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Background:Sjögren’s disease (SS) is a systemic autoimmune pathology manifested mainly by a dry syndrome, intense asthenia and arthromyalgia. Systemic manifestations may also occur. Since 2019, immunosuppressant agents (IS) or biotherapies are recommended only for patients with systemic involvement. However, before 2019, in some cases, paucisymptomatic patients had been treated with IS/biotherapies, often off-label.Objectives:We propose to evaluate the benefit and safety of using IS/biotherapy in patients with SS without systemic involvement.Methods:We retrospectively collected the clinical records of all patients with SS diagnosed according to ACR/EULAR diagnostic criteria followed up between January 1980 and October 2023 at Grenoble University Hospital (France).Results:Eighty-three patients were included: 64 with an initially non-systemic form. Of these patients with an initially non-systemic form, 24 were treated with IS/biotherapy. None of them developed secondary systematization, whereas 11 out of 40 patients in the untreated group did (p<0.05). On the other hand, IS/biotherapy did not appear to improve dry syndrome. There were no serious adverse events.Conclusion:Early introduction of an IS/biotherapy treatment appears to provide a benefit for the patient without side effects.REFERENCES:[1] Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren’s syndrome: A consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis. 2017;76:9–16.[2] Ramos-Casals M, Brito-Zerón P, Bombardieri S, et al. EULAR recommendations for the management of Sjögren’s syndrome with topical and systemic therapies. Ann Rheum Dis. 2020;79:3–18.[3] Brito-Zerón P, Retamozo S, Kostov B, et al. Efficacy and safety of topical and systemic medications: a systematic literature review informing the EULAR recommendations for the management of Sjögren’s syndrome. RMD Open. 2019;5:e001064.Figure 1.Percentage of onset of systematic manifestations over time in patients followed up for SS with a non-systemic form at baseline (A, B), with ESSDAI 0 (C), or with systemic form at baseline (D) treated with IS or biotherapy (A, C, D) or immunomodulatory treatment (IS/biotherapy and HCQ) (B). HCQ: Hydroxychloroquine, IS: Immunosuppressant. *: p<0.05.Figure 2.Evolution of dry syndrome in patients with SS treated or not with pilocarpine (A) or IS/Biotherapy. A major improvement corresponds to a regression of the dry syndrome of more than 50%, a moderate regression to a regression of less than 50%. IS: immunosuppressive agent.Acknowledgements:NIL.Disclosure of Interests:None declared.

Lung ultrasound (LUS) has emerged as a simple, rapid, and non-invasive method for the dynamic assessment of pulmonary congestion, a major prognostic factor and a therapeutic target in acute heart failure (AHF). In a single-center prospective observational study, 42 patients hospitalized for AHF in the post-emergency polyvalent medicine department of CHU Grenoble were successively included between May 2021 and July 2022. Patients undergoing hemodialysis, those with pneumonectomy or lung fibrosis, or those placed under guardianship or deprived of freedom were excluded. Clinical examination, LUS, and electrolyte panel results were collected daily. Vital status was assessed 30 days after the last LUS. The primary endpoint was the evolution of the number of B-lines in relation to the dose of diuretic administered. Secondary endpoints included the evolution of B-lines according to clinical signs of congestion and plasma creatinine levels, the agreement between LUS and clinical findings at discharge, and the prognostic value of LUS at discharge for 30-day re-admission for AHF and all-cause mortality. A total of 188 LUS were performed. The patients were elderly (85.8 years [SD 8.1]) and comorbid. The median number of B-lines decreased from 17 at admission to 7 mid-hospitalization, then stabilized. The median daily intravenous diuretic dose declined from 40 mg to 20 mg. Patients with chronic kidney disease (CKD) had more B-lines at admission (24.2 (SD 11.6) vs. 8.2 (SD 8.8)). However, B-line evolution was independent of creatinine levels. Higher B-lines at discharge were significantly associated with 30-day mortality (15.2 vs. 3.9, p < 0.001). In the absence of a gold standard for the assessment of pulmonary congestion, LUS appears to be an additional tool for optimizing the management of AHF.

Background:The treatment and prognosis of cryoglobulinemia vasculitis (CryoVas) depend on etiology. Rituximab (RTX) and corticosteroids (CS) are the first line treatment for mixed essential (ME) CryoVas and connective tissue disease (CTD)-related CryoVas. The prognosis and long term outcomes of these forms of CryoVas are as yet unknown.Objectives:The aim of this study was therefore to describe the risk of relapse and treatment-related morbidities in patients with ME and CTD-related CryoVas.Methods:A retrospective study was conducted of 63 patients in remission of ME or CDT-related CryoVas after RTX-CS therapy, with a median follow-up time of 58 months (interquartile range, 33–88 months).Results:Thirty-nine out of 63 patients (62%) had a relapse a median of 42 (23–65) months after the initial flare. The relapse incidence was 38% at 2 years and 46% at 3 years. The factors associated with relapse were purpura at the time of the qualifying flare (HR, 2.2; 95% confidence interval (CI), 1.1–4.4; p = 0.002) and prior history of CryoVas flares (HR, 1.9; 95% CI, 1.0–3.7; p = 0.04). Maintenance therapy was associated with a lower risk of relapse 6–24 months after the initial flare (HR, 0.27; 95% CI, 0.09–0.78; p = 0.02), but not thereafter (HR, 2.0; 95% CI, 0.7–5.7; p = 0.21). The most common form of maintenance therapy was 500 mg RTX every 6 months. The most frequent complication was infection, and maintenance RTX therapy was associated with a higher risk of severe infection (HR, 2,2; 95% CI, 0.9–5,6; p = 0.08).Conclusion:In this group of patients in RTX-CS remission of ME and CTD-related CryoVas, relapses were common and the risk of relapse was significantly associated with purpura during the qualifying flare and a prior history of relapse. Maintenance RTX was associated with a lower risk of relapse but was also associated with an increased risk of severe infection.REFERENCES:[1] Saadoun D, Sellam J, Ghillani-Dalbin P, Crecel R, Piette JC, Cacoub P. Increased Risks of Lymphoma and Death Among Patients With Non–Hepatitis C Virus–Related Mixed Cryoglobulinemia. Arch Intern Med. 2006 Oct 23;166(19):2101–8.[2] Cacoub P, Comarmond C, Domont F, Savey L, Saadoun D. Cryoglobulinemia Vasculitis. Am J Med. 2015 Sep 1;128(9):950–5.[3] Terrier B, Krastinova E, Marie I, Launay D, Lacraz A, Belenotti P, et al. Management of noninfectious mixed cryoglobulinemia vasculitis: data from 242 cases included in the CryoVas survey. Blood. 2012 Jun 21;119(25):5996–6004.[4] Terrier B, Carrat F, Krastinova E, Marie I, Launay D, Lacraz A, et al. Prognostic factors of survival in patients with non-infectious mixed cryoglobulinaemia vasculitis: data from 242 cases included in the CryoVas survey. Ann Rheum Dis. 2013 Mar 1;72(3):374–80.[5] Quartuccio L, Bortoluzzi A, Scirè CA, Marangoni A, Del Frate G, Treppo E, et al. Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC). Clin Rheumatol. 2023 Feb 1;42(2):359–70.[6] Terrier B, Marie I, Launay D, Lacraz A, Belenotti P, de Saint-Martin L, et al. Predictors of early relapse in patients with non-infectious mixed cryoglobulinemia vasculitis: Results from the French nationwide CryoVas survey. Autoimmun Rev. 2014 Jun 1;13(6):630–4.[7] Foessel L, Besancenot JF, Blaison G, Magy-Bertrand N, Jaussaud R, Etienne Y, et al. Clinical Spectrum, Treatment, and Outcome of Patients with Type II Mixed Cryoglobulinemia without Evidence of Hepatitis C Infection. J Rheumatol. 2011 Apr 1;38(4):716–22.[8] Visentini M, Tinelli C, Colantuono S, Monti M, Ludovisi S, Gragnani L, et al. Efficacy of low-dose rituximab for the treatment of mixed cryoglobulinemia vasculitis: Phase II clinical trial and systematic review. Autoimmun Rev. 2015 Oct;14(10):889–96.[9] Colantuono S, Mitrevski M, Yang B, Tola J, Carlesimo M, De Sanctis GM, et al. Efficacy and safety of long-term treatment with low-dose rituximab for relapsing mixed cryoglobulinemia vasculitis. Clin Rheumatol. 2017 Mar 1;36(3):617–23.Acknowledgements:NIL.Disclosure of Interests:Claire POGGI: None declared, Eric Hachulla BOEHRINGER INGELHEIM, GSK, SANOFI,, JANSSEN-CILAG, Bayer HealthCare SAS, GSK, BRISTOL MYERS SQUIBB, IQVIA Operations France, United Therapeutics Corporation, NOVARTIS PHARMA SAS, CHUGAI PHARMA FRANCE, ASTRAZENECA, MSD, JANSSEN-CILAG, Bayer HealthCare SAS, GSK, BRISTOL MYERS SQUIBB,, GENZYME, SANOFI, RE-IMAGINE Health Agency, Otsuka Pharmaceutical France SAS, AXONAL, PFIZER SAS, LIVE! BY GL EVENTS, SHIRE France S.A., Cemka, ROCHE SAS, Galapagos SASU, PATIENTYS, Alexandre Karras Alnylam France SAS, BOEHRINGER INGELHEIM FRANCE, NOVARTIS PHARMA SAS, ASTRAZENECA, Otsuka Pharmaceutical France SAS, LABORATOIRE GLAXOSMITHKLINE, PFIZER SAS, Vertex Pharmaceuticals Incorporated, TRAVERE THERAPEUTICS, INC., Retrophin, Inc, Antoine BRIANTAIS BOEHRINGER INGELHEIM FRANCE,, ROCHE SAS, LABORATOIRE GLAXOSMITHKLINE, Genzyme, Camille Ravaiau: None declared, Pierre GOBERT Alexion Pharma France, MENARINI FRANCE, SANOFI AVENTIS FRANCE, Alban Deroux VIFOR FRANCE, EUSA Pharma (France) SAS, BOEHRINGER INGELHEIM FRANCE, LABORATOIRE GLAXOSMITHKLINE, SANOFI AVENTIS FRANCE, EXELTIS SANTE, Celltrion Healthcare France SAS, SWEDISH ORPHAN BIOVITRUM, Sarah Nicolas HD MEDICAL, MSD FRANCE, Hélène François SANOFI AVENTIS FRANCE,, Matthieu Groh SANOFI AVENTIS FRANCE, LABORATOIRE GLAXOSMITHKLINE, ASTRAZENECA, CSL BEHRING SA, CHUGAI PHARMA FRANCE, BRISTOL-MYERS SQUIBB, Jonathan London AMICUS THERAPEUTICS SAS, CORIN FRANCE, AMICUS THERAPEUTICS SAS, CORIN FRANCE, JANSSEN-CILAG, AbbVie, Julien Campagne SHIRE France S.A., SANOFI AVENTIS FRANCE,, BOEHRINGER INGELHEIM FRANCE,, VIFOR FRANCE SA, SANDOZ, Alnylam France SAS, AMGEN, Jean-Sébastien Allain LEO Pharma, LABORATOIRE GLAXOSMITHKLINE, Emmanuelle Dernis BRISTOL-MYERS SQUIBB, LILLY FRANCE, MSD France, JANSSEN-CILAG, Galapagos SASU, AbbVie, NORDIC PHARMA SAS, UCB Pharma SA, CHUGAI PHARMA FRANCE, FRESENIUS KABI FRANCE, MSD France, BRISTOL-MYERS SQUIBB,, NOVARTIS PHARMA SAS, AMGEN SAS, MEDAC SAS, RE-IMAGINE Health Agency, Cécile-Audrey Durel VIFOR FRANCE, NOVARTIS PHARMA SAS, Genzyme, NOVARTIS PHARMA SAS, Genzyme, Takeda France, SHIRE France S.A., BOEHRINGER INGELHEIM FRANCE, Thomas Le Gallou NOVARTIS PHARMA SAS, LABORATOIRE GLAXOSMITHKLINE, Alexandre Curie PFIZER SAS, LABORATOIRE GLAXOSMITHKLINE, SHIRE France S.A., Philippe Kerschen: None declared, Noémie Gensous Alnylam France SAS, SWEDISH ORPHAN BIOVITRUM, NOVARTIS PHARMA SAS, AMGEN SAS, ASTRAZENECA, AMGEN SAS, Anne-Hélène Reboux: None declared, Hélène Béhal: None declared, Benjamin Terrier VIFOR, ASTRAZENECA, GSK, ASTRAZENECA, LFB BIOMEDICAMENTS, BRISTOL-MYERS SQUIBB, PFIZER SAS, Lilly France SAS, GRIFOLS France, Oséus, Terumo BCT Europe SA, SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT, BOEHRINGER INGELHEIM FRANCE, FRESENIUS KABI FRANCE, SWEDISH ORPHAN BIOVITRUM, BRISTOL-MYERS SQUIBB, NOVARTIS PHARMA SAS, ROCHE SUISSE, JANSSEN-CILAG, MSD France, RE-IMAGINE Health Agency, LFB BIOMEDICAMENTS, Thomas Quéméneur VIFOR, LEO Pharma, ASTRAZENECA, VIFOR, OVERCOME,, VIFOR, SANOFI, GENZYME, GSK.

Background:Rheumatoid arthritis (RA) regularly affects women of childbearing age1. A higher obstetric morbidity in women with RA is suggested in the literature in several countries, but no comparison between patients with RA and women in the general population is available for France.Objectives:The aim of the study was to compare adverse fetal, maternal and pregnancy outcomes in women with RA with matched controls from the French general population.Methods:We conducted a matched comparative study of RA patients included in the GR2 (Groupe de Recherche sur la Grossesse et les Maladies Rares) national multicentre cohort from 2014 to June 2021 and controls from the French general population included in the French national perinatal surveys (Enquête Nationale Périnatale)2. The latter is a national survey carried out for one week every 5 years and recording around 13 000 births. As births before 22 gestational week (GW) and birth weights < 500 grams were excluded from the French national perinatal survey, the same exclusion criteria were applied to women with RA from the GR2 cohort. Each pregnancy in patients with RA was matched to 4 pregnancies in controls on age group (≤ 29, 30-34, 35-39, or ≥ 40 years), parity, area of residence, and gemellity. These matching variables were chosen according to their association with adverse pregnancy outcomes (potential confounders). Births in the GR2 cohort between 2015 and 2018 were matched to births in the 2016 survey and those between 2019 and 2021 were matched to births in the 2021 survey. RStudio’s MatchIt package was used to match RA patients to controls. The frequency of each adverse pregnancy outcome was compared between the two groups using Fisher’s exact test or Chi-2. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated for each variable.Results:Of the 92 patients with RA included in the GR2 cohort, 83 (including one twin pregnancy) were retained after excluding births before 22 GW and/or birth weight < 500 grams. They were matched with 332 control pregnancies from the French national perinatal survey (180 pregnancies from the 2016 survey and 152 from the 2021 survey). The mean age of RA patients was 33.7 (± 5.06) years and 53% were nulliparous. Preterm birth was significantly higher in newborns of RA patients than in newborns of controls (16.9% versus 6.3%, p < 0.01). Among the cases of preterm birth, only one case of extreme prematurity (at 30 GW) and no case of very extreme prematurity were found in the GR2 cohort. However, there was no significant difference for gestational diabetes nor macrosomia (despite the use of corticosteroids at least once during pregnancy in 42.1% of RA patients), gestational hypertension, low birth weight, severe postpartum hemorrhage, maternal or neonatal transfer to intensive care unit or congenital malformation between the two populations (Table 1).Conclusion:This study found an increased risk of preterm delivery in RA patients compared with control women in the French general population, which is consistent with an increased risk observed in other countries. These results raise the need for particular attention to obstetrical follow-up in these patients and providing useful insights for physician-patient dialogue.Table 1. Matched comparative analysis of adverse fetal, maternal and pregnancy outcomes in RA patients (GR2 cohort) and control women of the French general population (2016 and 2021 French national perinatal surveys).REFERENCES:[1] Van den Brandt S. Arthritis Res Ther. 2017;19(1):64.[2] https://enp.inserm.fr/Acknowledgements:The GR2 Cohort is supported by the French Society of Rheumatology, the French Internal Medicine Society, and unrestricted grants from UCB.Disclosure of Interests:None declared.

Background:Spondyloarthritis (SpA) regularly affects women of childbearing age [1]. A higher obstetric morbidity in women with SpA is suggested in the literature in several countries, but no comparison between SpA patients and women in the general population is available for France. Furthermore, there is very few data on fertility in SpA patients.Objectives:The aim of the study was to compare use of medically assisted reproduction and adverse fetal, maternal and pregnancy outcomes in women with SpA with matched controls from the French general population.Methods:We conducted a matched comparative study of SpA patients included in the GR2 (Groupe de Recherche sur la Grossesse et les Maladies Rares) national multicentre cohort from 2014 to June 2021 and controls from the French general population included in the French national perinatal surveys (Enquête Nationale Périnatale) [2]. The latter is a national survey carried out for one week every 5 years and recording around 13 000 births. As births before 22 gestational week (GW) and birth weights < 500 grams were excluded from the French national perinatal survey, the same exclusion criteria were applied to women with SpA from the GR2 cohort. Each pregnancy in patients with SpA was matched to 4 pregnancies in controls on age group (≤ 29, 30-34, 35-39, or ≥ 40 years), parity, area of residence, and gemellity. These matching variables were chosen according to their association with adverse pregnancy outcomes (potential confounders). Births in the GR2 cohort between 2015 and 2018 were matched to births in the 2016 survey and those between 2019 and 2021 were matched to births in the 2021 survey. RStudio’s MatchIt package was used to match SpA patients to controls. The frequency of each adverse pregnancy outcome was compared between the two groups using Fisher’s exact test or Chi-2. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated for each variable.Results:Of the 126 SpA patients included in the GR2 cohort, 116 pregnancies were selected after excluding births before 22 GW and/or birth weight < 500 grams. They were matched with 464 control pregnancies from the French national perinatal survey (224 pregnancies from the 2016 survey and 240 from the 2021 survey). The mean age of SpA patients was 32.0 (+/- 4.1) years and 54.3% were nulliparous. 54.8% of them were treated with biologics during pregnancy. The use of assisted reproductive techniques was higher in women with SpA 12.9% versus 7.1% (OR 1.95 95% CI [1.02-3.76]). However, there was no significant difference between the two populations regarding preterm birth, gestational diabetes, fetal macrosomia, gravidic hypertension, low birth weight, severe postpartum hemorrhage, maternal or fetal transfer to intensive care unit or congenital malformation (Table 1).Conclusion:Women with SpA in the GR2 cohort required assisted reproductive techniques more frequently than control women from the French general population. However, the obstetrical issues were comparable in this selected population of women who were mostly treated with TNF inhibitors during pregnancy. This study therefore provides useful information for improved management of women of childbearing age with spondyloarthritis.Table 1. Matched comparative analysis of use of assisted reproductive techniques and adverse fetal, maternal and pregnancy outcomes in SpA patients (GR2 cohort) and control women of the French general population (2016 and 2021 French national perinatal surveys).REFERENCES:[1] Mokbel A. Clin Rheumatol. 2021 Sep;40(9):3465-3480.[2] https://enp.inserm.fr/Acknowledgements:The GR2 Cohort is supported by the French Society of Rheumatology, the French Internal Medicine Society, and unrestricted grants from UCB.Disclosure of Interests:None declared.

BackgroundThe occurrence of a TMA during SLE is a rare event that complicates 1% to 4% of lupus. The full spectrum of TMA can be encountered in the course of SLE: acquired thrombotic thrombocytopenic purpura (PTT), TMA associated with glomerulonephritis (TMA GN), atypical hemolytic uremic syndrome (aHUS), microangiopathic antiphospholipid syndrome (MAPS; defined or probable catastrophic antiphospholipid syndrome) or HELLP syndrome during pregnancy.ObjectivesTo describe the clinical phenotype of TMA in lupus, to specify the prognosis and to identify factors allowing early classification and management of the different subtypes.MethodsWe performed a French multicentric retrospective study from January 1987 to December 2017 in units of internal medicine, nephrology and ICU. Inclusion criteria associated SLE defined by the ACR and/or SLICC criteria and a TMA defined either by the presence of microangiopathic anaemia and peripheral thrombocytopenia, either by histological signs of TMA.Results68 events of TMA occurred in 60 SLE patients; median age was 24 years; 56 women (F/M ratio: 14). Diagnosis of SLE was assessed at a paediatric age in 24 (35.8%) patients. Clinical manifestations of SLE were: acute cutaneous lupus (n=48, 71%), arthritis (n=36, 53%), pleuritis (n=13, 19%), pericarditis (n=25, 37%), renal involvement (n=39, 57% including 20 class IV glomerulonephritis) and auto-immune cytopenia (n=22, 32%). Triggering factors of TMA were: lupus flare (n=38), infections (n=12), pregnancy and peripartum (n=3), or therapeutic rupture (n=4). Clinical and biological features at diagnosis of each subtypes of TMA are presented in table 1. A platelet count lower than 28 000/mm3 was predictive of TTP diagnosis (Se=90,5%, Sp=88,5%), likewise a creatinine plasma level greater than 100 µmol/L was predictive of TMA GN (Se=88,5%, Sp=85%). The treatment of TMA included (alone or in combination): corticosteroids in all cases, plasma exchange (n=52), cyclophosphamide (n=28), Rituximab (n=15), Eculizumab (n=2), antiplatelet agent (n=36), and/or effective anticoagulation (n=26). The median duration of follow-up was 150 months. Among TMA GN patients, the final median GFR was 58 mL/min (range: 0–120) with 5 individuals on chronic dialysis and 1 kidney transplant. Among TTP patients, one died from TMA, whereas the final median GFR of survivors (n=59) was 97 mL/min (range: 64–150), without any patient requiring dialysis.Table 1 Comparisons of clinical and laboratory data in different subtypes of TMA in SLEConclusionsSLE-associated TMA is a heterogeneous syndrome. TTP with a decreased ADAMTS13 activity and a low platelets level (<28000/mm3) have a good renal prognosis, whereas TMA GN with a high creatinine level (>100 µmol/L) have a poor renal prognosis. Early subtypes classification is mandatory for the clinician to provide prompt and appropriate management of this life-threatening complication.Disclosure of InterestNone declared

BackgroundPrimary Sjogren’s syndrome (pSS) is a chronic inflammatory disorder characterised by diminished lacrimal and salivary gland functions. Joint involvement is reported in 20% to 60% of pSS patients, and among them one third of patients present synovitis. There is a lack of data concerning therapeutic management during pSS-associated synovitis.ObjectivesTo describe the characteristics and the outcome of pSS associated arthritis and to compare the efficacy of different therapeutic regimen.MethodsWe conducted a retrospective study using Club Rhumatisme and Inflammation (CRI) and French Internal Medicine Society (SNFMI) networks. All patients with a diagnosis of primary Sjögren’s Syndrome (pSS) and at least one clinical and/or echographic synovitis were included. Patients with synovitis (cases) were compared to pSS patients without synovitis (controls).Results57 patients (93% women) were included with a median age of 54 years.45–63 Patients with synovitis had more frequently lymph node enlargement (12.3% vs. 1.8%, p=0.007) and a higher ESSDAI score (86–12 vs. 2,1–4 p<0.0001). There was no difference concerning CRP levels, rheumatoid factor and CCP-antibodies positivity. Among 57 patients with synovitis, 101 lines of various treatments have been used during the follow-up of 40 [22.5–77] months. First line treatment consisted in steroids alone (3.5%), steroids in association (79%) with hydroxychloroquine (HCQ) (49%), methotrexate (MTX) (35%), rituximab (RTX) (5.3%) or other immunosuppressive drugs (7%). The number of complete/partial joint responses significantly increased considering the number of overall lines of treatment for MTX, HCQ and RTX: 52% for the first line, 76% for the second line and 83% for the third line (p<0.05), and data were similar considering each drug separately. There was no difference of efficacy between HCQ, MTX, and RTX concerning tender and swollen joint count, CRP level, ESSDAI score and steroids sparing effect at the end of each drug regimen. We performed a propensity score based analysis to determine whether HCQ, MTX, or RTX treatment was associated with better joint outcome. No difference could be shown for the joint response between three treatment regimen (MTX vs. HCQ, OR 1.55 [0.18–13.55], p=0.69; MTX vs. RTX, OR 5.08 [0.49–52.17], p=0.17; HCQ vs. RTX OR 3.28 [0.28–38.02], p=0.34). All 3 treatments (HCQ, MTX, and RTX) were associated with a significant reduction of ESSDAI score and a significant steroids-sparing effect.ConclusionspSS articular manifestations may include synovitis which could mimic rheumatoid arthritis but differ by the absence of structural damage. Even if the use of HCQ, MTX, and RTX seem to be effective for joint involvement, the best regimen remains to be determined.Disclosure of InterestNone declared

To identify patients with autoimmune diseases who are at high risk of developing vascular cell dysfunction, early biomarkers must be identified. This study was designed to detect and characterize circulating autoantibodies to VE-cadherin (AAVEs) in patients with early-stage autoimmune diseases. An enzyme-linked immunosorbent assay (ELISA) was developed to capture autoantibodies, using a recombinant human VE-cadherin fragment covering the extracellular domains as a target antigen. AAVEs specificity for the target antigen was confirmed by western blotting. Basal AAVEs levels were determined for healthy donors ( n =75). Sera from patients ( n =100) with various autoimmune diseases, including rheumatoid arthritis ( n =23), systemic lupus erythematosus (SLE, n =31), systemic sclerosis ( n =30), and Behçet’s disease (BD, n =16) were also tested. Levels of AAVEs were significantly higher in rheumatoid arthritis ( P <0.0001), SLE ( P <0.05), and BD ( P <0.05) populations than in healthy subjects. Purified immunoglobulin G (IgG) from a BD patient with exceptionally high AAVEs levels recognized the EC1-4 fragment in western blots. Further characterization of the epitopes recognized by AAVEs showed that BD patients had antibodies specific for the EC3 and EC4 domains, whereas SLE patients preferentially recognized the EC1 fragment. This suggests that distinct epitopes of human VE-cadherin might be recognized in different immune diseases. Purified IgG from BD patients was found to induce endothelial cell retraction, redistribution of VE-cadherin, and cause the formation of numerous intercellular gaps. Altogether, these data demonstrate a potential pathogenic effect of AAVEs isolated from patients with dysimmune disease. This is the first description of AAVEs in humans. Because regions EC1 and EC3-4 have been shown to be involved in homophilic VE-cadherin interactions, AAVEs produced in the course of dysimmune diseases might be specific biomarkers for endothelial injury, which is part of the early pathogenicity of these diseases.

BackgroundGiant cell arteritis (GCA) is a vasculitis of large and medium sized arteries affecting people older than 50 years. Glucocorticosteroids (GC) are the mainstay of therapy but relapses are common, resulting in prolonged treatment course and adverse events. IL-6 correlates with disease activity of GCA and temporal artery biopsy samples show enhanced IL-6 production. Cases series and open label studies reported the efficacy of tocilizumab (TCZ) on symptoms and inflamamtory markers in GCA.ObjectivesTo report the French experience on the efficacy and safety of TCZ in patients with GCA and the evolution after treatment withdrawal.MethodsA retrospective multicenter study on patients treated with TCZ for their GCA was conducted. Treatment efficacy was evaluated at a clinical and biological level. Side effects and evolution after treatment withdrawal were also recorded.ResultsThirty-four patients (27 women and 7 males) aged 70.5±8.2 (mean±SD) were included. Diagnosis of GCA was based on the ACR criteria (30 patients) and/or on imaging abnormalities suggestive of GCA (8 patients). Giant cell disease was treated by GC and another immunosuppressant was added before TCZ introduction in 20/34 patients. Tocilizumab (8 mg/kg monthly) was introduced after a mean disease evolution of 18 months (0–107). It was efficient in all but 6 patients who still had mild symptoms while CRP was reduced from 40.4 mg/L to 1.5 mg/L (p<0,0001) and GC were tapered from 26.3 to 10.3 mg/day (p<0.0001). One patient died from a septic shock and 3 patients had to stop TCZ for adverse events. Among the 23 patients who stopped treatment (planned medical decision in 20 cases and side effects in 3 cases) eight patients experienced relapses that occurred after a mean of 3.5±1.3 months.ConclusionsTCZ therapy leads to rapid and maintained improvement in patients with refractory GCA. However, side effects should be kept in mind in this population. Questions remain regarding the suspensive nature of this treatment and this should be specifically studied in future studies.Disclosure of InterestNone declared

Background Behçet's disease (BD) is a systemic large vessel vasculitis with recurrent genital and oral ulceration, uveitis, cardio-vascular, joints, neurological or gut symptoms. Treatment of BD is dependent of the nature and the severity of clinical manifestations. Increased levels of TNF alpha and soluble TNF receptors have been found in the serum, plasma and in the aqueous humor of patients with BD. Although, anti-TNF alpha have proved effective in refractory uveitis, few data are available relative to its efficacy in extraocular manifestations of BD. Objectives The aim of this study is to report on the efficacy and the safety of anti-TNF alpha in BD. Methods We performed a retrospective multicenter study of main characteristics and outcomes of 92 patients with BD treated with anti-TNF alpha. Results Ninety two observations were collected in 18 French centers. Mean ± SD age at the anti-TNF alpha introduction was 34±10 years with 55% of men. Seventy nine (79%) patients received at less one immunosuppressive therapy before the use of anti-TNF alpha. The main indications of anti-TNF alpha were uveitis (n=71, 77%), mucocutaneous manifestations (n=14, 15%) [oral (n=13) and genital ulcerations (n=5)], articular (n=12, 13%), neurologic (n=7, 8%), cardio-vascular (n=4, 4%) and digestive manifestations (n=3, 3%). Infliximab was frequently used (60%), followed by adalimumab (35%), etanercept (4%) and golimumab (1%). Associated therapy included prednisolone (82%), azathioprine (30%), mycophenolate mofetil (6%), and methotrexate (5%). Median duration of follow up was 32 months [10-57]. 96% and 92% of BD patients achieved a complete or partial response of uveitis and extraocular manifestations, respectively. Anti-TNF alpha had a significant corticosteroid sparing effect (daily prednisolone dose of 40mg at time of introduction of anti-TNF alpha vs 10mg and 5mg at 6 and 12 months, respectively; p<0,0001). The median time for clinical improvement was 61 days [31-92]. Adverse events were reported in 26% of patients, mainly with infliximab. They included infections (19%), hypersensitivity reactions (2%), injection site reactions (2%), cancers (2%) and lupus (1%). Serious adverse events were reported in 8 patients (of whom 7 with infliximab) and required treatment interruption in all cases. Conclusions These preliminary results show that TNF alpha inhibitors are highly and rapidly efficient in all BD manifestations. Although tolerance seems satisfactory, infliximab is associated with more frequent and more serious side effects. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5903