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Resume Objectifs Peu de donnees sont disponibles sur le devenir des grossesses dans l’axSpA recente, en particulier concernant l’impact de l’activite de la maladie. Nous avions pour objectif d’identifier a) les facteurs associes a la survenue d’une grossesse durant le suivi et b) les facteurs associes a des complications de la grossesse (ex. fausse couche, interruption medicale ou prematurite) dans une population de ax SpA recentes. Methodes Cohorte francaise observationnelle prospective (DESIR) avec un suivi a 6 ans, incluant 381 femmes naives d’anti-TNF et atteintes de SpAax recente. Les facteurs associes a la survenue d’une grossesse durant le suivi et les facteurs associes a une complication de la grossesse ont ete estimes par des analyses multivariees (modeles a fragilites partagees ou modeles mixtes). Resultats On rapporte 124 grossesses survenues au cours du suivi. Les patientes ayant eu une grossesse au cours du suivi etaient plus susceptibles d’avoir interrompu leur traitement par anti-TNF au cours des 6 mois precedents la grossesse (HR = 2,0 [IC 95 % 1,1-3,3], P = 0,01) et d’avoir une CRP elevee a la visite DESIR precedant la grossesse (HR = 1,7 [IC 95 % 1,2-2,5], P = 0,01). L’accouchement a terme etait de loin l’evenement le plus frequent (75 % de toutes les grossesses) et seule la prise d’AINS au cours des 6 mois precedant la fin de la grossesse a ete associee a une issue defavorable (OR = 2,5 [IC 95 % 1,1-5,0], P = 0,02). Aucune association n’a ete retrouvee entre la prise d’anti-TNF et une complication de la grossesse. Conclusion L’accouchement a terme etait le devenir de la grossesse le plus frequent. Contrairement aux anti-TNF, la prise d’AINS au cours des 6 mois precedant l’issue a ete associee a une complication de la grossesse dans cette cohorte de axSpA recentes.

Cardiac involvement in systemic lupus (SL) and antiphospholipid syndrome (APS) can be due to variables and involve different presentations. Pericarditis is the most common lupus manifestation and occurs in 16% to 25% of patients. While corticosteroids are usually very effective, colchicine may avoid steroids and prevent relapse. Myocarditis during SL is rare and often inaugural. They may manifest as chest pain, acute heart failure, arrhythmias or conduction disturbances, and may progress to dilated cardiomyopathy and/or permanent heart failure. Their prognosis is however generally good, even in the absence of treatment with cyclophosphamide for the less serious forms. Finally, coronary involvement in SL is most often due to atherosclerotic, thrombotic origin (generally in the context of associated APS), and exceptionally explained by coronary vasculitis. During APS, valve disease is frequent and usually asymptomatic. Thrombotic damage can be (1) coronary, typically manifesting as a myocardial infarction in a young subject with healthy coronary arteries, (2) much more rarely intracardiac, or (3) microcirculatory, generally as part of a catastrophic antiphospholipid syndrome (CAPS) leading to a multiorgan failure. Finally, iatrogenic cardiac manifestations can exceptionally be seen during treatment with cyclophosphamide or antimalarials characterized by conduction disorders and/or heart failure.

Resume Introduction Il s’agit d’un cas clinique illustrant une toxicite aux antipaludeens de synthese (APS) qu’il faut savoir systematiquement evoquer et rechercher. Observation Un homme de 59 ans avec antecedent de cardiopathie etiquetee ischemique revelee par des troubles de la conduction, et de lupus cutane traite par hydroxycholoroquine puis chloroquine, consultait pour une alteration de l’etat general. A l’examen clinique, il presentait une amyotrophie, un deficit moteur et une abolition des reflexes osteo-tendineux aux membres inferieurs. Une toxicite musculaire et cardiaque aux APS etait evoquee. Le diagnostic etait confirme par une biopsie musculaire montrant une myopathie vacuolaire floride typique. L’arret du medicament incrimine permettait une regression lente des atteintes. Conclusion La toxicite cardiaque et musculaire peripherique des APS, rare et parfois fatale, doit etre systematiquement evoquee et recherchee chez un patient expose plusieurs annees. La biopsie musculaire peut permettre le diagnostic en evitant la biopsie cardiaque.

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Background Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients. Methods HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ Results The mean (± SD) HCQ levels were 469 ± 223 ng/mL in serum and 916 ± 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 ± 0.15. In the multivariate analysis, low whole-blood HCQ levels (P = 0.023), but not serum HCQ levels, were independently associated with active SLE. From the mean serum/whole-blood level ratio, a serum HCQ level of 106 ng/mL was extrapolated as the corresponding cut-off to identify non-adherent patients with a sensitivity of 0.87 (95% CI 0.76–0.94) and specificity of 0.89 (95% CI 0.72–0.98). All serum HCQ levels of patients with whole-blood HCQ below the detectable level ( Conclusions These data suggest that whole blood is better than serum for assessing the pharmacokinetic/pharmacodynamic relation of HCQ. Our results support the use of serum HCQ levels to assess non-adherence when whole blood is unavailable.

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Backgroundpatients with chronic rheumatic inflammatory diseases (CRID, i.e. rheumatoid arthritis (RA) or spondyloarthritis (SpA)) have been reported to have poorer pregnancy outcomes than the general population.Objectivesto describe the pregnancy outcomes of singleton in patients with CRID in France in the past decade.Methodsthis is an analysis of the French Health Insurance claims database (SNDS), which represents 87% of the French population) from 2008 to 2016. To be included in the analysis patients had to be identified as RA or SpA according to existing diagnostic algorithms, to have at least one pregnancy declaration in the database, and to have continuous health insurance from 1-year before pregnancy onset to 1-year after end of the pregnancy or until death (if death occured before the 1-year-period after the end of pregnancy) to be included. Only the first singleton pregnancy occurring during the study period was included in this analysis. Both maternal and pregnancy outcomes were considered. Outcomes were identified either by ICM-10 codes or hospital discharge summaries discharge between 2008-2016.ResultsAmong the 35 737 identified adult females with a CRID diagnosis (40.7% with RA and 59.3% with SpA), 27 722 (78%) had a pregnancy during the study period. 11 274 (42%) had received at least one DMARD prior to the pregnancy and were included in the analysis. Among them, only 4025 (36%) were exposed to DMARDs during pregnancy.Mean (SD) age of females at the start of the pregnancy was 32 (5) years, and mean (SD) disease duration was 4 (4) years. Pregnancy ended before 13 WG in 21% and after 37 WG in 70% cases. Live-birth represented the most frequent pregnancy outcome (76.9%), and overall 34.7% patients presented at least one unfavorable outcome (see Table 1).Table 1.Unfavourable outcomeN(%)Pregnancy outcomesMiscarriage ()579 (5.3%)Abortion91 (0.8%)Stillbirth48 (0.4%)Preterm delivery (>= 22WG and )779 (7.1%)Low weight at birth ()287 (2.6%)Perinatal mortality (22WG to 6 days of life)2 (0%)Maternal outcomesSevere maternal infection*211 (1.9%)Newborn outcomesHospitalisation in neonatal intensive care > 48h in full-term newborns (after 37 WG)95 (0.8%)Neonatal mortality (27 first days of life)2 (0%)Severe infection * during first year603 (5.3%)ConclusionMore than 75% pregnancies in patients with CRID resulted in a live-birth. Prevalence of miscarriage was surprisingly low, probably related to under-coding. Maternal and infant outcomes seemed comparable to general population. Whether medications had an impact on such outcomes is currently under evaluation.Disclosure of InterestsNone declared

BackgroundTreatment of patients with chronic rheumatic inflammatory diseases (CRID) during pregnancy has changed in the last decade, namely due to the availability of new DMARDs labelled to be used during pregnancy.ObjectivesTo describe the anti-rheumatic drug use during pregnancy in women with CRID (i.e. rheumatoid arthritis (RA) or spondyloarthritis (SpA)) in France over the past decade.MethodsThis is a retrospective cohort study within the French Healthcare database (SNDS), which covers 98% of the French population. Adult women were included if they had RA or SpA according to CIM-10 codes, had started a singleton pregnancy between 2008 and 2017 (index date), and were continuously covered by this health insurance from 1-year before pregnancy onset to 1-year after end of the pregnancy or death (whichever comes first). The treatment exposures of interest were: NSAIDs, oral corticosteroids, csDMARD (methotrexate, leflunomide, sulfasalazine, azathioprine, hydroxychloroquine), biologics (anti-TNF, rituximab, abatacept, tocilizumab, ustekinumab, anakinra). Exposure during pregnancy was defined as at least one drug reimbursement from the 6 months before the last menstrual period (LMP) to the end of pregnancy period.ResultsAmong the 35,737 adult women with a CIRD (40.7% with RA and 59.3% with SpA) who had a past history of DMARD reimbursement, 11,274 (41.7%) started a singleton pregnancy during the study period. In total, during preconception and pregnancy, 4,773 (42.3%) women were not delivered any DMARD nor corticosteroids, 769 (6.8%) were delivered corticosteroids alone, 3,639 (32.2%) a csDMARD alone and 2,862 (25.4%) a biologic (among whom 33.1% associated a csDMARD). Biologics delivered during pregnancy were mainly anti-TNFs (92.1%).Exposure to NSAIDs was more frequent during the first trimester (30% patients) of pregnancy but occurred all along the pregnancy (6% and 2% in the second and third trimesters, respectively). Conversely, exposure to oral corticosteroids was stable during the pregnancy (33% to 27%); however, more than half of the prescriptions corresponded to doses higher than 10mg. Exposure to DMARDs including bDMARDs during pregnancy was more frequent during the first trimester, compared to the rest of the pregnancy (see graph).ConclusionOverall, less than 50% of women with a CRID who received a DMARD prior to the pregnancy continued to retrieve such treatment during pregnancy, and overall less than 20% were delivered biologics during pregnancy. Whether the withdrawal of DMARDs led to unfavorable maternal and pregnancy outcomes needs to be evaluated.AcknowledgementsThis study was conducted thanks to a grant from the French Ministry of Health - Programme Hospitalier de Recherche CliniqueDisclosure of InterestsAnna Moltó Consultant of: UCB, Abbvie, Lilly, Pfizer, BMS, MSD, Novartis, Biogen, Janssen, Grant/research support from: UCB, Aya Ajrouche: None declared, Diep Tran: None declared, Barbara Roux: None declared, Nathalie Costedoat-Chalumeau Grant/research support from: UCB, Elisabeth Elefant: None declared, Vassilis Tsatsaris: None declared, Jeanne Fresson: None declared, Brigitte Bader-Meunier: None declared, Bruno Fautrel: None declared, Florence Tubach: None declared

BackgroundThe patient reported Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) includes the six components fatigue, neck, back or hip pain, pain or swelling in other joints, tenderness, morning stiffness severity and duration on a 0-10 scale.ObjectivesTo explore the driving factors for the BASDAI in pregnant patients with axial spondyloarthritis (axSpA).MethodsAnonymized pooled data of the European Network of Pregnancy Registries in Rheumatology (EuNeP) were used. The four participating registries are located in France, Germany, Norway and Switzerland, and collect data of women with child wish, during and after pregnancy prospectively and nationwide on regular time points. For the analysis, women who fulfilled ASAS classification criteria for axSpA and for whom a pregnancy outcome was reported until 12/2019 or 07/2020, depending on the registry, were selected. Mean BASDAI and its components were analysed descriptively.ResultsA total of 332 pregnancies from 304 women with axSpA were eligible. The Norwegian registry contributed half of the pregnancies (50.3%), followed by Germany (26.2%), France (15.4%) and Switzerland (8.1%). Mean maternal age was 31 years, the average disease duration 5 years.Mean BASDAI was 3.0 before conception, 3.4, 3.4 and 3.5 in the 1st, 2nd and 3rd trimester, and 3.4 within 6 months postpartum. The figure shows mean values of the BASDAI and its individual components in the different time periods. Fatigue was higher than the mean score during all phases, and especially elevated in the 1st and 3rd trimester. Furthermore, values for neck, back or hip pain were higher than the mean score, especially from 2nd trimester on. All other components were lower than the mean score.Data were not reported for all pregnancies and all time periods. Availability was highest in the 2nd and 3rd trimester with reported BASDAI in 60% and 62% of the pregnancies, respectively. Lowest reporting was 24% in the preconception period because only a part of the women was also observed before pregnancy.ConclusionThe BASDAI is a validated instrument for assessing disease activity in patients with axSpA. Since the calculation of the score also includes factors that can be influenced by pregnancy, it may only be of limited value for measuring disease activity in pregnancy. This analysis shows that mainly fatigue and back pain in particular have an impact on the mean BASDAI. A limitation of this analysis is that data were not available for all measured time points of the individual pregnancies. Therefore, the results should be confirmed by other studies.Figure 1.Means of BASDAI components before, during and after pregnancy (the table presents means ± standard deviation).AcknowledgementsThis work was supported by a research grant from FOREUM Foundation for Research in Rheumatology.Disclosure of InterestsYvette Meissner Speakers bureau: Pfizer, Anna Moltó Consultant of: UCB and BioGen, Grant/research support from: UCB, Nathalie Costedoat-Chalumeau Grant/research support from: to my institution (UCB), Rebecca Fischer-Betz: None declared, Frauke Förger Speakers bureau: UCB pharma, GSK, Consultant of: UCB pharma, GSK, Roche, Grant/research support from: UCB pharma, GSK, Marianne Wallenius: None declared, Anja Strangfeld Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, Pfizer, Roche, Sanofi, UCB.

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

BackgroundRheumatoid arthritis (RA) is one of the most common chronic inflammatory diseases and regularly affects women of childbearing age1. However, there is limited knowledge about the impact of the disease and its treatment on fertility.ObjectivesThe aim of the study was to determine factors associated with time-to-conception in women with RA.MethodsAll RA patients (diagnosis according to the Rheumatologist) included in the national multicenter GR2 cohort from 2015 to June 2021 were included in the analysis. Patients could be included either with a pregnancy wish (i.e., preconceptional period) or because of a clinical pregnancy (12 months or non-achievement of pregnancy), as well as the number exposed to csDMARDs and biologics in the preconception period. We performed survival analyses, using a Cox model including a random effect for the center to account for heterogeneity of practices among participating centers. We used a multiple imputation to address missing data among the explanatory variables. Results are presented as a hazard ratio (HR) with confidence interval (CI) to assess associations between the factors studied and time-to-conception.ResultsAmong the 167 patients with RA included in the GR2 cohort, 78 were selected for the main analysis of time-to-conception. Of these, 40 (51.3%) had a clinical pregnancy during follow-up. Subfertility was observed in 33 (42.3%) women and median time-to-conception was 19.1 months; mean preconception DAS28-CRP score was 2.3 (+/- 1.2).Patients were treated during the preconceptional period with NSAIDs, corticosteroids, csDMARDs and biotherapy in 10 (12.8%), 35 (44.9%), 24 (30.8%), and 32 (41.0%) cases, respectively. The multivariate model adjusted for age, BMI, DAS28-CRP, disease duration, ACPA positivity, and exposure to corticosteroids and biologics in the preconception period found an association between increased preconception delay and age (HR (per year) 1. 12 95% CI [1.04-1.16] p = 0.01) as well as disease duration (HR (per year) 1.06 95% CI [1.02-1.15] p = 0.03).ConclusionThis study provides original results on fertility in women with RA. It found a median time-to-conception of 19.1 months, with a subfertility rate of 42.3%, which is significantly higher than the general population2. In this context, it seems essential to discuss this topic from the beginning of the disease in women of childbearing age.References[1]Van den Brandt S. Arthritis Res Ther. 2017;19(1):64.[2]Junul S. Hum Reprod. 1999;14(5):1250-4.Table 1.Survival analyses (Cox model): factors associated with time-to-conception in women with RA.Univariate analysesMultivariate analysesCrude HR 95% CIpAdjusted HR 95% CIpAge1.11 [1.04-1.18]0.0021.12 [1.04-1.16]0.015BMI1.06 [0.99-1.16]0.1031.08 [0.99-1.16]0.062ACPA positivity1.75 [0.90-3.39]0.1071.44 [0.65-2.86]0.310Disease duration1.03 [0.98-1.08]0.2671.06 [1.02-1.15]0.032DAS28-CRP score1.08 [0.81-1.45]0.5921.08 [0.92-1.32]0.170Corticosteroids0.91 [0.51-1.65]0.7690.86 [0.42-1.68]0.620Biologics1.52 [0.82-2.81]0.1891.30 [0.62-2.78]0.630Figure 1.Cumulative incidence curves for pregnancies in women with RA.AcknowledgementsThe GR2 Cohort is supported by the French Society of Rheumatology, the French Internal Medicine Society, and unrestricted grants from UCB.Disclosure of InterestsSABRINA HAMROUN: None declared, Marion Couderc: None declared, Laure Gossec: None declared, Rene-Marc Flipo: None declared, Hubert MAROTTE: None declared, Christophe Richez Speakers bureau: CR has received consulting/speaker’s fees from Abbvie, Amgen, Astra Zeneca, Biogen, BMS, Celltrion, Eli Lilly, Galapagos, GSK, MSD, Novartis, and Pfizer, all unrelated to this manuscript., Aline Frazier-Mironer: None declared, Jérémie SELLAM: None declared, Elisabeth Gervais: None declared, Valerie Devauchelle-Pensec: None declared, Alban Deroux: None declared, Rakiba Belkhir: None declared, AZEDDINE DELLAL: None declared, Laëtitia Dunogeant: None declared, Cédric Lukas: None declared, Emmanuel Chatelus: None declared, Nathalie Costedoat-Chalumeau: None declared, Anna Moltó: None declared

BackgroundSpondyloarthritis (SpA) is one of the most common chronic inflammatory diseases and regularly affects women of childbearing age1. However, there is limited knowledge about the impact of the disease and its treatment on fertility2.ObjectivesThe aim of the study was to determine factors associated with time-to-conception in women with SpA.MethodsWe performed an analysis of SpA patients (diagnosis according to the rheumatologist) included in the national multicenter cohort GR2 from 2015 to June 2021. Patients could be included either with a pregnancy wish (i.e., preconceptional period) or because of a clinical pregnancy (12 months or non-achievement of pregnancy), as well as the number exposed to csDMARDs and biologics in the preconception period. We performed survival analyses, using a Cox model including a random effect for the center to account for heterogeneity of practices among participating centers. We used a multiple imputation to address missing data among the explanatory variables. Results are presented as a hazard ratio (HR) with confidence interval (CI) to assess associations between the factors studied and time-to-conception.ResultsAmong the 207 patients with SpA included in the GR2 cohort, 88 were selected for analysis of time-to-conception (i.e., include preconceptionally). Of these, 56 (63.6%) had a clinical pregnancy during follow-up. Subfertility was observed in 40 (45.4%) women and the median time-to-conception was 16.1 months. The mean preconceptional BASDAI score was 2.9 (+/- 2.1). Patients were treated with NSAIDs, corticosteroids, csDMARDs and biotherapy in 23 (26.1%), 8 (9.1%), 12 (13.6%), and 61 (69.3%) cases, respectively. The multivariate model adjusted for age, BMI, nulligestity, BASDAI, disease duration, smoking, form of spondyloarthritis (axial, peripheral, or both), and exposure to NSAIDs, csDMARDs, and biotherapy in the preconception period found an association between longer time-to-conception and age (HR 1. 22 95% CI [1.08-1.40] p < 0.001), as well as the use of NSAIDs during preconception (HR 3.01 95% CI [2.15-3.85] p = 0.01).ConclusionThis study provides original results on fertility in women with SpA. The factors associated with a longer time-to-conception were age and the NSAIDs use during the preconception period, which argues for their cautious use in case of pregnancy wish in patients needing continuous NSAID intake for the management of their disease.References[1]Van den Brandt S. Arthritis Res Ther. 2017;19(1):64.[2]Hamroun S. Rheumatology. 2021; Jul 23: keab589.Figure 1.Cumulative incidence curves for pregnancies in women with SpA according to NSAIDs use in preconception period.AcknowledgementsThe GR2 Cohort is supported by the French Society of Rheumatology, the French Internal Medicine Society, and unrestricted grants from UCB.Disclosure of InterestsSABRINA HAMROUN: None declared, Marion Couderc: None declared, Rene-Marc Flipo: None declared, Jérémie SELLAM: None declared, Christophe Richez Speakers bureau: CR has received consulting/speaker’s fees from Abbvie, Amgen, Astra Zeneca, Biogen, BMS, Celltrion, Eli Lilly, Galapagos, GSK, MSD, Novartis, and Pfizer, all unrelated to this manuscript., Emmanuelle Dernis: None declared, Aline Frazier-Mironer: None declared, Laure Gossec: None declared, Elisabeth Gervais: None declared, Hubert MAROTTE: None declared, Laëtitia Dunogeant: None declared, Cédric Lukas: None declared, Alban Deroux: None declared, Nathalie Costedoat-Chalumeau: None declared, Anna Moltó: None declared

BackgroundSpondyloarthritis (SpA) is one of the most common chronic inflammatory diseases and regularly affects women of childbearing age1. However, there is limited knowledge about the impact of the disease and its treatment on pregnancy.ObjectivesThe aim of the study was to determine the factors associated with adverse pregnancy outcome in women with SpA.MethodsAll SpA patients (diagnosis according to the Rheumatologist) included in the national multicenter GR2 cohort from 2015 to June 2021 were included in the analysis. Patients could be included either with a pregnancy wish (i.e., preconceptional period) or because of a clinical pregnancy (ResultsAmong the 207 pregnancies in women with SpA included in the GR2 cohort, 126 were retained for analysis of obstetrical outcome. Of these, 29 (23.0%), 14 (11.1%), 69 (54.8%) were exposed to corticosteroid, NSAID and biologics at least once during pregnancy, respectively. An active disease at least once during pregnancy was found in 47 (37.3%) pregnancies. A live birth was found in 116 (92.1%) women, including 110 (87.3%) full-term births. Early miscarriages and stillbirths were observed in 7 (0.06%) and 3 (0.02%) women, respectively. A caesarean section was performed in 20 (17.2%) cases.A favorable pregnancy outcome was found in 80 (63.5%) of the women. Unfavorable pregnancy outcome was most frequently due to small for gestational age, observed in 22 (19%) pregnancies. The multivariate model adjusted for age, BMI, nulliparity, active disease during pregnancy, smoking, and exposure to NSAIDs and corticosteroids during pregnancy found an association between unfavorable pregnancy outcome with nulliparity (OR 2.63 95% CI [1.01-6.81] p = 0.05).ConclusionThis study provides original results on pregnancy in women with SpA. It found a favorable pregnancy outcome in 63.5% of women. Unfavorable pregnancy outcome was most frequently due to small for gestational age, which should lead to a coordinated management with obstetricians for the follow-up of pregnancy in women with SpA.References[1]Van den Brandt S. Arthritis Res Ther. 2017;19(1):64.Table 1.Multilevel logistic regression model: factors associated with unfavorable pregnancy outcome in women with SpA.Univariate analysesMultivariate analysesCrude OR 95% CIpAdjusted OR 95% CIpAge1.01 [0.92-1.10]0.8591.05 [0.95-1.17]0.297BMI0.99 [0.91-1.07]0.7960.99 [0.90-1.08]0.747Nulliparity2.16 [0.94-4.94]0.0712.63 [1.01-6.81]0.049Smoking0.84 [0.23-3.03]0.8050.84 [0.22-3.21]0.805Disease activity*0.98 [0.40-2.43]0.9641.15 [0.43-3.07]0.778Corticosteroids**1.09 [0.45-2.65]0.8761.15 [0.51-2.71]0.902NSAIDs**0.65 [0.18-2.33]0.1960.67 [0.18-2.56]0.565* BASDAI score ≥ 4 at least once during pregnancy.** Use at least once during pregnancyAcknowledgementsThe GR2 Cohort is supported by the French Society of Rheumatology, the French Internal Medicine Society, and unrestricted grants from UCB.Disclosure of InterestsSABRINA HAMROUN: None declared, Marion Couderc: None declared, Rene-Marc Flipo: None declared, Jérémie SELLAM: None declared, Christophe Richez Speakers bureau: CR has received consulting/speaker’s fees from Abbvie, Amgen, Astra Zeneca, Biogen, BMS, Celltrion, Eli Lilly, Galapagos, GSK, MSD, Novartis, and Pfizer, all unrelated to this manuscript., Rakiba Belkhir: None declared, Laure Gossec: None declared, Hubert MAROTTE: None declared, Emmanuelle Dernis: None declared, Aline Frazier-Mironer: None declared, Elisabeth Gervais: None declared, Cédric Lukas: None declared, Valerie Devauchelle-Pensec: None declared, Laëtitia Dunogeant: None declared, Alban Deroux: None declared, Nathalie Costedoat-Chalumeau: None declared, Anna Moltó: None declared

BackgroundThe detection of somatic mutations in genes of myeloid cells in asymptomatic patients - defining clonal hematopoiesis of indeterminate potential (CHIP) - predisposes to cardiovascular events (CVE) in the general population.ObjectivesWe aimed to determine whether CHIP was associated with CVE in SLE patients.MethodsThe study is an ancillary study of the randomized, double-blind, placebo-controlled, multicenter trial PLUS study conducted from June 2007 through August 2010 at 37 centers in France involving 573 SLE patients. The search for somatic mutations by high-throughput sequencing of 53 genes involved in clonal hematopoiesis was performed on genomic DNA collected at PLUS inclusion. The CHIP prevalence was assessed in SLE and in a retrospective cohort of 479 patients free of hematological malignancy. The primary outcome was the incident CVE in SLE.ResultsScreening for CHIP was performed in 438 SLE patients (38 [29-47] years, 91·8% female). Overall, 63 somatic mutations were identified in 47 patients defining a CHIP prevalence of 10·7% in SLE. Most SLE patients (78·7%) carried a single mutation. Most variants (62·5%) were located in the DNMT3A gene. CHIP was associated with age, age at SLE diagnosis and a lower frequency of antiphospholipid antibodies. CHIP occurred more than 20-years earlier (pConclusionThe prevalence of CHIP is high in SLE with respect to age but was not associated with incident CVE.Disclosure of InterestsNone declared

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)

BackgroundPrediction models based on traditional cardiovascular risk factors underestimate the risk of cardiovascular events (CVE) in systemic lupus erythematosus (SLE).ObjectivesWe aimed to determine whether sCD163, a biomarker for SLE-associated atherosclerosis, may predict CVE in SLE.MethodsAll SLE patients included between 2007 and 2010 in the randomized, double-blind, placebo-controlled, multicenter PLUS trial were screened. Patients with no past history of CVE at inclusion and a follow-up period of >20 months were analyzed. sCD163 level was measured using enzyme-linked immunosorbent assay on serum collected at PLUS inclusion. The primary outcome was the incident CVE. Factors associated with incident CVE and sCD163 level were analyzed.ResultsOverall, 442 SLE patients (of the 573 included in the PLUS study) were analyzed for the primary outcome with a median follow up of 110 (interquartile range: 99–120) months. Among them, 29 (6.6%) experienced at least one CVE that occurred at a median of 67 (interquartile range: 31–91) months after inclusion. In the multivariate analysis, dyslipidaemia, age and increased sCD163 were associated with CVE onset. Multivariate Cox models analysis showed that a concentration of sCD163> 263 ng/mL at inclusion increased by 2.7 [hazard ratio 2.7 (95% CI: 1.0, 7.0)] the risk of CVE in SLE. Increased sCD163 was also associated with immunosuppressive treatment, higher body mass index (BMI) and SLEDAI score.ConclusionMacrophage-specific sCD163 serum level reflects lupus disease activity and predicts CVE in SLE.Disclosure of InterestsNone declared

BackgroundRheumatoid arthritis (RA) is one of the most common chronic inflammatory diseases and regularly affects women of childbearing age1. However, there is limited knowledge about the impact of the disease and its treatment on pregnancy.ObjectivesThe aim of the study was to determine the factors associated with adverse pregnancy outcome in women with RA.MethodsAll RA patients (diagnosis according to the Rheumatologist) included in the national multicenter GR2 cohort from 2015 to June 2021 were included in the analysis. Patients could be included either with a pregnancy wish (i.e., preconceptional period) or because of a clinical pregnancy ( 3.2 at least once during pregnancy. We performed a multilevel logistic regression model, in which we considered patient and center random effects (patient random effect for some women included in the cohort two times). We used a multiple imputation procedure to address missing data among the explanatory variables. Results are presented as an odds ratio (OR) with confidence interval (CI).ResultsAmong the 167 pregnancies in women with RA included in the GR2 cohort, 92 were retained for analysis of obstetrical outcome. Of these, 43 (46.2%), 8 (7.9%), 40 (43.5%) were exposed to corticosteroid, NSAID and biologics at least once during pregnancy, respectively. A moderate or severe disease activity at least once during pregnancy was found in 20 (21.8%) pregnancies. A live birth was found in 83 (90.2%) women, including 69 (83.1%) full-term births. Early miscarriages were observed in 9 (0.1%) women. A caesarean section was performed in 22 (23.9%) cases.A favorable pregnancy outcome was found in 52 (56.5%) of the women. Unfavorable pregnancy outcome was mainly due to prematurity and small for gestational age, observed in 14 (16.9%) and 17 (20.5%), respectively. The multivariate model adjusted for age, BMI, nulliparity, active disease during pregnancy, smoking, and exposure to biologics and corticosteroids during pregnancy found an association between an unfavorable pregnancy outcome and nulliparity (OR 6.2 95% CI [2.1-17.8] p = 0.002), age (OR (per year) 1.1 95% CI [1.0-1.3] p = 0.02) and exposition to corticosteroids during pregnancy (OR 3.2 95% CI [1.1-9.6] p = 0.04).ConclusionThis study provides original results on pregnancy in women with RA. It found a favorable pregnancy outcome in 56.5% of women. Unfavorable pregnancy outcome was associated with age, nulliparity and corticosteroids use during pregnancy, which argues for their careful use during pregnancy.References[1]Van den Brandt S. Arthritis Res Ther. 2017;19(1):64.Table 1.Multilevel logistic regression model: factors associated with unfavorable pregnancy outcome in women with RA.Univariate analysesMultivariate analysesCrude OR 95% CIpAdjusted OR 95% CIpAge1.09 [1.01-1.19]0.0361.14 [1.02-1.28]0.019BMI0.93 [0.83-1.04]0.1960.91 [0.77-1.08]0.204Nulliparity4.18 [1.66-10.53]0.0036.16 [2.13-17.76]0.002Smoking1.08 [0.29-3.36]0.9961.65 [0.37-7.22]0.141Disease activity*1.06 [0.40-2.81]0.9110.98 [0.21-2.28]0.753Corticosteroids**2.45 [1.05-5.68]0.0393.22 [1.09-9.57]0.038Biologics**1.05 [0.11-3.54]0.5892.02 [0.70-4.12]0.194* Moderate or severe disease activity at least once during pregnancy.** Use at least once during pregnancyAcknowledgementsThe GR2 Cohort is supported by the French Society of Rheumatology, the French Internal Medicine Society, and unrestricted grants from UCB.Disclosure of InterestsSABRINA HAMROUN: None declared, Marion Couderc: None declared, Rene-Marc Flipo: None declared, Laure Gossec: None declared, Christophe Richez Speakers bureau: CR has received consulting/speaker’s fees from Abbvie, Amgen, Astra Zeneca, Biogen, BMS, Celltrion, Eli Lilly, Galapagos, GSK, MSD, Novartis, and Pfizer, all unrelated to this manuscript., Rakiba Belkhir: None declared, Aline Frazier-Mironer: None declared, Valerie Devauchelle-Pensec: None declared, Hubert MAROTTE: None declared, Jérémie SELLAM: None declared, Elisabeth Gervais: None declared, Alban Deroux: None declared, Cédric Lukas: None declared, Emmanuelle Dernis: None declared, Emmanuel Chatelus: None declared, Nathalie Costedoat-Chalumeau: None declared, Anna Moltó: 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

Purpose The purpose of this study was to evaluate the safety of antithrombotic treatments prescribed during pregnancy in patients with antiphospholipid syndrome (APS). Methods This international, multicenter study included two cohorts of patients: a retrospective French cohort and a prospective US cohort (PROMISSE study). Inclusion criteria were (1) APS (Sydney criteria), (2) live pregnancy at 12 weeks of gestation (WG) with (3) follow-up data until six weeks post-partum. According to APS standard of care, patients were treated with aspirin and/or low-molecular weight heparin (LMWH) at prophylactic (pure obstetric APS) or therapeutic doses (history of thrombosis). Major bleeding was defined as abnormal blood loss during the pregnancy and/or post-partum period requiring intervention for hemostasis or transfusion, or during the peripartum period greater than 500 mL and/or requiring surgery or transfusion. Other bleeding events were classified as minor. Results Two hundred and sixty-four pregnancies (87 prospectively collected) in 204 patients were included (46% with history of thrombosis, 23% with associated systemic lupus). During pregnancy, treatment included LMWH ( n = 253; 96%) or low-dose aspirin ( n = 223; 84%), and 215 (81%) patients received both therapies. The live birth rate was 89% and 82% in the retrospective and prospective cohorts, respectively. Adverse pregnancy outcomes occurred in 28% of the retrospective cohort and in 40% of the prospective cohort. No maternal death was observed in either cohort. A combined total of 45 hemorrhagic events (25%) occurred in the retrospective cohort, but major bleeding was reported in only six pregnancies (3%). Neither heparin nor aspirin alone nor combined therapy increased the risk of hemorrhage. We also did not observe an increased rate of bleeding in the case of a short interval between last LMWH (less than 24 hours) or aspirin (less than five days) doses and delivery. Only emergency Caesarean section was significantly associated with an increased risk of bleeding (odds ratio (OR) 5.03 (1.41–17.96); p=.016). In the prospective cohort, only one minor bleeding event was reported (vaginal bleeding). Conclusion Our findings support the safety of antithrombotic therapy with aspirin and/or LMWH during pregnancy in high-risk women with APS, and highlight the need for better treatments to improve pregnancy outcomes in APS. PROMISSE Study ClinicalTrials.gov identifier: NCT00198068.

Relapsing polychondritis (RP) is a rare condition characterized by recurrent inflammation of cartilaginous tissue and systemic manifestations. Data on pathophysiology are scarce and suggest an autoimmune mechanism. Recently, the possibility of dividing patients with RP into three distinct clinical phenotypes has been suggested: the hematological form representing less than 10% of patients, essentially older men with associated myelodysplasia and poor prognosis, the respiratory form representing about 25% of patients with predominant tracheobronchial involvement, and the mild and most frequent form, representing 65% of patients, with a good prognosis. Recent data on survival shows an improvement of overall prognosis compared to historical series. Reported poor prognosis factors are male gender, associated haemopathies and cardiac involvement. Few recent series suggest an interest for positron emission tomography for the diagnosis and the follow-up of treatment. Due to the lack of randomized therapeutic trial, treatment remains empirical and is mainly based on oral corticosteroids sometimes associated with immunosuppressive agents. The use of biologic agents has recently been reported in small retrospective series with different outcome. Finally, some selected patients with mild and occasional peripheral chondritis might justify a treatment with colchicine or a therapeutic abstention with occasional short-term corticosteroids therapy.

Objective To study the influence of Maghrebian ethnicity on lupus nephritis. Methods We retrospectively reviewed the files of a cohort of 194 patients with proliferative lupus nephritis followed in seven lupus centres belonging to three groups: Europeans living in Belgium/France (E; n = 111); Maghrebians living in Europe, in casu Belgium/France (ME; n = 43); and Maghrebians living in Morocco (MM; n = 40). Baseline presentation was compared between these three groups but complete long-term outcome data were available only for E and ME patients. Results At presentation, the clinical and pathological characteristics of lupus nephritis did not differ between E, ME and MM patients. Renal relapses were more common in ME patients (54%) than in E patients (29%) ( P Conclusion Despite a similar disease profile at onset, the prognosis of lupus nephritis is more severe in Maghrebians living in Europe compared to native Europeans, with a higher relapse rate.

Introduction La sarcoidose est une granulomatose systemique d’etiologie indeterminee [1] . De nombreux cas et des series d’infections opportunistes (IO) chez des patients atteints de sarcoidose sont rapportes dans la litterature medicale [2] , [3] . Sont generalement exclues les aspergilloses cavitaires et les tuberculoses, associees respectivement a la fibrose et a des elements demographiques communs. Les agents opportunistes rapportes sont varies (Cryptococcus neoformans, JC virus, mycobacteries atypiques, Nocardia spp.) mais actuellement aucun facteur de risque d’infection opportuniste n’est decrit au cours de la sarcoidose. Patients et methodes Nous avons effectue un recueil de la litterature medicale via le moteur de recherche Medline et realise un appel a observations via le groupe sarcoidose francophone a la recherche d’associations « infection opportuniste » et « sarcoidose ». Les caracteristiques cliniques des IO ont ete comparees a une population temoin constituee de patients porteurs d’une sarcoidose sans IO issus d’une cohorte de notre service. Resultats La revue de la litterature a permis de recenser 164 cas d’infections qualifiees d’opportunistes chez des patients porteurs d’une sarcoidose. Parmi ces 164 infections, 83 etaient des cryptococcoses (51 %) et 39 etaient des leuco-encephalopathies multifocales progressives (LEMP) (24 %). Notre appel a observations a permis de recenser 50 IO chez 49 patients, incluant : 24 cryptococcoses (49 %), 12 LEMP (24 %), 7 pneumocystoses (14 %) et 7 autres infections (14 %) dont 3 mycobacterioses atypiques, 2 nocardioses et 2 infections a cytomegalovirus. Ces 49 patients avec IO ont ete compares a 135 controles porteurs d’une sarcoidose sans IO. Dans le groupe infection opportuniste, le compte lymphocytaire moyen etait de 1000/mm3 (100-2680/mm3) et 14 patients ne presentaient pas de lymphopenie (29 %). Les facteurs de risques identifies en analyse univariee etaient : le sexe masculin (OR = 4,76; IC95 % [2,12 ; 10,00]), la presence d’adenopathies peripheriques (OR = 3,45 ; [1,49 ; 8,04]), d’une hepatomegalie (OR = 8,10 ; [1,91 ; 40,41]) ou d’une splenomegalie (OR = 9,00, [1,80 ; 58,86]), la presence d’une atteinte pulmonaire de stade ≥2 (OR = 6,66 ; [2,80 ; 17,74]), d’une atteinte neurologique centrale (OR = 8,73 ; [1,98 ; 53,52]) ou d’une insuffisance renale (OR = 5,65 ; [1,33 ; 25,24]), la corticotherapie (OR = 10,26 ; [4,15 ; 29,22]) et l’utilisation du cyclophosphamide (OR = 9,42 ; [1,61 ; 98,92]) ou d’un anti-TNFα (OR = 7,68 ; [1,21 ; 83,62]). En analyse multivariee (ajustement sur l’âge et le sexe), les facteurs de risque identifies etaient l’utilisation de corticoides (OR = 10,60 ; [4,31 ; 29,57]) ou d’un anti-TNFα (OR = 13,47 ; [2,05 ; 129,43]), la presence d’une hepatomegalie (OR = 9,91 ; [2,23 ; 55,85]), une atteinte pulmonaire de stade 2 ou superieur (OR = 5,65 ; [2,34 ; 15,36]) et l’insuffisance renale (OR = 11,76 ; [2,32 ; 68,35]). La lymphopenie Conclusion Les facteurs de risque d’IO dans notre etude sont associes a la gravite de la sarcoidose et/ou a sa diffusion systemique. Il existe un facteur confondant lie a l’utilisation des immunosuppresseurs chez des patients avec une sarcoidose plus severe. Dans notre serie, 6 % des patients ont developpe une infection opportuniste sans aucun facteur de risque, suggerant neanmoins une immunosuppression propre a la sarcoidose dans ces cas.

Introduction Les valvulopathies associees au lupus erythemateux systemique (LES) et/ou au syndrome des anti-phospholipides (SAPL), dont l’endocardite de Libman-Sachs, sont des complications rares de ces deux pathologies. L’objectif de cette etude etait de decrire les caracteristiques cliniques, biologiques, echo-cardiographiques et evolutives des patients porteurs de valvulopathies severes liees au LES et/ou SAPL ayant necessite un remplacement valvulaire, et d’etudier leurs histologies valvulaires. Materiels et methodes Etude Francaise retrospective observationnelle et multicentrique (n = 5), proposee par le Centre Hospitalier Universitaire de Reims et realisee sous l’egide de la SNFMI. Les patients inclus devaient avoir une valvulopathie severe ayant necessite un recours a la chirurgie valvulaire et etre porteurs d’un LES et/ou SAPL repondant aux criteres internationaux. Le compte-rendu de l’histologie valvulaire devait etre disponible. Resultats Vingt-trois patients (dont 20 femmes) âges en moyenne de 39 ± 15 ans au diagnostic de valvulopathie, ont ete inclus dans l’etude. Tous etaient porteurs d’un SAPL, avec evenements thrombotiques chez 22 (96 %) d’entre eux, de phenotype arteriel chez 15 (65,2 %) patients dont 6 (26 %) avaient au moins un episode de syndrome catastrophiques des anti-phospholipides (CAPS). Onze patients (48 %) avaient un LES associe au SAPL. La maladie systemique (SAPL avec ou sans LES) etait connue avant la mise en evidence de la valvulopathie chez seulement 12 (52 %) patients. Vingt patients (87 %) etaient porteur d’un anticoagulant circulant lupique, 20 (87 %) d’un anti-cardiolipine et 13 (56 %) avaient une triple positivite APL. Vingt patients (87 %) avaient une seule valve pathologique, 18 patients etaient porteurs d’une valvulopathie mitrale (78 %) et 8 (35 %) d’une valvulopathie aortique. Les epaississements (n = 19 ; 83 %) et les insuffisances valvulaires (n = 19 ; 83 %) etaient les anomalies les plus frequemment observees. Quinze patients (62 %) ont eu un remplacement valvulaire par valve mecanique, deux par une bioprothese (8,7 %) et 6 d’une chirurgie valvulaire conservatrice (26 %), dont 5 ont du etre reoperes dans un delais moyen de 1 ± 1,8 ans. Neuf (39 %) patients ont presente des complications postoperatoires precoces dont trois CAPS, une thrombose de prothese et un deces postoperatoire precoce (echec d’extubation apres deux mois de reanimation). Dix-huit patients (78,3 %) avaient un fonctionnement valvulaire juge normal a distance de l’intervention. La moitie des patients avaient des sequelles neurologiques (liees a des evenements ischemiques peri operatoires) a la fin du suivi (47 %). Quatre patientes du groupe chirurgie reparatrice ont eu une grossesse normale apres la chirurgie. Trois types de lesions valvaires histologiques ont ete observees au sein des valves prelevees : 8 (34 %) patients avaient une endocardite de Libman-Sacks typique (avec de larges vegetations delabrantes), 9 (39 %) une valvulopathie fibro-calcifiee degenerative et 6 (26 %) des lesions combinees (fibro-degeneratives et petites exulcerations). Conclusion Les valvulopathies graves (necessitant une chirurgie) au cours du LES et/ou du SAPL sont fortement associees au SAPL thrombotique, surtout de phenotype arteriel. La moitie des patients avaient des sequelles neurologiques en rapport avec des evenements ischemiques au dernier suivi et la chirurgie valvulaire comportait un risque eleve de CAPS.

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.)

Introduction Les evenements cardiovasculaires (ECV) sont en France la premiere cause de mortalite des patients lupiques. Les ECV en contexte lupique ne sont pas expliques par les seuls facteurs de risque cardiovasculaire classiques. L’hematopoiese clonale est la detection par sequencage a haut debit de mutations somatiques de genes impliques dans l’hematopoiese maligne. Elle est dite de signification indeterminee (HCSI) lorsqu’elle est detectee chez des patients sans hemopathie maligne. L’HCSI est liee a l’âge et predispose aux pathologies myeloides. L’HCSI predispose egalement aux ECV dans la population generale. Notre objectif etait de tester le lien entre l’HCSI et la survenue d’ECV majeurs chez les patients lupiques. Patients et methodes Les patients inclus entre 2007 et 2010 dans l’etude multicentrique PLUS ont ete analyses. Le sequencage haut debit cible, d’un panel de 53 genes associes aux hemopathies myeloides (hematopoiese clonale), a ete realise sur l’ADN genomique extrait du sang circulant preleve a l’inclusion dans PLUS (biologie moleculaire des hemopathies - laboratoire d’hematologie - CHU de Lille). Le critere principal de jugement etait la survenue d’un 1er evenement cardiovasculaire majeur depuis l’inclusion dans PLUS. Resultats L’ADN genomique etait disponible chez 452 patients lupiques et le sequencage haut debit des genes d’interet etait analysable chez 438 (âge median 45 ans, 91,8 % de femmes) d’entre eux. Le sequencage haut debit mettait en evidence 63 variants d’interet chez 47 patients lupiques (47/438, 10,7 %) en l’absence de toute maladie hematologique maligne. La profondeur mediane de lecture etait de 3409 [IQR: 2517–12018] reads. La frequence mediane de l’allele variant (VAF) etait de 2,1 [1,2–4,4] %. Comparativement a une cohorte controle (n = 303) ayant beneficie d’une recherche d’hematopoiese clonale selon la meme technique et pour un meme seuil de positivite (1 %), la prevalence de l’HCSI avant 60 ans etait pres de 2 fois plus elevee chez les patients lupiques (40/420, 9.5 %) que chez les controles (10/196, 5,1 %, p = 0,061). Parmi les 47 patients lupiques avec HCSI, 37 (78,7 %) etaient porteurs d’une unique mutation somatique. Le gene regroupant le plus de variants d’interet etait le gene DNMT3A (40 variants identifies chez 70,2 % (33/47) des patients avec HCSI) suivi de TET2 (7 variants identifies chez 12,8 % (6/47) des patients avec HCSI). Les patients lupiques avec HCSI (vs sans HCSI) etaient plus âges (52 [41–57] ans vs 37 [28–45] ans, p Le critere principal de jugement etait analysable chez 333 des 438 patients (76,0 %) pour lesquels le sequencage a ete realise. Parmi eux, 19 (5,7 %) avaient presente un ECV majeur pour une duree mediane de suivi de 109 [97–118] mois. La presence d’une HCSI n’etait pas associee a la survenue d’un ECV [1/38 (2,6 %) dans le groupe avec HCSI versus 18/295 (6,1 %) dans le groupe sans HCSI, p = 0,39]. Conclusion La prevalence de l’hematopoiese clonale de signification indeterminee chez les patients atteints de lupus systemique est elevee mais ne semble pas associee a la survenue d’evenements cardiovasculaires majeurs.

Introduction L’HTAP associee au lupus est une complication rare mais severe. La place respective du traitement immunosuppresseur et du traitement vasodilatateur reste discutee: l’efficacite du traitement immunosuppresseur est inconstante et le traitement vasodilatateur est volontiers reserve aux patients les plus severes. Depuis les premieres publications sur le sujet, des scores pronostiques de l’HTAP ont ete developpes et la prise en charge therapeutique repose desormais sur leur evaluation. L’objectif de cette etude est d’evaluer l’impact respectif du traitement immunosuppresseur et du traitement specifique au cours de l’HTAP associee au lupus. Patients et methodes Trois groupes de patients issus de Registre francais d’hypertension arterielle pulmonaire et suivis a l’hopital Bicetre (France) ont ete analyses: des patients atteints de lupus traites par immunosuppresseurs seuls (LES-IS), des patients atteints de lupus traites par immunosuppresseurs et traitement specifique de l’HTAP (LES-IS + VD) et des patients avec HTAP idiopathique apparies au groupe LES-IS + VD sur l’âge, le sexe, le nombre de criteres ESC de faible risque selon la methode francaise, le type et le nombre de traitement specifique. Les donnees cliniques, hemodynamiques et 3 scores de risque (methode francaise selon le nombre de criteres ESC, methode COMPERA et score REVEAL) ont ete evalue a l’inclusion et a M6. Resultats Trente-trois patients avec HTAP associee a un lupus ont ete analyses: 17 avaient recu un traitement immunosuppresseur seul et 16 avaient recu un traitement immunosuppresseur et specifique de l’HTAP. Le groupe controle etait constitue de 16 patients atteints d’HTAP idiopathique. Les patients des groupes LES-IS et LES-IS + VD avaient tous recu du cyclophosphamide et des corticoides. Ils presentaient des anti-SSA/SSB dans 70 % et 56 % des cas et des anti-RNP dans 47 % et 43 % des cas respectivement. A l’exception de 3 patients, l’HTAP etait la seule manifestation systemique au moment du diagnostic de l’HTAP. A l’inclusion, les patients du groupe LES-IS + VD avaient une classe fonctionnelle NYHA plus elevee (p = 0,04), un index cardiaque plus bas (2,38 [2,07–2,61] versus 3,36 [2,63–3,89] L/min/m2 ; p Discussion Bien qu’ils soient plus graves, les patients traites par immunosuppresseur et traitement specifique de l’HTAP presentent une amelioration significative des parametres cliniques, hemodynamiques et des scores de risque alors que ces parametres restent stables chez les patients traite par IS seul. Cela remet en question l’efficacite du traitement immunosuppresseur et soutient une utilisation systematique du traitement specifique de l’HTAP dans la prise en charge des patients lupiques. La reponse therapeutique de certains patients du groupe LES-IS et l’amelioration plus marquee en donnees individuelles des patients du groupe LES-IS + VD compares aux patients HTAPi sont deux elements distincts qui suggerent neanmoins un benefice du traitement immunosuppresseur. Conclusion Le traitement immunosuppresseur seul ne permet pas d’ameliorer significativement les scores pronostiques des patients traites pour HTAP associee a un lupus. L’amelioration hemodynamique et des scores pronostiques repose essentiellement sur le traitement specifique. L’impact reel du traitement immunosuppresseur seul semble persister mais reste a evaluer. Des etudes prospectives, difficiles a conduire du fait de la rarete de la maladie, seraient necessaires pour mieux repondre a cette question.