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Objective:To evaluate the relevance of the blood B-cell subset profile for the diagnosis of Sjögren syndrome.Methods:The distribution of mature blood B cells from Bm1 through Bm5 was determined in 161 patients, of whom 25 fulfilled the American–European Consensus Group criteria for primary SS (pSS), and 136 served as disease controls.Results:The percentage of Bm2 and Bm2′ cells was increased in the patients with pSS compared with 54 patients with rheumatoid arthritis (RA) and 18 with systemic lupus erythematosus (SLE) (p<0.001 for the two comparisons). In contrast, those of early Bm5 (eBm5) and Bm5 were decreased in patients with pSS, compared with patients with RA and with SLE (p<0.001 for the two comparisons). The receiver operating characteristic curves allowed for an optimising cut-off value of Bm2+Bm2′ cells at 71.1% for 88.0% sensitivity and 83.1% specificity, that of eBm5+Bm5 cells at ⩽13.5% for 84.0% sensitivity and 83.1% specificity, and, consequently, that of Bm2+Bm2′/eBm5+Bm5 at ⩾5 for 88.0% sensitivity and 84.6% specificity.Conclusion:Given its presentation as a signature for pSS, relative to RA and SLE, such a distribution of B-cell subsets might provide a useful diagnostic tool.

Background:Osteoarticular reading X-rays can be complex, especially for medical students.Objectives:To evaluate using eye-tracking the strategies adopted by students when analysing radiographs and to examine their correlation with the quality of interpretation and responsiveness to dedicated instruction.Methods:To study the impact of reading methods on multiple-choice questionnaires (MCQs), a group of students (Group A) analysed three radiographs and answered MCQs. To evaluate the impact of a lesson on reading, a second group (Group B) of students was randomly assigned (1:1) to receive or not receive a lesson in radiograph reading before reading and answering the MCQs. Eye-tracking data were recorded using Tobii Pro Lab software during all readings.Results:Fifty-one students in Group A and 40 students in Group B participated. Most students in Group A did not systematically analyse either the bone contour or structure on the radiographs. No correlation was found between MCQ scores and reading time, number of fixation points or number of saccades. Conversely, analysis of vertebral structures (p = 0.03) and bone contours (p= 0.02) was associated with higher scores on MCQs. Students in Group B who received dedicated instruction had more fixation points (p=0.02) and saccades (p =0.01) and analysed more contours (p = 0.04) and structures (p < 0.001) than those who did not. The Figure 1 shows three examples of spine readings by three different students using a gaze plot (A-C) and one example of a pelvic radiograph reading evaluated by a gaze plot (D) and heatmap (E). In Figure 1A, the student looked all the data (vertebral contours, vertebral structure and soft tissues). In Figure 1B, the student showed the abnormality at L3-L4 without considering the other bone structures or soft tissues. In Figure 1C, the student looked at the bone contours and soft tissues but less at the bone structure.Conclusion:This study demonstrated the usefulness of eye-tracking technology for assessing medical students’ ability to analyse standard radiographs and determine the impact of learning methods.Figure 1.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Sjögren’s Syndrome (SjS) is a complex autoimmune disease predominantly affecting the salivary and lacrimal glands, leading to hallmark symptoms such as dry eyes and mouth. Its distinctive clinical manifestations, coupled with symptom overlap with other disorders, make its diagnosis challenging. Traditional diagnostic criteria, as outlined by the American College of Rheumatology (ACR), encompass clinical assessments, including Anti-Ro/SSA antibody levels, focus score, and quantification of dry eye and mouth. Despite their utility, these criteria often suffer from issues of reproducibility and sensitivity. This underscores the pressing need for more advanced and reliable diagnostic techniques in the field.Objectives:In this work we developed a deep learning algorithm that combines clinical data with histopathological images of minor salivary glands in order to predict for Sjögren’s syndrome. By analyzing H&E stained labial gland biopsies using a Convolutional Neural Network (CNN) encoder in conjunction with a Multi-Layer Perceptron (MLP) and the ACR criteria. This strategy aims to improve diagnostic precision above and beyond the capabilities of traditional techniques, providing a notable improvement in the diagnosis and treatment planning of Sjögren’s Syndrome patients.Methods:Data for this study was sourced from the DIApSS (Diagnostic Suspicion of Primitive Sjögren’s Syndrome - Brest Cohort, NCT03681964) observational study. Our dataset comprised 167 patients, 95 confirmed Sjögren’s patients and 72 non-Sjögren’s participants. Patients were split into three groups training: 99 for training, 33 for validation, and 33 for testing. Our pipeline includes a Multi-Layer Perceptron (MLP) and a Convolutional Neural Network (CNN) encoder, implemented using PyTorch. The MLP processes clinical data: gender, xerophthalmia symptoms, Schirmer’s test, and Anti-Ro/SSA (UA/mL) and the CNN encoder, which processes H&E stained labial gland biopsy images. The combined output of both models is then fed into a classification head for prediction.Results:Evaluating the diagnostic precision using the clinical data alongside H&E Whole Slide Images (WSI), we obtained an Area Under the Curve (AUC) of 0.98, Accuracy of 0.86, kappa score 0.69, and a recall of 0.86. Cohen’s kappa score of 0.69 indicates that the model’s predictions show a moderate degree of agreement that goes beyond chance.Conclusion:This study successfully demonstrates the potential of integrating clinical data and histopathological images to obtain significant diagnostic accuracy. This approach paves the way for more reliable and reproducible diagnoses of Sjögren’s Syndrome.In future studies we will focus on refining the trained models and exploring further the analysis of the histopathological images.REFERENCES:NILAcknowledgements:NIL.Disclosure of Interests:None declared.

Background:Reading hand and foot X-rays in rheumatoid arthritis patients is complex, difficult and time-consuming. Indeed, physicians use the modified Sharp van der Heijde Sharp (mvdH) score which is calculated using reading of hand and foot radiographs. The aim of this study was to create a new method of determining the mvdH via eye tracking and to study its concordance with the mvdH score.Objectives:The aim of this study was to create a new method of determining the mvdH via eye tracking and to study its concordance with the mvdH score.Methods:We created a new method of quantifying the mvdH score based on reading time (two seconds = one Sharp score point) of a reader monitored via eye tracking (Tobii Pro Lab software) after training with the aid of a metronome. Radiographs were read twice by the trained eye-tracking reader and once by an experienced reference radiologist. Concordance between two eye-tracking readings (intraclass) and between the eye-tracking reading and the reference (interclass) was assessed.Results:A total of 440 radiographs were selected; 416 were interpreted for erosive involvement, and 396 were interpreted for joint space narrowing when read by eye tracking (eye tracking could not measure the time spent when two pathological joints were too close together). The intraclass agreement with the eye-tracking reading method was excellent (0.9; 95% CI: 0.88-0.92) for erosions and narrowings. Interclass agreement with the reference reading was also excellent for erosions (0.89; 95% CI: 0.87-0.91) and narrowings (0.89; 95% CI: 0.87-0.92).Figure 1 shows X-rays of hands for narrowing. Eye-tracking readings of two patients with Sharp scores and eye-tracking scores (E-T) in milliseconds. A-B: Patient with a high Sharp score. C-D: Patient with a low Sharp score.Conclusion:Eye-tracking reading is strongly correlated with classical mvdH-Sharp. The heatmaps allow segmentation of hand and foot joints in rheumatoid arthritis patients.Figure 1.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

polymyalgia rheumatica (PMR) is a chronic inflammatory disorder affecting elderly people. Glucocorticoids (GC) are the mainstay of therapy for PMR. Despite this treatment, the disease may relapse or GC dosage cannot be tapered. Methotrexate (MTX) may be helpful in these cases. Blockade of IL-6 has an effective steroid-sparing effect in patients with giant cell arteritis (GCA) and may improve the clinical symptoms of patients with PMR. The pathophysiology of PMR still remains uncertain but there are evidences for a participation of Th1 and Th17 lymphocytes. Recently, blockade of the costimulatory pathway by abatacept (ABA) gave favorable results in GCA. to report our experience (efficacy and safety) of ABA in the treatment of patients with isolated PMR who required longstanding GC and who failed to respond to MTX and/or IL-6 receptor blocking agents. a call for observations of all cases of patient with PMR who received at least one dose (SC or IV) of ABA was sent to the members of the French specialist network “Club Rhumatismes & Inflammation” (CRI: www.cri-net.com)(rheumatologist and internal medicine). Patients must satisfy the EULAR/ACR criteria for PMR and have isolated PMR without associated GCA. 4 cases were declared during a 12 months period: 2 men and 2 women; age (median [range]): 60.7 [50-68] years; disease duration 30 [7-48] months; duration of GC treatment before starting ABA: 60 [10-72] months. They all required prednisolone with a daily dosage of 14.5 mg [10-20]. Before ABA administration, they all received MTX while 2 patients were treated by IL-6R inhibitor (tocilizumab 6 months and sarilumab 3 months, respectively) without improvement. ABA was given as a monthly infusion (10 mg/kg) in one case and subcutaneously (every week) in 3 cases. ABA treatment duration ranged from 3 to 18 months. Two patients responded to the treatment with a progressive decline of DAS-PMR and GC dosage tapering during a 12 month follow-up, while there was no improvement for the 2 others (Table 1). CRP levels also decreased for one responder. The safety was excellent for all. ABA was still maintained in one responder. Among the non-responders, one patient was switched to tocilizumab and the second still received high GC dosage. ABA may be effective in certain PMR patients who were unable to taper GC, with a good safety profile. A randomized controlled trial is required in order to determine its place in the treatment of PMR and to select the appropriate patients who could potentially benefit from this biological agent. [1]Langford CA et al. Vasculitis Clinical Research Consortium. A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Giant Cell Arteritis. Arthritis Rheumatol. 2017; 69: 837-845 None declared Table 1changes in DAS-PMR and CRP levels in 4 patients with PMR while receiving abatacept (M: months; CRP in mg/L).CasesDAS- PMR M0DAS- PMR M3DAS-PMR M6DAS -PMR M12CRP M0CRP M3CRP M6CRP M121202121NA58.68.4NA231.130.5NANA2125NANA310.78.3551337.222.722224182217.2121.23.33.53

Background:The epidemiological and immunopathogenic association between Sjögren disease (SD) and non-Hodgkin’s lymphoma (NHL) is well-established. However, the epidemiological data on this complication mostly relies on data from tertiary centers, introducing selection bias and limiting comprehensive case capture.Objectives:This study aimed to evaluate accurately the characteristics of lymphoma in primary or associated SD using data from the French nationwide healthcare information system (“système national des données de santé” [SNDS]).Methods:SD patients were identified in the SNDS database based on a validated algorithm [1] (ICD10 code for SD and reimbursement for at least 2 SD-prescribed drugs). Primary SD was defined in the absence of an ICD10 code for other autoimmune diseases, and associated SD was defined otherwise. The study analyzed, primary, associated and all SD patients and lymphoma occurrences between 2009 and 2022. Analysis of risk factors of lymphoma included demographic variables such as age, sex, disease duration, and proxy reflecting disease activity including notably cryoglobulinemic vasculitis and monoclonal gammopathy of unknown significance (MGUS).Results:Patients with primary SD In the 30,221 patients with primary SD (65.7% of the total cohort of patients with SD; 88.8% women, median age 60 [48;70], median follow-up 11.6 years [9.4;13.2]; hydroxychloroquine use in 35.1%, methotrexate [11.5%], leflunomide [1.2%], azathioprine [4.4%], mycophenolate [3.1%], cyclophosphamide [0.4%], and rituximab [5.5%]), lymphoma occurred in 1228 patients with a prevalence of 4.1%. Marginal zone lymphomas (MZL) were the predominant lymphoma subtype (53.8%) (especially MALT-MZL [30.9%]) followed by diffuse large B-cell lymphoma (DLBCL) (25.4%), follicular lymphoma (FL) (12.1%), Hodgkin’s lymphoma (8.2%), and T/NK lymphoma (7.2%). Mortality was higher in patients with lymphoma (379/1228 [30.9%] versus 4335/28993 [15%], p<0.001). Preliminary risk factor analysis revealed associations with MGUS and cryoglobulinemic vasculitis: MGUS was observed in 3.2% of SD patients without lymphoma, compared to 10.8% in those with lymphoma (p < 0.001), and cryoglobulinemic vasculitis occurred in 2.2% of SD patients without lymphoma, as compared with 10% of patients with lymphoma (p < 0.001).Patients with associated SD In the 15,791 patients with associated SD (34.3% of the total cohort, including rheumatoid arthritis [20.4%], systemic lupus [10%], systemic sclerosis [6.2%], other connective tissue disorders [3.2%], and juvenile arthritis [0.3%]), 483 patients developed lymphoma (3.1%).Total SD cohort In the total SD cohort, including 46,012 patients with either primary or associated SD (89.4% women, median age 59 [47;69], median follow-up 11.8 years [9.5;13.2]), lymphoma occurred in 1749 patients, with a 3.8% prevalence. Lymphoma subtypes were distributed similarly to the primary SD cohort, and associations between lymphoma and MGUS and cryoglobulinemic vasculitis were observed. Mortality was higher in patients with lymphoma compared to those without lymphoma (30.9% versus 14.8% [p < 0.001]).Conclusion:This extensive epidemiological nationwide study demonstrates a 4% prevalence of lymphoma in primary SD, and 3% prevalence in associated SD. Preliminary risk factor analysis confirms the association between SD-related lymphoma and MGUS and cryoglobulinemic vasculitis.REFERENCES:[1] Seror et al. (2024 in press) Development of an Algorithm to Identify Sjögren’s Syndrome Patients in the French National Healthcare Claims Database. RMD Open.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Sjögren disease (SjD) is the autoimmune disease with the highest risk of lymphoma. The most common histology is marginal zone (MZ) lymphoma particularly the mucosa-associated lymphoid tissue (MALT) lymphoma. There is a continuum between autoimmunity and lymphoma, and disease activity is a major risk factor for lymphoma development. Managing lymphoma complicating SjD remains non-consensual with different options: wait and watch, local or systemic therapy.Objectives:To describe characteristics of non-Hodgkin lymphoma in Sjögren disease (SjD), therapeutic strategies, and the impact of these strategies on the prognosis of lymphoma and SjD.Methods:This multicentric retrospective study included all lymphoma patients of the ASSESS prospective cohort, enriched with patients recruited in 15 French Rheumatology and Internal Medicine departments. We collected biological and clinical manifestations of SjD, lymphoma characteristics, and treatment strategy. Exploratory analysis identified factors associated with lymphoma relapse, SjD relapse and overall survival (OS). Propensity scores were created using key clinical variables to compare patients depending on treatment strategy. Three outcomes were analyzed: lymphoma progression-free survival (Lymphoma-PFS), Sjögren Disease progression-free survival (SjD-PFS), and OS.Results:One hundred and six patients were included. The most frequent histological subtype was MZ lymphoma (82 patients) including 68 MALT, followed by 14 diffuse large B cell lymphoma.Among the 82 patients with MZ lymphoma, after multivariate adjustment on age, localization, Bendamustine use, Ann arbor stage and calendar year at lymphoma diagnosis, older age and pulmonary involvement were negatively associated with overall survival (HR 1.15 CI 95% [1.05-1.26] and HR 6.40 CI 95% [1.10-37.1]). We did not find individual factors associated with lymphoma or SjD-PFS. Fifty (61%) MZ patients received systemic treatment with chemotherapy and/or rituximab. These patients had more frequently pulmonary lymphoma locations (24% vs 3.1%, p = 0.012) and tended to have higher SjD disease activity at lymphoma diagnosis. After a median follow-up of 7 years, 26 patients (32%) experienced lymphoma relapse, 9 (11%) died, and 27 (33%) experienced SjD relapse. After propensity score adjustment, patients treated with first line systemic treatments for lymphoma, displayed a longer SjD progression-free survival (PFS) (HR=0.43 [95% CI 0.21-0.90], p = 0.026) than patients without systemic treatment (including watch and wait strategy or local treatment alone). There was no difference in lymphoma relapse nor overall survival. Patients treated with first-line combo-therapy (anti-CD20 and chemotherapy) had a longer lymphoma-PFS than patients with first-line monotherapy (anti-CD20 or chemotherapy): HR 0.36 [95% CI 0.14-0.96], p = 0.041. There was no difference in SjD-PFS or overall survival between the two groups. Of note, none of the patients with anti-CD20 maintenance therapy relapsed (0% vs 36%, log-rank p = 0.04)Conclusion:In patients with SjD and MZ lymphoma, older age and pulmonary involvement were negatively associated with OS. Systemic first-line treatment of lymphoma reduced the risk of SjD relapse suggesting that in case of indecisiveness between treatment and watch and wait attitude, activity of SjD beyond lymphoma is a strong argument in favor of a systemic treatment. A combination of B-cell targeted therapy and chemotherapy may be considered for decreasing the risk of lymphoma relapse.Figure 1.A) Probability of Sjögren progression free survival according to systemic treatment vs no systemic treatment at lymphoma diagnosis, after propensity score adjustment. B) Probability of Lymphoma-PFS according to combotherapy vs monotherapy, after propensity score adjustment.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Maxime Beydon: None declared, Juliette Rocca: None declared, Véronique Le Guern: None declared, Eric Hachulla: None declared, Marion Couderc: None declared, Sandrine Jousse-Joulin: None declared, Valerie Devauchelle-Pensec: None declared, Jacques-Eric Gottenberg Abbvie, Astra Zeneca, Sanofi, Lilly, Galapagos, Gilead, Roche Chugai, Pfizer, Bristol Myer Squib, MSD, Pfizer, Abbvie, Lilly, Olivier Vittecoq: None declared, Christian Lavigne: None declared, Jean Schmidt: None declared, Claire Larroche: None declared, Xavier Mariette Astra Zeneca, Bristol Myer Squib, Galapagos, GSK, Novartis and Pfizer, Raphaèle Seror GSK, Bristol Myer Squib, Boerhinger and Janssen, Gaetane Nocturne: None declared.

BackgroundPolymyalgia rheumatica (PMR) is an inflammatory disease. But it’s pathophysiology and the impact of the treatments on immune cells are poorly known.ObjectivesOur objectives were to describe the immune cells of patients with PMR dependent from glucocorticoids and to analyze their evolution under tocilizumab.MethodsThe SEMAPHORE trial (NCT02908217, (1)) was a randomized control trial including patients with PMR dependent from glucocorticoids. Between inclusion and week 12, patients were blindly treated with either tocilizumab infusion or placebo infusion every 4 weeks associated to a tapering of glucocorticoids. Age and sex-matched healthy controls (HC) were recruited in the rheumatology department of the Brest University Hospital. HC did not have any history or presence of cancer, auto-immune disease or active infection and did not received treatment with a known impact on the immune system. We analyzed immune cells on whole fresh blood after red cell lysis on flow cytometry (Navios, Cytoflex, Beckmann Coulter) after staining for CD16, CD56, CD19, CD14, CD4, CD8, CD3, CD45, IgD, IgM, CD21, CD27, CD24, CD38, CD5 CD126, CD62L, CD45RA, CD127, CD25, in four different panels.ResultsSamples were obtained for 40 PMR patients and 34 HC. At inclusion, in PMR patients, compared to HC, CD14+CD16- classical monocytes were increased (82±1% vs 77±2%, p=0.01), CD14-CD16+ non-classical monocytes were decreased (4±0.3% vs 7±0.6%, p<0.0001), granulocytes were increased (63±2% vs 52±2%, p<0.0001), natural killer cells were decreased (8±1% vs 13±1%, p=0.007). B cells were decreased (8±0.6% vs 10±0.8%, p=0.03), but with an enrichment in CD27-IgD- senescent B cells (p<0.0001) and in CD21low B cells (p=0.04). T cells were increased (70±2% vs 64±2%, p=0.02) with an enrichment in CD4+ T cells (p=0.02) and in CD4+CD25highCD127- regulatory T cells (p<0.0001). At week 12, in PMR patients receiving tocilizumab therapy, compared to PMR patients receiving placebo, granulocytes were lower (58±5% vs 73±2%, p=0.006) and monocytes were higher (8±1% vs 5±0.5%, p=0.02).ConclusionIn patients with a PMR dependent from glucocorticoids, immune cells homeostasis is disturbed. Tocilizumab has an impact more pronounced on granulocytes and monocytes. Knowledge about immune disturbance in PMR might help to choose to use a targeted therapy when glucocorticoids are not sufficient.Reference[1]Devauchelle-Pensec V, Carvajal-Alegria G, Dernis E, Richez C, Truchetet ME, Wendling D, et al. Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial. JAMA. 20 sept 2022;328(11):1053‑62.Acknowledgements:NIL.Disclosure of InterestsGuillermo CARVAJAL ALEGRIA Speakers bureau: Abbvie, Lilly, Novartis, Chugai, Biogen, BMS, Galapagos, Pfizer, Consultant of: Abbvie, Lilly, Novartis, Galapagos, Pfizer, Sara Boukhlal: None declared, Sophie Hillion: None declared, Pierre Pochard: None declared, Emmanuelle Porchet: None declared, Alain Saraux Speakers bureau: Chugai, Consultant of: Chugai, Grant/research support from: Chugai, Sandrine Jousse-Joulin Speakers bureau: Chugai, Consultant of: Chugai, Grant/research support from: Chugai, THIERRY MARHADOUR: None declared, Dewi Guellec: None declared, Divi Cornec Speakers bureau: Chugai, Consultant of: Chugai, Grant/research support from: Chugai, Valerie Devauchelle-Pensec Speakers bureau: Chugai, Consultant of: Chugai, Grant/research support from: Chugai.

BackgroundThe diagnosis of primary Sjögren Disease (SjD) is currently based on a combination of clinical, histological and biological findings [1]. Current thinking supports anti-Ro60 antibodies as the most specific serum marker, while the impact of anti-Ro52 remains unclear [2].ObjectivesThe aim of this study was to characterize the clinical, serological, biological, transcriptomic and interferon profiles of SjD patients according to their anti-Ro52 status and discuss the role of anti-Ro52 in the prognosis of SjD.MethodsSjD patients were recruited from the European PRECISESADS (378 patients) [3] and the independant Brittany DIApSS cohorts (160 patients) [4]. Four groups were defined: double negative (Ro52-/Ro60-), isolated anti-Ro52 positive (Ro52+), isolated anti-Ro60 positive (Ro60+), and double positive (Ro52+/Ro60+) patients. Clinical information, disease activity, and biological markers linked to disease severity were evaluated. Transcriptome data on whole blood by RNAseq and Type I and type II interferon signatures [5,6] were analyzed for PRECISESADS SjD patients.ResultsIn both cohorts, arthritis, parotidomegaly, and biological markers (hypergammaglobulinemia, rheumatoid factor and inflammation) [7] were significantly more frequent in the double positive group as compared to other groups. ESSDAI, a score representing systemic activity [8], was also significantly higher in double positive patients compared to the others. Transcriptome analysis demonstrated that anti-Ro52 positivity was associated with a strong interferon pathway activation as the lead cause to explain the clinical associations.ConclusionTaken together, these results suggest that SjD patients with anti-Ro52 positivity adopt a more severe phenotype as compared to their negative counterparts, independently of anti-Ro60 positivity.References[1]Brito-Zerón P, Baldini C, Bootsma H, Bowman SJ, Jonsson R, Mariette X, et al. Sjögren syndrome. Nat Rev Dis Primer. 2016 Jul 7;2(1):1–20.[2]Decker P, Moulinet T, Pontille F, Cravat M, De Carvalho Bittencourt M, Jaussaud R. An updated review of anti-Ro52 (TRIM21) antibodies impact in connective tissue diseases clinical management. Autoimmun Rev. 2022 Mar;21(3):103013.[3]Soret P, Le Dantec C, Desvaux E, Foulquier N, Chassagnol B, Hubert S, et al. A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome. Nat Commun. 2021 Jun 10;12(1):3523.[4]Cornec D, Jousse-Joulin S, Pers JO, Marhadour T, Cochener B, Boisramé-Gastrin S, et al. Contribution of salivary gland ultrasonography to the diagnosis of Sjögren’s syndrome: toward new diagnostic criteria? Arthritis Rheum. 2013 Jan;65(1):216–25.[5]Kirou KA, Lee C, George S, Louca K, Papagiannis IG, Peterson MGE, et al. Coordinate overexpression of interferon-alpha-induced genes in systemic lupus erythematosus. Arthritis Rheum. 2004 Dec;50(12):3958–67.[6]Chiche L, Jourde-Chiche N, Whalen E, Presnell S, Gersuk V, Dang K, et al. Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures. Arthritis Rheumatol Hoboken NJ. 2014 Jun;66(6):1583–95.[7]Baldini C, Pepe P, Quartuccio L, Priori R, Bartoloni E, Alunno A, et al. Primary Sjögren’s syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients. Rheumatology. 2014 May 1;53(5):839–44.[8]Brito-Zerón P, Kostov B, Solans R, Fraile G, Suárez-Cuervo C, Casanovas A, et al. Systemic activity and mortality in primary Sjögren syndrome: predicting survival using the EULAR-SS Disease Activity Index (ESSDAI) in 1045 patients. Ann Rheum Dis. 2016 Feb;75(2):348–55.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

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.