 (14.6)0 Abatacept36 (17.6)27 (15.8)9 (26.5) Rituximab91 (44.4)68 (39.8)23 (67.7)Associated treatments at time of 1st vaccination CsDMARDs, n (%)126 (61.5)107 (62.6)19(55.9)0.56 Methotrexate91 (44.4)78 (45.6)13 (38.2)0.46 Median dose in users (mg /week) [IQR]15 [10-17.5]13.8 [10-15.6]15 [13.8-20]0.07 Corticosteroids, n (%)25 (12.2)19 (11.1)6 (17.6)0.29 Median dose (mg /day) [IQR]0 [0-0]0 [0-0]0 [0-2]0.0350.016Previous COVID-19 infection, n (%)23 (11.2)21 (12.3)2 (5.9)0.38Type of vaccine, n (%)0.62 Pfizer169 (82.4)142 (83.0)27 (79.4)0.62 Moderna14 (68.3)11 (6.4)3 (8.8)0.71 Astra-Zeneca17 (8.3)15 (8.8)2 (5.9)0.74 Janssen5 (2.4)3 (1.8)2 (5.9)0.19Vaccination, n (%) Complete167 (81.5)141 (82.5)28 (16.8)0.47 Complete + 1 booster dose56 (27.3)43 (25.1)13 (38.2)0.14Figure 1.Cumulative seropositive rate according to the interval (days) between the last course of rituximab administration and vaccinationConclusionABA and RTX alter the anti-SARS-CoV-2 vaccine response and were associated with nearly all vaccine non-responses in the present study. Corticosteroid therapy was associated with a lower vaccine response regardless of its indication or the concomitant use of bMARD.Disclosure of InterestsNone declared

BackgroundDespite a high morbi-mortality rate, there are no definite strategy for subclinical interstitial lung disease (ILD) screening in patients with rheumatoid arthritis (RA).ObjectivesOur objectives were: 1. to identify risk factors for subclinical RA-ILD in a prospective discovery cohort (ESPOIR) 2.to develop a risk score for subclinical RA-ILD and 3. to validate the risk score in an independent replication cohort (TRANSLATE 2).MethodsPatients without pulmonary symptoms from 2 prospective RA cohorts who underwent chest HRCT scans were included. All patients were genotyped for MUC5B rs35705950. A risk score based on independent risk factors for subclinical RA-ILD was developed using multiple logistic regression in the discovery cohort. The risk score was tested for validation in the replication cohort.ResultsDiscovery and replication cohorts included 163 and 89 patients, respectively. Subclinical ILD was detected in 19.0% and 16.9% of the patients, respectively. In the discovery cohort, independent risk factors for subclinical RA-ILD were the MUC5B rs35705950 T risk allele (odds ratio [OR]=3.74; 95% confidence interval [CI] [1.37–10.39], male sex (OR=3.93; 95%CI [1.40–11.39]), older age at RA onset (for each year, OR=1.10; 95%CI [1.04–1.16]) and increased mean DAS28-ESR (for each unit, OR=2.03; 95%CI [1.24–3.42]). We developed a risk score for subclinical RA-ILD with AUC=0.82; 95%CI [0.70–0.94] (sensitivity (Se)=71.0%) and specificity (Sp)=79.6%). The risk score was validated in the replication cohort with AUC=0.78; 95%CI [0.65–0.92] (Se=86.7%, Sp=62.2%).ConclusionOur risk score could help identifying patients at high-risk for subclinical RA-ILD before the onset of pulmonary symptoms.Disclosure of InterestsPierre-Antoine Juge Speakers bureau: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Consultant of: Bristol Myers Squibb, Benjamin Granger: None declared, Marie-Pierre Debray: None declared, Esther Ebstein: None declared, Fabienne Louis-Sidney: None declared, Joanna KEDRA: None declared, Tracy Doyle: None declared, Raphael Borie: None declared, Arnaud Constantin Consultant of: Abbvie, Amgen, Biogen, BMS, Boehringer Ingelheim, Fresenius Kabi, Galapagos, Janssen, Lilly, Medac, MSD, Mylan, Novartis, Pfizer, Procter & Gamble, Roche, Sanofi, UCB, Viatris, Bernard Combe Consultant of: AbbVie, BMS, Eli-Lilly, Gilead, Janssen, Merck, Novartis, Pfizer, Roche-Chugai, Sanofi, UCB, René-Marc Flipo Consultant of: Abbvie, Janssen, MSD and Pfizer. He reports research grants from Abbvie, Janssen, Novartis and Pfizer, Xavier Mariette Consultant of: BMS, Gilead, Janssen, Pfizer, Samsung, UCB, Olivier VITTECOQ: None declared, Alain Saraux: None declared, Guillermo CARVAJAL ALEGRIA: None declared, Jean Sibilia Consultant of: AbbVie, Lilly, MSD, Amgen, Pfizer, BMS, Janssen, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Novartis, Grant/research support from: AbbVie, Lilly, MSD, Amgen, Pfizer, BMS, Janssen, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Novartis, Francis Berenbaum: None declared, Caroline Kannengiesser: None declared, Catherine Boileau: None declared, Jeffrey Sparks Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer, Grant/research support from: National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers R01 AR077607, P30 AR070253, and P30 AR072577), The R. Bruce and Joan M. Mickey Research Scholar Fund, Bristol Myers Squibb,Bruno Crestani Speakers bureau: Boehringer Ingelheim, AstraZeneca, Roche, Sanofi, Grant/research support from: MedImmune, Roche, Boehringer Ingelheim, Bruno Fautrel Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Fresenius Kabi, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, SOBI, UCB, Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Philippe Dieudé Speakers bureau: Roche – Chugai, Bristol Myers Squibb, Consultant of: Pfizer, Roche – Chugai, Bristol Myers Squibb, Abbvie, MSD, Grant/research support from: Novartis

BackgroundThe Fibrosis-4 (FIB4) score, including age, transaminases and platelets, can detect severe fibrosis (F3-F4) in patients with Non Alcoolic Steato Hepatitis (NASH) and could be of interest in the follow-up of patients with RA. Indeed, platelets contribute to the pathophysiology of RA, transaminases are used in the liver monitoring of our treatments. In addition, retrospective data suggested the association between FIB4 and mortality in RA (1).ObjectivesWe aimed to evaluate the value of the FIB4 score as a prognostic factor in RA in the prospective ESPOIR cohort.MethodsPatients of the ESPOIR cohort diagnosed with RA according to ACR-EULAR criteria were included in our analysis. The formula for the FIB-4 score is as follows: [Age (years) × ASAT (U/L)] / [Platelet count (10^9/L) × ALT (U/L)1/2]. The analyses were based on linear mixed-effects models with a random effect on the subject to account for repeated measures throughout time.Results633 of the 813 patients included met the ACR/EULAR criteria for RA and had a calculable FIB4 score. Median FIB4 was 0.75 IQR (0.53-0.99) and 61 patients (9.6%) had a high FIB4 score at baseline. Baseline FIB4 was significantly higher in patients with a chronic alcohol consumption (p=0.021) or viral hepatitis (pTable 1.Associations of FIB4 score with DAS28 and modified Sharp score evolutions in multivariate analysesVariableVariables included in modelp-valueDAS28TimeAge0.97Baseline number of swollen jointsBaseline Rheumatoid Factor0.51evolution over timeBaseline ACPA (presence)0.97Baseline CRPBaseline modified Sharp score > 00.15Baseline FIB40.26Modified Sharp scoreTime0.052Age0.0005Baseline number of swollen joints0.38Baseline Rheumatoid Factor0.61evolution over timeBaseline ACPA (presence)0.012Baseline CRP0.84Baseline FIB40.25ConclusionOur study was the first to evaluate the value of FIB4 in a prospective cohort of RA patients. The present prospective cohort study with a 10-year follow-up did not find a prognostic role of FIB4 in RA, in contrast to previous retrospective studies. Reassuringly, FIB4 score was not increased by DMARD treatment after 10 years of follow-up, confirming the absence of long-term DMARD-related hepatotoxicity.References[1]Seung Up Kim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Yong-Beom Park, Kwang-Hyub Han & Sang-Won Lee (2018): Fibrosis-4 index at diagnosis can predict all-cause mortality in patients with rheumatoid arthritis: A retrospective monocentric study, Modern Rheumatology, DOI: 10.1080/14397595.2018.1558760Figure 1.Impact of baseline FIB4 score on DAS28, HAQ and total modified-Sharp score over time.AcknowledgementsAn unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. The French Society of Rheumatology, Pfizer, Abbvie, Lilly, Sanofi also supported the ESPOIR cohort study.We also wish to thank Nathalie Rincheval (CHU Montpellier and EA 2415) who did expert monitoring and data management and all the investigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine, MC. Boissier, Paris-Bobigny, A. Cantagrel, Toulouse, B. Combe, Montpellier, M. Dougados, Paris-Cochin, P. Fardellone et P. Boumier Amiens, B. Fautrel, Paris-La Pitié, RM. Flipo, Lille, Ph. Goupille, Tours, F. Liote, Paris- Lariboisière, O. Vittecoq, Rouen, X. Mariette, Paris Bicetre, P. Dieude, Paris Bichat, A. Saraux, Brest, T. Schaeverbeke, Bordeaux, J. Sibilia, Strasbourg) V. Devauchelle and C Lukas for expert X-ray reading.Disclosure of InterestsNone declared.

Introduction La leucemie a grands lymphocytes a grains (LGL) est une lymphoproliferation rare, caracterisee par la proliferation clonale de lymphocytes matures T ou NK, se manifestant par des cytopenies (neutropenie chronique) et des manifestations auto-immunes. 30 % des LGL s’associent a une polyarthrite rhumatoide (PR): on parle de syndrome pseudo-Felty. Les indications therapeutiques sont: neutropenie profonde ( [1] , [2] . Patients et methodes Etude retrospective multicentrique (SNFMI/CRI) incluant des patients majeurs avec: – Diagnostic de PR definie selon les criteres ACR/EULAR-2010. – Diagnostic de LGL selon les criteres proposes par Lamy et al. [3] : – presence de grands lymphocytes a grains > 0,3 g/L au frottis et population LGL T ou NK clonale mise en evidence par cytometrie en flux, PCR du TCRγ ou mutation stat3. La reponse hematologique etait definie comme: – Reponse complete (RC): normalisation de l’hemogramme (hemoglobine > 120 g/L, plaquettes > 150 g/L, polynucleaires neutrophiles > 1.5 g/L, lymphocytes Resultats 14 patients (10 femmes, 4 hommes, âge moyen 55,2 ± 14,2 ans) ont ete inclus. La PR etait seropositive dans 13 cas, erosive dans 4 cas. Le diagnostic de PR precedait celui de LGL de 9,5 ans. Tous les patients ont recu au moins un traitement de fond de la PR, incluant MTX (n = 13), hydroxychloroquine (n = 5), sulfasalazine (n = 5), leflunomide (n = 4), anti-TNFα (n = 5), tocilizumab, (n = 1) et anakinra (n = 1). Treize patients avaient une LGL-T, une patiente une LGL-NK. Au diagnostic de LGL, le taux median de polynucleaires neutrophiles (PNN) etait de 0,9 G/L et le taux median de LGL etait de 1,4 G/L. Neuf patients ont recu d’autres traitements avant d’etre traites par RTX pour la LGL, incluant MTX (n = 8), CYC (n = 2), facteurs de croissances des granuleux (G-CSF, n = 4). Le suivi median apres RTX etait de 35 mois. Cinq patients ont recu le RTX en 1° ligne: 3 ont obtenu une RC et 2 une RP. Parmi les 6 patients traites par MTX pour la LGL, aucun n’etait en RC a l’introduction du RTX (4) ont obtenu une RC sous RTX seul et 2 ont obtenu une RP en associant au RTX des injections hebdomadaires de G-CSF. Deux patientes ont recu du RTX devant une activite elevee de la PR alors que la LGL etait en RC apres un traitement par CYC: la LGL est restee en RC sous RTX, puis a rechute a 22 et 34 mois de la derniere injection. A la rechute, un nouveau traitement par RTX a permis l’obtention d’une RP pour chacune des patientes. Enfin une patiente a recu du RTX au cours d’une polychimiotherapie pour un lymphome B diffus a grandes cellules diagnostique 6 ans apres la LGL: apres 2 cycles de traitement la LGL etait en RC. La tolerance du traitement etait satisfaisante, aucun patient n’a presente de complication infectieuse imputee au traitement. Discussion Plusieurs hypotheses pour expliquer l’efficacite du RTX dans la LGL peuvent etre proposes: modification de “l’ambiance cytokinique” (diminution de la production d’interleukine 2 et 10, et d’interferon γ), alteration de la presentation antigenique via la depletion lymphocytaire B, polarisation des lymphocytes T vers un phenotype T-regulateur, diminution de l’activation lymphocytaire T, depletion directe des lymphocytes T CD20+ et diminution de la proliferation lymphocytaire T. Nous rapportons ici la plus grande serie de patients traites par RTX pour une LGL associee a une PR. Le taux global de reponse eleve (100 %) doit etre interprete avec precaution du fait du caractere retrospectif de notre travail. La bonne tolerance et l’absence d’evenement infectieux rapporte suggere que le RTX peut etre utilise a la fois en 1° ligne ou apres traitement conventionnel dans la LGL associe a la PR. Conclusion Le RTX semble etre une option therapeutique efficace et bien toleree dans letraitement du syndrome pseudo-Felty.

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

The arrival of new drugs and new therapeutic strategies allowed to reach sustained remission in an increasing number of patients with rheumatoid arthritis. The study of biologic disease-modifying anti-rheumatic drugs (bDMARDs) adaptation strategies is a need to optimize the benefit/risk balance and cost/effectiveness ratio of these molecules. Current recommendations such as EULAR 2016 propose tapering bDMARDs, especially when combined with a csDMARD, when the patient is in remission after stopping persistent glucocorticoids. The analysis of literature comprising 22 studies shows that a bDMARD adaptation is possible in established rheumatoid arthritis when clinico-biological and ultrasound remission is maintained over six months. Priority should be given to a progressive tapering strategy doses controlled by disease activity while maintaining "tight control" to identify and effectively treat a relapse, a retreatment being usually favorable.

Introduction La sclerodermie systemique (ScS) est une affection generalisee du tissu conjonctif, des arterioles et des micro-vaisseaux, caracterisee par la survenue de phenomenes de fibrose et d’obliteration vasculaire : – l’atteinte pulmonaire interstitielle est une des complications les plus severes de la sclerodermie systemique. La PID-ScS est caracterisee par sa chronicite, sa progressivite, et son association a une mortalite accrue ; – l’objectif de cette etude est de decrire les caracteristiques, la prise en charge et d’estimer la survie globale des patients atteints de PID-ScS a partir de la base de donnees EUSTAR. Methodes Tous les patients PID-ScS francais de la base de donnees EUSTAR diagnostiques entre janvier 2009 et avril 2018, âges de 18 ans et plus, remplissant les criteres de classification de l’American College of Rheumatology 1980 (ACR) ou European League Against Rheumatism (EULAR)/ACR 2013 et renseignes quant a l’existence d’une PID-ScS a leur date d’inclusion dans EUSTAR, sur une radiographie de thorax ou scanner thoracique haute resolution, ont ete inclus. Resultats Parmi les 14 centres francais participants a EUSTAR, 814 patients ScS ont ete inclus dont 229 (28 %) patients avec PID-ScS sur la periode de l’etude. Parmi les patients PID-ScS, 47,8 % etaient positifs pour les auto-anticorps anti-topo-isomerase. La majorite des patients etaient des femmes (72,9 %), d’âge moyen 56,6 ± 14,0 ans. L’anciennete de la maladie (depuis le 1er symptome hors Raynaud) etait de 8,0 ± 7,9 ans et 54,4 % des patients presentaient une forme cutanee diffuse. Le score moyen de CVF predite des patients PID-ScS etait de 88,1 % et 19,6 % des patients avaient une dyspnee evaluee a III ou IV avec l’echelle NYHA. Un traitement immunosuppresseur (hors biotherapie) a ete prescrit chez 53,1 % des patients : 38,0 % ont recu du mycophenolate mofetil, 14,2 % du methotrexate et 0,90 % du cyclophosphamide. Une biotherapie a ete prescrite chez 8,9 % des patients dont 3,1 % des patients ont recu du rituximab et 2,7 % du tocilizumab. Une analyse de survie realisee sur 157 patients PID-ScS, de duree moyenne de suivi de 3,6 ans, a montre que les proportions de sujets vivants etaient de 82,1 % a 5 ans et de 76,9 % a 9 ans. Conclusion Cette etude fournit une analyse supplementaire sur les caracteristiques, la prise en charge et la survie globale des patients PID-ScS francais.

Background Gateway access to a medical school currently represents 10% of medical students in France. It should increase to 40% in the coming years, starting with the 2020–2021 academic year, due to the implementation of a national reform designed to diversify the selection process and ease access to medical education. The objective of this study was to describe and analyze characteristics of gateway students and their academic performance in France. Methods A retrospective multicentric study on gateway students (Passerelle) enrolled between 2011 and 2019 at three medical schools was conducted. Student characteristics, academic performance (examination results from second to sixth year) and rankings at the national residency exam, Epreuves Classantes Nationale (ECN), were described. A multiple correspondence analysis (MCA) described those with an ECN ranking between 1 to 4000. Results In total, there were 243 gateway entry students, with females representing 57.6% (n = 140). The mean age of students was 26.2 ± 3.6 years. Those with a degree in sciences accounted for 89.3% of the total. Gateway students that dropped out accounted for 6.6%, and mostly at the end of second year (n = 10). 110 gateway entry students completed the ECN with a mean ranking position of 5,624 ± 2,108. ECN rankings between 1 to 4000 were significantly associated with (i) males, (ii) having a mention (score ≥ 12/20) on the French baccalaureate, (iii) never having enrolled in the first year of medical school, and iv) having a low number of uncompleted modules. With the MCA, a mention of ‘very good’ on the French baccalaureate exam (score ≥ 16/20) was associated with an ECN ranking between 1 to 4000. Conclusions This study was the first to describe the characteristics of gateway medical students in France. Most students came from a sciences academic background and had a low rate of dropping out. Future studies on academic performance should be conducted.

Background:Dermatomyositis (DM) is a rare autoimmune muscle disease characterized by an atrophy and a type-I interferon signature in perifascicular fibers. We recently showed that muscle mitochondrial dysfunction is also a characteristic of this disease that participates to both decrease exercise capacity and maintenance of inflammation (1). Pathophysiological mechanisms underlying these characteristics are unknown.Objectives:The objective of this study is to reveal the mechanisms underlying the modifications of perifascicular fibers during DM, taking advantage of a method combining transcriptomic and topographical information.Methods:Fourteen patients with recent (http://david.abcc.ncifcrf.gov) were used to determine the deregulated molecular pathways in the perifascicular fibers during DM.Results:482 transcripts were differently expressed in perifascicular fibers of patients with DM compared to perifascicular fibers of the 2 other groups (348 overexpressed and 134 underexpressed). The most overexpressed transcripts were involved in the type I interferon response while the most underexpressed transcripts were involved in mitochondria and in proteasome functioning. The study of the transcripts differentially expressed in perifasicular versus endofascicular fibers revealed that there is a physiological perifascicular signature: in patients without myopathy, 83 genes were overexpressed and 54 were underexpressed in perifascicular fibers compared to endofascicular fibers. This physiological perifascicular signature was abolished in patient with myositis (DM and other myositis). In the group of patients with DM (but not other myositis), a specific perifascicular signature (18 genes overexpressed and 10 genes underexpressed in perifascicular fibers compared to endofascicular fibers) was identified. The most deregulated transcripts in DM perifascicular fibers were involved in autophagy/mitophagy, mitochondria and proteasome pathways.Conclusion:In the physiological state, perifascicular fibers are characterized by a different transcriptomic profile from endofascicular fibers. During DM, this physiological perifascicular signature is abolished and replaced by a transcriptomic signature that reveal a potential role of proteasome and autophagy deregulation in the pathophysiology of DM.References:[1]Meyer et al. IFN-β-induced reactive oxygen species and mitochondrial damage contribute to muscle impairment and inflammation maintenance in dermatomyositis Acta Neuropathol. 2017;134:655-666.[2]Huang, D. W. et al. The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol 8, R183 (2007).Disclosure of Interests:None declared

Background:Interstitial lung disease (ILD) is an extra-articular manifestation of rheumatoid arthritis (RA) detected in 20% to 60% of patients with RA on high-resolution computed-tomography (HRCT) chest scan and is clinically significant in near 10%. Despite a high morbi-mortality rate, a definite strategy for preclinical ILD screening in patients with RA remains to be determined. To date, several factors have been reported to increase the risk of RA-ILD occurrence (i.e. older age at RA onset, ACPA positivity, male sex, RA disease activity, the MUC5B rs35705950 promoter variant...). However, none of these risk factors has been validated in a prospective cohort of patients with RA. The ESPOIR prospective cohort includes patients aged 18 to 70 years with recent arthritis (less than 6 months) and a definite or probable diagnosis of RA.Objectives:To identify in the ESPOIR cohort factors associated with ILD after at least 10 years of RA duration in order to develop a predictive score to identify patients with preclinical RA-ILD.Methods:An ILD detection by chest HRCT scan was systematically offered to every patient with definite RA after at least 10 years-follow-up. Chest HRCT scans were centrally reviewed by an experienced radiologist. Potential predictors of ILD were prospectively collected from baseline to the date of the HRCT scan, and all included patients were genotyped for MUC5B rs35705950. To take into account repeated measures, trajectories were determined for disease activity, C reactive protein, smoking, treatment exposure (i.e. prednisone, methotrexate [MTX] and biological disease modifying anti-rheumatic drugs [bDMARDs]). A logistic model was used to identify independent predictors for the occurrence of ILD on HRCT scans. Confidence intervals were estimated using sampling methods. A predictive score for preclinical ILD occurrence was developed based on the identified predictors.Results:163 RA patients according to 2010 ACR/EULAR classification criteria, none of whom had pulmonary symptoms, were investigated with a chest HRCT scan (128 women (78.5%), mean RA duration 13.7 ± 1.1 years, age at inclusion 47.6 y/o ± 10.4, mean disease activity score [DAS]-28 during follow up was 3.1 ± 1.0). ILD was detected in 31 patients (19.0%). The MUC5B rs35705950 minor allele frequency (MAF) was 22.2% and 10.0% in the RA-ILD and RA-noILD populations, respectively (OR univariate=2.6 CI95% [1.2-5.5], P=0.01). After logistic regression, independent predictors for preclinical RA-ILD were male sex (OR=3.9 CI95% [1.4-11.4]), older age at RA onset (OR=1.1 per year CI95% [1.0-1.2]), mean DAS-28 score during the follow-up (OR=2.0 CI95% [1.2-3.4]) and MUC5B rs35705950 T risk allele (OR=3.7 CI95% [1.4-10.4]) (Figure 1). No influence of the use of RA-related drugs (prednisone, MTX or bDMARDs) was identified as risk factor. The logistic model could predict preclinical ILD occurrence after 13 years of RA duration with an AUC=0.82 CI95% (0.72-0.91). A predictive score for preclinical RA-ILD based on the 4 identified predictive risk factors was developed (Sensitivity 80%, Specificity 56%).Figure 1.Factors independently associated with preclinical ILD after 13 years of RA durationConclusion:In this cross-sectional study of the prospective ESPOIR cohort, we identified clinical and genetic predictors for ILD after 13 years of RA duration. We developed a predictive score that could improve risk stratification for preclinical RA-ILD and help physicians identify patients with RA in whom a HRCT scan should be performed.Disclosure of Interests:Pierre-Antoine Juge Consultant of: BMS, Benjamin Granger: None declared, Marie-Pierre Debray: None declared, Esther Ebstein: None declared, Fabienne Louis Sidney: None declared, Joanna KEDRA: None declared, Raphael Borie: None declared, Arnaud Constantin Consultant of: Bristol-Meyers Squibb, Chugai, Roche, Abbvie, MSD, Pfizer, and UCB, Bernard Combe Consultant of: Abbvie, Bristol-Meyers Squibb, Lilly, MSD, Janssen, Pfizer, Roche, Chigai, and Sanofi, Grant/research support from: Abbvie, Bristol-Meyers Squibb, Lilly, MSD, Janssen, Pfizer, Roche, Chugai, and Sanofi, René-Marc Flipo Consultant of: Bristol-Meyers Squibb, Roche, Chugai, Abbvie, and Pfizer, Grant/research support from: Roche, Chugai, Abbvie, and Pfizer, Xavier Mariette Consultant of: Bristol-Meyers Squibb, GSK, Janssen, Pfizer, and UCB, Olivier VITTECOQ Consultant of: Bristol Myers Squibb, Roche, Chugai, MSD, Novartis, Pfizer, Abbvie, and Lilly, Alain Saraux Consultant of: Roche, Chugai, and Bristol-Meyers Squibb, Grant/research support from: Roche, Chugai, and Bristol-Meyers Squibb, Guillermo CARVAJAL ALEGRIA: None declared, Jean Sibilia Consultant of: Roche, Chugai, Bristol-Meyers Squibb, UCB, GSK, LFB, Actelion, Pfizer, MSD, Novartis, Amgen, Hospira, AbbVie, Sandoz, Gilead, Lilly, Sanofi, Janssen, and Mylan, Francis Berenbaum Consultant of: Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Elli Lilly, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4P Pharma, Caroline Kannengiesser: None declared, Catherine Boileau: None declared, Bruno Crestani Consultant of: Boehringer Ingelheim, Roche, Sanofi, Apellis, Astra-Zeneca, Grant/research support from: MedImmune, Boehringer Ingelheim, Bruno Fautrel Consultant of: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, SOBI, UCB, Grant/research support from: AbbVie, MSD, Pfizer, Philippe Dieudé: None declared

Background:Gout and psoriatic arthritis (PsA) can co-exist in the same patient. These 2 diseases seem strongly linked, but the pathophysiological mechanisms of this link have not yet been defined. Hyperuricemia could be an important determinant of PsA1.Objectives:To study the impact of hyperuricemia on clinical presentation, severity and associated comorbidities of PsA.Methods:We conducted a retrospective bicenter case–control study in Strasbourg and Colmar, France. Patients with PsA (according to “L40.5 arthropathic psoriasis” ICD-10 coding) and at least one available serum urate level measurement, were included from 2009 to 2019. Demographic, comorbidities, clinical and radiographic data were collected. Hyperuricemia was defined as serum urate level ≥ 360 µmol/L. We defined “good responders to ongoing PsA treatment” as patients with no outbreak of PsA, biological inflammatory syndrome and therapeutic modification at the last follow-up. Patients with “destructive” disease had one or more erosion(s) seen on standard X-ray, ultrasonography, MRI or TDM.Results:We included 242 patients. 73 (30.2%) had hyperuricemia and 15 (6.2%) met criteria for gout. On univariate analysis, as compared with normo-uricemic patients, hyperuricemic patients were more often male (72.6% vs. 39.1%, p = 1.6x10-06), had higher BMI (30.9 vs. 28.7 kg/m2, p = 0.015) and had more comorbidities (Charlson Comorbidity Index: 2.6 vs. 1.8, p = 0.005). In hyperuricemic versus normo-uricemic patients, PsA started at an older age (47.5 vs 43 years, p = 0.016); PsA was more polyarticular (56.2% vs 41.9%, p = 0.049) than axial (9.6% vs 22.8%, p = 0.019) and more destructive (52.8% vs. 37.4%, p = 0.032). Median uricemia was higher in patients with destructive than non-destructive PsA (321 vs 288.8 μmol/l, p = 0.0038), and hyperuricemia was more frequent with than without joint destruction (37.6% vs 25.8%, p = 0.047). The multivariate analysis confirmed hyperuricemia associated with peripheral joint involvement (OR 2.98, p = 0.025) and less good response to PsA treatment (OR 0.35, p = 0.024).Figure 1.Description of normo- and hyperuricemic psoriatic arthritisCRF: moderate to severe chronic renal failure. MACEs: major adverse cardiovascular events. HBP: high blood pressure. MetS: metabolic syndrome. PsA: psoriatic arthritisConclusion:Patients with hyperuricemic PsA have less good response to PsA treatment than those with normo-uricemia and more peripheral and destructive joint damage. Recognition of PsA in which hyperuricemia would play an aggravating role could modify the management. This would justify a diagnostic reassessment in case of doubt, the possible introduction of hypouricemic treatment and the careful use of NSAIDs in the context of multiple morbidities.References:[1]Felten R, Duret P-M, Gottenberg J-E, Spielmann L, Messer L. At the crossroads of gout and psoriatic arthritis: « psout ». Clin Rheumatol. Febr 2020.Acknowledgements:We thank all participating patients. We also thank the medical secretaries for their help with the ICD-10 extraction, and Dr Thomas Lavaux for helping with serum urate tests at Strasbourg University Hospital.Disclosure of Interests:None declared

Background:Vaccination is an important and effective tool to prevent infections in the general population as well as in patients with systemic autoimmune or inflammatory rheumatic diseases (AIIRDs) who may be at increased risk of serious infection. While the global race for vaccines against COVID-19 has already lead to first authorizations and vaccinations in some countries, multiple questions arise for access and provisions as well as for the acceptance of vaccine policies by immunocompromised patients.Objectives:We conducted an international survey about expectations and potential concerns regarding SARS-CoV-2 vaccine in patients with AIIRDs and healthcare professionals.Methods:The online study consisted of 57 questions which addressed determinants associated with SARS-2-CoV-2 vaccine willingness. Dissemination was ensured through social media and patient associations between December 12 and December 21, 2020.Results:The study included 1266 patients with AIIRDs and 265 healthcare professionals from 56 countries. SARS-CoV-2 vaccine willingness was reported by 54.2% of AIIRD patients (uncertainty in 32.2% and unwillingness in 13.6%) and 74.0% of healthcare professionals. In patients, the willingness to get vaccinated increased significantly with age (pSubject groupsPatientsHealthcare professionalsN1266265Age (years), median [IQR25-75]50 [40-61]40 [32.5-53]Female, n (%)1141 (90.1%)150 (56.6%)Male, n (%)115 (9.9%)115 (43.4%)Country, n (%) France320 (25.3%)159 (60%) UK345(27.3%)4 (1.5%) Chile123 (9.7%)4 (1.5%) USA114 (9.0%)7 (2.6%) Venezuela43 (3.4%)26 (9.8%) Spain57 (4.5%)3 (1.1%) Mexico53 (4.2%)3 (1.1%) Argentina45 (3.6%)8 (3.0%) Other*166 (13.1%)51 (19.2%)Rheumatic diagnosis, n (%)1266- Systemic lupus erythematosus492 (38.9%)- Spondyloarthritis176 (13.9%)- Rheumatoid arthritis160 (12.6%)- Giant cell arteritis / Polymyalgia rheumatica144 (11.4%)- Primary anti-phospholipid syndrome64 (5.1%)- Inflammatory myositis62 (4.9%)- Relapsing polychondritis45 (3.6%)- Other**123 (9.7%)--Health professionals, n (%)-265 Doctor-203 (76.6%) Nurse (or equivalent)-23 (8.7%) Nursing assistant-11 (4.2%) Other***-28 (10.6%)Associated comorbidities, n (%) Diabetes69 (5.5%)6 (2.3%) Hypertension267 (21.1%)24 (9.1%) Myocardial infarction, stroke, transient stroke60 (4.7%)1 (0.4%) Respiratory disease (asthma, chronic bronchitis, emphysema, etc.)169 (13.3%)13 (4.9%)Renal failure47 (3.7%)1 (0.4%)Obesity (BMI > 30)228 (18.0%)18 (6.8%)At least one associated comorbidity, n (%)588 (46.4%)50 (18.9%)Smoker, n (%)128 (10.2%)22 (8.3%) Current411 (32.7%)51 (19.2%) Past719 (57.1%)192 (72.5%) NeverUse of oral glucocorticoids, n (%)551 (56.1%)3 (1.1%)Immunocompromised$, n (%)770 (60.8%)0On a 0 to 10 scale, median8 (6-10)5 (3-8)[IQR25-75]9 (7-10)5 (1-8)−Afraid to get infected by SARS-CoV-2−Afraid to get a severe COVID-19Willing to get vaccinated (Yes / uncertain / No), %54.2 / 32.2 / 13.674.0 / 18.1 / 7.9Vaccine hesitancy, n (%)357 (28.2%)59 (22.3%)Conclusion:Data from this study are crucial to understand the main expectations and concerns regarding SARS-CoV-2 vaccination in patients with AIIRDs and healthcare workers and allow the identification of valuable strategies to increase vaccine coverage in those populations.Acknowledgements:We wish to acknowledge the crucial role of the following patient associations: LupusEurope (tweeter: @LupusEurope), Agrupacion Lupus Chile (@Lupus_Chile), RarasNoInvisibles (@Noinvisibles), Lupus UK, Lupus France, SPONDYL’ASSO, Spondyl(O)action, AFL+, in the dissemination of the survey. We are indebted to Gonzalo Tobar Carrizo (@pinkycito) for the Spanish translation of the survey, all patients, families, and health professionals for their kind participation in our study. We wish to thank Ms. Sylvie Thuong for her invaluable assistance.Disclosure of Interests:Renaud FELTEN Speakers bureau: Pfizer, Maxime Dubois: None declared, Manuel F. Ugarte-Gil Speakers bureau: Janssen and Pfizer, Jérémy Fort: None declared, Luc PIJNENBURG: None declared, Aurore Chaudier: None declared, Lou Kawka: None declared, Charlotte Costecalde: None declared, Hugo Bergier: None declared, Emmanuel Chatelus: None declared, Rose-Marie Javier: None declared, Christelle Sordet: None declared, Jacques-Eric Gottenberg Speakers bureau: Pfizer and Astra-Zeneca, Jean Sibilia Speakers bureau: Pfizer, Yurilis Fuentes-Silva: None declared, Laurent Arnaud Speakers bureau: Pfizer and Astra-Zeneca.

Introduction La pneumopathie interstitielle diffuse (PID) est une manifestation extra-articulaire frequente de la polyarthrite rhumatoide (PR) associee a une forte morbi-mortalite. La prevalence exacte de la PR-PID clinique ou infraclinique varie ainsi selon les etudes entre 20 et 60 % et depend de la methode de depistage et de sa temporalite par rapport au debut de la PR. Recemment, le variant du promoteur de MUC5B rs35705950 a ete associe a la presence d’une PID chez les patients atteints de PR. La cohorte ESPOIR a inclus et suivi des patients âges de 18 a 70 ans souffrant d’une PR recente probable ou certaine. Nos objectifs etaient : – d’estimer la prevalence de la PID infraclinique au sein de la cohorte ESPOIR apres au moins 10 ans d’evolution ; – d’evaluer l’interet du genotypage de MUC5B rs35705950 comme marqueur predictif de survenue d’une PR-PID. Patients et methodes Dans cette etude transversale au sein de la cohorte ESPOIR, un depistage d’une PID par scanner thoracique haute-resolution (HRCT) a ete systematiquement propose aux patients inclus dans ESPOIR apres 13 ans de suivi. Une lecture centralisee des HRCT a ete realisee par un radiologue expert qui a classe les patients en fonction de la presence ou l’absence de PID. En cas de PID, l’extension et l’aspect ont ete evalues. Deux patients issus de la cohorte ESPOIR precedemment decedes d’une PR-PID ont ete inclus dans l’analyse afin d’identifier les facteurs prognostiques. Tous les patients inclus ont ete genotypes pour MUC5B rs35705950. Une regression logistique a ete utilisee afin d’identifier les facteurs collectes a l’inclusion dans ESPOIR et predictifs de la presence d’une PID apres au moins 10 ans d’evolution de la PR. Les intervalles de confiance ont ete estimes par methode d’echantillonnage. Resultats Parmi les 170 patients explores par HRCT [133 femmes (78,2 %), duree moyenne de la PR 13,7 ± 1,1 ans], une PID infraclinique etait detectee chez 31 patients (18,2 %) : 19 femmes (61,3 %), âge moyen 67,9 ± 8,7 ans, âge moyen au diagnostic de PR 54,3 ± 8,6 ans. L’etendue de la PID etait 10 % chez 9 patients (5,3 %). Quatre patients presentaient un aspect de pneumopathie interstitielle commune, 4 patients presentaient un aspect de pneumopathie interstitielle non specifique. Des signes scannographiques de fibrose pulmonaire etaient detectes chez 16 patients (9,4 %). Parmi les europeens caucasiens (n = 160), la frequence de l’allele mineur de MUC5B rs35705950 etait de 26,5 % chez les patients PR-PID et de 8,9 % chez les patients PR-non PID (OR = 6,0 ; IC95 %(1,2–7,2)). Apres regression logistique, les facteurs presents au diagnostic de PR et predictifs de survenue d’une PID a 13 ans etaient le sexe masculin (OR = 2,6 IC95 %(1,0-6,6)), un âge au debut de la PR > 49 ans (OR = 5,2 IC95 %(2,0-15,1)), un nombre d’articulations gonflese >9 (OR = 2,9 IC95 %(1,2-7,2)), le caractere migrateur et non fixe des arthrites (OR = 3,4 IC95 %(1,4-8,7)) et l’allele a risque T de MUC5B rs35705950 (OR = 3,8 IC95 %(1,5-10,1)). Ce modele logistique permettait de predire la presence d’une PID apres au moins 10 ans d’evolution de la PR avec une aire sous la courbe = 0,80 IC95 %(0,72-0,90). Conclusion Dans la cohorte ESPOIR, apres au moins 10 ans d’evolution de la PR, la prevalence de la PID infraclinique etait de 18,2 %. Au diagnostic de PR, en association avec certaines donnees cliniques, le genotypage de MUC5B rs35705950 permet d’ameliorer la stratification des patients a risque de developper ulterieurement une PID.

Introduction Nous avons recemment observe une prevalence elevee de myosite a inclusion dans une cohorte de patients atteints de syndrome de Sjogren (SS) primaire. La signification du SS chez les patients ayant une myosite est inconnue. L’anticorps anti 5′-nucleotidase 1A cytosolique (cN1A) a recemment ete propose comme biomarqueur de myosite a inclusion mais cet anticorps est aussi frequent chez les patients ayant un SS. Son utilite pour le diagnostic de myosite a inclusion chez les patients atteints de SS et de myosite est inconnue. Ce travail a pour objectif de decrire la signification du SS chez les patients atteints de myosites. Patients et methodes Dans cette etude monocentrique, les donnees des patients repondant aux criteres EULAR/ACR 2017 de myosite, et evalues pour le SS (criteres ACR/EULAR 2016) ont ete analysees. Quatre-vingt-dix-neuf patients ont ete inclus, couvrant l’ensemble des sous-groupes de myosite EULAR/ACR 2017, avec un suivi median de 6 ans [extremes 1,0 a 37,5]. Les 34 patients ayant une myosite avec SS (myosite/SS + ) ont ete compares aux 65 patients ayant une myosite sans SS (myosite/SS-). Resultats Une myosite a inclusion etait presente chez 24 % des patients myosite/SS+ contre 6 % du groupe myosite/SS- (p = 0,02). Aucun des patients presentant une myosite a inclusion n’a repondu au traitement immunomodulateur, qu’il soit atteint de SS ou non. L’anti-cN1A etait plus frequent chez les patients myosites/SS+ (38 % contre 6 %, p = 0,0005), independamment de la prevalence plus elevee de myosite a inclusion dans ce groupe (valeur p multivariee : 0,02). La specificite des anticorps anti-cN1A pour le diagnostic de myosite a inclusion etait de 0,96 [IC 95 %, 0,87–0,99] dans le groupe myosite SS- mais de seulement 0,70 [IC 95 %, 0,48–0,85] dans le groupe myosite/SS+. Conclusion Chez les patients atteints de myosite, la presence d’un SS est associee a une plus forte prevalence de myosite a inclusion et de l’anticorps anti-cN1A de facon independante au diagnostic de myosite a inclusion. En consequence, l’anti-cN1A a une specificite basse pour le diagnostic de myosite a inclusion chez les patients atteints de myosite avec SS associe.

Introduction Des recommandations pour les patients atteints de maladies auto-immunes (MAI) ont ete emises face a la pandemie a COVID-19. Toutefois, l’impact d’une infection a SARS-CoV2 sur une MAI et sa prise en charge est mal connu. L’objectif de notre etude etait d’evaluer la prevalence et les facteurs predictifs d’infection a SARS-CoV2 ainsi que le risque de poussee inflammatoire chez les patients atteints de MAI et systemique rares (MAISR). Patients et methodes Les patients presentant une MAISR (lupus, Sjogren, myosites inflammatoires, sclerodermie systemique, vascularites et autres connectivites) et suivis dans notre Centre national de reference ont ete contactes par telephone (3 appels en l’absence de reponse) et invites a repondre a un questionnaire standardise evaluant : les facteurs de risque d’exposition et de severite au SARS-CoV2, la prevalence des symptomes evocateurs, la documentation de l’infection ainsi que les informations concernant la MAISR, son traitement et une eventuelle poussee de celle-ci. Chaque participant recevait une ordonnance pour realiser une serologie SARS-CoV2. L’enquete telephonique a eu lieu entre le 9 avril et le 2 juillet 2020. Celle de seroprevalence entre le 18 mai et le 2 juillet 2020. Resultats Au total, 1232 patients ont ete contactes. Parmi eux, 7 n’ont pas pu etre joints (5 deces anterieurs au COVID et 2 demenagements a l’etranger) et 171 ont ete exclus (58 absences de consentement, 110 presentant une autre maladie, 3 non suivis dans notre centre). Un total de 1054 patients a ete analyse avec des donnees serologiques pour 469 (44,5 %). Il s’agissait de 840 femmes (79,6 %) d’âge median 53 ans ([IQR25–75] 38–65) et suivis pour lupus (n = 205, 19,5 %), syndrome de Sjogren (n = 189, 17,9 %), sclerodermie systemique (n = 159, 15,1 %), myopathies inflammatoires (n = 113, 10,7 %), arthrite juvenile idiopathique (n = 110, 10,4 %), vascularites (n = 94, 8,9 %) et d’autres MAISR (n = 184, 17,5 %). Au total 201 patients (19,1 %) ont rapporte des symptomes evocateurs de SARS-CoV2 mais seuls 40 sur les 495 disposant de donnees de RT-PCR, scanographiques ou serologiques avaient une infection prouvee (8,1 %) : par RT-PCR (n = 14), TDM pulmonaire (n = 6) ou serologie (n = 31). Parmi eux, seulement 3 patients avaient consulte aux urgences et 3 avaient ete hospitalises dont 1 en reanimation. Parmi les 146 patients rapportant des symptomes evoquant un COVID-19 et dont les resultats de PCR, TDM et/ou serologie etaient disponibles, seuls 34 (23,3 %) avaient une infection confirmee. L’arret de travail preventif (ATP) n’etait pas statistiquement protecteur de l’infection a SARS-CoV2 (5,8 % si ATP vs 8,1 %, p = 0,78). L’infection a SARS-CoV2 etait statistiquement associee a la modification du traitement de fond de la MAISR (27,5 % de modifications en cas de COVID confirme vs 6,8 % p Conclusion Cette enquete systematique chez plus de 1000 patients atteints de maladie auto-immune systemique rare rapporte une faible prevalence d’infection prouvee a SARS-CoV2 (8,1 %), probablement en rapport avec une bonne observance des mesures prophylactiques chez ces patients. L’interruption des traitements immunosuppresseurs s’accompagne d’un sur-risque important de poussee justifiant les recommandations actuelles.

Introduction La dermatomyosite (DM) est une maladie autoimmune rare du muscle qui se caracterise par une atrophie et une signature interferon de type 1 dans les fibres perifasciculaires. En analysant l’ensemble du muscle des patients nous avons recemment montre que des dysfonctions mitochondriales musculaires etaient aussi une caracteristique de cette maladie. Les mecanismes physiopathologiques qui sous-tendent ces lesions sont inconnus. L’objectif de ce travail etait de reveler les mecanismes qui sous-tendent les lesions des fibres perifasciculaires au cours de la DM. Patients et methodes Quatorze patients atteints de myosites (DM : n = 7, autres myosites : n = 7), recentes ( Resultats 28 transcrits etaient differentiellement exprimes dans les fibres perifasciculaires des patients atteints DM par rapport aux fibres perifasciculaires des deux autre groupes (18 surexprimes et 10 sous exprimes), Les transcrits les plus surexprimes etaient impliques dans la reponse interferon de type 1 alors les transcrits les plus sous-exprimes etaient impliques dans le fonctionnement de la mitochondrie. L’etude des transcrits differentiellement exprimes dans les fibres perifasciculaires par rapport aux fibres endofasciculaires a montre qu’il existait une signature perifasciculaire physiologique : chez les patients sans myopathie, 83 genes etaient surexprimes et 54 sous-exprimes dans les fibres perifasciculaires par rapport aux fibres endofasciculaires. Cette signature perifasciculaire physiologique etait abolie chez les patients atteints de myosite (DM et autres myosites). Dans le groupe des patients atteint de DM, une signature perifasciculaire specifique (18 genes surexprimes et 10 genes sous-exprimes dans les fibres perifasciculaires par rapport aux endofasciculaires) a ete identifiee. Conclusion A l’etat physiologique, les fibres perifasciculaires se caracterisent par un profil transcriptomique different des fibres endofasciculaires. Au cours de la DM, cette signature perifasciculaire physiologique est abolie et remplacee par une signature transcriptomique specifique a la maladie. Ces resultats ont des implications pour le diagnostic (immunomarquages), la comprehension et l’identification de cibles therapeutiques au cours de la DM.

Background:Overlap between systemic sclerosis (SSc) and another auto-immune systemic disease (AISD) in the same patient seems to be more frequent than each disease’s prevalence would explain.Objectives:Our aim was to investigate for overlap syndrome from 2 French cohorts of SSc patients and to compare their characteristics with non-overlap SSc.Methods:Our study was retrospective observational and bicentric. Patients responding to the 2013 ACR-EULAR scleroderma classification criteria for SSc were screened for concomitant AISD. Patients satisfying 2010 ACR-EULAR diagnostic criteria for rheumatoid arthritis (RA) and/or 2016 ACR-EULAR classification criteria for Sjögren’s syndrome (SgS) and/or 2012 SLICC systemic lupus erythematosus (SLE) classification criteria were included in our study. Patient, disease, and treatment characteristics were retrospectively retrieved from medical records and were compared to a SSc cohort.Results:A population of 534 SSc patients was studied. Thirty-four (6.4%) patients were identified as having overlap syndrome. There was 21 (3.9%) patients with RA, 14 (2.6%) with GSS and 4 (0.7%) with SLE (5 patients had 2 AISD). Diagnosis of RA, SLE or SgS was made after diagnosis of SSc for 22 (65%) patients, concomitantly for 10 patients (29%), and before for 2 (6%) patients. Interestingly, two patients with SSc/RA overlap were tested ACPA-positive 2 and 5 years before the first arthritis, respectively. Patients with SSc/RA were severe with 81% of them having erosive disease and despite treatment, only 48% (10/21) patients achieved RA remission (DAS28-CRP < 2.6) at the time of their last visit. Disease duration was longer in patients with SSc overlap syndrome compared to non-overlap patients (15.5 ± 10.6 yearsvs.9.5 ± 8, p < 0.001). Proportion of limited cutaneous SSc was similar in overlap and non-overlap groups (70.6%vs.75.5%, respectively, p = NS), as was the positivity for anti-centromeres antibodies (50%vs.43.2%, respectively, p = NS). The disease phenotype of SSc overlap syndrome was similar to the one of non-overlap SSc in terms of prevalence of pulmonary arterial hypertension, interstitial lung disease, digital ulcer and mortality. With respect to treatments, patients with overlap were more likely to receive glucocorticoids (85.3%vs.45%, p < 0.001), immunosuppressive drugs (82.4%vs.49.2%, p < 0.001) and biologic DMARD (bDMARD, 52.9 %vs.3.8%, p < 0.001). The most prescribed bDMARDs in the overlap population was tocilizumab (40.6%), TNF-alpha inhibitor (29.4%) and rituximab (26.5%) (p < 0.001 for all comparisonvs.non-overlap SSc).Conclusion:We found a prevalence of overlap syndrome higher than 5% among SSc patients. While SSc overlap and non-overlap share common characteristics, overlap patients are more likely to receive glucocorticoids and biologics such as anti-TNF. These overlap should be searched actively (eg, screening for ACPA) since some treatment used for other autoimmune diseases such as glucocorticoids or TNF-alpha inhibitor may be harmful in SSc.Disclosure of Interests:Marc SCHERLINGER Consultant of: Amgen, Mylan, Fresenius Kabi, Johanna Lutz: None declared, Jean Sibilia: None declared, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Thierry Schaeverbeke: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Emmanuel Chatelus: None declared, Marie-Elise Truchetet: None declared

Background Myositis prevalence in primary Sjogren’s syndrome (pSS) and whether it is associated with peculiar extra-muscular involvement and/or a biological profile is unknown. Objectives To refine prevalence and characteristics of patients with pSS and myositis. Methods In the national multicenter prospective cohort ASSESS (395 patients with pSS with a 5 year-prospective follow-up), patients with suspected myositis were identified. Their charts were reviewed and the patients were compared with the rest of the cohort. Results Myositis was suspected in 38 patients (2 men, 36 women, 5829–78 yr old) because of myalgia and/or exercise intolerance (n=38) along with high blood CK level (n=28). As compared with the rest of the cohort, they had higher patient-reported signs including pain VAS, dryness VAS and patient reported index ESSPRI (6.3 vs 5.3, p=0.007). In contrast, proportion of systemic involvements (76.3% vs 70.9%, p=0.57) and systemic disease activity measured by the ESSDAI, without taking the muscular domain into account (2 vs 3, p=0.93), were not different from patients without suspected myositis. Demographic characteristics and disease duration were also similar. Electromyographic recording and/or muscle histology performed in these 38 patients objective muscular involvement in only 4 patients (1% of the cohort). - Three patients were diagnosed with inclusion body myositis (sIBM). Accordingly, age at first sign was 49 years,49–60 muscle disease had progressive onset as suggested by the 11 years1–28 delay between first muscle sign and diagnosis. CK level was - One pSS patient with myositis was a 39 years old woman with polymyositis. She developed proximal muscle weakness, CK was 750UI/L and muscle biopsy found endomysial infiltrate. Muscle force and CK level normalised with immunomodulatory drugs. Compared to the rest of the cohort, patient with myositis had longer disease duration at inclusion (15 vs 5 year, p=0.01) and tended to be younger at pSS diagnosis (41.5 vs 53 year, p=0.07). They had more frequent history of systemic manifestations (100% vs 65.0%, p=0.011) but ESSDAI at baseline (2 vs 3, p=0.56) and the biological characteristics were not different from patients without myositis. In contrast with the patients with suspected but not confirmed myositis, patient-reported signs (i.e. fatigue, pain, dryness and ESSPRI score) were similar to patients without myositis. Conclusions Myositis is frequently suspected in patients with pSS, especially when patients-reported signs are particularly disabling. Myositis occurs very infrequently (1% of the cohort), in patients with longer disease duration. sIBM was the most predominant subset of myositis in the present study. Disclosure of Interest None declared

Background CD180, a related member of the Toll-like receptor family, seems to be underexpressed at the plasma membrane in circulating B cells of auto-immune disease (systemic lupus especially),1 and is lost in various B-cell lymphomas except marginal zone lymphomas (MZL), the most severe complication of primary Sjogren’s Syndrome (pSS).2 Objectives To define the expression of CD180 at the plasma membrane of circulating B cells of pSS and determine its association with systemic disease activity. Methods The expression of CD180 at the plasma membrane of circulating B cells was studied by flow cytometry, in 69 successive patients with pSS, in comparison to patients with systemic lupus (SLE) (n=7) and healthy controls (n=28). Results The cohort of pSS was composed of 65 women for 4 men, median age of 59 years.25–89 Median clinESSDAI was 2 [0–18], 46 patients with a clinESSDAI >0 (low disease activity), 18 patients with a clinESSDAI >5 (moderate disease activity) and 6 patients≥14 (high disease activity). The more frequently involved domains of the ESSDAI were biological (39%, n=27), glandular (32%, n=22), articular (20%, n=14), and peripheral neurological (9%, n=6) domains. Fourty patients were anti-SSA+, 16 anti-SSA and anti-SSB+. 18 had a hypergammaglobulinemia, 17 a hypocomplementemia, 7 a cryoglobulinemia, 18 a rheumatoid factor and 9 a lymphopenia. - CD180-negative B cells in pSS, SLE and controls The proportion of total lymphocytes, B cells, T cells, NK cells or CD180-negative B cells (0.85% vs 0.95%, p=0.64) was not significantly different between pSS patients and healthy controls. Patients with SLE had significantly fewer lymphocytes (860 vs 1544, p=0.0012), B cells and T cells than those with pSS (p=0.023 and p=0.0016); CD180-negative B cells tended have a higher proportion in SLE than in pSS patients (1.9% vs 0.85%, p=0.055). - Increase of CD180-negative B cells in patients with pSS and high systemic disease activity CD180-negative B cells subset was significantly higher in patients with high systemic disease activity (2.55% CD180-negative B cells in patients with clinESSDAI ≥14 vs 0.8% in patients with clinESSDAI Conclusions Blood CD180-negative B cells are increased in pSS patients with high systemic disease activity or in immunologically active pSS. Fonctionnality of CD180 and the prognostic interest of CD180 staining on blood B cells to predict lymphoma in pSS patients, have now to be studied. Reference [1] Kikuchi Y, et al. RP105-negative B cells in patients with Sjogren’s syndrome. [2] Mayeur-Rousse C, et al. CD180 expression in B-cell lymphomas: A multicenter GEIL study. Disclosure of Interest None declared

Background Patients treated with biologic DMARDs have to be aware of the specific adverse events and have to be able to manage their treatments in case of infectious disease. Therapeutic Patient Education aims to enable patient to acquire these safety skills. Objectives To assess the impact of Therapeutic Patient Education on safety skills and management of infectious events in patients treated with biologic DMARDs in rheumatology. Methods Bi-centric analytical study comparing safety skills and infectious events between two cohorts of patients (TPE and TPE-naive). Safety skills were assessed by an auto-assessment called “Biosecure”, rated on a scale from 0 to 100. This assessment explores several dimensions of treatment management and was validated for assessment of safety skills in patients treated with biologic DMARDs in rheumatology in a preliminary study. Infectious events and their management were self-reported by patients. A cluster analysis aimed to separate patients into working group based on their shortcomings (on the basis of their answers to the Biosecure Assessment). Results 414 patients answered the assessment. The median Biosecure Score was 70.98/100 (Q1Q3: 60.97–84.63) 47% attended Therapeutic Patient Education. The median Biosecure Score was significantly higher in the TPE group than in the TPE-naive group (74.88 versus 67.20/100; p Cluster analysis based on Biosecure assessment separated patients into 3 level groups but failed to identify specific patient profiles. Conclusions Therapeutic Patient Education could provide better safety skills and better treatment management in patients treated with biologic DMARDs in rheumatology. Prospective studies may confirm the impact of TPE on treatment management during infectious events. Further studies may assess the impact of TPE on incidence of serious infectious events. References [1] Orefice D, Beauvais C, Gossec L, Flipon E, Fautrel B, Marguerie L, et al. Cross-sectional study of self-care safety skills in 677 patients on biodrugs for inflammatory joint disease. Jt Bone Spine Rev Rhum. dec 2014;81(6):502. [2] Rat A-C, Fautrel B, Flipon E, Gossec L, Marguerie L, Nataf H, et al. Factors associated with knowledge and safety skills of arthritis patients receiving biologics: A survey of 677 patients. Joint Bone Spine. Disclosure of Interest None declared

Background Patient adhesion to biosimilars DMARDs have become a big medico-economic issue. Indeed, savings will depend on penetration rate of biosimilars on the biologics market. Like generics, biosimilars are unknown by the general population and patients reluctance appears to be an obstacle to the diffusion of these therapeutics. Objectives To assess patients‘knowledge, information and concerns about biosimilars and to identify levers and obstacles to adhesion to biosimilars prescription. Methods National cross-sectional study assessing information, knowledge and concerns about biosimilars of french patients treated for a rheumatism (whether they were treated by a bDMARDs or not). The data were collected from march to july 2017 by an online assessment. Results 629 patients answered the assessment. 43% knew the definition of biosimilars. 65% felt unsufficiently informed about biosimilars. The principal sources of information were the rheumatologist and the patient associations. 44% of patients treated with a biosimilar were not informed before they received a biosimilar. Patients concerns focused on molecular structure (46%), efficacy (60%) and tolerance (57%) comparatively to originator bDMARDs. Receiving information about biosimilars and understanding the definition of biosimilarity were two characteristics associated with better adhesion to biosimilars. The rheumatologist was considered the most influent source of information about biosimilar. Patients trust him concerning the decision to switch from the originator biologic to its biosimilar. Patient were reluctant to substitution by the pharmacist (2%). Conclusions Biosimilars are largely unknown by french patients at present. Information seems to be instrumental in patient adhesion to biosimilars and in the preservation of the therapeutic relationship. References [1] Jacobs I, Singh E, Sewell L, Al-Sabbagh A, Shane LG. Patient attitudes and understanding about biosimilars: an international cross-sectional survey. Patient Prefer Adherence. MAI2016;937. [2] Beck M, Michel B, Rybarczyk-Vigouret M-C, Leveque D, Sordet C, Sibilia J, et al. Rheumatologists’ Perceptions of Biosimilar Medicines Prescription: Findings from a French Web-Based Survey. BioDrugs Clin Immunother Biopharm Gene Ther. Dec2016;30(6):585–92. Disclosure of Interest None declared

Background Inflammatory myopathies (IM) are life-threatening but treatable diseases. The risk factors for admission in Intensive care unit (ICU), the management and the outcome of patients with IM admitted to ICU has not yet been assessed. Objectives To assess the clinical features, risk factors and outcome of patients with IM admitted in ICU. Methods A single centre cohort of 509 patients with IM was screened for admission in ICU from 1992 to 2017. Patients admitted for trauma or for complications from elective surgery were excluded. Control patients with IM who had not been hospitalised in ICU were randomly selected from the cohort. Results Thirty-two ICU admissions were recorded in 27 IM patients during the study period ( Characteristics and prognosis of patients in ICU Patients hospitalised in ICU had a mean age of 63 y.±15 with SAPS II score of 58±24 and LODS score of 9±5 corresponding to an intermediate severity at admission in ICU. The delay between IM diagnosis and first ICU admission was 27±43 months. It is noteworthy that 12 patients (44%) were admitted in the ICU within the first month of IM diagnosis, among whom 4 (15%) were diagnosed with IM during ICU stay. Sixteen patients (60%) were not treated at the time of their first ICU admission. In 56% of the ICU stays, patients had active disease at admission. Patients were most frequently admitted for respiratory failure (88%) but cardiac (47%), renal (47%), neurologic (47%), haematological (22%) and hepatic (15%) failures were also recorded. Infections were present in 72% of the ICU stays, with septic shock in 44%. Nine patients (33%) died in ICU and 3 others (11%) within 90 days of the last ICU discharge (vs. 15% during a 7.5±5 years period of follow-up in the control group, p Risk factors of ICU admission The case control analysis identified 6 risk factors significantly associated with hospitalisation in the ICU, 3 of which were independently associated with hospitalisation in multivariate analysis. ICU patients had a higher age at first clinical signs of illness (62±13 years old vs. 53±13 years old, p The type of myositis was not significantly associated with admission in ICU, although no patient admitted in ICU had sIBM. It is noteworthy that cumulative number of immunomodulatory treatments in patients at the time of hospitalisation in ICU was lower than in the control group (0.5±0.7 vs. 1.9±0.8 p Conclusions IM patients admitted in ICU frequently have recent onset and untreated active IM with respiratory failure. Admission to ICU is associated with older age and a higher number of comorbidities. Mortality of IM patients in ICU is high. Disclosure of Interest None declared

Background Arthritis is frequent in antisynthetase syndrome (ASS) but the prevalence, the characteristics and the risk factors of radiographic lesions have been poorly assessed. Objectives To report prevalence, characteristics and risk factors of radiographic abnormalities in ASS patients with arthralgia. Methods A mono-centric cohort of 101 patients with ASS and arthralgia was screened for hand X-ray availability. Patients with osteoarthritic lesions were excluded from the analysis. ASS patients with radiographic lesions were compared to ASS patients with normal X-ray. Results Thirty one patients were included. Thirteen patients (41.9%) had radiographic lesions on hand X-ray, including periarticular calcifications (53.8%), joint pinching (46.1%), erosions (23%), and subluxations (15.3%). Age (54.15±4.5 vs 49.17±3.3 years old, p=0.17) and sex ratio were similar in both groups. Duration of ASS was two-fold longer at first hand X-ray with radiographic lesion compared to the ASS patient without radiographic lesion at last radiographic follow-up (10,08±2,4 years vs. 4,83±1,6, p=0,06). However, the cumulative number of immunomodulatory drugs at first hand X-ray with radiographic lesion or last hand X-ray if normal tended to be lower in patients with radiographic lesions (0,818 vs 1,28, p=0,55). History of extra-articular involvements (including myositis, interstitial lung disease, skin lesions and Raynaud phenomenon) were not different in both groups, although mechanic’s hand tended to be less frequent in patients with radiographic lesions (23.1% vs 61.1%, p=0.07). Patients with radiographic lesions had more frequently anti-EJ (31% vs. 0%, p Conclusions Hand X-ray lesions are frequent in ASS patients with arthralgia, whatever the extra-articular features and the ASS serotype and was associated is a longer duration of ASS. Disclosure of Interest None declared

Background Fatigue is an important issue in systemic lupus and has a major impact on quality of life of the patients. Data are controversial about the factors associated with this complex symptom.1 Objectives To identify the factors associated with fatigue and severe fatigue in patients with systemic lupus erythematosus (SLE) in a large cohort using a multivariate model to precise the importance of each parameter in this multidimensional symptom. Methods We used the LBBR data base, a German French data base of SLE patients. All patients fulfilled the 1997 ACR criteria for SLE. The Fatigue Scale for Motor and Cognitive Functions (FSMC) was used to assess fatigue and severe fatigue. The depression and anxiety were measured with Hospital Anxiety and Depression Scale (HADS). Tests were performed at sampling. Results A total of 570 patients were included (89.1% female). The median age was 42 years (QR25–75: 34–52). The median value of the SELENA-SLEDAI was 2 (QR25–75: 0–4) and 136 patients had a SELENA-SLEDAI score >6. Fatigue was reported by 386 patients (67.7%) including severe fatigue by 209 (36.7%). In univariate analysis among the individual components of the SLEDAI arthritis (p=0.003) and oral ulcers (p=0.002) were associated with severe fatigue. In multivariate analysis fatigue was strongly associated with anxiety (OR: 4.49 [95%CI: 2.60–7.77], p Severe fatigue was strongly associated with depression (OR:6.87 [95%CI: 3.12–15.11], p Conclusions Fatigue is a common symptom in SLE patients and is strongly associated with anxiety and depression. While remission remains an important therapeutic target, these manifestations should also be taken care of with psychological counselling and pharmacological intervention, when needed. Reference [1] Cleanthous S, Tyagi M, Isenberg DA, Newman SP. What do we know about self-reported fatigue in systemic lupus erythematosus?Lupus. 2012Apr;21(5):465–76 Disclosure of Interest None declared

Background Respiratory involvement in rheumatoid arthritis (RA) is the most common extra-articular localisation, affecting 50% of patients, even though only 5% become symptomatic. Lung pathology as RA related interstitial lung disease is associated with significant morbidity and mortality. Involvement of the respiratory system seems frequent but remains underestimated because of the absence of guidelines about its detection in patients with RA. Objectives This study aimed at determining the prevalence of respiratory involvement among symptomatic and asymptomatic patients with rheumatoid arthritis managed in a university hospital. Methods We conducted a prospective observational study from May 2017 to January 2018 at the Strasbourg University Hospital. The patients included were over 18 years of age, had rheumatoid arthritis according to the ACR/EULAR 2010 criteria and signed informed consent. They responded to a self-administered questionnaire about their medical history, cardiorespiratory symptoms and lifestyle. Epidemiological, clinical and radiological data were assessed. All of the patients had a chest computed tomography (CT) and respiratory function tests (RFT). A collection of salivary flow and a test of Shirmer were carried out, to investigate the presence of a sicca syndrome. Chest CTs were interpreted by a radiologist specialised in lung area. Results We included 102 successive patients, 73 women and 29 men. The average disease duration was 34 years. 60 patients were seropositive for rheumatoid factor and 68 for anti-CCP. 59 patients had bone erosions. The average disease activity score (DAS28-CRP) at inclusion was 3.5. 49 patients had associated Sjogren’s syndrome. 22 were active smoker. 43 patients were taking long-term corticosteroid therapy. 96 patients were treated with conventional DMARD treatment, 28 with anti-TNF alpha therapy, 16 with Tocilizumab, 12 with Abatacept, 2 with JAK selective inhibitor, and 16 patients were under Rituximab. Of the 87 RFT performed, 39 were abnormal: 14 reported an obstructive syndrome, 8 a restrictive syndrome, 32 peripheral expiratory braking, suggestive sign of bronchiolitis, and 24 a decrease in the DLCO. Of the 91 chest CTs, 42 revealed lung nodules (42%), 15 of which were more than 6 mm; 29 interstitial syndrome (29%), among which 5 were non-specific interstitial pneumonitis (PINS), 3 common interstitial pneumonitis (PIC), and the other were non specific interstitial syndrome. 2 chest CT showed pleural effusion and 1 pericarditis. 44 patients had coronary calcifications, among whom 32 had no lipid-lowering therapy. Conclusions Pulmonary systemic assessment of RA patients show high prevalence of respiratory involvement: 42% of patients had lung nodules and 29% had an interstitial syndrome. Detection of interstitial lung disease may raise questions about RA treatment such as anti-TNF alpha therapy. Rheumatologist should be more aware of respiratory involvement in RA patients and RFT, a non-invasive test, might be useful at diagnosis and follow-up. Disclosure of Interest None declared

Introduction Les resultats de l’essai MAINRITSAN [1] ont demontre une superiorite du rituximab sur l’azathioprine pour maintenir la remission des vascularites associees aux ANCA (VAA). Au cours de cet essai, a 28 mois, 5 % des patients traites par rituximab avaient presente une rechute majeure, mais a 60 mois de suivi, le taux de survie sans rechute majeure etait seulement de 49,4 % [2] . L’essai MAINRITSAN3 ( NCT02433522 ) visait a evaluer l’efficacite de l’administration a long terme du rituximab pour prevenir les rechutes de VAA chez les patients en remission apres une premiere phase du traitement d’entretien par rituximab. Patients et methodes Pour etre inclus, les patients devaient avoir participe a l’essai MAINRITSAN2 [3] : essai controle randomise comparant deux strategies de perfusion de rituximab chez des patients atteints VAA en remission complete apres le traitement d’induction : les patients du bras « a la demande » avaient recu une perfusion de 500 mg de rituximab lors de la randomisation, avec reinjection de rituximab uniquement apres la reapparition de lymphocytes B CD19 + ou des ANCA ou lorsque le titre des ANCA avait nettement augmente ; les patients du bras systematique recevaient des injections a j0, j14 puis aux mois 6, 12 et 18. Si les patients etaient en remission complete a 28 mois, ils pouvaient etre randomises de nouveau pour recevoir 4 perfusions supplementaires de rituximab ou de placebo, a l’inclusion et aux mois 34, 40 et 46. La premedication pour tous les patients comprenait du paracetamol (1000 mg), de la methylprednisolone (100 mg) et de la dexchlorpheniramine (5 mg). Le critere d’evaluation principal etait la survie sans rechute a 56 mois. La rechute etait definie comme un ou plusieurs nouveaux symptomes ou une aggravation de la maladie avec BVAS > 0 et a ete evaluee par un comite d’adjudication independant. Resultats Entre mars 2015 et avril 2016, 97 patients ont ete randomises dans 45 centres en France : 50 dans le bras rituximab et 47 dans le bras placebo. L’âge moyen etait de 63,9 ans, 35,1 % etaient des femmes, 68 (70,1 %) avaient une granulomatose avec polyangeite et 29 (29,9 %) une polyangeite microscopique et 50 % des patients avaient des ANCA a l’inclusion. Les taux de survie sans rechute des bras rituximab et placebo etaient respectivement de 96 % [intervalle de confiance (IC) a 95 %, 90,7–100 %] vs 74,3 % [62,8–88 %], hazard ratio : 7,5 [1,67–33,6 %] (p = 0,008) ; les taux de survie sans rechute majeure etaient de 100 % [100–100 %] vs 87,1 % [78–97,3 %] (p = 0,009). Douze (24 %) des patients sous rituximab vs 14 (29,8 %) des controles ont presente au moins un evenement indesirable grave (EIG) (p = 0,65). Aucun patient n’est decede. Six (12 %) des patients sous rituximab ont presente 9 effets indesirables graves d’origine infectieuse (2 chocs septiques, 2 infections d’origine urinaire ; 1 maladie de Lyme, 1 angiocholite, 1 neutropenie febrile, 1 bronchite, 1 pneumonie) vs 4 (8,5 %) temoins avec 6 EIG (4 pneumonies, 1 grippe, 1 infection a Pneumocystis jiroveci chez un patient recevant du methotrexate et des glucocorticoides apres etre sorti de l’etude). Conclusion La prolongation du traitement d’entretien des VAA avec du rituximab a permis de reduire significativement le taux de rechute. Les effets indesirables graves n’etaient pas plus frequents chez les patients traites par rituximab.

Resume Propos L’objectif de ce travail etait de proposer des recommandations relatives aux modalites de depistage et de prise en charge des facteurs de risque cardiovasculaire au cours du lupus systemique. Methodes Trente-neuf experts internistes, rhumatologues ou nephrologues francais, membres du reseau des centres de reference et de competence du lupus systemique ont pris part a un vote visant a retenir ou non des recommandations preparees par un groupe de travail a partir d’une revue de la litterature. Resultats Les experts ont souligne que les facteurs de risque cardiovasculaires modifiables doivent etre recherches au moins annuellement au cours du lupus systemique. La prescription d’une statine en prevention primaire depend du taux de LDL-cholesterol et du nombre de facteurs de risque cardiovasculaires, en considerant le lupus systemique comme un facteur de risque cardiovasculaire supplementaire. En prevention secondaire, les experts s’accordent a proposer une cible de LDL-cholesterol Conclusions Ces recommandations vont permettre d’ameliorer et d’homogeneiser la pratique des differents medecins francais impliques dans la prise en charge du lupus systemique. L’actualisation de ces recommandations pourra etre ulterieurement envisagee, en fonction des nouvelles donnees publiees.

Background Despite its high prevalence and mortality, little is known about the pathogenesis of RA–associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA–ILD frequently share the usual interstitial pneumonia pattern and common environmental risk factors, we hypothesized that the two diseases may share additional risk factors including FPF-linked genes. Objectives Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD. Methods We used whole-exome sequencing (WES) followed by restricted analysis of a discrete number of FPF-linked genes and performed a Burden test to assess the excess number of mutations in RA–ILD patients compared to controls. Results Among the 101 RA–ILD patients included, 12 (11.9%) had 13 WESidentified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA–ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations for RA–ILD patients (p=9.45’10-4, odds ratio [OR] 3.17 95% CI 1.53 – 6.12). Telomeres were shorter for RA-ILD patients with a TERT, RTEL1 or PARN mutation than controls (p=2.87x10-2). Conclusions Our results support the contribution of FPF-linked genes to RA–ILD susceptibility. Disclosure of Interest None declared

Background The benefit/risk ratio of infliximab in refractory patient with Takayasu arteritis (TA) is assumed to be favorable, based on retrospective studies with limited sample size [1, 2] in which infliximab has been prescribed off-label. Since 2013, the French Temporary Recommendation of Use (RTU) provides a temporary framework allowing the use of infliximab originator in “TA patients refractory to conventional treatment” during a 3-year period. Objectives The aim of the study was to evaluate the real-life efficacy and safety of infliximab originator in TA patients initiating or with ongoing infliximab treatment. Methods Prospective, multicenter, observational, open-label, study of TA patients treated with infliximab originator. Results As of 2016 (2 years of follow-up), the study included 14 patients (13/14 were female; median age 32 [range 12–56] years) with TA (diagnosis according to Ishikawa criteria). At study entry, the median TA duration was 4.7 (0.4–16) years, 12 patients were already treated with infliximab originator (for a median duration of 34 [1–78] months) and 11 patients were receiving corticosteroids (CS). Infliximab originator was administered at a median dose of 5 (3–6) mg/kg with a median interval of 8 (2–67) weeks between each infusion. Seven patients had an improvement in at least 1 of the NIH disease activity criteria for TA [3] after a median follow-up time of 2 (0.4–11) months), 4 had smoldering disease and 1 patient worsened. The median daily dose of CS decreased from 13 (5–35) mg/day of prednisone or equivalent at baseline to 7 (5–10) mg/day at 6 months, to 5 (5–6) mg/day at 12 months, and remained stable up to 22 months of follow-up. Infliximab was discontinued in 6 patients due to inefficacy (n=3), prior to pregnancy (n=2), or remission of TA (n=1). Two adverse events (1 disease flare and 1 spontaneous miscarriage) were reported, without infliximab interruption. Conclusions Infliximab originator appears to provide an effective and favourable benefit:risk treatment option to refractory TA patients. References Mekinian et al, Efficacy of Biological-Targeted Treatments in Takayasu Arteritis: Multicenter, Retrospective Study of 49 Patients, Circulation 132(18) (2015) 1693–700. Mekinian et al, Efficacy and tolerance of infliximab in refractory Takayasu arteritis: French multicentre study, Rheumatology (Oxford) 51(5) (2012) 882–6. Kerr and al. Takayasu arteritis. Ann Intern Med. 1994; 120: 919–29. Acknowledgements The patients were included by AP-HP Cochin (Dr X Puechal), CHU Angers (Dr C Lavigne), CHU Tours (Pr E Diot), CHU Besancon (Pr N Magy, Dr H Gil), CHU Lille (Pr E Hachulla, Pr M Lambert, Dr H Maillard), AP-HP Kremlin-Bicetre (Pr I Kone-Paut), AP-HM Marseille (Pr JR Harle, Dr N Schleinitz), HEGP Pompidou (Dr JE Kahn), CH Royan (Dr A Bonnin), CHU Strasbourg (Pr T Martin, Dr V Poindron), CHU Bordeaux (Pr J Constans). Disclosure of Interest J.-F. Kleinmann Consultant for: MSD, L. Arnaud: None declared, E. Sauleau Consultant for: MSD, N. Gouyette Employee of: MSD, R. Tajima: None declared, J. Sibilia Consultant for: MSD