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Resume Objectif L’osteoarthropathie neuropathique (ON) ou pied de Charcot est une complication rare mais grave de la neuropathie peripherique car elle conduit a une deformation et a un handicap. Aucun traitement pharmacologique n’est disponible. L’activite osteoclastique, par l’intermediaire du receptor activator of nuclear factor ligand (RANK-L), joue un role central dans le pied de Charcot actif. L’objectif de ce travail etait de decrire l’effet clinique, radiologique et metabolique du denosumab, un anticorps humanise anti-RANK-L, dans le traitement de l’ON actif. Methodes Dans cette etude ouverte, conduite dans un centre tertiaire, tous les patients consecutifs avec ON refractaire au traitement usuel ont ete inclus. Une evaluation clinique, biologique, structurale (radiologie) et metabolique (imagerie nucleaire) a ete effectuee a l’initiation du traitement et apres traitement. Resultats Sept patients ont ete traites par denosumab entre 2017 et 2020 et suivis en mediane 16 mois [6–39]. Tous les patients ont ete ameliores cliniquement. Quatre ont rechute apres une mediane de 4 mois [3–33] et ont ete retraites avec une efficacite comparable. L’imagerie de suivi, disponible pour 5 patients a montre une stabilisation des lesions structurales (radiologiques) et une diminution significative de l’activite metabolique en TEP–TDM au FDG pour 4 d’entre eux. Aucun evenement indesirable, notamment hypocalcemie, n’a ete observe. Conclusion Chez les patients souffrant d’ON actif, le denosumab semblait cliniquement efficace, prevenait la destruction osteoarticulaire et avait un effet metabolique evalue par TEP–TDM au FDG. Ces resultats justifient son evaluation dans l’ON actif au cours d’un essai controle randomise contre placebo.

BackgroundIt is now well established that patients treated with rituximab (RTX) for auto-immune disease (AID) have a diminished antibody response to COVID-19 vaccines after two doses. Optimizing antibody response is a key objective in this population. To achieve this goal, a 3rd booster dose may be considered.ObjectivesFocusing on the population of AID patients treated with RTX without any antibody response after two doses we sought to explore how these patients could respond to a 3rd dose and identify factors of response.MethodsWe performed a French retrospective bicentric observational trial which is a follow up of previously published work (1). We included consecutive patients treated with RTX that were non-responders regarding their anti-Spike antibody (anti-S) status at least one month after the second dose of COVID-19 vaccination. Patients were included between March and October 2021. All patients then received a third dose according to local guidelines and had an anti-S measurement at least one month after the third dose. Some patients without response to a third dose had a fourth dose. Anti-S were measured in serum with various kits, but all results were in BAU/mL with upper quantification limit at 243. Patients with anti-S above 49 BAU/mL, which has been demonstrated to be the threshold associated with detectable neutralizing response were considered as responders (1).Results60 patients treated with RTX without response to 2 doses (Anti-S Ab < 49 BAU/mL) were included in the study. 9/60 (15%) patients responded to the 3rd vaccine dose with anti-S > 49BAU/ml.Responders and non-responders had similar demographic characteristics (Table 1). There was a positive correlation between anti-S Ab levels after dose 3 and time between 2nd and 3rd doses (r=0,41 p=0,001) (Figure 1). Nevertheless, the median time between 2nd and 3rd doses was numerically but not significantly higher in responders than in non-responders (129 vs 80 days, p=0.30). There was no correlation between anti-S levels after the third dose and the time between the last RTX infusion and the third vaccine dose. There was a trend towards more patients with methotrexate co-medication in the non-responder group 31/51 (61%) vs 3/9 (33%) in the responder group (p=0,15). Seven non-responder patients after the 3rd dose received a 4th dose and 4 (57%) responded.Table 1.Characteristics of patients without response after the second dose of vaccine treated with Rituximab for auto-immune diseases according to their seroconversion status after the third dose.Non responders (n=51)Responders (n=9)pAge, median (min-max)61 (17-85)58 (36-78)0,33Female sex n (%)42 (82)6 (67)0,36Underlying disease n (%) Rheumatoid Arthritis36 (69)5 (56)0,46 Other auto-immune disease16 (31)4 (44)Rituximab treatmentReceived a RTX infusion between dose 2 and 3 n (%)14(27)3(33)0,70Time between the last RTX infusion and the 3rd dose of vaccine in days median (min-max)162 (1-687)187 (79-959)0,16Previous number of RTX injections, median (min-max)7 (0-34)6 (1-22)0,58Vaccination schemeInterval between 2nd and 3rd vaccine dose in days, median (min-max)80 (23-287)129 (24-220)0,30Less than 3 months between 2nd and 3rd vaccine dose n (%)27(53)2(22)0,14Co-medicationsPatients on steroids n (%)20(40)5 (37,5)0,99Prednisone equivalent dose per day in mg median (min-max)5(2-25)5(5-10)0,48Figure 1.Correlation between anti- spike Ab levels after the third dose and time in days between doses 2 and 3.ConclusionA third vaccine dose of COVID-19 vaccine leads to only 15% of response in previously non-responding RTX treated AID patients. A longer time between 2nd and 3rd doses might positively influences response to a 3rd COVID-19 vaccine. Finally exploratory findings show that a fourth dose could be useful to obtain response non-responders.References[1]Bitoun S, Henry J, Desjardins D, et al. Rituximab impairs B-cell response but not T-cell response to COVID-19 vaccine in auto-immune diseases. Arthritis Rheumatol Hoboken NJ Published Online First: 28 December 2021.Disclosure of InterestsNone declared

Objective Active Charcot Neuro-osteoarthropathy (CN) is a rare and severe complication of peripheral neuropathy that leads to deformity and disability. No pharmacological treatment is available. Increased osteoclastic activity plays a central role in active CN, particularly via receptor activator of nuclear factor ligand (RANK-L). We aimed to describe clinical, morphological and metabolic imaging effects of denosumab, a fully human monoclonal anti- RANK-L antibody, in active CN. Methods In this open-label study, we included all consecutive patients with active refractory CN treated with denosumab in our tertiary center. Baseline and follow-up assessment included clinical examination, biological and imaging procedures (morphological and metabolic) before and after treatment. Results Seven patients were treated with denosumab between 2017 and 2020 and followed for a median of 16 months [6–39]. All patients clinically improved, 4 further relapsed after a median of 4 months [3–33]. Four patients were retreated with the same efficacy. Imaging follow-up available in 5 patients showed stability of structural damage (radiography) and a significant decrease of metabolic activity (FDG PET-CT) in 4 of them. No adverse event or hypocalcemia was observed. Conclusion In patients with refractory active CN, denosumab had a clinical effect, prevented bone and joint destruction, together with a metabolic effect, as assessed by FDG PET-CT. These results justify the conduction of a randomized controlled trial to assess the efficacy of denosumab in acute CN.

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

BackgroundCervical involvement in ankylosing spondylitis (AS) is particularly disabling and has been poorly studied yet. Actual radiologic scoring design to assess disease progression does not provide a comprehensive picture of the cervical involvement in AS. [1] Association with clinical features such as psoriasis are discussed.ObjectivesWe aimed to assess radiographic features of cervical involvement in AS and clinico-biological parameters associated with this specific radiographic location.MethodsCross-sectional study based on radiographic analysis of a subgroup of patients included in the French BambooSpine cohort, originally designed to study the genetic risk factors of AS structural severity. The analysis was based on patients included in Parisian hospitals to have access to images of the entire spine on the Picture Archiving and Communication System (PACS) shared by all University Hospitals in Paris. A double reading of the images was performed by a rheumatologist/radiologist pair until consensus was reached, to identify syndesmophytes, zygapophyseal joint (ZJ) involvement and posterior ligament structures (PLS) at each cervical level, syndesmophytes in the thoracic region, and ZJ and PLS involvement in the lumbar region.ResultsOf the 113 assessed patients, 101 were men, mean age 53 years (+/- 11 years) with 27 years (+/- 13 years) of disease duration (Table 1). Of those whose HLA B27 status was known, 85% (70/82) were carriers. Among 86 patients with radiological cervical involvement, 83% had syndesmophytes, 86% had ZJ involvement and 24% had PLS involvement. In the cervical region, 13 patients (15%) had zygapophyseal fusion without syndesmophytes. 26/113 patients were completely free of any cervical involvement while 30/113 had a maximal cervical involvement (anterior and posterior). In univariate analyses, HLA-B27 was significantly associated with ZJ involvement at the cervical and lumbar level (p=0.016). Cervical involvement of any type was not associated with psoriasis. Low educational level (not beyond secondary school) was significantly associated with syndesmophytic involvement (p=0.035). There was a non-significant trend for an association between arthritis and ZJ involvement.Table 1.Clinical featuresMen (n,%)101/11389,4%Age at diagnosis (mean, SD)31,211,68Duration of evolution (mean, SD)27,013,0Smoking ever (n,%)65/11258,0 %Chronic Back Pain (for > 3 months) (n,%)109/11396,5%Chest pain45/11040,9%Buttock pain78/10971,6%Arthritis36/11132,4%Enthesitis38/11233,9%Dactylitis6/1115,4%HLA B2770/8285,4%CRP87/10384,5%X ray sacro-iliitis112/112100%Personnal history -Uveitis41/11336,3% -Inflammatory bowel disease13/11311,5% -Reactive arthritis2/1121,8% -Psoriasis19/11117,1%ConclusionCervical involvement was very frequent (76% of this severe AS population) but not associated with psoriasis, as usually thought. Zygapophyseal involvement was present in 86 % of cases and exclusive in 15 % of cases. This latter radiological form of the disease, i.e. without syndesmophytes, is usually more difficult to diagnose, and should be systematically assessed among AS patients with cervical pain and/or patients with reduced cervical mobility.References[1]Wanders AJB, Landewé RBM, Spoorenberg A, et al. What is the most appropriate radiologic scoring method for ankylosing spondylitis? Arthritis & Rheumatism 2004Disclosure of InterestsNone 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

BackgroundSolitary bone plasmacytoma (SPB) is a rare malignancy whose main risk is progression to multiple myeloma (MM).ObjectivesTo describe the characteristics and outcome of patients treated for SBP and to identify factors associated with progression to MM and death.MethodsThis retrospective study was conducted between 1992 and 2020. Patients were included if they met the International Myeloma Working Group (IMWG) criteria for the diagnosis of SBP (1). Treatment response was assessed according to the IMWG criteria (2) for patients with detectable monoclonal protein and according to radiological response only for non-secretory SBP. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated by Cox proportional hazards models, adjusted for potential confounders. When available, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were reviewed by two experienced nuclear physicians.ResultsA total of 77 patients diagnosed with SBP were included. The median age was 59 years [range: 27-89]. Median follow-up duration was 87.1 months [range: 1.6-306.8]. At the end of the follow-up, 45 (58.4%) patients had developed a MM and 13 (16.9%) deaths occurred, including 10 patients with progression to MM. Five-year myeloma-free survival and overall survival were 47.9% and 86.8% respectively. All patients received radiotherapy with a median dose of 45 Grays [range: 30-55]. Chemotherapy was prescribed in 32 (41.6%) patients, concomitant to radiotherapy in 8, because of high risk of local extension, or adjuvant in 24 because of persistent disease after radiotherapy. Chemotherapy included mainly immunomodulatory drugs (28/32 (87.5%)) and/or proteasome inhibitors (11/32 (34.4%)) based combinations. Adjuvant chemotherapy after radiotherapy was associated with a reduced risk of MM compared to patients treated by radiotherapy alone, in a multivariate model adjusted for potential confounding factors, including response after radiotherapy alone (adjuvant chemotherapy versus no chemotherapy, HR 0.30, 95%CI [0.14-0.64]). Response to the first line of treatment (radiotherapy +/- chemotherapy) was the main factor associated with progression to MM (complete response versus partial response or progressive disease, HR 0.25, 95%CI [0.11-0.59]) and death (HR 0.22, 95%CI [0.05-0.99]). A non-significant trend between bone marrow plasmacytosis ≥ 5% at diagnosis and higher risk of MM was observed (≥ 5% versus 18F-FDG PET/CT images were available for review in only 36/77 patients. A significant decrease of 18F-FDG uptake after treatment was observed whereas the lesion size was unchanged. No association was observed with the risk of MM but the limited available images may have resulted in underpowered analyses.ConclusionIn this large study of patients with SBP, we observed that even though mostly prescribed for insufficient response to radiotherapy alone, treatment with adjuvant chemotherapy was associated with a decreased risk of evolution to MM, suggesting that this treatment might be systematically prescribed in addition to radiotherapy alone. These observations need to be confirmed and justify conduction of a prospective trial evaluating adjuvant chemotherapy in patients with SBP.References[1]Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos M-V, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. nov 2014;15(12):e538-548.[2]Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. août 2016;17(8):e328‑46.AcknowledgementsThe authors are indebted to all participants for their continued participation.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

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

Introduction/Background Case report: we present a case of 48 yr old single lady presenting with weakness, severe anemia and abnormal uterine bleeding and large pelvic mass of 30 week size. Ultrasound abdomen and pelvis : showed Mild right hydronephrosis; large heterogeneous lesion in pelvis likely to suggest a ?fibroid. MRI showed large posterior wall fibroid presenting as pelvi abdominal mass with cystic and hyaline degeneration for excision and pathological confirmation to rule out sarcomatous change. As patient was single she requested conservative surgery. She was counseled about the risk of hemorrhage and need for hysterectomy and underwent total abdominal hysterectomy with removal of tubes and ovaries. Histopathological examination showed undifferentiated endometrial sarcoma (high grade) in background of atrophic endometrium and leiomyomata uteri Post surgery she was investigated with oncology and multidisciplinary team and CT scan of abdomen and pelvis showed lung metastasis. Patient was counseled but she was in denial and did not attend for follow up and palliative surgery. Methodology Case report Results Histology slides and MRI slides will be uploaded in the poster Conclusion High grade endometrial stromal sarcoma is rare but serious diagnosis. High Degree of suspicion pre operatively specially in large fibroids and patient requesting conservative surgeries is required. We present this case due to its rarity and difficulty in managing the patient pre and post operatively as she was requesting conservative surgery pre operatively and due to denial failed to continue post operative follow up and therapy. Also this case again emphasized that most of this cases present as common perimenopausal complaints like abnormal menstrual bleeding and pelvic masses and diagnosed in late stage of disease which carries poor prognosis. Therefore high degree of suspicision is required for early diagnosis, counseling and management of such cases. Disclosure Nothing to disclose

Background:Acute Charcot neuroarthropathy (CN) of the foot is a rare and severe complication of peripheral neuropathy leading to joint destruction. Usual treatment rely on standard pressure offloading and no pharmacological treatment is available. Inflammation and increased osteoclastic activity via receptor activator of nuclear factor (RANK) ligand are major features of acute CN.Objectives:To assess clinical, metabolic and radiographic effect of denosumab, a fully human monoclonal antibody against RANK ligand, in acute CN.Methods:In this open study, we included all consecutive patients with acute CN treated with denosumab 60 mg in our mixed rheumatology/diabetes clinic dedicated to diabetic foot. Diagnosis of acute CN was based on clinical presentation and supported by biology, radiography, magnetic resonance imaging (MRI). Baseline and follow-up assessment included clinical examination and emission tomography–computed tomography (PET-CT).Results:Seven patients with acute CN were treated with denosumab between 2017 and 2019 (age from 43 to 70 years). Five were diabetic. All patients received denosumab, because of failure of standard pressure offloading, with evolving joint destruction of midfoot. CN evolves since a median of 6 months (2 to 20) at denosumab initiation. All patients clinically improved after denosumab injection (table). After a mean follow-up of 16 months, only 1/7 patients had a new flare. In the 4 patients with available follow-up X-ray, structural damage remained stable. In all 3 patients with available PET-CT evolution, the maximum standardized uptake lean value (SUL max) decreased.Table 1.Baseline characteristics and follow up treatmentThree patients were retreated, with a mean interval of 6 months: One patients because of persistent clinical and biological inflammation (CRP 17 mg/L), one because of relapse due to intensive walking, and one due to an associated osteoporosis.No adverse event and hypocalcemia was observed.Conclusion:One to three injection of denosumab 60 mg was efficient in preventing flare and further bone destruction in a 16 months medium follow up. These results justify the conduction of a randomized control study to assess the efficacy of denosumab as the first-line pharmacological therapy in acute CN.References:[1]Molines L and al. Charcot’s foot: Newest findings on its pathophysiology, diagnosis and treatment. Diabetes Metab. Sept 2010;36(4):251-5.[2]Mabilleau G, and al. Increased osteoclastic activity in acute Charcot’s osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligand. Diabetologia. juin 2008;51(6):1035-40.Disclosure of Interests:None declaredDisclosure of Interests:Sandrine Carvès: None declared, Julien Henry: None declared, Murielle BOURGEON GHITTORI: None declared, Rakiba Belkhir: None declared, Gaetane Nocturne: None declared, Florent Besson: None declared, Guillaume Cluzel: None declared, Maud Creze: None declared, Raphaèle Seror Consultant of: BMS UCB Pfizer Roche, Xavier Mariette Consultant of: BMS, Gilead, Medimmune, Novartis, Pfizer, Servier, UCB

Background: We needed to assess the impact of our patient education program on Sjogren’s syndrome (SESAME) in order to continuously improve it. Objectives: A playful online questionnaire was designed and implemented to assess patients’ knowledge about Sjogren’s syndrome. Methods: A interprofessional team (3 rheumatologists, 3 pharmacists) and a 4-patient group who participated in the education program together proceeded to the questionnaire design: 1) definition of a competency framework for patients with Sjogren’s syndrome; 2) from literature review, identification of quality requirements for a questionnaire (scientific quality, opportunity to interact, means of expression, logical chaining of questions, simplicity, utility, shortness, bias prevention, playfulness, variety, online diffusion). To fulfill these criteria, we used a clear vocabulary and concise questions, included open-ended questions on patient experience, focused on the artwork, randomized the order of answer choices, and shared the questionnaire online. Once the SESAME quiz was established, a scoring system was defined by the expert group. Face validity, feasibility and reproducibility were assessed to validate the questionnaire. 25 patients were contacted to complete the questionnaire twice. Patients also evaluated the content, structure and feasibility using 12 items (understandable language, unambiguous sentences, length of the questionnaire, difficulty, web access). Reproducibility was calculated using intraclass correlation coefficient (ICC) on patient answers separated by 48 hours. Results: The questionnaire includes 28 questions divided into 4 parts: Sjogren’s signs, Sjogren’s causes, treatment, daily life with the disease. The 25 patients filled in the questionnaire twice (96% women, 54 years min-max[23;74], 4 years since the diagnosis min-max[1;20]). The questionnaire was filled in from a computer (n=38), a tablet (n=3) or a smartphone (n=9). The average response time was 19 minutes. The median score was 34 points min-max[22;46] out of 50. 18 patients evaluated the questionnaire. 15 patients or more regarded its content, organization and feasibility as “very good”. 5 patients found it difficult. The reproducibility was very high (total ICC=0.87 IC95% [0.74–0.94], ICC on each part between 0.61 et 0.87). Conclusions: The SESAME quiz is now freely available (https://etp-rhumato.typeform.com/to/qsVhR1) and all the Hospital centers caring for Sjogren patients can use it for their follow up. Disclosure of Interest: None declared

Background Primary Sjogren’s syndrome (pSS) is the autoimmune disease having the highest risk of lymphoma. The differential diagnosis between benign and malignant lymphoproliferation is sometimes difficult. Among imaging procedures, 18F-FDG PET could be useful for that purpose. Objectives To compare 18F-FDG PET results between patients with and without lymphoma to identify PET pattern associated with lymphomas in pSS Methods Retrospective study conducted in 2 centres including pSS patients (according to ACR/EULAR 2016 criteria) who undergo 18F-FDG PET. We compared PET abnormalities in patients with and without lymphoma, the PET having been done before any chemotherapy. Two independent readers analysed PET blind to lymphoma diagnosis. ESSDAI-PET score previously described by Cohen et al.[1 was calculated. Results 45 patients were included; 15 had lymphoma: MALT (n=12), nodal marginal zone with plasmacytic differentiation (n=2), diffuse large B-cell (n=1). Patients with lymphoma had more frequently parotid gland swelling (67% vs 20%, p=0.003) and higher ESSDAI score (24 [13.5–29] vs 9,5–20 p=0.03), even after exclusion of lymphoma item (1911–27 VS 9,5–20 p=0.03). Compared to non-lymphoma patients, mean size (45.538–56 mm vs. 4037–41 mm; p=0.048) and maximum standardised uptake value (SUVmax) of the parotid glands (5.6 [5–6.9] vs 3.8 [3.2–4.4]; p=0.001) were higher in lymphoma patients. 53.3% of patients with lymphoma and 43.3% without lymphoma had lymph node FDG uptake, but neither their number nor their repartition or mean SUV differ between them. Pulmonary uptake was observed in 6 (40%) patients with lymphoma and 6 (20%) without lymphoma (p=0.17). But in lymphoma patients, this uptake was focal in 5 (33.3%) patients (nodules or condensation) c and in only one (3.3%) patient without lymphoma (p=0.01). Remaining patients had interstitial FDG uptake. Mean PET score (42–4 vs. 21–3 p=0.04) and SUVmax at any site (6.3 [5.6–7.3) vs. 4.2 [3.7–5.9] p=0.02) were significantly higher in lymphoma group. 20 patients had PET guided biopsy of a hypermetabolic lesion that conducted to lymphoma diagnosis in 7 cases (46.6%). After chemotherapy for lymphoma, PET was available for 10 patients: complete regression of hypermetabolic lesions was observed in 6 patients (60%), and decreased uptake intensity in the 4 remaining patients. Conclusions Some of the systemic manifestation of pSS (lung, lymph nodes and salivary glands) can be assessed by 18F-FDG PET. Lymph nodes hypermetabolism is frequent and not associated with lymphoma. The 18F-FDG PET abnormalities associated with lymphoma diagnosis are SUV max at any site >6, SUV max of parotid glands>5 and focal nodular hypermetabolic lung lesions. Finally, PET can be helpful to guide biopsy toward the most hypermetabolic structure for diagnosing lymphoma. Reference [1] Cohen C, Mekinian A, Uzunhan Y, Fauchais A-L, Dhote R, Pop G, et al. 18F-fluorodeoxyglucose positron emission tomography/computer tomography as an objective tool for assessing disease activity in Sjogren’s syndrome. Autoimmun Rev. 2013Sep;12(11):1109–14. Disclosure of Interest None declared

Background Despite the role of chronic low-grade inflammation in osteoarthritis (OA), prevalence of OA during inflammatory or auto-immune diseases remains poorly assessed. A single study without a valid control group [1] and daily practice suggest an increased frequency of hand OA (HOA) in primary Sjogren Syndrome (pSS). Objectives We aimed investigate the prevalence of radiographic, symptomatic or erosive HOA in pSS and to compare these results with age and sex-matched control population suffering from dry eyes and mouth without auto-immune manifestation (sicca patients). Methods We included women with pSS fulfilling 2002 AECG European-American criteria and control women suffering from sicca symptoms without autoimunity who underwent a multidisciplinary day hospital. Standardized radiographs of hands were performed and were all read by an experimented reader. Radiographic HOA was defined as Kellgren-Lawrence score ≥2 on at least one joint. Erosive HOA was defined using the Verbruggen scoring system (phase E, subchondral erosion or R, remodelling of subchondral plate). Symptomatic HOA was defined as radiographic HOA associated with spontaneous hand joint pain and/or with a FIHOA ≥5 at the time of radiographs. We compared pSS versus sicca patients, pSS with radiographic HOA (pSS+, HOA+) versus pSS without radiographic HOA (pSS+, HOA-), and finally pSS with radiographic HOA (pSS+, HOA+) versus sicca patients with radiographic HOA (pSS-, HOA+). Results We included 34 patients with pSS (median age [range] 54.5 [28–84] years) and 54 patients with only sicca symptoms (57 [24–85] years). Among pSS patients, 41% had radiographic HOA, 12% had symptomatic HOA and 9% had erosive HOA. These prevalences did not differ from sicca patients (52% radiographic HOA p=0.45, 28% symptomatic HOA p=0.11, 9% erosive HOA p=1.0). The trend for a higher prevalence of symptomatic HOA in sicca patients compared to pSS is expected since these patients frequently suffer from dryness associated with fibromyalgia. In pSS patients, radiographic HOA was associated with a higher average age (pSS+HOA+:63,5 versus pSS+HOA-: 48,5 years old, p Conclusions The prevalence of HOA is not increased in pSS, a model of auto-immune diseases. Patients with pSS have the same HOA risk factors than in general population (age and menopause) and also hypothyroidism that may be involved in OA pathophysiology. References Aksoy and al, J Rheumatol 2016. Mariette and al, Rheumatology (Oxford) 2003. Haugen and al, Ann Rheum Dis 2011. Acknowledgements Osteoarthritis group of French Society of Rheumatology. Disclosure of Interest None declared

Background The BAFF (or BLyS) cytokine plays a key role in pathogenesis of primary Sjogren9s syndrome (pSS), thus testing belimumab (biological treatment inhibiting soluble BAFF/BLyS) in pSS patients, seems appealing. Clinical results of the BELISS study have been previously reported [1]. Objectives To address changes in blood lymphocyte sub-populations and labial salivary gland (LSG) inflammation after belimumab in patients with primary Sjogren9s syndrome (pSS) and identify predictors of response to treatment.To address changes in blood lymphocyte sub-populations and labial salivary gland (LSG) inflammation after belimumab in patients with primary Sjogren9s syndrome (pSS) and identify predictors of response to treatment. Methods Sequential blood lymphocyte subsets and LSG biopsies were analysed between week 0 (W0) and W28 in 15 pSS patients (all females, median age =44 [36.5-63.5] years, median disease duration=1 [0.5-6.5] years) treated with belimumab. Systemic response to treatment was defined as a decrease of the ESSDAI ≥3 points at W28. Results After belimumab, we observed a decrease in blood B lymphocytes primarily involving CD27-IgD+ naive B-cells (151 [24-186] at W0 vs 10 [6-40] at W28, p=0.008, n=9). No significant change in the total lymphocyte, total T-cell, CD4 or CD8 T-cell counts was observed. By contrast, there was a significant increase in the number of NK cells (p=0.032) Regarding histological pattern, lymphocytic sialadenitis (focus score >1) present in 12 (80.0%) patients before belimumab, became negative in 5 after treatment (p=0.03). The median LSG B-cell /T-cell ratio decreased from 0.58 [0.5-0.67] to 0.50 [0.5-0.5] (p=0.06). BAFF staining was detected in 11/14 (78.6%) patients, before, compared to 7/14 (50.0%) after belimumab (p=0.10). The median percentage of BAFF positive cells in foci significantly decreased from 27.5% [10-40] to 5% [0-20], after belimumab (p=0.03). Systemic response was obtained in 6 (40%) patients. The only predictor of response was the presence of a low number of NK cells both in blood (8.5% [7-10] vs. 11% [9-21], p=0.04) and in LSG (20.6/mm 3 [20.0-21.4] vs 30.0/mm 3 [25.0-100.0], p=0.003). Serum BAFF levels did not influence response to treatment. Conclusions Low blood and salivary NK cells numbers are associated with a better response to belimumab. This suggests that 2 distinct subsets of pSS may exist: one with predominant type-I INF/BAFF/B-cell axis, good responders to belimumab, and one with predominant type-II IFN/NK-cell axis, non-responders. References Mariette X, Seror R, Quartuccio L, Baron G, Salvin S, Fabris M, et al. Efficacy and safety of belimumab in primary Sjogren9s syndrome: results of the BELISS open-label phase II study. Annals of the rheumatic diseases. 2013. Disclosure of Interest None declared

We present the results of a preliminary study (the first of this kind in Algeria) in which 4 families presenting with congenital deficiency of the C1-esterase inhibitor (C1-INH) responsible for hereditary angioneurotic oedema were biologically explored. The complement fractions C1-INH, C4 and C3d were assayed in 38 subjects of the 4 families. Extending this biological evaluation to all members of theses families enabled us to identify all asymptomatic subjects (46 percent in our series). In 2 patients the congenital disease was associated with systemic lupus erythematosus. Some clinico-biological discordances are reported and discussed in the light of data from the literature.