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Introduction Hereditary transthyretin related amyloidosis (h-ATTR) classically presents as a small fiber neuropathy with positive family history, but can also be revealed by various other types of peripheral neuropathy. Objective To describe the initial electro-clinical presentation of patients from in a single region (northern France) of h-ATTR when it presents as a polyneuropathy of unknown origin. Method We reviewed the records of patients referred to two neuromuscular centers from northern France with a peripheral neuropathy of unknown origin who were subsequently diagnosed with h-ATTR. Results Among 26 h-ATTR patients (10 Val30Met, 16 Ser77Tyr), only 14 patients had a suspicious family history (53.8%). The electro-clinical presentation was mostly a large-fiber sensory motor polyneuropathy (92.3%), which could be symmetric or not, length-dependent or not, or associated with nerve entrapment or not. Demyelinating signs were observed in 17 patients (70.8%), among whom nine fulfilled the criteria for a definite diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (37.5%). Conclusion h-ATTR may have a wide spectrum of clinical profiles, and should be considered in the screening of polyneuropathies of unknown origin.

Introduction. La télé-expertise est avant tout un moyen qui permet à un médecin de demander à un autre médecin un avis à propos d’un patient via un contact sécurisé. Depuis le 10 février 2019, les actes de télé-expertise sont rémunérés par l’Assurance maladie dans certaines conditions. Les patients ayant la maladie de Parkinson sont concernés par cette réforme. Leurs symptômes moteurs et non-moteurs peuvent compliquer l’accès à un avis spécialisé. La télé-expertise pourrait pallier leurs difficultés de déplacement et favoriser leur prise en charge neurologique, dont l’impact positif sur la qualité de vie des patients a été démontré. L’adhésion des patients est indispensable à la mise en place d’un tel dispositif. Le but de cette étude était d’évaluer si les patients sont prêts à intégrer la télé-expertise dans leur parcours de soins et ce qu’ils en attendent. Méthodes. Une étude qualitative incluant 15 patients ayant la maladie de Parkinson sans démence ni dysarthrie, a été réalisé par entretiens téléphoniques audio-enregistrés. Les données ont été transcrites ad integrum, triangulées et analysées à l’aide du logiciel NVivo12®. Résultats. Les patients considéraient la télé-expertise comme un moyen d’améliorer la qualité et la rapidité d’accès aux soins. La communication entre médecin généraliste et neurologue ou autre spécialiste permet l’accompagnement approprié et centré sur la personne. Ils craignent cependant une perte de contact humain et l’émergence d’une médecine paternaliste. Ils soulignaient aussi les difficultés techniques et organisationnelles d’un tel dispositif. Conclusion. Les patients semblaient prêts à intégrer la télé-expertise dans leurs parcours de soins, sans pour autant se substituer totalement aux consultations en présentiel. Elle représente un moyen novateur pour éviter la rupture de la continuité des soins lorsque les délais de rendez-vous avec un médecin spécialiste sont de plusieurs mois, et favorise la prise de décision collégiale. Reste à démocratiser cette technologie dans le milieu médical et à développer une collaboration interprofessionnelle.

National audience; Systemic sclerosis (SSc) is an autoimmune disease associated to fibrotic manifestations. Interstitial lung disease (SSc-ILD), one of the main fibrotic features of SSc, is the first cause of SSc-related death. The management of SSc-ILD has recently benefited from the results of key randomised controlled trials. French authorities have approved Nintedanib for the treatment of SSc-ILD, and tocilizumab has recently been approved by the Food and Drug Administration (FDA) in the United-States (US). These recent approvals challenge the management of this fibrotic manifestation of SSc. This narrative literature review, at the crossroad of internal medicine and pulmonology, discusses what could be an up-to date approach, in terms of diagnostic and therapeutic strategies for SSc-ILD, in the light of the results from recent clinical trials.

BackgroundThere is a paucity of data in the literature about the outcome of patients with idiopathic inflammatory myopathy (IIM) who have been infected with SARS-CoV-2.ObjectivesTo investigate factors associated with severe COVID-19 outcomes in patients with IIM.MethodsData on demographics, number of comorbidities, region, COVID-19 time period, physician-reported disease activity, anti-rheumatic medication exposure at the clinical onset of COVID-19, and COVID-19 outcomes of IIM patients were obtained from the voluntary COVID-19 Global Rheumatology Alliance physician-reported registry of adults with rheumatic disease (from 17 March 2020 to 27 August 2021). An ordinal COVID-19 severity scale was used as primary outcome of interest, with each outcome category being mutually exclusive from the other:a) no hospitalization, b) hospitalization (and no death), or c) death. Odds ratios (OR) were estimated using multivariable ordinal logistic regression. In ordinal logistic regression, the effect size of a categorical predictor can be interpreted as the odds of being one level higher on the ordinal COVID-19 severity scale than the reference category.ResultsComplete hospitalization and death outcome data was available in 348 IIM cases. Mean age was 53 years, and 223 (64.1%) were female. Overall, 167/348 (48.0%) people were not hospitalized, 136/348 (39.1%) were hospitalized (and did not die), and 45/348 (12.9%) died. Older age (OR=1.59 per decade of life, 95%CI 1.32-1.93), male sex (OR=1.63, 95%CI 1.004-2.64; versus female), high disease activity (OR=4.05, 95%CI 1.29-12.76; versus remission), presence of two or more comorbidities (OR=2.39, 95%CI 1.22-4.68; versus none), prednisolone-equivalent dose >7.5 mg/day (OR=2.37, 95%CI 1.27-4.44; versus no glucocorticoid intake), and exposure to rituximab (OR=2.60, 95%CI 1.23-5.47; versus csDMARDs only) were associated with worse COVID-19 outcomes (Table 1).Table 1.Multivariable logistic regression analysis of factors associated with the ordinal COVID-19 severity outcomes. AZA, azathioprine; CI, confidence interval; combo, combination; CSA, ciclosporin; CYC, cyclophosphamide; DMARD, disease-modifying anti-rheumatic drug; b/tsDMARD, biologic/targeted synthetic DMARD, csDMARD, conventional synthetic DMARD; HCQ, hydroxychloroquine; IVIg, intravenous immunoglobulin; LEF, leflunomide; MMF, mycophenolate mofetil; mono, monotherapy; MTX, methotrexate; OR, odds ratio; Ref, reference; RTX, rituximab; SSZ, sulfasalazine; TAC, tacrolimus.VariableOR (95%CI)P-valueVariableOR (95%CI)P-valueAge (per decade)1.59 (1.32-1.93)ComorbiditiesMale sex1.63 (1.004-2.64)0.048NoneRefNAPrednisolone-equivalent doseOne1.46 (0.79-2.72)0.228NoneRefNATwo or more2.39 (1.22-4.68)0.011>0 to 7.5mg/day1.10 (0.57-2.11)0.779Physician-reported disease activity>7.5mg/day2.37 (1.27-4.44)0.007RemissionRefNAIVIg0.41 (0.15-1.16)0.093Low/moderate1.23 (0.67-2.28)0.504DMARDsHigh4.05 (1.29-12.76)0.018csDMARD only (mono or combi - HCQ, MTX, LEF, SSZ)RefNARegionNo DMARD1.84 (0.90-3.75)0.094EuropeRefNAb/tsDMARD mono or combi (except RTX)1.60 (0.49-5.26)0.435North America0.89 (0.49-1.61)0.694CSA/CYC/TAC mono or combi (except RTX or b/tsDMARDs)1.55 (0.52-4.58)0.429Other4.25 (2.21-8.16)AZA mono1.70 (0.69-4.19)0.249Time periodMMF mono1.22 (0.53-2.82)0.634Before 15 June 2020RefNAAZA/MMF combi (except RTX or b/tsDMARDs)0.71 (0.25-2.00)0.51716 June - 30 September 20200.58 (0.26-1.27)0.171RTX mono or combi2.60 (1.23-5.47)0.012After 1 October 20200.58 (0.35-0.95)0.032ConclusionThese are the first global registry data on the impact of COVID-19 on IIM patients. Older age, male gender, higher comorbidity burden, higher disease activity, higher glucocorticoid intake and rituximab exposure were associated with worse outcomes. These findings will inform risk stratification and management decisions for IIM patients.ReferencesNoneDisclosure of InterestsSu-Ann Yeoh: None declared, Milena Gianfrancesco: None declared, Saskia Lawson-Tovey: None declared, Kimme Hyrich Speakers bureau: AbbVie unrelated to this work, Grant/research support from: Pfizer, BMS, both unrelated to this work, Anja Strangfeld Speakers bureau: AbbVie, Celltrion, MSD, Janssen, Lilly, Roche, BMS, Pfizer, all unrelated to this work, Laure Gossec Consultant of: AbbVie, Amgen, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, all unrelated to this work, Grant/research support from: Amgen, Galapagos, Lilly, Pfizer, Sandoz, all unrelated to this work, Loreto Carmona: None declared, Elsa Mateus Consultant of: Boehringer Ingelheim Portugal, not related to this work, Martin Schaefer: None declared, Christophe Richez Speakers bureau: Abbvie, Amgen, Astra Zeneca, Biogen, BMS, Celltrion, Eli Lilly, Galapagos, GSK, MSD, Novartis, and Pfizer, all unrelated to this abstract, Consultant of: Abbvie, Amgen, Astra Zeneca, Biogen, BMS, Celltrion, Eli Lilly, Galapagos, GSK, MSD, Novartis, and Pfizer, all unrelated to this abstract, Eric Hachulla Speakers bureau: Johnson & Johnson, GlaxoSmithKline, Roche-Chugai, all unrelated to this work, Consultant of: Bayer, Boehringer Ingelheim, GlaxoSmithKline, Johnson & Johnson, Roche-Chugai, Sanofi-Genzyme, all unrelated to this work, Grant/research support from: CSL Behring, GlaxoSmithKline, Johnson & Johnson, Roche-Chugai, Sanofi-Genzyme, all unrelated to this work, Marie Holmqvist: None declared, Carlo Alberto Scirè Grant/research support from: AbbVie, Lilly, both unrelated to this work, Rebecca Hasseli: None declared, Arundathi Jayatilleke: None declared, Tiffany Hsu: None declared, Kristin D’Silva: None declared, Victor Pimentel-Quiroz: None declared, Monica Vasquez del Mercado: None declared, Samuel Katsuyuki Shinjo: None declared, Edgard Reis Neto: None declared, Laurindo Rocha Jr: None declared, Ana Carolina de Oliveira e Silva Montandon Speakers bureau: GSK, not related to this work, Paula Jordan: None declared, Emily Sirotich: None declared, Jonathan Hausmann Speakers bureau: Novartis, Biogen, Pfizer, not related to this work, Consultant of: Novartis, Biogen, Pfizer, not related to this work, Jean Liew Grant/research support from: Pfizer research grant, completed in 2021, not related to this work, Lindsay Jacobsohn: None declared, Monique Gore-Massy Speakers bureau: Aurinia Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, not related to this work, Consultant of: Aurinia Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, not related to this work, Paul Sufka: None declared, Rebecca Grainger Speakers bureau: AbbVie, Janssen, Novartis, Pfizer and Cornerstones, all unrelated to this work, Consultant of: AbbVie, Novartis, both unrelated to this work, Suleman Bhana Shareholder of: Pfizer, Inc, Speakers bureau: AbbVie, Horizon, Novartis, and Pfizer, all unrelated to this work, Consultant of: AbbVie, Horizon, Novartis, and Pfizer, all unrelated to this work, Employee of: Pfizer, Inc, Zachary Wallace: None declared, Philip Robinson Speakers bureau: Abbvie, Janssen, Roche, GSK, Novartis, Lilly, UCB, all unrelated to this work, Paid instructor for: Lilly, unrelated to this work, Consultant of: GSK, Kukdong, Atom Biosciences, UCB, all unrelated to this work, Grant/research support from: Janssen, Pfizer, UCB and Novartis, all unrelated to this work, Jinoos Yazdany Consultant of: Aurinia, Astra Zeneca, Pfizer, all unrelated to this work, Grant/research support from: Astra Zeneca, Gilead, BMS Foundation, all unrelated to this work, Pedro Machado Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this work., Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this work.

BackgroundEnrichment strategies from clinical trials for progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) have been partly successful but have not been tested in a real life cohort.ObjectivesAnalyse the efficacy, representativeness and feasibility of enrichment strategies in SSc-ILD patients from the EUSTAR cohort.MethodsWe applied the inclusion criteria of major recent SSc-ILD trials (focuSSced, SLS II and SENSCIS) in SSc-ILD patients and assessed progressive ILD, defined as absolute change in forced vital capacity (FVC) and as significant progression (FVC decline >10%) over time. Data were compared to all patients and patients not fulfilling any inclusion criteria.ResultsIn total, 2258 SSc-ILD patients were included, with 31.2% meeting SENSCIS, 5.8% SLS II, 1.6% focuSSced criteria and 1529 (67.7%) not meeting any criteria (Table 1). In the first 12+/-3 months, a slow FVC% decline of –0.1% was seen in the total, unselected cohort and in patients fulfilling SENSCIS criteria. Patients fulfilling criteria from focuSSced showed a strong FVC decline of –3.7%. Notably, patients enriched for SLS II criteria showed FVC improvement of +2.3% (Figure 1). Similarly, compared to the total unselected cohort, the number of significant progressive events was numerically higher in patients fulfilling focuSSced criteria, the same for SENSCIS criteria and even slightly lower for patients fulfilling the SLS2 criteria.Table 1.Demographics and baseline clinical characteristics of EUSTAR patientsNot fulfilling any criteria (n=1529)focuSSced (n=36)SLS II (n=132)SENSCIS (n=704)Age, years (SD)58.4 (2.9)51.5 (12.2)†51.2 (12.7) †54.2 (13.8) †Male, n (%)231 (15.1)7 (19)35 (27)**156 (21)*Disease duration, months (SD)156.3 (99.4)16.1 (13.9)†40.7 (25.2) †39.4 (23.9) †DcSSc, n (%)597 (43.8)36 (100) †85 (65) †35 (52) †ATA, n (%)735 (51.1)24 (67)*85 (69) †370 (56)mRSS, mean (SD)9.5 (8.3)21 (6.5)*13 (9.6)*11 (9.2)GERD, n (%)1002 (65.9)25 (69)92 (70)430 (62)ESR, mean (SD)27 (20.5)43.1 (23) †29.6 (19.6) †24.7 (20.7)MMF, n (%)75 (16.5)0 (0) †0 (0) †52 (22) †MTX, n (%)42 (9.2)0 (0) †2 (5)20 (9)FVC % predicted, mean (SD)85.7 (22.5)88 (13.6)*66 (9.1) †88 (19.8)DLCO% predicted, mean (SD)58.9 (21.5)61 (12.7)49(14.6)†59 (14.2)NYHA class, n (%)3261 (17.8)6 (19)28 (21)72 (10)*440 (2.7)0 (0)3 (2)4 (1)**P-value: 0.001–0.05; †PIn the second 12 months period, SENSCIS enriched patients had a further absolute FVC% decline as described for the total cohort. In contrast, patients fulfilling the focuSSced and SLS II inclusion criteria showed numerical improvement of lung function in the second period (Figure 1). There were no significant associations of enrichment criteria and ILD progression in the second period.Over the mean observation period of 2.3 years, patients not fulfilling any inclusion criteria showed the same FVC decline of –0.9 (12.1) as observed for the total cohort (–0.9% (12.6)). There were numerical differences in FVC changes in the enriched patient cohorts, varying from –2.8% FVC decline in patients fulfilling the focuSSced criteria to +3.4% FVC improvement with SLS II criteria.ConclusionApplication of enrichment criteria from previous clinical trials showed enrichment for progression with variable success but led to selected patient populations reducing feasibility of recruitment. These findings are important for future clinical trial design and interpretation of the results of published trials.AcknowledgementsWe thank all EUSTAR collaborators.Disclosure of InterestsAnna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Grant/research support from: Boehringer Ingelheim, Cathrine Brunborg: None declared, Paolo Airò Speakers bureau: Bristol-Myers-Squibb, Boehringer Ingelheim, Consultant of: Bristol-Myers-Squibb, Grant/research support from: Bristol-Myers-Squibb, Roche, Jannsen, CSL Behring, Lidia P. Ananyeva Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, László Czirják Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Actelion (now GSK), MSD, Novartis, Pfizer, Roche, Lilly, Grant/research support from: Boehringer Ingelheim, Actelion (now GSK), MSD, Novartis, Pfizer, Serena Guiducci: None declared, Eric Hachulla Speakers bureau: GSK, Roche-Chugai, Johnson & Johnson, Boehringer Ingelheim, Consultant of: CSL Behring, GSK, Roche-Chugai, Johnson & Johnson, Boehringer Ingelheim, Grant/research support from: CSL Behring, Boehringer Ingelheim, GSK, Roche-Chugai, Sanofi Genzyme, Mengtao Li: None declared, Carina Mihai Speakers bureau: MEDtalks Switzerland, Mepha, Grant/research support from: Roche, Boehringer Ingelheim, Janssen, Gabriela Riemekasten Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Petros Sfikakis Consultant of: Boehringer Ingelheim, Gabriele Valentini Consultant of: Boehringer Ingelheim, Sanofi, Grant/research support from: BMS, Otylia Kowal-Bielecka Speakers bureau: Boehringer Ingelheim, Novartis, Pfizer, Gilead Sciences, Janssen-Cilag, MEDAC, MSD, Abbvie, Sandoz, Consultant of: Boehringer Ingelheim, Health Care system Navigator, CSL Behring, MSD, Novartis, Grant/research support from: CSL Behring, Boehringer Ingelheim, Abbvie, Roche, MEDAC, Yannick Allanore Speakers bureau: Boehringer, Abbvie, Consultant of: Boehringer, Bayer, Astra-Zeneca, Prometheus, Sanofi, Genentech/Roche, Boehringer, Grant/research support from: Alpine Immunosciences, OSE Immunotherapeutics, Medsenic, Oliver Distler Speakers bureau: Bayer, Boehringer Ingelheim, Janssen, Medscape, Consultant of: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, 4P Science, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Roivant, Sanofi and Topadur, Grant/research support from: Kymera, Mitsubishi Tanabe, Boehringer Ingelheim

Resume Propos L’education therapeutique (ETP) doit aider le patient atteint de lupus systemique a mieux comprendre sa maladie pour ameliorer sa qualite de vie. L’objectif de notre etude etait d’evaluer les dimensions de la personne pour proposer un environnement motivationnel propice a l’ETP. Methodes Les patients lupiques suivis dans le service de medecine interne du CHU de Lille repondaient a un questionnaire evaluant cinq dimensions de la personne comme propose par Giordan : les dimensions cognitive (connaissances), perceptive (fatigue et douleurs), affective (symptomes anxieux et depressifs), infra-cognitive (raisonnements intimes) et metacognitive (regard sur le monde). La qualite de vie etait egalement evaluee. Resultats Cent-vingt-quatre patients (114 femmes (92 %) d’âge moyen 44,3 ± 14,3 ans) ont repondu au questionnaire. Concernant la dimension cognitive : la quantite d’informations au moment du diagnostic etait jugee insuffisante pour 57 patients (46 %). L’observance de la prise medicamenteuse evaluee par une echelle avait pour mediane 97 mm (88–100). Concernant la dimension perceptive : les douleurs etaient evaluees a 59 mm (44–78) et la fatigue a 66 mm (50–79) aux echelles visuelles. Concernant la dimension affective : des symptomes anxieux etaient presents chez 83 patients (67 %) et depressifs chez 35 (28 %). Concernant la dimension infra-cognitive : 78 patients (63 %) avaient un lieu de controle externe. Concernant la dimension metacognitive, le lupus avait des repercussions negatives sur la vie professionnelle et familiale et sur la qualite de vie. Conclusions De multiples dimensions du patient lupique sont a prendre en consideration pour un environnement motivationnel optimal pour la pratique de l’ETP.

Introduction Les patients atteints de maladies musculosquelettiques inflammatoires/auto-immunes (I-RMD) n’ont pas ete inclus dans les etudes de tolerance des vaccins contre le SARS-CoV-2 et sont souvent inquiets quant a la tolerance de la vaccination. Notre objectif est d’etudier la tolerance des vaccins contre le SARS-CoV-2 chez les patients atteints de maladies musculosquelettiques inflammatoires/auto-immunes (I-RMD). Patients et methodes Pour cela, nous avons cree avec l’EULAR un registre international de cas rapportes par les medecins rhumatologues et internistes de patients atteints d’I-RMD et de RMD non inflammatoire (NI-RMD) vaccines contre le SARS-CoV-2. Du 5 fevrier 2021 au 27 juillet 2021, nous avons recueilli des donnees sur la demographie, la vaccination, le diagnostic de RMD, l’activite de la maladie, les traitements immunomodulateurs/immunosuppresseurs, les poussees, les evenements indesirables (EI) et les infections COVID-19 chez les patients vaccines. Les donnees ont ete analysees de maniere descriptive. Resultats L’etude a inclus 5121 participants de 30 pays, la majorite de France (40 %), Italie (16 %) et Portugal (14 %), 90 % avec des I-RMD (n = 4604, 68 % de femmes, âge moyen 60,5 ans) et 10 % avec des NI-RMD (n = 517), 77 % de femmes, âge moyen 71,4 ans. La polyarthrite rhumatoide (33 %), les connectivites (18 %), les spondyloarthrites (11 %), le rhumatisme psoriaqique (10 %) et les vascularites (12 %) etaient les diagnostics les plus frequents ; 54 % des patients ont recu des traitements de fond synthetiques conventionnels (csDMARD), 42 % des DMARD biologiques ou cibles et 35 % des immunosuppresseurs. La plupart des patients ont recu le vaccin Pfizer/BioNTech (70 %), 17 % AstraZeneca/Oxford et 8 % Moderna. Une infection COVID post-vaccination a ete signalee dans 0,7 a 1,1 % des cas, selon le statut vaccinal (entierement/partiellement vaccine) et le groupe RMD. Des poussees d’I-RMD ont ete signalees dans 4,4 % des cas (0,6 % de poussees severes), dont 1,5 % ont entraine des changements de medicaments. Des EI ont ete signales dans 37 % des cas (37 % I-RMD, 40 % NI-RMD), des EI severes dans 0,4 % des cas, tres divers et avec une frequence comparable et meme inferieure a celle observee chez les patients atteints de NI-RMD (1,1 %). Discussion La tolerance au vaccin n’etait pas differente entre les groupes I-RMD et NI-RMD. Dans les essais cliniques de vaccins a ARN contre le SRAS-CoV-2 dans la population generale, les taux d’EI graves etaient tres semblables a ceux de notre etude, allant de 0,4 % a 0,6 % dans le groupe vaccine et de 0,5 % a 0,6 % dans le groupe temoin, ce qui suggere que ces EI graves ne sont pas necessairement lies au vaccin. Conclusion Il s’agit de la plus grande etude de la tolerance des vaccins anti-SRAS-CoV-2 chez pres de 5000 patients atteints de maladies inflammatoires/auto-immunes rhumatologiques. Le profil de securite des vaccins contre le SRAS-CoV-2 chez les patients atteints d’I-RMD etait rassurant, et comparable a celui des patients atteints de NI-RMD. La majorite des patients ont bien tolere leur vaccination, avec de rares poussee d’I-RMD et de tres rares EI severes probablement non lies a la vaccination. Ces resultats devraient rassurer les rhumatologues et les personnes vaccinees, et favoriser la confiance dans la securite du vaccin COVID-19 chez les patients atteints de I-RMD.

BackgroundRisk-stratification is key in a heterogeneous disease like systemic sclerosis (SSc). Until now, SSc patients are stratified according to the extent of skin involvement into limited cutaneous, diffuse cutaneous and sine scleroderma subtypes. However, this classification remains inaccurate to capture disease heterogeneity. Autoantibodies are found in more than 90% of the patients and can be detected before onset of the disease. Among them, three predominant and specific antibodies are used: anti-centromere, anti-Scl70 and RNA polymerase III antibodies.ObjectivesTo compare the performances of stratification into LeRoy’s cutaneous subtypes versus autoantibody status in SSc versus combination of cutaneous subtypes and autoantibodies status.MethodsPatients from the EUSTAR database were classified either as (i) limited cutaneous, diffuse cutaneous or sine scleroderma (based on the recording made by the treating physician) or (ii) according to autoantibodies with the following subclassifications: (1) no specific autoantibodies, (2) isolated ANA, (3) anti-centromere antibodies, (4) anti-Scl70 antibodies and (5) anti-RNA polymerase III antibodies or (iii) according to combination of cutaneous subset and auto-antibodies. The respective performance of each model to predict overall survival (OS), progression-free survival (PFS), disease progression and different organ involvements was assessed and the three models were compared by the area under the receiver operating characteristic curve (AUC 95%CI) and the net reclassification improvement (NRI). Missing data were imputed through multiple imputation using chain equations.ResultsIn all, 10’711 patients were included: 84.6% females, mean age: 54.4±13.8 years, mean disease duration: 7.9±8.2 years. In the prospective analysis (n= 6’467 to 7’829 according to the outcome), after a mean follow-up of 56 months and a mean of three visits per patient, we did not identify any difference in AUC between the cutaneous-based model and the antibody-based model for prediction of OS and disease progression. However, the NRI showed a significant improvement in prediction of OS (0.57 [0.46-0.71] vs. 0.29 [0.19-0.39]) and disease progression (0.36 [0.29-0.46] vs. 0.21 [0.14-0.28]) at 4 years using the antibody-based model. Regarding prediction of each organ involvement in longitudinal analyses, the antibody-based model showed better performance than the cutaneous-one for renal crisis (AUC: 0.719 [0.696-0.742] vs. 0.664 [0.643-0.685]), with the highest association observed with anti-RNA polymerase III (OR: 7.47 [1.63-34.24], p= 0.010). Similarly, the antibody-based model was better than the cutaneous model in predicting lung fibrosis (AUC 0.719 [0.715-724] vs. 0.653 [0.647-0.659]) and restrictive lung fibrosis (AUC 0.759 [0.749-0.766] vs. 0.711 [0.701-0.721]) which were both associated with anti-Scl70 antibodies (OR: 9.29 [8.17-10.55] and 7.92 [5.37-11.69], respectively, pConclusionAuto-antibody status outperforms the common cutaneous subsetting to risk-stratify SSc patients in the EUSTAR cohort. This easily performed subclassification using autoantibodies specific status can be used by the clinicians to risk-stratify their patients and to adapt disease monitoring in routine practice.Disclosure of InterestsMuriel Elhai Speakers bureau: BMS outside of the submitted work, Marouane Boubaya: None declared, Nanthara Sritharan: None declared, Alexandra Balbir-Gurman: None declared, Elise Siegert: None declared, Eric Hachulla: None declared, Jeska de Vries-Bouwstra: None declared, Gabriela Riemekasten: None declared, Jörg H.W. Distler: None declared, Douglas Veale: None declared, Edoardo Rosato: None declared, Francesco Del Galdo: None declared, Fabian A Mendoza: None declared, Daniel Furst Consultant of: Abbvie, Novartis, Pfizer, R-Pharm, Grant/research support from: Emerald, Kadmon, PICORI, Pfizer,Prometheus, Talaris, Mitsubishi, Carlos De la Puente Bujidos: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Grant/research support from: Boehringer Ingelheim, Armando Gabrielli: None declared, Oliver Distler Speakers bureau: Bayer, Boehringer Ingelheim, Janssen, Medscape, Consultant of: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, 4P Science, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Roivant, Sanofi and Topadur, Grant/research support from: Kymera, Mitsubishi Tanabe, Boehringer Ingelheim, Coralie Bloch-Queyrat: None declared, Yannick Allanore Consultant of: Actelion, Bayer, BMS, Boehringer-Ingelheim, Inventiva, Roche, Sanofi-Aventis, Grant/research support from: Actelion, Bayer, BMS, Boehringer-Ingelheim, Inventiva, Roche, Sanofi-Aventis

BackgroundSince the COVID-19 vaccination campaign was launched all over Europe, there has been general agreement on how benefits of SARS-CoV2 vaccines outweigh the risks in patients with rare connective tissue diseases (rCTDs). Yet, there is still limited evidence regarding safety and efficacy of such vaccines in these patients, especially in the long-term. For this reason, in the framework of ERN-ReCONNET, an observational long-term study (VACCINATE) was designed in order to explore the long-term outcome of COVID-19 vaccination in rCTDs patients. The consent form was developed thanks to the involvement of the ERN ReCONNET ePAG Advocates (European Patients Advocacy Group).ObjectivesTo evaluate the safety profile of COVID-19 vaccination in rCTDs patients and the potential impact on disease activity. Primary endpoints were the prevalence of adverse events (AEs) and of disease exacerbations post-vaccination. Secondary endpoints were the proportion of serious adverse events (SAEs) and adverse events of special interest for COVID-19 (adapted from https://brightoncollaboration.us/wp-content/uploads/2021/01/SO2_D2.1.2_V1.2_COVID-19_AESI-update-23Dec2020-review_final.pdf)MethodsThe first ad-interim analysis of the VACCINATE study involved 9 ERN-ReCONNET Network centres. Patients over 18 years of age with a known rCTD and who received vaccine against COVID-19 were eligible for recruitment. Demographic data and diagnoses were collected at the time of enrolment, while the appearance of AEs and potential disease exacerbations were monitored after one week from each vaccination dose, and then after 4, 12 and 24 weeks from the second dose. A disease exacerbation was defined as at least one of the following: new manifestations attributable to disease activity, hospitalization, increase in PGA from previous evaluation, addition of corticosteroids or immunosuppressants.ResultsA cohort of 300 patients (261 females, mean age 52, range 18-85) was recruited. Systemic lupus erythematosus (44%) and systemic sclerosis (16%) were the most frequent diagnoses, followed by Sjogren’s syndrome (SS,12%), idiopathic inflammatory myositis (IMM,10%), undifferentiated connective tissue disease (UCTD,8%), mixed connective tissue disease (MCTD,4%), Ehlers-Danlos’s syndrome (EDS,4%), antiphospholipid syndrome (APS,2%). AEs appearing 7 days after the first and second doses were reported in 93 (31%) and 96 (32%) patients respectively, mainly represented by fatigue, injection site reaction, headache, fever and myalgia. Otitis, urticaria, Herpes Simplex-related rash, stomatitis, migraine with aura, vertigo, tinnitus and sleepiness were reported with very low frequency. Less than 2% of patients experienced AEs within 24 weeks from the second dose. No SAEs or AEs of special interest were observed in the study period. There were 25 disease exacerbations (8%), 7 of which severe. The highest number of exacerbations was observed after 4 weeks from the second dose (12 within week 4, 6 within week 12 and 7 within week 24). Disease exacerbation was most frequent in patients with EDS (33%) and MCTD (25%).ConclusionThis preliminary analysis shows that COVID-19 vaccination is safe in rCTDs patients. AEs appear most often early after vaccination and are usually mild. Disease exacerbations are not frequent, but can be potentially severe and tend to occur most frequently within the first month after vaccination. Exacerbations can also occur 3-6 months after vaccination, although a causal relationship with the vaccination remains to be established. Our present data underline the importance of long-term observational studies.Table 1.AEs and disease exacerbations per diseaseDiagnosisPatients enrolled (%) (n=300)EAs after 1st and 2nd dose (%)Exacerbations (%)APS25714EDS45033IIM10527MCTD44225SS12598SLE44698SSC16492UCTD850-AcknowledgementsVACCINATE is a study promoted by the European Reference Network on rare and complex connective tissue diseases, ERN ReCONNET. This publication was funded by the European Union’s Health Programme (2014-2020)Disclosure of InterestsNone declared

BackgroundShort disease duration is a predictor for progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD), but studies assessing ILD progression in later disease stages are lacking. To individually tailor management of ILD in SSc patients in clinical practice it is, however, of high importance to understand disease behaviour also in patients with late disease.ObjectivesAnalyse ILD progression in SSc-ILD patients from the EUSTAR cohort segregated by subgroups of disease duration.MethodsWe segregated SSc-ILD patients into four categories of disease duration (≤3 years, >3- ≤7 years, >7- ≤15 years and >15 years after onset of Raynaud’s phenomenon). We assessed progressive ILD, defined as forced vital capacity (FVC) decline >10% or FVC decline ≥10% and FVC decline 5–10% and diffusing capacity of the lungs for carbon monoxide (DLCO) decline ≥15% (composite decline) over the first and second 12+/-3 months period after first registration (baseline) into EUSTAR. Clinical characteristics, pulmonary involvement, treatment at first registration and ILD progression were evaluated by descriptive statistics.ResultsIn total, 2258 SSc-ILD patients were included, with 469 (20.8%) having a disease duration ≤3 years, 550 (24.4%) between >3- ≤7 years, 752 (33.3%) between >7- ≤15 years and 488 (21.6%) of >15 years (Table 1). Baseline characteristics and treatment patterns differed between the four subgroups, with more younger male patients with diffuse cutaneous SSc, anti-topoisomerase I antibody and higher Rodnan skin score having ≤3 years disease duration. Lung function with FVC and DLCO were similar between the four groups (Table 1). Notably, in the first and second 12+/-3 months periods after first registration in the EUSTAR database, there were no significant difference in FVC decline >10% or composite FVC and DLCO decline within the four subgroups. For example, patients with disease duration >7- ≤15 years and >15 years frequently showed disease progression of FVC >10%: 41/347 (11.8%) and 32/228 (14%) compared to 38/244 (15.6%) and 33/273 (15.6%) for disease duration ≤3 years and >3- ≤7 years (P=0.529), respectively (Figure 1).Table 1.Demographics and baseline clinical characteristics of EUSTAR patientsDisease duration≤ years(n=460)>3- ≤7 years(n=550)>7- ≤15 years(n=752)>15 years(n=488)p-valueAge, years (SD)55 (13.5)55 (14.1)57 (13.1)61 (11.5)Male, n (%)123 (26.2)115 (20.9)112 (14.9)38 (7.8)DcSSc, n (%)228 (56.4)262 (45.8)311 (45.4)163 (31.2)ATA, n (%)236 (53.4)293 (55.9)374 (52.8)218 (48.0)0.099mRSS, mean (SD)12.3(10.1)10.4 (8.3)9.4 (8.1)8.7 (7.7)GERD, n/N (%)273 (58.7)353 (64.4)482 (64.4)344 (71.2)0.001ESR, mean (SD)26.9(21.7)24.2 (19.5)26.2 (19.9)28.3 (21.2)0.022MMF, n/N (%)33 (16.6)43 (25.2)37 (20.4)14 (9.3)0.002MTX, n/N (%)19 (10)17 (10.1)19 (10.6)8 (5.2)0.296Any IS, n/N (%)81 (38.6)89 (47.1)82 (40.8)46 (28.7)0.006FVC % pred, mean (SD)86 (20.9)87 (21.6)86 (21.4)87 (22.8)0.770DLCO % pred, mean (SD)58 (19.3)59 (19.3)59 (19.9)58 (19.7)0.405NYHA class 3&4, n (%)84 (18.6)78 (14.6)125 (17.5)22.6 (7.0)0.090Figure 1.FVC decline >10% and composite FVC and DLCO decline in the first and second 12+/-3 months within the four subgroups segregated by disease durationConclusionIt was long believed that ILD burned out in late disease stages. In our analysis of ILD progression by four disease duration categories, we showed that ILD frequently progressed also in late disease stages. This has important implications for clinical practise, as SSc patients need to be regularly monitored for ILD progression independent of disease duration.Disclosure of InterestsAnna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Grant/research support from: Boehringer Ingelheim, Cathrine Brunborg: None declared, Paolo Airò Speakers bureau: Bristol-Myers-Squibb, Boehringer Ingelheim, Consultant of: Bristol-Myers-Squibb, Grant/research support from: Bristol-Myers-Squibb, Roche, Jannsen, CSL Behring, Lidia P. Ananyeva Speakers bureau: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim, László Czirják Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Actelion (now GSK), MSD, Novartis, Pfizer, Roche, Lilly, Grant/research support from: Boehringer Ingelheim, Actelion (now GSK), MSD, Novartis, Pfizer, Serena Guiducci: None declared, Eric Hachulla Speakers bureau: GSK, Roche-Chugai, Johnson & Johnson, Boehringer Ingelheim, Consultant of: CSL Behring, GSK, Roche-Chugai, Johnson & Johnson, Boehringer Ingelheim, Grant/research support from: CSL Behring, Boehringer Ingelheim, GSK, Roche-Chugai, Sanofi Genzyme, Mengtao Li: None declared, Carina Mihai Speakers bureau: MEDtalks Switzerland, Mepha, Grant/research support from: Roche, Boehringer Ingelheim, Janssen, Gabriela Riemekasten Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Petros Sfikakis Consultant of: Boehringer Ingelheim, Gabriele Valentini Consultant of: Boehringer Ingelheim, Grant/research support from: Sanofi/BMS, Otylia Kowal-Bielecka Speakers bureau: Boehringer Ingelheim, Novartis, Pfizer, Gilead Sciences, Janssen-Cilag, MEDAC, MSD, Abbvie, Sandoz, Consultant of: Boehringer Ingelheim, Health Care system Navigator, CSL Behring, MSD, Novartis, Grant/research support from: CSL Behring, Boehringer Ingelheim, Abbvie, Roche, MEDAC, Yannick Allanore Speakers bureau: Boehringer, Abbvie, Consultant of: Boehringer, Bayer, Astra-Zeneca, Prometheus, Sanofi, Genentech/Roche, Boehringer, Grant/research support from: Alpine Immunosciences, OSE Immunotherapeutics, Medsenic, Oliver Distler Speakers bureau: Bayer, Boehringer Ingelheim, Janssen, Medscape, Consultant of: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, 4P Science, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Roivant, Sanofi and Topadur, Grant/research support from: Kymera, Mitsubishi Tanabe, Boehringer Ingelheim

BackgroundPatients with autoimmune/inflammatory rheumatic diseases (AIRD) were suspected to be an at-risk population of severe COVID-19. However, whether this higher risk is linked to the disease or to its treatment is difficult to determine.ObjectivesTo identify, among AIRD patients, factors associated with occurrence of moderate-to-severe COVID19 infection and to evaluate if having an AIRD was associated with an increased risk of severe form of COVID19 infection (defined by hospitalization in ICU or death), compared to general population.MethodsData source: The “Entrepôt des Données de Santé (EDS)” collect data from electronic health records of all patients hospitalized or followed in the AP-HP (39 hospitals in Paris area, France). The French RMD COVID19 cohort is a national multi-center cohort that included patients with confirmed AIRD and diagnosed with COVID-19. All AIRD patients diagnosed with COVID-19 before September 2020 from both cohorts were included.-We Identified factors associated with severe COVID-19 was made in a combined analysis of the 2 cohorts.-Then, we compared COVID-19 infection severity in the EDS-COVID database in AIRD patients and controls, by a propensity score (PS)-matched case-control (1:4) studyResultsAmong 1213 patients (334 in EDS and 879 in RMD cohort), 195 (16.1%) experienced a severe COVID19. In multivariate analysis, greater age, history of interstitial lung disease, arterial hypertension, obesity, sarcoidosis, vasculitis, auto-inflammatory disease and treatment with corticosteroids or rituximab were associated with severe COVID-19 (Table 1).Table 1.AIRD patient’s characteristics associated with severity of COVID-19Patients with mild or moderate infectionPatients with severe infectionOR ajustés 95%CIp-value(N = 1018)(N = 195)Patients characteristics Age55.9 (16.7%)70.3 (14.3%)1.05 [1.03;1.07] Gender: Female695 (68.3%)105 (54.1%)0.59 [0.38;0.94]0.025 Interstitial pneumonia38 (3.7%)20 (10.3%)2.94 [1.34;6.34]0.008 Obesity143 (17.8%)38 (27.7%)2.09 [1.26;3.43]0.004 Hypertension268 (26.3%)114 (58.5%)1.81 [1.13;2.89]0.013Underlying Disease: Chronic inflammatory arthritis618 (60.8%)72 (36.9%)Ref. Auto-inflammatory disease29 (2.9%)5 (2.6%)3.91 [1.2;11.32]0.025 Other29 (2.9%)4 (2.1%)0.35 [0.06;1.41]0.15 Connectivitis190 (18.7%)34 (17.4%)1.13 [0.62;2.01]0.69 Sarcoidosis40 (3.9%)24 (12.3%)5.19 [2.15;12.3] Vasculitis111 (10.9%)56 (28.7%)1.8 [1.02;3.16]0.044Treatments Corticosteroid318 (31.2%)117 (60.0%)2.47 [1.58;3.87] Leflunomide44 (4.3%)2 (1.0%)0.13 [0;0.97]0.045 Rituximab37 (3.7%)22 (11.5%)4.05 [1.96;8.27]Not significant in multivariate analysisCOPD, Asthma, Coronary heart diseases, stroke, diabetes, smoking, cancer, non-steroidal anti-inflammatory drugs, colchicine, hydroxychloroquine, methotrexate, salazopyrine, mycophenolate mofetil, azathioprine, intravenous immunoglobulins, anti-TNFα, anti-IL1, -IL6, -IL17, Abatacept, JAK inhibitorAmong 35741 COVID-19 patients in EDS, 316 with AIRD were compared to 1264 PS-matched controls. Severe form occurred in 118 (37,3%) AIRD cases and 384 (30.4%) controls (Adjusted OR (aOR) for severe form= 1.43 [1.1;1.9], p=0,01). In analysis restricted to rheumatoid arthritis (RA) and spondylarthritis (SpA), no increased risk of severe form (aOR=1.11 [0.68;1.81]) form or death (aOR=1.00 [0.55;1.81]) was observed.ConclusionIn this multicenter study we confirmed that AIRD patients treated with rituximab or corticosteroids were at increased risk of severe COVID-19, as were those with vasculitis, auto-inflammatory disease, and sarcoidosis. Also, when compared to controls from the same cohort of hospitalized patients, AIRD patients had, overall, an increased risk of severe COVID-19, increased risk not observed in an analysis restricted to patients with RA or SpA.AcknowledgementsFAI2R /SFR/SNFMI/SOFREMIP/CRI/IMIDIATE consortium and contributorsPatricia MartelAll clinicians/physicians implicated in COVID-19 patient care in APHP hospital and generated EDS patient dataDisclosure of InterestsNone declared

BackgroundSkin fibrosis is a cardinal feature of systemic sclerosis (SSc) and associated with significant disability. The early trajectory of skin fibrosis provides insights into the course of the disease including mortality; however, little is known about late skin fibrosis in SSc.ObjectivesThe aims of our study were to ascertain the prevalence and characteristics of late skin fibrosis in SSc.MethodsWe developed and tested three conceptual scenarios of late (>5 years after 1st non-RP sign or symptom) skin fibrosis (Figure 1):Figure 1.Conceptual models/scenarios of late skin fibrosis in SSc. A: worsening and then improvement (>3 mRSS) during the first 5 years, and then worsened again after 5 years. B: worsening for the first time after 5 years. C: worsening in the first 5 years and stayed high after 5 years (i.e., failure to improve).A. Worsening and then improvement (>3 mRSS) during the first 5 years, and then worsened again after 5 years.B. Worsening for the first time after 5 years.C. Worsening in the first 5 years and stayed high after 5 years (i.e., failure to improve).We defined skin worsening as modified Rodnan skin score (mRSS) ≥ 5 units or ≥ 25%. Using strict inclusion criteria including complete mRSS, we identified 1,043 (out of 19,115) patients within the EUSTAR database for our analysis. We further restricted analysis within 887 (out of 1,043) patients who had limited (lcSSc) or diffuse cutaneous SSc (dcSSc) at baseline.ResultsOne-fifth of patients among the whole cohort (n=208/1043, 19.9%) including in patients with lcSSc or dcSSc at baseline (n=193/887, 21.8%) developed late skin fibrosis. This was largely due to new skin worsening or failure to improve. Patients with lower baseline mRSS and lcSSc were more likely to develop late skin fibrosis. Anti-Scl-70 antibodies (Table 1) were associated with progression from baseline lcSSc to dcSSc, and anticentromere antibodies were protective.Table 1.Impact of autoantibody status on progression from baseline limited to diffuse cutaneous SSc (dcSSc).Skin worsening after 5 years (Scenario B) (n=70)Skin worsening within 5 years and failed to improve after 5-year window (Scenario C) (n=61)Progressed to dcSSc (n=23)Not progressed to dcSSc(n=47)P-valueProgressed to dcSSc (n=37)Not progressed to dcSSc(n=24)P-valueAnticentromere+ve2/22 (9.1%)19/42 (45.2%)0.00346/34 (17.6%)14/21 (66.7%)0.0002-ve20/22 (90.9%)23/42 (54.8%)28/34 (82.4%)7/21 (33.3%)Anti-Scl-70+ve15/23 (65.2%)14/44 (31.8%)0.008822/36 (61.1%)8/23 (34.8%)0.0485-ve8/23 (34.8%)30/44 (68.2%)14/36 (38.9%)15/23 (65.2%)Anti-RNA-Polymerase-III+ve0/12 (0.0%)1/22 (4.5%)1.00000/6 (0.0%)0/14 (0.0%)---ve12/12 (100%)21/22 (95.5%)6/6 (100%)14/14 (100%)ConclusionLate skin fibrosis affects approximately 20% of SSc patients >5 years after onset of disease. We have identified different patterns relevant to clinical practice and trial design. Late skin fibrosis is usually due to new worsening or failure of skin to improve. Progression from baseline limited to diffuse cutaneous SSc was associated with anti-Scl-70 antibodies, and anticentromere antibodies were protective. Late skin fibrosis is a neglected manifestation of SSc and warrants further investigation including to determine clinical outcomes and optimal therapeutic strategy.AcknowledgementsOn behalf of EUSTAR collaborators.Disclosure of InterestsMichael Hughes Speakers bureau: Speaking fees from Actelion pharmaceuticals, Eli Lilly, and Pfizer, outside of the submitted work, Suiyuan Huang: None declared, Juan Jose Alegre Sancho Speakers bureau: Speaking and/or investigational fees from Actelion pharmaceuticals, Eli Lilly, Pfizer, Boehringer Ingelheim, Roche, and GSK, outside of the submitted work, Grant/research support from: Speaking and/or investigational fees from Actelion pharmaceuticals, Eli Lilly, Pfizer, Boehringer Ingelheim, Roche, and GSK, outside of the submitted work, Patricia Carreira: None declared, Merete Engelhart: None declared, Eric Hachulla Speakers bureau: Received consulting fees/meeting fees from Johnson & Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, Sanofi-Genzyme; speaking fees from Johnson & Johnson, GSK, Roche-Chugai; and research funding from CSL Behring, GSK, Roche-Chugai and Johnson & Johnson., Consultant of: Received consulting fees/meeting fees from Johnson & Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, Sanofi-Genzyme; speaking fees from Johnson & Johnson, GSK, Roche-Chugai; and research funding from CSL Behring, GSK, Roche-Chugai and Johnson & Johnson., Jörg Henes Speakers bureau: Lectures for CHUGAI, Boehringer-Ingelheim, Eduardo Kerzberg: None declared, Maria Rosa Pozzi: None declared, Gabriela Riemekasten: None declared, Vanessa Smith: None declared, Gabriella Szucs: None declared, Marie Vanthuyne: None declared, Elisabetta Zanatta: None declared, Oliver Distler: None declared, Armando Gabrielli: None declared, Anna-Maria Hoffmann-Vold: None declared, Viginia Steen: None declared, Dinesh Khanna Shareholder of: DK has stock options in Eicos Sciences, Inc., Consultant of: Consultant for Acceleron, Amgen, Boehringer Ingelheim, CSL Behring, Chemomab, Genentech/Roche, Horizon, Mitsubishi Tanabe Pharma, Prometheus, Talaris., Grant/research support from: Has received grants from Bayer, BMS, Horizon and Pfizer (to University of Michigan).

BackgroundMixed connective tissue disease (MCTD) is a systemic auto-immune disorder, being probably the least common among the connective tissue diseases. Symptoms can be severe and could affect health-related quality of life (HRQoL). Identification of the burden of MCTD patients is of key importance to provide appropriate pharmacological and non-pharmacological care. No reports on HRQoL have been published in adult patients with MCTD.ObjectivesTo perform an explorative study to evaluate HRQoL and its main determinants in MCTD patients, and compare HRQoL between MCTD and matched systemic sclerosis (SSc) patients.MethodsMCTD patients fulfilling the Kahn criteria and participating in the MCTD prospective follow-up cohort of the Leiden University Medical Center were included. In addition, SSc patients matched for age, gender and disease duration were included for comparison. Data on disease characteristics, functional disability and HRQoL were collected annually for both disease groups. HRQoL was evaluated using the 36-Item Short Form Health Survey (SF36) and EuroQol (EQ5D). At baseline, HRQoL, as reflected by SF36 mental component score (MCS), SF 36 physical component score (PCS) and EQ5D were compared between MCTD and SSc patients. For MCTD patients, factors associated with HRQoL at baseline were identified using linear regression and change in HRQoL over 3 years was evaluated using linear mixed models. In addition, characteristics of MCTD patients who showed worsening of MCS and/or had PCS superior to the minimal clinical important difference of three points were identified.ResultsThirty-four MCTD patients (121 visits; 82% female, mean age 42 years, median disease duration 45 months) and 102 SSc patients (424 visits; 82% female, mean age 45 years, median disease duration 49 months) were included. At baseline, MCTD-patients more often had ILD (47% vs. 34%, p=0.027), cardiac involvement (30% vs. 2%, pBaseline HRQoL in MCTD was comparable to HRQoL in SSc, with mean SF36-PCS of 40.2 (SD:9.1) and mean SF36-MCS of 44.9 (SD:9.9), which is (nearly) one standard deviation lower than the general Dutch population. The SF36 subscore “general health perception” was the most impacted in both groups (MCTD: 38.5 [SD:7.0], SSc: 39.9 [SD:8.9]). The median EQ5DNL was 0.38 (IQR:0.14 – 0.54) and comparable between SSc and MCTD.At baseline, in MCTD, ILD was significantly associated with SF36-PCS (β:6.98, 95% CI: 1.10 to 12.86) and SF36-MCS (β:-8.10, 95% CI:-14.93 to -1.26). Sclerodactyly was significantly associated with EQ5DNL (β:0.006; 95% CI:0.002 to 0.010) and SF36-PCS (β:0.12, 95% CI:0.03 to 0.21). No other significant associations were identified.Over time, in MCTD, both the SF36-MCS and SF36-PCS improved significantly (MCS: β:2.35/year [95% CI:0.58 to 4.13], PCS: β:1.34/year [95% CI:0.03 to 2.65), whereas EQ5DNL was stable. Explorative analyses did not reveal a specific clinical characteristic with significant impact on the change of HRQoL over time. With an MCID of 3 points on the MCS and PCS, 7 MCTD-patients worsened on the MCS and 3 on the PCS. Patients who showed worsening of MCS over time tended to be older, more often had ILD, sclerodactyly and GI complaints, and had worse exercise tolerance. All these differences did not reach statistical significance. The patients who decreased PCS more often had ILD (100% vs. 41%, p=0.015), and used glucocorticoids more often (33% vs. 0%, p=0.046), were slightly older and had a worse exercise tolerance as compared to those who showed a stable/improving PCS over time.ConclusionLike in SSc, HRQoL is significantly impaired in MCTD, especially the general health perception of patients. Cardiac involvement, ILD, age and worse functional disability might specifically impact HRQoL in MCTD. However, these associations need further evaluations in larger cohorts.Disclosure of InterestsNone declared

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

BackgroundLupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with an induction immunosuppressive therapy (IST), followed by a maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST for proliferative LN is unknown.ObjectivesThe WIN-Lupus trial tested whether IST discontinuation after 2-3 years in proliferative LN was non-inferior to IST continuation for 2 more years.MethodsWIN-Lupus is an investigator-initiated academic randomized controlled trial, conducted in 28 French centers. Patients on maintenance IST with azathioprine or mycophenolate mofetil for a minimum of 2 years and a maximum of 3 years, and who were taking Hydroxychloroquine, were randomized (1:1) between 2 groups: IST continuation and IST discontinuation. The primary endpoint was the relapse rate of proliferative LN at 24 months. Secondary endpoints were the rate of severe SLE flares, survival without renal relapse or severe flare, adverse events, kidney function, disease activity, corticosteroid exposure, patient-reported outcome and medico-economic impact.ResultsBetween 2011 and 2016, 125 patients were screened and 96 were randomized in the trial: 48 in the IST continuation group, 48 in the IST discontinuation group. In the per-protocol population, a relapse of proliferative LN occurred in 5/40 (10.4%) patients with IST continuation, and in 12/44 (25%) patients with IST discontinuation (difference 14.8%, 95%CI [-1.9; 31.5]). Non-inferiority was not demonstrated for relapse rate. Time to renal relapse did not differ between groups (p=0.092). Severe SLE flares (renal or extra-renal) were less frequent in patients with IST continuation compared to IST discontinuation (5/40 vs 14/44 patients, p=0.035). IST discontinuation was associated with lower health-related costs. Adverse events did not differ between groups.ConclusionNon-inferiority of maintenance IST discontinuation after 2 to 3 years was not demonstrated for renal relapse. IST discontinuation was associated with a higher risk of severe SLE flare.References[1]Moroni G et al. When and how is it possible to stop therapy in patients with lupus nephritis? Clin J Am Soc Nephrol. 2021. CJN.04830421. doi: 10.2215/CJN.04830421.[2]Fanouriakis A et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis. 2020;79(6):713-723.[3]Jourde-Chiche N et al. Proliferative lupus nephritis treatment: practice survey in nephrology and internal medicine in France. Nephrol Ther. 2014;10(3):170-6.[4]Zen M et al. Immunosuppressive therapy withdrawal after remission achievement in patients with lupus nephritis. Rheumatology (Oxford). 2021;keab373. doi: 10.1093/rheumatology/keab373.[5]Malvar A et al. Kidney biopsy-based management of maintenance immunosuppression is safe and may ameliorate flare rate in lupus nephritis. Kidney Int. 2020;97(1):156-162.AcknowledgementsGroupe Coopératif sur le Lupus Rénal (GCLR)Disclosure of InterestsNoemie JOURDE-CHICHE Speakers bureau: Vifor Pharma, Grant/research support from: Fresenius Medical Care: grant paid to my institution (AP-HM) for the CINEVAS study in ANCA-associated vasculitis, Nathalie Costedoat-Chalumeau Grant/research support from: AP-HP received a research support from ROCHE for the OBILUP trial, Karine Baumstarck: None declared, LAURENCE BOUILLET Speakers bureau: GSK, novartis, biocryst, takeda, behring, Paid instructor for: takeda, novartis, Consultant of: GSK, novartis, biocryst, takeda, behring, blueprint, Grant/research support from: takeda, gsk, sanofi, biocryst, novartis, Stéphane Burtey: None declared, Valerie Caudwell: None declared, Laurent Chiche Speakers bureau: BMS, Paid instructor for: BMS, Lionel Couzi Speakers bureau: Astellas, Chiesi, Novartis, Sandoz, Ostuka, GSK, Biotest, Consultant of: Biotest, Hansa, Novartis, Grant/research support from: Novartis, Astellas, Christophe DELIGNY: None declared, Bertrand Dussol Speakers bureau: Genzyme, Novonordisk, Grant/research support from: Shire, Stanislas Faguer Speakers bureau: Asahi, Vifor Pharma, Sanofi, Consultant of: Abyonyx Pharma, Pierre Gobert: None declared, Guillaume Gondran Speakers bureau: Pfizer, Novartis, Consultant of: Genzyme, Antoine Huart Speakers bureau: Janssen, Paid instructor for: Pfizer, Aurélie Hummel: None declared, Emilie Kalbacher: None declared, Alexandre Karras Speakers bureau: Vifor, GSK, Astra-Zeneca, Roche, Paid instructor for: Vifor, Sanofi, Alexion, Consultant of: Novartis, GSK, Bohringer-Ingelheim, Marc Lambert Speakers bureau: CHUGAI-ROCHE, BAYER, PFIZER, LEOPHARMA, Paid instructor for: CHUGAI-ROCHE, Consultant of: CHUGAI-ROCHE, BAYER, PFIZER, LEOPHARMA, Grant/research support from: CHUGAI-ROCHE, Véronique LE GUERN: None declared, Sandrine Loubiere: None declared, Helene Maillard: None declared, Francois Maurier: None declared, Micheline Pha: None declared, Viviane Queyrel Paid instructor for: GSK, Consultant of: Boehringer Ingelheim, Francoise Sarrot-Reynauld: None declared, David Verhelst: None declared, Eric Hachulla Speakers bureau: Johnson & Johnson, GSK, Roche-Chugai, Consultant of: Johnson & Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, Sanofi-Genzyme, Grant/research support from: CSL Behring, GSK, Roche-Chugai and Johnson & Johnson, Zahir Amoura Speakers bureau: GSK, CSL Behring, Consultant of: GSK, Grant/research support from: GSK, Eric Daugas Speakers bureau: GSK, Amgen, Paid instructor for: GSK, Astra Zeneca, Consultant of: GSK, Astra Zeneca, Amgen, Grant/research support from: ROCHE for the OBILUP trial (AP-HP)

BackgroundThe course of SSc-ILD is variable, and may include periods of stability or even improvement in forced vital capacity (FVC) as well as periods of decline.ObjectivesTo investigate the baseline characteristics of patients with SSc-ILD in the placebo group of the SENSCIS trial whose ILD improved or progressed over 52 weeks.MethodsThe SENSCIS trial enrolled patients with SSc with first non-Raynaud symptom in the prior ≤7 years, extent of fibrotic ILD on high-resolution computed tomography (HRCT) ≥10% and FVC ≥40% predicted. Patients who had been taking a stable dose of mycophenolate for ≥6 months were allowed to participate. We investigated the baseline characteristics of patients in the placebo group whose ILD showed improvement (absolute increase in FVC ≥5% predicted), stability (absolute decline or increase in FVC ResultsOf 288 patients, 21 (7.3%) showed improvement, 166 (57.6%) stability, and 101 (35.1%) ILD progression, of whom 37 (12.8% of all patients) had significant ILD progression over 52 weeks. Most baseline characteristics were similar across the groups based on progression, but there were differences in DLCO % predicted (p=0.02) and in the proportion of patients taking mycophenolate (p=0.09) among patients who showed improvement, stability and progression (Table 1).Table 1.Baseline characteristics of patients in the placebo group of the SENSCIS trial in subgroups based on course of SSc-ILD over 52 weeks.Improvement (n=21)Stability (n=166)Progression (n=101)Significant progression (n=37) (subset of Progression)P-value for comparison of Improvement, Stability, ProgressionAge, years55.9 ± 12.053.2 ± 12.653.1 ± 12.855.3 ± 11.80.64Female71.475.970.373.00.59Years since first non-Raynaud symptom3.7 ± 1.73.5 ± 1.73.5 ± 1.93.6 ± 1.90.81Diffuse cutaneous SSc47.649.453.556.80.78Anti-topoisomerase I antibody positive61.958.466.356.80.44High sensitivity C-reactive protein, mg/L5.1 ± 8.97.8 ± 23.05.6 ± 9.94.2 ± 4.40.62Modified Rodnan skin score9.3 ± 7.310.5 ± 8.411.9 ± 9.712.7 ± 11.30.29History of gastroesophageal reflux disease (GERD)76.272.978.278.40.62Extent (%) of fibrotic ILD on HRCT*26.4 ± 16.235.5 ± 20.436.6 ± 21.840.8 ± 23.50.12Presence of honeycombing on HRCT14.316.815.526.50.94Presence of ground glass opacities on HRCT81.086.689.784.80.51FVC % predicted77.1 ± 18.071.7 ± 17.273.3 ± 15.274.2 ± 14.80.33DLco % predicted61.5 ± 14.953.4 ± 14.851.1 ± 15.147.3 ± 14.50.02Taking mycophenolate71.448.245.535.10.09Data are mean ± SD or % at baseline. Missing data were excluded. *Assessed visually in whole lung to nearest 5%. The assessment did not include pure (non-fibrotic) ground glass opacities.ConclusionThese findings suggest that in the SENSCIS trial, patients who had higher DLCO % predicted or who were taking mycophenolate at baseline were less likely to show progression of SSc-ILD over 52 weeks.AcknowledgementsThe SENSCIS trial was funded by Boehringer Ingelheim. Oliver Distler was a member of the SENSCIS trial Steering Committee.Disclosure of InterestsAnna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme, Roche, Paid instructor for: Boehringer Ingelheim, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme, Roche, Grant/research support from: Boehringer Ingelheim, Eric Hachulla Speakers bureau: Johnson & Johnson, GlaxoSmithKline, Roche-Chugai; and research funding from CSL Behring, GlaxoSmithKline, Johnson & Johnson, Roche-Chugai, Consultant of: Bayer, Boehringer Ingelheim, GlaxoSmithKline, Johnson & Johnson, Roche-Chugai, Sanofi-Genzyme, Grant/research support from: GlaxoSmithKline, Roche-Chugai, Sanofi-Genzyme, Ariane Herrick Speakers bureau: Janssen, Consultant of: Arena, Boehringer Ingelheim, Camurus, CSL Behring, Gesynta, Grant/research support from: Gesynta, Teng Moua: None declared, Gabriela Riemekasten Speakers bureau: Boehringer Ingelheim, Janssen, Consultant of: Boehringer Ingelheim, Janssen, Madelon Vonk Speakers bureau: Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, MSD, Novartis, Roche, Consultant of: Boehringer Ingelheim, Corbus, Janssen, Grant/research support from: Boehringer Ingelheim, Ferrer, Galapagos, Janssen, Alexandra James Employee of: Alexandra James is an employee of Elderbrook solutions GmbH that is contracted by Boehringer Ingelheim, Margarida Alves Employee of: Margarida Alves is employee of Boehringer Ingelheim, Oliver Distler Speakers bureau: OD has/had relationships with the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years:Speaker fee: Bayer, Boehringer Ingelheim, Janssen, Medscape, Consultant of: OD has/had relationships with the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years:Consultancy fee: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, 4P Science, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Roivant, Sanofi and TopadurOD has/had relationships with the following companies in the area of potential treatments for arthritides in the last three calendar years:Consultancy fee: Abbvie, Grant/research support from: OD has/had relationships with the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years:Research Grants: Boehringer Ingelheim, Kymera, Mitsubishi Tanabe

BackgroundThe use of glucocorticoids (GC) in systemic sclerosis (SSc) is controversial (1). Despite the lack of solid evidence about their efficacy in SSc, GC are prescribed to control musculoskeletal symptoms, or in combination with immunosuppressive drugs (1). The extent of GC use over the disease course has been poorly investigated in SSc. As long-term GC exposure is detrimental even at low doses, estimating the use of GC and identifying patients at high risk for long-term utilization is crucial to plan better management of SSc patients.ObjectivesTo estimate the prevalence of GC use in a large sample of SSc patients, identify patient characteristics associated with time spent on GC, and describe the variations in GC utilization over time and across main recruiting countries.MethodsWe included SSc patients with at least one visit in the EUSTAR database from January 2013 (defined as baseline visit) to November 2019. We analyzed the prevalence and the main features of patients using GC at baseline, and the exposure to GC over time. Multivariable linear regression analysis identified patient characteristics associated with the proportion of follow-up time spent on GC. Time trends and variations in GC utilization across main recruiting countries were explored. Missing data were imputed using multiple imputation with chained equations.ResultsThe 9819 patients included were mostly females (85%), with limited cutaneous (lc) SSc (73%), and median age of 58 years. At baseline, 2769 (34%) patients (48% diffuse cutaneous (dc) SSc vs. 29% lcSSc) were on GC, at a median dose 7.5 mg/day [IQR 5-9 mg]. Only 2% of patients (n = 162) received >15 mg/day prednisone equivalent. GC were mostly used in combination with an immunosuppressive drug, mainly methotrexate (29%), cyclophosphamide (21%), and mycophenolate mofetil (21%). Compared to patients not receiving GC at baseline, GC users were more frequently males (18% vs. 14%), anti-Scl70 positive (42% vs. 27%), had more synovitis (21% vs. 8%), pericardial effusion (9% vs. 5%), C-reactive protein elevation (33% vs. 19%), increased CK (12% vs. 8%), and significantly lower respiratory volumes. In the subgroup of patients with an early disease duration (< 3 years from first non-Raynaud’s onset) (n = 1896), the prevalence of GC users was similar to that observed in the entire sample, but more dcSSc patients were receiving GC in combination with immunosuppressors. On average, GC users spent 25% of their follow-up time (median 33.2 months) on GC, with no significant difference between lcSSc and dcSSc patients. Notably, 971 (33%) and 647 (22%) patients followed-up for >1 year received GC for >6 or >12 months, respectively. In multivariable analysis, patient characteristics poorly explained the variability of GC exposure (adjusted-R2 = 0.062, P < 0.001). The yearly proportion of glucocorticoids users (2013 - 2018) gradually decreased over time (36% in 2013 vs. 23% in 2018). The rate of GC users and the median proportion of follow-up time spent on GC was highly heterogeneous within and across countries.ConclusionGC are widely and long-term used in SSc, mainly to patients with dcSSc, with significant between- and within-country(ies) differences. A gradual decrease in their utilization over time is observed.References[1]Iudici M, et al. Glucocorticoids in systemic sclerosis: weighing the benefits and risks - a systematic review. Clin Exp Rheumatol. 2013;31(2 Suppl 76):157-65.Disclosure of InterestsMichele Iudici: None declared, Denis Mongin: None declared, Elise Siegert: None declared, Patricia Carreira: None declared, Jörg H.W. Distler: None declared, Jörg Henes Speakers bureau: Roche/Chugai, Janssen, Neovii and Boehringer-Ingelheim, Elisabetta Zanatta: None declared, Eric Hachulla Speakers bureau: speaking fees from Johnson & Johnson, GSK, Roche-Chugai; and research funding from CSL Behring, GSK, Roche-Chugai and Johnson & Johnson., Consultant of: consulting fees/meeting fees from Johnson & Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, Sanofi-Genzyme, Giacomo De Luca: None declared, CAROLINA SOUZA MULLER Speakers bureau: speaker for Janssen and Boehringer-Ingelheim, Maria Joao Salvador: None declared, Jose Luis Tandaipan: None declared, Breno Valdetaro Bianchi: None declared, Maria De Santis: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: A-MH-V reports research funding, consulting fees, or other remuneration from Actelion, Boehringer Ingelheim, Roche, Bayer, Merck Sharp & Dohme, ARXX therapeutics, Lilly, and Medscape., Consultant of: A-MH-V reports research funding, consulting fees, or other remuneration from Actelion, Boehringer Ingelheim, Roche, Bayer, Merck Sharp & Dohme, ARXX therapeutics, Lilly, and Medscape., Grant/research support from: A-MH-V reports research funding, consulting fees, or other remuneration from Actelion, Boehringer Ingelheim, Roche, Bayer, Merck Sharp & Dohme, ARXX therapeutics, Lilly, and Medscape., Armando Gabrielli: None declared, Oliver Distler Speakers bureau: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos NV, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Italfarmaco, Kymera, Medac, Medscape, Mitsubishi Tanabe, MSD, Novartis, Pfizer, Roche, Roivant, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos NV, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Italfarmaco, Kymera, Medac, Medscape, Mitsubishi Tanabe, MSD, Novartis, Pfizer, Roche, Roivant, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos NV, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Italfarmaco, Kymera, Medac, Medscape, Mitsubishi Tanabe, MSD, Novartis, Pfizer, Roche, Roivant, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Delphine Courvoisier: None declared

BackgroundThe COVID-19 pandemic has raised concerns about its psychological effects. Sleep disturbances, anxiety and/or depressive symptoms, post-traumatic stress symptoms have been reported in general population. Patients with chronic rheumatism, systemic autoimmune disease or auto-inflammatory disease, due to immunosuppression, are at risk of severe forms of infection. Currently, there is little information on psychological impact of the pandemic on the mental health of these more vulnerable patients.ObjectivesTo compare psychological assessment between patients with chronic rheumatic, autoimmune and/or autoinflammatory diseases who presented with COVID-19 infection between March and September 2020, first wave of French pandemic, and patients with same diseases who did not presented with infection to date.MethodsThe MentCOVRMD study was a multicenter descriptive study. Cases were patients with chronic rheumatic, autoimmune and/or autoinflammatory diseases from the French RMD cohort who presented COVID-19 infection between March and September 2020. Controls were patients with same diseases who did not develop infection. The study is registered in Clinical Trials under number 2020-A02058-31.For participants, following criteria were collected: demographics (age, gender, smoking status); psychological assessment questionnaires: Insomnia Severity Index (ISI); Post-traumatic stress disorder (PTSD) checklist; Patient Health Questionnaire (PHQ9) Depression; Generalized Anxiety Disorder (GAD7) Anxiety; Patient Health Questionnaire-15 (PHQ-15) and Somatic Symptom Disorder (SSD)-12.ResultsBetween February and December 2021, 60 cases (46 (76.7%) women), median age 52.0 (39.0; 63.0) were included, of which 15 (25%) had been hospitalized during infection, and 169 controls (148 (87.6%) women), median age of 52.0 (38.0; 63.0). There were more smokers in the group of cases 12 (20%) than controls 14 (9.1%) (p=0.028) as well as more cases on ARA2 treatment (8 (13.3%)) than controls (7 (4.5%)) (p=0.035) with no statistically significant difference in others comorbidities or treatments.There was no statistically difference concerning the ISI scores between cases (11.83 ± 7.31) of which 60% had sleep disorders and controls (11.64 ± 6.82) of which 70.4% had sleep disorders. There was no statistically significant difference in PTSD scores of 15.5 (5.0 to 28.0) for cases and 18.0 (8.0 to 35.0) for controls, of which respectively 12 (20%) had values indicating possible PTSD for cases and 50 (29.6%) for controls. There was no statistically significant difference in PHQ-9 scores (5.5 (1.5 to 11.0)) of which 50% had depressive symptoms and controls (6.0 (2.0 to 11.0)) of which 54.5% had symptoms. There was no statistically significant difference in GAD-7 scores (3.5 (0.0 to 8.0)) of which 40% had anxiety symptoms and controls (4.0 (0.0 to 8.0)) of which 43.2% had symptoms. There was no statistically significant difference in PHQ-15 scores (11.4 ± 6.7), 85% of whom reported presence of symptoms, and controls (10.9 ± 6.2), 82.3% of whom reported symptoms. There was no statistically significant difference in SSD scores between cases (17.7 ± 10.9) and controls (18.4 ± 10.9).There was a statistically significant difference in reported VAS scores of pain related to inflammatory rheumatism in cases with a median of 4.5 (3.0 to 6. 0) compared to controls with a median of 4.0 (1.0 to 6.0) (p=0.011).There was no statistically significant difference in any of the psychological assessment scores between the inpatient and outpatient COVID cases.ConclusionThere was no statistically significant difference between COVID cases and controls in the evaluation of these psychological parameters. Prevalence of all these variables were high in the whole study population, testifying to the need to manage these psychological aspects for patients with chronic rheumatisms, autoimmune and/or autoinflammatory diseases.Disclosure of InterestsNone declared

Introduction Les atteintes cutanees sont habituelles au cours du syndrome de Gougerot-Sjogren primitif (SSp), mais leur prevalence et leurs caracteristiques sont difficiles a etablir precisement en raison du nombre limite de patients etudies dans la plupart des cohortes, de la variabilite des signes fonctionnels et cliniques evalues dans chaque cohorte, de la rarete de certains de ces signes et de l’heterogeneite des evaluations des etudes precedentes. L’objectif principal de cette etude etait de determiner, a partir de 3 groupes francais de patients souffrant de SSp (TEARS, ASSESS, DiapSS) dans lesquels differents criteres d’evaluation ont ete utilises, la prevalence des atteintes dermatologiques, les parametres cliniques et paracliniques qui leur sont associes. Materiel et methodes Nous avons utilise les donnees de deux cohortes francaises (ASSESS, qui a evalue la prevalence des atteintes cutanes chez 395 patients atteints de SSp, et DiapSS, qui comprend 139 patients atteints du syndrome de Gougerot-Sjogren diagnostique selon les criteres ACR-EULAR de 2016 parmi 325 patients suspectes d’etre atteints du SSp) et les donnees de base de l’essai randomise TEARS (110 patients atteints de SSp recent ou actif traites par rituximab ou placebo, evalues pour la secheresse cutanee a l’aide d’une echelle visuelle analogique sur 100). Resultats Les manifestations cutanees incluses dans l’indice EULAR d’activite du syndrome de Gougerot-Sjogren (ESSDAI) etaient rares dans la cohorte ASSESS (n = 16/395, 4,1 %), mais elles etaient associees a une activite dans les autres domaines de l’ESSDAI. L’etude TEARS a montre une forte prevalence de la secheresse cutanee (EVA > 50 ; 48,2 %) et a constate que les patients ayant la peau seche presentaient des scores EVA de douleur et de secheresse globale plus eleves (p = 0,003 et p Discussion Les signes dermatologiques inclus dans l’ESSDAI sont rares. Ces atteintes cutanees actives sont associees a l’activite de l’ESSDAI dans divers domaines. Un examen systematique par un dermatologue permettrait de mieux estimer les manifestations cutanees specifiques et non specifiques du syndrome de Gougerot-Sjogren. L’atteinte cutanee la plus courante est la secheresse cutanee mais elle n’est pas incluse dans les criteres d’evaluation de la maladie. Elle devrait donc etre evaluee par une EVA specifique.

Additional file 3.

Additional file 2.

L'effet des antipaludeens de synthese sur les infections virales est etudie depuis plusieurs annees, y compris l'hypothese d'un effet sur le SARS [1]. L'efficacite in vitro de la chloroquine contre le SARS-CoV-2 a ete decrite [2] , ainsi que la superiorite potentielle de l'hydroxycholoroquine. De nombreuses etudes in vivo ont ete menees. Il existe peu de donnees sur l'impact d'un traitement au long cours par hydroxychloroquine (HCQ) sur l'infection a SARS CoV-2 et les tests diagnostiques. Nous avons pour cela analyse les donnees des patients atteints de COVID-19 et suivis pour un rhumatisme inflammatoire chronique et/ou une maladie auto-immune systemique (iRMD-COVID-19) selon la prise ou non d'hydroxychloroquine comme DMARD. Les patients ont ete inclus a partir de la cohorte francaise iRMD-COVID-19 [3]. Les donnees cliniques, diagnostiques et d'evolution de l'infection a SARS CoV-2 des patients traites au prealable par HCQ ont ete comparees a celle des patients n'ayant pas de traitement par HCQ au moment de l'infection. Les criteres d'appariement etaient l'âge, le sexe, les comorbidites, un traitement immunosuppresseur, et l'utilisation de la PCR nasale. Parmi les 871 patients, 82 patients etaient traites par HCQ. Soixante et onze cas traites par HCQ ont pu etre apparies et compares a 191 temoins. Le taux de PCR nasale positive etait de 85 % dans le groupe HCQ contre 81 % dans le groupe controle (absolute standardized difference = 6,0 %). Il n'y avait pas de difference significative entre les cas et les controles concernant les signes cliniques, le taux d'hospitalisation (33,8 % vs 27,7 % ;OR = 1,75 (0,86-3,56) ;p = 0,12), le taux d'admission en soins intensifs (11,3 % vs 9,4 % ;OR= 1,94 (0,69-5,41) ;p = 0,21) et le taux de deces (5,9 % vs 6,6 % ;OR = 1,10 (0,30-4,04) ;p = 0,89). Chez les patients atteints de COVID-19 et suivis pour un rhumatisme inflammatoire chronique et/ou une maladie auto-immune systemique de la cohorte French RMD Covid 19, la prise d'HCQ comme DMARD n'a pas modifie le taux de positivite de la PCR nasale, n'a pas modifie la presentation clinique et n'a pas prevenu la survenue de forme severe de l'infection a SARS CoV-2 comparativement aux patients sans HCQ. (French) [ABSTRACT FROM AUTHOR] Copyright of Revue de Medecine Interne is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)