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La maladie de Sjögren est une maladie systémique hétérogène, touchant principalement les femmes. Les symptômes principaux incluent des symptômes subjectifs, dont la sécheresse buccale ou oculaire, de la fatigue et des douleurs articulaires, impactant considérablement la qualité de vie. De plus, des manifestations systémiques surviennent chez environ 30 à 50 % des patients et peuvent toucher tous les organes. Récemment, trois phénotypes distincts de patients ont été décrits à partir d'une analyse en clusters : 1/ biologiquement actifs avec peu de symptômes (BALS) ; 2/ forte activité systémique (HSA) ; 3/ symptomatiques avec faible activité systémique (LSAHS). Nous avons cherché à évaluer si ces clusters étaient associés à des biomarqueurs distincts et à la valeur pronostique de la signature IFN. La cohorte ASSESS est une cohorte prospective de 20 ans de patients atteints de SjD. Les biomarqueurs suivants ont été comparés : IFN-a2, IFN-b, CXCL10, CXCL13, BAFF, IL7, CCL19 et TNF-RII. La signature IFN a été évaluée par analyse transcriptomique. Nous avons ensuite comparé l'évolution systémique et symptomatique, ainsi que le risque de nouvelle prescription d'immunosuppresseurs et de lymphome, en fonction de la signature IFN dans les trois clusters. Trois cent quatre-vingt-quinze patients (94 % de femmes, âge médian 53 [43–63] ans) ont été inclus. Des niveaux plus élevés de CXCL-13, IL7 et TNF-RII ont été observés dans les clusters BALS et HSA par rapport au cluster LSAHS. Une signature IFN élevée a été principalement retrouvée dans le cluster BALS (57 % contre 48 % et 38 % dans les clusters HSA et LSAHS, respectivement). Cette signature IFN était principalement due à l'IFN de type I, avec des niveaux plus élevés d'IFN-a2. Dans le cluster BALS, une signature IFN élevée était associée à un risque accru de traitement immunosuppresseur (HR 9,38 ; IC 95 % 1,22–72,16) (Fig. 1). Tous les lymphomes du cluster BALS sont survenus chez des patients avec une signature IFN élevée (Fig. 2). Notre étude a démontré que notre stratification, définie par les symptômes, les signes cliniques systémiques et les données biologiques de routine, repose sur différents mécanismes physiopathologiques, en particulier l'activation des lymphocytes B et T et la voie de l'interféron alpha. L'activation de la voie interféron pourrait aider à prédire l'évolution du cluster BALS, un cluster biologique mais peu symptomatique, pour envisager une surveillance plus étroite et/ou des traitements précoces afin de prévenir les complications. Ces résultats plaident également pour une meilleure stratification des essais thérapeutiques et contribuent à la compréhension de l'hétérogénéité des patients atteints de maladie de Sjögren. [ABSTRACT FROM AUTHOR]

Background: The PEXIVAS (Plasma exchange and glucocorticoids in severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis) trial showed that a reduced-dose glucocorticoid regimen (redGC) was non-inferior to a standard-dose regimen (standGC) with respect to death or end-stage kidney disease (ESKD) in patients with ANCA-associated vasculitis (AAV). However, the primary endpoint did not include disease progression or relapse, cyclophosphamide was the main induction therapy and rituximab (RTX)-treated patients tended to have a higher risk of death or ESKD with redGC. We aimed to evaluate the real-world use of redGC., Methods: We conducted a retrospective, multicentre study comparing PEXIVAS redGC with standGC in patients with AAV. The primary composite outcome was the occurrence of death, ESKD, AAV progression before remission or relapse within the 12 months following induction. Inverse probability of treatment weighting was used to correct for baseline imbalance between groups. Factors associated with the occurrence of the primary outcome were estimated., Results: A total of 234 patients were included. The primary composite outcome occurred in 42/126 (33%) patients with redGC versus 20/108 (19%) with standGC. In unweighted multivariable analysis and in weighted analysis, redGC was independently associated with the primary outcome but not with death or ESKD. Among redGC-treated patients, those with serum creatinine>300 µmol/L were more likely to achieve the primary outcome. RTX-treated patients who received redGC were more likely to experience death or ESKD and to achieve the primary outcome., Conclusion: In this study of patients with AAV primarily treated with RTX, redGC was associated with an increased risk of the primary outcome consisting of death, ESKD, AAV progression before remission or relapse., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objective: Many negative randomized controlled trials (RCTs) report spin in their conclusions to highlight the benefits of the experimental arm, which could correspond to a non-inferiority (NI) objective. We aimed to evaluate whether some negative superiority RCTs comparing two active interventions could correspond to an NI situation and to explore associated trial characteristics., Study Design and Setting: We searched PubMed for superiority RCTs comparing two active interventions with non-statistically significant results for the primary outcome that were published in 2021 in the 5 journals with the highest impact factor in each medical specialty. Three reviewers independently evaluated whether trials could correspond to an NI situation (i.e., an evaluation of efficacy as the primary outcome, with the experimental intervention presenting advantages including better safety profile, ease of administration, or decreased cost as compared with the control intervention)., Results: Of the 147 trials included, 19 (12.9%, 95% CI [7.9%, 19.4%]) corresponded to a potential NI situation, and as compared with trials not in a potential NI situation, they were published in a journal with a lower impact factor (median impact factor 8.7 vs 15.6), were more frequently rated at high or some concerns regarding risk of bias (n=14, 73.7% vs. n=69, 53.9%) and reported spin in the article conclusions (n=11, 57.9% vs. n=24, 18.8%)., Conclusion: A non-negligible proportion of superiority negative trials comparing two active interventions could correspond to an NI situation. These trials seemed at increased risk of bias and frequently reported spin in the conclusions, which may distort the interpretation of results., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Target trial emulation is an approach that is increasingly used to improve transparency in observational studies and help mitigate biases. For studies declaring that they emulated a target trial, we aimed to evaluate the specification of the target trial, examine its consistency with the observational emulation and assess the risk of bias in the observational analysis., Design: Methodological systematic review reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement., Data Sources: The database MEDLINE (Medical Literature Analysis and Retrieval System Online) was interrogated for all studies published from 1 January 2021 to 3 July 2022. We performed an additional manual search of 20 general medical and specialised journals that spanned the same period., Eligibility Criteria: All studies that declared emulating a hypothetical or real randomised trial were eligible., Data Extraction and Synthesis: Two independent reviewers performed the whole systematic review process (screening and selection of studies, data extraction and risk of bias assessment). The main outcomes were the definition of the key protocol components of the target trial and its emulation, consistency between the target trial and its emulation and risk of bias according to the ROBINS-I (Risk Of Bias In Non-randomised Studies - of Interventions) tool., Results: Among the selected sample of 100 studies, 24 (24%) did not specify the target trial. Only 40 studies (40%) provided detailed information on all components of the target trial protocol. Eligibility criteria, intervention strategies and outcomes were consistent between the target trial and its emulation in 35 studies (46% of those specifying the target trial). Overall, 28 studies (28%) exhibited serious risk of bias and 41 (41%) had misalignments in the timing of eligibility assessment, treatment assignment and the start of follow-up (time-zero). As compared with studies that did not specify the target trial, those that did specify the trial less frequently seemed to have both time-zero issues (39% vs 52%) and serious risk of bias (26% vs 33%)., Conclusions: One-quarter of studies declaring that they emulated a target trial did not specify the trial. Target trials and their emulations were particularly inconsistent for studies emulating a real randomised trial. Risk of methodological issues seemed lower in observational analyses that specified versus did not specify the target trial., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare that they have no competing interest related to the study. GLM declares consulting fees from Synapse Medicine, unrelated to the study., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sjögren's disease is the autoimmune disease with the highest risk of lymphoma development. There is no consensus on the optimal way to manage Sjögren's disease complicated by lymphoma. We aimed to describe characteristics, therapeutic strategies, and outcomes of non-Hodgkin lymphoma associated with Sjögren's disease, and their effect on lymphoma and Sjögren's disease prognoses., Methods: We did a multicentre, retrospective, observational study including patients with Sjögren's disease according to the 2016 American College of Rheumatology-European League Against Rheumatism criteria who did not fulfil diagnostic criteria for other connective tissue diseases. We included patients with a lymphoma diagnosis made before Jan 1, 2020, from two expert centres in Paris (France); from the French, multicentre, prospective Assessment of Systemic Signs and Evolution of Sjögren's Syndrome cohort; and via practitioners registered with the Club Rhumatismes et Inflammation. Using inverse probability of treatment weighting, the effect of lymphoma treatment was compared in relation to three endpoints: lymphoma progression-free survival, new Sjögren's disease systemic activity, and overall survival. Exploratory analyses also aimed to identify factors associated with lymphoma relapse, new Sjögren's disease systemic activity, and overall survival. People with lived experience were not involved in this research., Findings: 106 patients with Sjögren's disease who developed lymphoma were included in the study. The most frequent histological subtype was mucosa-associated lymphoid tissue lymphoma (68 [64%] of 106 patients), followed by other marginal zone subtypes (14 [13%] of 106 patients) and diffuse large B-cell lymphoma (14 [13%] of 106 patients). Among the 82 patients with marginal zone lymphoma (72 [88%] women and ten (12%) men; mean age at lymphoma diagnosis 57·5 years [SD 14·8]), multivariable analysis showed that pulmonary localisation was associated with mortality (hazard ratio [HR] 7·92 [95% CI 1·70-37·0]). A watch and wait approach was proposed in 19 (23%) of 82 patients with marginal zone lymphoma, 13 (16%) had first-line localised treatment (surgery or radiotherapy), and 50 (61%) had first-line systemic treatment. After a median follow-up of 7 years, 26 patients (32%) had lymphoma relapse, nine (11%) died, and 27 (33%) had new Sjögren's disease systemic activity. After inverse probability of treatment weighting, patients with systemic treatment at lymphoma diagnosis had a reduced risk of new Sjögren's disease activity (HR 0·43 [95% CI 0·21-0·90]). When comparing patients treated with a combination of chemotherapy and anti-CD20 therapy (n=32) with patients treated with monotherapy (n=18) as a first-line therapy for lymphoma, lymphoma-progression-free survival was improved in patients treated with combination therapy (HR 0·36 [95% CI 0·14-0·94]). The were no differences in new Sjögren's disease systemic activity or overall survival according to combination therapy or monotherapy., Interpretation: A systemic treatment strategy for Sjögren's disease-associated lymphoma, rather than localised treatment or a watch and wait strategy, reduces the risk of new Sjögren's disease systemic activity and combination therapy is associated with decreased risk of lymphoma relapse., Funding: None., Competing Interests: Declaration of interests VLG received consulting fees from Novartis; honoraria from Novartis and Bristol Myers Squibb; and travel fees from AstraZeneca and Novartis. MC received honoraria from Lilly and travel fees from Novartis, Janssen, UCB, and Pfizer. XM received consulting fees from AstraZeneca, Bristol Myers Squibb, Galapagos, GSK, Novartis, and Pfizer. RS received consulting fees from GSK, Bristol Myers Squibb, Boehringer, and Janssen; honoraria from GSK, Bristol Myers Squibb, Boehringer, Amgen, Pfizer, and Roche; and travel fees from Amgen and GSK. GN received honoraria from Novartis, Boehringer, AbbVie, and Galapagos SASU and travel fees from Amgen, AbbVie, and UCB. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: Sjögren's disease (SjD) is a heterogenous disease with a wide range of manifestations, ranging from symptoms of dryness, fatigue, and pain, to systemic involvement. Considerable advances have been made to evaluate systemic activity or patient-reported outcomes, but most of the instruments were not able to assess all domains of this multifaceted disease. The aim of this scoping review was to generate domains that have been assessed in randomized controlled trials, as the first phase of the Outcome Measures in Rheumatology (OMERACT) process of core domain set development., Methods: We systematically searched Medline (Pubmed) and EMBASE between 2002 and March 2023 to identify all randomized controlled trials assessing relevant domains, using both a manual approach and an artificial intelligence software (BIBOT) that applies natural language processing to automatically identify relevant abstracts. Domains were mapped to core areas, as suggested by the OMERACT 2.1 Filter., Results: Among the 5,420 references, we included 60 randomized controlled trials, focusing either on overall disease manifestations (53%) or on a single organ/symptom: dry eyes (17%), xerostomia (15%), fatigue (12%), or pulmonary function (3%). The most frequently assessed domains were perceived dryness (52% for overall dryness), fatigue (57%), pain (52%), systemic disease activity (45%), lacrimal gland function (47%) and salivary function (55%), B-cell activation (60%), and health-related quality of life (40%)., Conclusion: Our scoping review highlighted the heterogeneity of SjD, in the study designs and domains. This will inform the OMERACT SjD working group to select the most appropriate core domains to be used in SjD clinical trials and to guide the future agenda for outcome measure research in SjD., Competing Interests: Declaration of competing interest Yann Nguyen, Maxime Beydon, Nathan Foulquier, Rachael Gordon, Coralie Bouillot, and Katherine M. Hammit declared no competing interest. Simon Bowman reports receiving funds for consulting from Bristol-Myers Squibb, Iqvia, Janssen, Kiniksa, Novartis, Otsuka-Visterra. His-salary is part funded by the NIHR Birmingham Biomedical Research centre, Birmingham, UK. Xavier Mariette received consulting fees from Astra-Zeneca, Bristol Myer Squib, Galapagos, GSK, Novartis and Pfizer; travel fees from Novartis. Sara McCoy received consulting fees from BMS, Novartis, Otuska/Visterra, Horizon, Target RWE, Horizon, and Kiniksa. Her time is supported by the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant 1KL2TR002374 and NIH/NIDCR R03DE031340. Divi Cornec declares no personal financial competing interests and received research funding from Novartis and GSK. Raphaele Seror reports receiving funds for consulting to Bristol-Myers Squibb, Novartis, GSK, Janssen, Amgen, and Boehringher; honoria from Bristol-Myers Squibb, Boehringher, GSK, and travel fees from Amgen and GSK., (Copyright © 2024. Published by Elsevier Inc.)

Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity., Competing Interests: Declaration of competing interest Valerie Devauchelle reports receinving funds for consulting to Novartis, Abbvie, Fresenius Kabi. Divi Cornec declares no personal financial competing interests and received research funding from Novartis and GSK. Benjamin A. Fisher has undertaken consultancy for Novartis, BMS, Servier, Galapagos, Roche, UCB, Sanofi and Janssen, and received grant/research support from Janssen, Celgene, Galapagos, Servier. Alberta Hoi reports receiving research funding from AstraZeneca, Bristol-Myers Squibb, Novartis, Janssen. Chiara Baldini reports receiving funds for consulting to GSK, Novartis and Horizon, honoraria for educational events from GSK and Sanofi, support for attending meetings from Abbvie and Bristol-Myers Squibb. WF Ng has consulted for Novartis, GlaxoSmithKline, Abbvie, BMS, Sanofi, MedImmune, Resolves Therapeutics, Janssen and UCB. Simon Bowman receiving funds for consulting from Bristol-Myers Squibb, Iqvia, Janssen, Kiniksa, Novartis, Otsuka-Visterra. His-salary is part funded by the Birmingham Biomedical Research Centre, Birmingham, UK. Karina Torralba reports receiving funds for consulting to Horizon, AstraZeneca, Janssen; for contracted research work with Bioclinica; for clinical trial funding from Novartis, AstraZeneca, GlaxoSmithKline, Amgen. Athena Papas declares grant funding from Novartis and Horizon; advisory board for Novartis. Ionut Pintilie reports receiving funds for consulting to Abbvie, Novartis, Pfizer, Sandoz, Ewopharma, KRKA, Stada, Boehringer Ingelheim, MagnaPharm, MSD. Xavier Mariette declares consulting fee from Astra Zeneca, BMS, Galapagos, GSK, Novartis, and Pfizer. Maria Antonietta D'Agostino, MD, PhD Speakers, or consultant fees from Amgen, Abbvie, BMS, Novartis, Galapagos, UCB, Pfizer, Lily, Janssen. Alan Baer reports receiving funds for consulting to Bristol-Myers Squibb and iCell Gene Therapeutics. Blake M. Warner declares research funding and material transfer agreements with Pfizer, Inc., and Mitobridge, Inc. Soumya D. Chakravarty is an employee of Janssen Scientific Affairs, LLC, and owns stock or stock options in Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly owned subsidiary. Nevsun Inanc reports claims to have received speakers fee from Novartis, Abbvie, Pfizer, UCB, Eli-Lilly and consultancy fee from Abbvie, UCB, Eli-Lilly. Vibeke Strand reports being a founding member of the executive committee of Outcome Measures in Rheumatology (OMERACT) [1992 – present], an international consensus organization that develops and validates outcome measures in rheumatology randomized controlled trials and longitudinal observational studies and has received arms-length funding from as many as 36 sponsors. Md Yuzaiful Md Yusof has received speaker fees from Roche and Novartis and consultancy fees from Aurinia Pharmaceuticals and UCB. Suzanne Arends declares consultancy fees from Argenx and Novartis. Anas Alexis Benyoussef is a consultant for Horus Pharma and Quantel Medical. Sharmila Masli is a consultant for Stellular Bio Inc. and Proteris Biotech. Maureen Rischmueller has undertaken consultancy/speaker engagements for AbbVie, Boehringer Ingelheim, Janssen Global Services, Novartis, Pfizer and Sandoz, and received grant/research support from AbbVie, Amgen, AstraZeneca, BMS, GSK, Janssen, Lilly, Novartis, Pfizer, Servier and UCB. Sara McCoy reports receiving funds for consulting to Bristol-Myers Squibb, Horizon, Novartis, Kiniksa, Targe RWE, Otsuka, Visterra, and iCell. Her time is supported by the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant 1KL2TR002374 and NIH/NIDCR R03DE031340. Raphaele Seror reports receiving funds for consulting to Bristol-Myers Squibb, Novartis, GSK, Janssen, Amgen. Hendrika Bootsma declares consultancy fees from Argenx, Novartis, BMS, AztraZeneca, Galapagos.Independent grants from AstraZeneca, Novartis, BMS., (Copyright © 2024. Published by Elsevier Inc.)

Sjögren syndrome is a phenotypically varied autoimmune disorder that can occur alone in primary Sjögren syndrome or in association with other connective tissue diseases (CTDs), including rheumatoid arthritis, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). The estimation of the prevalence and incidence of Sjögren syndrome varies depending on diagnostic criteria and study design, making it difficult to estimate geographical and temporal trends. Nonetheless, disease phenotype is influenced by geographical origin, which is a risk factor for systemic activity. Whether mortality in primary Sjögren syndrome is increased compared with that of the general population is not yet known, but extra-glandular manifestations, in particular lymphomas, are clear risk factors for mortality. In CTDs associated with Sjögren syndrome, lymphoma risk seems higher than that of patients with CTD alone, and there is potentially lower disease activity in SLE with Sjögren syndrome and in SSc with Sjögren syndrome than in SLE or SSc alone., (© 2023. Springer Nature Limited.)

Objectives: To estimate prevalence, incidence and mortality rates, and annual healthcare costs of primary Sjögren's syndrome (pSS) and SS associated with other autoimmune disorders (SS+AID) in France., Methods: French national healthcare claims-based study within the prospective Système National des Données de Santé database that includes the majority of the French population. An algorithm was developed to identify patients with SS and SS-related healthcare claims were analysed between 2011 and 2018., Results: Overall, 23 848 patients with pSS and 14 809 with SS+AID were identified. From 2011 to 2018, the prevalence rate increased slightly for pSS (23-32 per 100000) and SS+AID (16-20 per 100 000), with females comprising 90%-91% and 92%-93% of cases, respectively. The incidence rate of SS per 100 000 persons decreased from 2012 (pSS: 4.3; SS+AID: 2.0) to 2017 (pSS: 0.7; SS+AID: 0.3). Mortality rates per 100 000 persons increased from 2012 to 2018 in patients with pSS (0.2-0.8) or SS+AID (0.1-0.5); mean age of death also increased. Artificial tears and hydroxychloroquine were the most common drug reimbursements. Less than half of patients received annual specialist care from a dentist or ophthalmologist. Healthcare costs associated with SS increased from 2011 to 2018 and exceeded the national estimate of expected costs for chronic diseases., Conclusion: In this large French population database study, the low prevalence of pSS confirms that it is an orphan disease. SS is clinically and economically burdensome; these findings may help clinicians better understand routine healthcare received by patients., Competing Interests: Competing interests: RS is a consultant for Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius Kabi, GlaxoSmithKline, Janssen, Pfizer and Roche. LC is a consultant for Bristol Myers Squibb. GD is a consultant for Bristol Myers Squibb and a consultant with no fees for Roche. JZ and VV-M are employees of and shareholders in Bristol Myers Squibb. VD-P is a consultant for AbbVie, Bristol Myers Squibb and Novartis, and has received grant/research support from Bristol Myers Squibb, Eli Lilly and Roche-Chugai. MB declares no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Older studies uncovered an increased risk of cancer in patients with rheumatoid arthritis between 10% and 30% compared to the general population, with a lack of data concerning infrequent cancers. In recent year, major therapeutic breakthroughs might have affected this risk of cancer by mitigating disease activity or on the contrary by impairing antitumoral immune response. The objectives of this study are to compare cancer risk in patients with treated rheumatoid arthritis to the general population, in all treated patients and according to treatment exposure., Methods: This is a nationwide population-based study within the French national claims database "Système National des Données de Santé" (SNDS) between January 1st 2010 and December 31st 2020, to estimate the age and sex-standardized incidence ratios of cancer (all sites and site specific) of treated rheumatoid arthritis patients, with the French population as reference (by use of the French Network of Population-Based Cancer Registries [FRANCIM])., Findings: During the study period, 257,074 treated patients with rheumatoid arthritis contributed to a total of 2,098,238 person-years for the main analysis. The all-cancer risk was increased in rheumatoid arthritis patients, with a SIR (Standardized Incidence Ratio) of 1.20 (95% CI [1.17-1.23]). This risk was increased particularly for lung (SIR 1.41, 95% CI [1.36-1.46], bladder (SIR 2.38 95% CI [2.25-2.51]), cervix (SIR 1.80, 95% CI [1.62-2.01]), prostate (SIR 1.08, 95% CI [1.04, 1.13]) cancers, melanoma (SIR 1.37, 95% CI [1.29-1.46]), diffuse large B cell lymphoma (SIR 1.79, 95% CI [1.63-1.96], multiple myeloma (SIR 1.42, 95% CI [1.27-1.60]) and Hodgkin's lymphoma (SIR 2.73, 95% CI [2.31-3.23]). Some cancers were less frequent than in the general population such as pancreatic (SIR 0.90, 95% CI [0.83-0.97]) as well as breast and endometrial cancers (SIR 0.91, 95% CI [0.88-0.94] and SIR 0.77, 95% CI [0.71-0.84] respectively). Although we observed a modest but significant relative increase of all-cancer risk over-time in rheumatoid arthritis patients, there was a trend towards a decrease in risk of non-Hodgkin's lymphoma. Patients treated with rituximab were the patients displaying the highest risk of cancer., Interpretation: Compared to the general population, treated rheumatoid arthritis patients were at greater risk of all-cancer and some site specific cancers, except for breast, pancreatic and endometrial cancers which were less frequent than in the general population., Funding: This work was supported by unrestricted grants from the InCA (national institute against cancer) and AP-HP (Assistance Publique des Hôpitaux de Paris)., Competing Interests: XM received fees from Astra-Zeneca, BMS, Galapagos, GSK, Novartis, Pfizer; RS received consulting fees from GSK, Bristol Myer Squib, Boerhinger, Amgen, Pfizer and Janssen; travel fees from Amgen and GSK; BF received research grants from AbbVie, Pfizer, Lilly, MSD, and consulting fees from AbbVie, Amgen, Biogen, BMS, Celltrion, Chugai, Fresenius Kabi, Galapagos, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, OWKIN, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Viatris and support for meetings/travel from Lilly; FT redistributed to her hospital consulting fees from MSD and Novartis., (© 2023 The Authors. Published by Elsevier Ltd.)

Objectives: We aimed to compare disease characteristics between primary Sjögren's syndrome (pSS) patients of African ancestry (AA) and Caucasian ancestry., Methods: We conducted a retrospective, case-control study in a French national and European referral centre for pSS. All patients with pSS of AA were matched with two Caucasians patients having similar follow-up duration. We explored clinical and biological parameters associated with a cumulative EULAR Sjögren's Syndrome Disease Activity Index (cumESSDAI ≥5) (consisting of individual clinESSDAI domain maximum throughout follow-up)., Results: We identified 74 patients of AA matched with 148 Caucasian. Median age at pSS diagnosis was younger in AA patients (43 years (IQR 33-51) vs 56 years (44.8-59.2), p<0.001). AA patients presented higher median titre of gammaglobulins (18.5 g/L (IQR 15-22.8) vs 13.4 g/L (9.9-16.9), p<0.001), more frequently positive for anti-SSA (88% vs 72%, p=0.007) and anti-RNP (11% vs 2.7%, p=0.023) antibodies. During the follow-up (median: 6 years (IQR 2-11)), AA patients presented more systemic complications: arthritis, myositis, interstitial lung disease, lymphadenopathy, central nervous system involvement. Median cumESSDAI score was higher in AA patients (7.5 (IQR 3.2-16.0) vs 4.0 (IQR 2.0-9.0), p=0.002). Interestingly, in multivariate analyses, factors associated with disease activity were sub-Saharan AA (OR 2.65 (95% CI 1.06 to 6.94)), rheumatoid factor (OR 2.50 (95% CI 1.28 to 4.96)) and anti-RNP positivity (OR 11.1 (95% CI 1.88 to 212))., Conclusion: Patients of AA display higher disease activity with a hallmark of higher B-cell activation. Studies to investigate biological drivers behind such differences are needed., Competing Interests: Competing interests: RS: consulting fees from GSK, BMS, Boerhinger, Jansen; payment or Honoria from GSK, BMS, Fresenius Kabi, Boerhinger, Jansen, Amgen, Pfizer, Roche; support for meeting attendance or travel from Amgen, GSK, astra Zeneca. VLG: consulting fees from Novartis; payment or Honoria from Brystel-Myers-Squibb; support for meeting attendance or travail Astra Zeneca. GN: consulting fees from Biogen, Pfizer, Novartis, Lilly and Amgen; participating in Advisory board for Boehringer Ingelheim; support for meeting attendance or travel Amgen. XM: consulting fees from Astra Zeneca, BMS, Galapagos, GSK, Novartis, Pfizer., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

IFNα and anti-IFNα autoantibodies have been implicated in susceptibility both for systemic lupus erythematosus (SLE) and viral infection. We aimed to analyze the SLE disease phenotype and risk for infection associated with anti-IFN-α IgG autoantibodies in SLE patients In this multidisciplinary retrospective single referral center study, all consecutive patients with SLE admitted between January 1st and November 30th 2020 were considered. All subjects fulfilled the ACR/EULAR 2019 criteria for SLE. Anti-IFNα IgG autoantibodies were quantified at admission by ELISA. Demographic, medical history, laboratory, treatment, and outcome data were extracted from electronic medical records using a standardized data collection form. 180 patients [female 87.2%, median age of 44.4 (34-54.2) years] were included. The median disease duration was 10 years [4-20] with a median SLEDAI score of 2 [0-4] at study time. Fifty-four (30%) patients had a past-history of lupus nephritis. One hundred and forty-four (80%) had received long-term glucocorticoids and 99 (55%) immunosuppressive drugs. Overall, 127 infections-mostly bacterial and viral-were reported in 95 (52.8%) patients. Twenty SLE patients (11.1%) had positive anti-IFNα IgG autoantibodies with a titer ranging from 10 to 103 UA/mL. Age, sex, SLE phenotype and treatment did not significantly differ between SLE patients with or without anti-IFNα. Infection rate was similar in both groups except for tuberculosis which was more frequent in patients with anti-IFNα (20% vs. 3.1%, p = 0.01). The prevalence of autoantibodies against IFNα is high in SLE and associated with a higher frequency of tuberculosis., (© 2022. The Author(s).)

Objectives: Coxiella and Bartonella spp. display particular tropism for endothelial or endocardial tissues and an abnormal host response to infections with induced autoimmunity. We aimed, through a case series combined with a comprehensive literature review, to outline characteristics of Coxiella and Bartonella infections presenting as systemic vasculitis., Methods: We retrospectively included cases of definite Coxiella and Bartonella infections presenting with vasculitis features and performed a comprehensive literature review., Results: Six cases of Bartonella infections were added to 18 cases from literature review. Causative pathogens were mainly B. henselae. Bartonella infection mimicked ANCA-associated vasculitis in 83% with PR3-ANCA and presented as cryoglobulinaemic vasculitis in 8%. GN was present in 92%, and 88% had endocarditis. Complement fractions were low in 82% and rheumatoid factor positive in 85%. Kidney biopsies showed cell proliferation, mostly crescentic, with pauci-immune GN in 29%. Outcome was favourable, with the use of antibiotics alone in one-third. Five cases of Coxiella infections were added to 16 from literature review. Sixteen had small-vessel vasculitides, mainly cryoglobulinaemia vasculitis in 75%. One patient had polyarteritis nodosa-like vasculitis and four large-vessel vasculitis. Outcome was good except for one death. A highly sensitive next generation sequencing analysis on three Coxiella- and two Bartonella-related vasculitides biopsies did not find any bacterial DNA., Conclusion: Coxiella and Bartonella are both able to induce vasculitis but display distinct vasculitis features. Bartonella mimics PR3-ANCA-associated vasculitis in the setting of endocarditis, whereas Coxiella may induce vasculitis involving all vessel sizes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Microbial HTS has been implemented at Rhône-Poulenc Rorer through the development of a dedicated robotic platform. This robot (Turbo) has been designed with the aim of fully integrating microbial HTS into the lead discovery processes. Innovative solutions have been found to reach high throughput as well as flexibility. This opens up new prospects for solid-phase microbial screening, taking advantage of the easy implementation and the very low costs of such screens. The different types of microbial screens done in our laboratory, as well as the throughputs and outputs obtained, are described. Some of the specific aspects of microbial HTS, as compared to biochemical and cell-based assays, are also discussed.