Introduction:The identification of prognostic factors for renal failure in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) remains a challenge. The benefit of plasma exchange (PLEX) has been questioned, and the target population remains to be defined. We investigated the outcome of patients requiring renal replacement therapy (RRT) at baseline and factors associated with their prognosis at 1 year. Methods:This retrospective multicenter study evaluated the 1-year composite end point of death or end-stage kidney disease (ESKD) in patients with biopsy-proven renal AAV involvement. Results:Of the 394 patients included, 105 (26.6%) were on dialysis at baseline. Of these, 60 (57.1%) reached the composite end point compared with 29 patients (10.0%) who were not on RRT at baseline (P < 0.001). On multivariate analysis, age and sex were not associated with the composite outcome (P = 0.945 and P = 0.154, respectively); however, myeloperoxidase (MPO)-ANCA was (odds ratio [OR]: 3.60; 95% confidence interval [CI]: 1.79-7.60), as was a high baseline histologic renal risk score (OR: 1.29; 95% CI 1.17-1.44). The most strongly associated factor remained the need for dialysis at baseline (OR: 10.91; 95% CI: 5.52-22.70). Of the 91 patients surviving after requiring dialysis at baseline, 45 were weaned from RRT (49.5%) at 1 year, and PLEX was independently associated with a reduced risk of the composite outcome (OR: 0.23, 95% CI: 0.05-0.80). Conclusion:MPO-ANCA, need for dialysis, and high histological renal risk score at baseline were associated with the 1-year composite end point of death or ESKD. Almost half of the patients on dialysis at baseline were off dialysis at 1 year, with a better prognosis in those who had received PLEX.

BACKGROUND:Prospective data on pregnancies in systemic sclerosis are scarce. We aimed to examine the frequency of adverse pregnancy outcomes and maternal disease progression in systemic sclerosis, as well as the factors that predict these events. METHODS:In this analysis, we studied pregnant women with systemic sclerosis (American College of Rheumatology-European League Against Rheumatism 2013 classification) or with Very Early Diagnosis of Systemic Sclerosis (VEDOSS criteria) included in the GR2 French prospective study. Frequency of composite adverse pregnancy outcomes (preterm birth at 34 weeks or less, placental insufficiency complications, small for gestational age, or fetal or neonatal death) and maternal disease course were the primary objectives. The secondary objectives were to assess other complications related to pregnancy (including delivery outcomes and postpartum complications) and compare these results with outcomes for age-matched controls from the French perinatal survey (ENP) 2016 (ie, general population), and to identify predictive factors associated with composite adverse pregnancy outcomes and maternal disease course using univariate analysis. FINDINGS:Between May 1, 2014, and Dec 27, 2020, we included 58 pregnancies (in 52 women), with 53 (91·4%) resulting in livebirths. Of the 53 ongoing pregnancies beyond 22 weeks of gestation, 14 (26·4%) had a composite adverse pregnancy outcome, including two (3·8%) preterm deliveries at 34 weeks of gestation or less, 12 (22·6%) placental insufficiency complications (pre-eclampsia or fetal growth restriction), and six (11·3%) small for gestational age. Among the 53 pregnancies, six (11·3%) severe postpartum haemorrhage events occurred. When compared with the 2016 ENP survey results, pre-eclampsia (seven [13·2%] of 53 vs 16 [3·0%] of 530, p=0·0010, preterm birth before 37 weeks of gestation (seven [13·2%] of 53 vs 31 [5·8%] of 530, p=0·047), birthweight of less than 2500 g (11 [21·1%] of 52 vs 23 [4·3%] of 530, p<0·0001), and severe postpartum haemorrhage (six [11·3%] of 53 vs seven [1·4%] of 516, p=0·0001) were more frequent than in the general population. No factors were significantly associated with the composite adverse pregnancy outcome in univariate analysis. Systemic sclerosis or VEDOSS worsened in 23 (39·7%) of 58 pregnancies, mainly during the postpartum period. In the univariate analysis, diffuse cutaneous systemic sclerosis (odds ratio 3·7 [95% CI 1·1-12·4]) and previous cutaneous vascular involvement (3·7 [1·2-11·5]) were associated with maternal disease progression, whereas the presence of anticentromere antibodies was inversely associated with stable disease (0·2 [0·1-0·8]). INTERPRETATION:Despite 53 (91·4%) of 58 livebirths, systemic sclerosis pregnancies were associated with higher rates of adverse pregnancy outcomes and severe postpartum haemorrhage. Disease worsened in 23 (39·7%) of 58 pregnancies, particularly during the postpartum period, especially in women with diffuse cutaneous systemic sclerosis, previous cutaneous vascular involvement, and antibodies other than anticentromere. FUNDING:Lupus France, Association des Sclérodermiques de France, Association Gougerot Sjögren, Association Francophone Contre la Polychondrite Chronique Atrophiante, AFM-Telethon, Société Nationale Française de Médecine Interne, Société Française de Rhumatologie, Cochin Hospital, French Health Ministry, Fondation for Research in Rheumatology, Association Prix Véronique Roualet, Union Chimique Belge.

OBJECTIVES:In this large multicentre study, we aimed to compare the effectiveness of intravenous infliximab (IFX) vs subcutaneous adalimumab (ADA) in patients with Takayasu arteritis (TAK). METHODS:We conducted a retrospective multicentre study across referral centres in France, Italy, Spain, Armenia, Israel, Japan, Tunisia, and Russia, analysing biologic targeted therapies in TAK from January 2017 to September 2019. RESULTS:A total of 135 TAK patients who received ADA (n = 34) or IFX (n = 101) for at least 3 months were included. Baseline demographics, TAK characteristics and concurrent treatments were comparable, except for a higher rate of Numano type V in the ADA group. At 6 months, 71% achieved complete response (NIH <2 with <7.5 mg/day prednisone), including 68% on ADA and 73% on IFX (P = 0.8). The factors associated with complete response to TNF-α inhibitors at 6 months in univariate analysis were age <30 years, tobacco use, vascular signs at the biologic initiation, NIH ≥2, CRP >20 mg/l, a starting dose >20 mg/day of prednisone, but not the use of either IFX or ADA. The cumulative incidence of treatment failure was not significantly different between IFX and ADA patients. During the median [IQR] follow-up of 23 [17, 42] and 48 [25, 99] months in patients who received i.v. IFX and s.c. ADA, respectively, the risk of relapse at 12 months was 10.9% [0, 21.9] and 16.8% [8.64, 24.27], respectively. The overall incidence of revascularizations was not significantly different. CONCLUSION:In this study, we confirm that IFX and ADA are both effective in TAK, without significant differences in the risk of relapse and revascularizations.

Objective To investigate the concordance between organ involvement at diagnosis and relapse in granulomatosis with polyangiitis and factors associated with new disease features at relapse.Methods Data from a national database of newly diagnosed patients was analysed. Clinical features were recorded at diagnosis and relapse, grouped by organ system. ORs and HRs were used to assess associations between baseline features and first relapse. Factors independently associated with new organ involvement at relapse were identified using multivariable logistic regression.Results Among 795 patients (median follow-up 3.5 years), 394 (50%) relapsed; organ involvement at relapse was available for 376 patients. Relapses most often affected ear, nose and throat (ENT), lungs and kidneys. Organ involvement at diagnosis was associated with a higher likelihood of relapse in the same organ: eyes (OR 6.69), lungs (OR 3.35), kidneys (OR 3.58), nervous system (OR 2.90), and mucocutaneous (OR 4.53). Major manifestations associated with a higher likelihood of recurrence were scleritis, pachymeningitis, subglottic stenosis and worsening renal function. For 56% of patients, the first relapse affected only the initially involved organs. Of the 165 patients with new organ manifestations, these were rarely isolated (n=34) and usually occurred alongside involvement of at least one previously affected organ (n=131). In multivariable analysis, systemic, ENT and lung manifestations at diagnosis were associated with a lower risk of new organ disease at relapse.Conclusion Although new features can still emerge, organ involvement at diagnosis is associated with a higher likelihood of relapse in the same organ.

Glandular involvement of the head and neck is an extremely rare feature in ANCA-associated vasculitis (AAV). The objective was to describe glandular involvement in AAV by analysing data from a national cohort and comparing the findings to those from a systematic literature review. A multicentric retrospective study was conducted through a survey promoted by the French Vasculitis Study Group and included patients aged ≥ 16 years who met the ACR/EULAR classification criteria for AAV and had lachrymal and/or salivary involvement. Demographic, clinical and biological findings were analysed and pooled with data from a MEDLINE review of the literature since inception until June 5, 2024. The study population included 20 patients with a median age of 52 years (IQR, 44.5–57.5 years). Granulomatosis with polyangiitis (n = 17) and PR3-ANCA (n = 10) were the most represented. Parotitis (n = 9) and dacryoadenitis (n = 8) were found to precede and/or were present at AAV onset and recurrences. All patients received glucocorticoids, usually in combination with immunosuppressants. The systematic review identified another 67 cases. Pooled analysis of all cases (n = 87) showed that salivary gland involvement was not only frequently associated with ENT features (OR = 4.01 (95

ObjectiveTo compare the long-term efficacy and safety of azathioprine (AZA), 18-month fixed-schedule rituximab (RTX), 18-month tailored RTX and 36-month RTX in preventing relapses in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who achieved a complete remission after induction therapy. Patients treated with 36-month RTX received either a fixed or a tailored regimen for the first 18 months and a fixed regimen for the last 18 months (36-month fixed/fixed RTX and 36-month tailored/fixed RTX, respectively).MethodsThe Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis (MAINRITSAN) trials sequentially compared: 18-month fixed-schedule RTX versus AZA (MAINRITSAN); 18-month fixed-schedule RTX versus 18-month tailored-RTX (MAINRITSAN2); and extended therapy to 36 months with four additional RTX infusions after MAINRITSAN2 versus placebo (MAINRITSAN3). Patients were then followed prospectively through month 84 and their data were pooled to analyse relapses and adverse events. The primary endpoint was relapse-free survival at month 84.Results277 patients were enrolled and divided in 5 groups: AZA (n=58), 18-month fixed-schedule RTX (n=97), 18-month tailored-RTX (n=40), 36-month tailored/fixed RTX (n=42), 36-month fixed/fixed RTX (n=41). After adjustment for prognostic factors, 18-month fixed-schedule RTX was superior to AZA in preventing major relapses at month 84 (HR 0.38, 95% CI 0.20 to 0.71). The 18-month tailored-RTX regimen was associated with an increased risk of major relapse compared with fixed-schedule regimen (HR 2.92, 95% CI 1.43 to 5.96). The risk of major relapse was similar between 36-month fixed/fixed and 18-month fixed-RTX (HR 0.69, 95% CI 0.38 to 1.25).ConclusionsAccording to these results, it appears that the 84-month remission rate is higher with an 18-month fixed RTX regimen compared with AZA and 18-month tailored RTX. Also, extending RTX to 36 months does not appear to reduce the long-term relapse rate compared with the 18-month fixed RTX regimen. However, as this study was underpowered to make this comparison, further prospective studies are needed to determine the potential long-term benefits of extending treatment in these patients.

Warm autoimmune hemolytic anemia (wAIHA) is a rare acquired autoimmune disease mediated by antibodies targeting red blood cells. The involvement of CD4 T-helper cells has been scarcely explored, with most findings extrapolated from animal models. Here, we performed quantification of both effector T lymphocytes (Teff) and regulatory T cells (Treg), associated with functional and transcriptomic analyses of Treg in human wAIHA. We observed a shift of Teff toward a Th17 polarization concordant with an increase in serum interleukin-17 concentration that correlates with red blood cell destruction parameters, namely lactate dehydrogenase and bilirubin levels. A decrease in circulating Treg, notably effector Treg, associated with a functional deficiency, as represented by their decrease capability to inhibit Teff proliferation, were also observed. Treg deficiency was associated with a reduced expression of Foxp3, the master transcription factor known to maintain the Treg phenotype stability and suppressive functions. Transcriptomic profiling of Treg revealed activation of the tumor necrosis facto (TNF)-α pathway, which was linked to increased serum TNF-α concentrations that were twice as high as in controls. Treg transcriptomic profiling also suggested that post-translational mechanisms possibly accounted for Foxp3 downregulation and Treg dysfunctions. Since TNF-α participates in the rupture of immune tolerance during wAIHA, its inhibition could be of interest. To this end, the effects of fostamatinib, a SYK inhibitor, were investigated in vitro, and we showed that besides the inhibition of erythrocyte phagocytosis by monocytes, fostamatinib is also able to dampen TNF-α production, thus appearing as a promising multitargeting therapy in wAIHA (clinicaltrials gov. Identifier: NCT02158195).

Introduction Les vascularites systémiques sont un groupe de maladies extrêmement hétérogènes dans leurs présentations. Les atteintes glandulaires qui leur sont associées sont peu décrites mais peuvent constituer un mode d’entrée dans la maladie. Les objectifs de notre étude étaient de décrire (i) les caractéristiques clinicobiologiques et (ii) leur évolution sous traitement. Patients et méthodes Il s’agit d’une étude rétrospective reposant sur un appel national à observations. Les patients de plus de 18 ans ayant un diagnostic de vascularite systémique répondant aux critères de classification, avec ou sans documentation histologique, mais associée à une manifestation glandulaire (lacrymale–salivaire–pancréatique) étaient inclus. L’élimination des autres causes d’atteinte glandulaire (lithiasique, néoplasique) était nécessaire. Les données démographiques, clinicobiologiques et l’évolution de la vascularite ont été analysées. Résultats Notre étude a inclus 19 patients, majoritairement des femmes (12 : 7), d’âge médian au diagnostic de 51 ans (IQR 41–57,5). La durée médiane de suivi était de 54 mois (IQR, 31–104 ; n=14). La granulomatose avec polyangéite (GPA) était la vascularite la plus fréquente (n=15), suivie de deux cas de GEPA, un cas d’artérite à cellules géantes et un cas de vascularite cryoglobulinémique.L’atteinte glandulaire était le plus souvent contemporaine du diagnostic (14/19) se répartissant en atteintes parotidiennes (n=7), des glandes sub-mandibulaires (n=4), des glandes lacrymales (n=8) et des pancréatites aiguës (n=2). La présentation clinique était plus fréquemment bilatérale (n=11/18) qu’unilatérale. Au moment du diagnostic, les patients présentaient des signes généraux (n=11), des manifestations ORL (n=15), des signes musculosquelettiques (n=9) et pulmonaires (n=10). Les atteintes cutanées ou rénales étaient plus rares (n=5). Le score BVAS médian était estimé à 14 (IQR, 10,25–22,75, n=16). Les marqueurs biologiques de l’inflammation étaient élevés avec une CRP médiane à 81mg/L (IQR, 20–154, n=14). Les ANCA-PR3 étaient positifs dans 9 cas, et la positivité ANCA-MPO a été décrite dans 3 cas.L’ensemble des patients recevait une corticothérapie systémique, en association avec un traitement immunosuppresseur, le plus souvent le rituximab (n=11) ou du cyclophosphamide (n=4). L’atteinte glandulaire était régressive sous corticothérapie. À la date des dernières nouvelles, 16/19 patients étaient en rémission de leur vascularite. 3 patients ont rechuté de leur maladie accompagnée d’une rechute de l’atteinte glandulaire. Ces dernières s’étaient manifestées par une récidive de la symptomatologique initiale. Aucun décès ni transformation néoplasique n’ont été constatés. Discussion Cette étude rétrospective française basée sur un appel national à observations a permis d’identifier 19 patients ayant présenté une atteinte glandulaire associée à une diagnostic de vascularite systémique. Sous réserve du biais induit par la méthodologie de l’étude, la prédominance de vascularites à ANCA est à souligner (17/19 patients). Il semblerait donc que ces atteintes soient spécifiques des vascularites à ANCA.Par ailleurs, il semble que les atteintes rénales soient relativement peu fréquentes chez les patients inclus. Cette donnée est également retrouvée dans le travail d’Akiyama [1], reprenant les données de la littérature sur les atteintes salivaires au cours des vascularites à ANCA. Ainsi, il serait intéressant de comparer les caractéristiques cliniques et les évolutions de patients présentant ou non une atteinte glandulaire, notamment au cours des vascularites à ANCA, pour identifier certaines associations cliniques ou encore un pronostic particulier. Un travail de type étude cas–témoin est prévu en ce sens. Conclusion Les atteintes glandulaires sont des atteintes rares et peu décrites des vascularites systémiques. Néanmoins, de plus en plus de publications rapportent des atteintes des glandes salivaires, pancréatiques ou encore lacrymales au cours des vascularites [2], [3].Dans cette cohorte, l’atteinte glandulaire est une manifestation semblant spécifique des vascularites associées aux ANCA, et en particulier de la granulomatose avec polyangéite, avec une prédilection pour la sphère ORL et lacrymale. Son évolution semble suivre celle de la vascularite systémique avec une bonne réponse à la corticothérapie. Enfin, elle peut annoncer la rechute de la maladie.Les atteintes glandulaires sont peu fréquentes et pourraient justifier leur inclusion dans les données regroupées dans les registres de maladies vasculaires systémiques.

OBJECTIVES:To measure the association between SLE remission and scores of patients-reported outcome (PRO) measures. METHODS:We performed a prospective cohort study of SLE patients with a 2-year follow-up, using Lupus Patient-Reported Outcome (LupusPRO), Lupus Quality of Life (LupusQoL), Systemic Lupus Erythematosus Quality of Life (SLEQOL) and 36-item Short Form (SF-36) questionnaires. Remission was defined as remission off treatment (ROFT) and remission on treatment (RONT) according to the definitions of remission in SLE consensus. Mixed models accounting for repeated measures were used to compare groups as follow: ROFT and RONT vs no remission and lupus low disease activity state (LLDAS) vs no LLDAS. RESULTS:A total of 1478 medical visits and 2547 PRO questionnaires were collected during the follow-up from the 336 recruited patients. A between-group difference in PRO scores reaching at least 5 points on a 0-100 scale was obtained in the following domains: lupus symptoms (LLDAS: +5 points on the 0-100 scale, RONT: +9, ROFT: +5), lupus medication (LLDAS: +5, RONT: +8, ROFT: +9), pain vitality (LLDAS: +6, RONT: +9, ROFT: +6) of LupusPRO; role emotional (LLDAS: +5, RONT: +8), role physical (RONT: +7 and ROFT: +7), bodily pain (RONT: +6), mental health (RONT: +5) and social functioning (RONT: +6) of SF-36. In contrast, a between-group difference reaching at least 5 points was not achieved for any of the LupusQoL and SLEQOL domains. CONCLUSIONS:RONT, ROFT and LLDAS were associated with significant and clinically relevant higher QoL in most PRO domains of the LupusPRO (disease specific) and SF-36 (generic) questionnaires, but not with LupusQoL and SLEQOL disease-specific questionnaires.

Primary antiphospholipid syndrome is characterized by thrombosis and autoantibodies directed against phospholipids or associated proteins. The genetic etiology of PAPS remains unknown. We enrolled 21 patients with thromboembolic events associated to lupus anticoagulant, anticardiolipin and anti β2 glycoprotein1 autoantibodies. We performed whole exome sequencing and a systematic variant-based analysis in genes associated with thrombosis, in candidate genes previously associated with APS or inborn errors of immunity. Data were compared to public databases and to a control cohort of 873 non-autoimmune patients. Variants were identified following a state-of-the-art pipeline. Enrichment analysis was performed by comparing with the control cohort. We found an absence of significant HLA bias and genetic heterogeneity in these patients, including when testing combinations of rare variants in genes encoding for proteins involved in thrombosis and of variants in genes linked with inborn errors of immunity. These results provide evidence of genetic heterogeneity in PAPS, even in a homogenous series of triple positive patients. At the individual scale, a combination of variants may participate to the breakdown of B cell tolerance and to the vessel damage.

Peu d’études ont évalué l’ouverture buccale (OB) dans la sclérodermie systémique (ScS). Aucune n’a étudié les trajectoires des OB. L’objectif de l’étude rapportée ici était de caractériser les trajectoires d’OB dans la ScS et d’évaluer l’OB en tant que facteur pronostic dans la ScS. Nous avons réalisé une étude multicentrique rétrospective des patients inclus dans la cohorte nationale Française de ScS ayant au moins une mesure d’OB. Nous avons décrit les caractéristiques à l’inclusion des patients selon leur mesure d’OB à l’inclusion, modélisé les trajectoires d’OB, et évaluer l’intérêt pronostic de l’OB dans la ScS. Nous avons inclus 1101 patients. L’OB à l’inclusion était associée à la gravité de la maladie. De plus, après analyse par courbes de survies de Kaplan-Meier, une OB à l’inclusion inférieure à 30 mm était associée à une survie à 30 ans plus mauvaise (p < 0,01) et à un risque plus important d’hypertension artérielle pulmonaire (p < 0,05). L’analyse longitudinale a montré que les trajectoires individuelles d’OB étaient hétérogènes entre les patients. Le meilleur modèle de trajectoires d’OB obtenu selon une modélisation mixte à processus latents a montré que 88,8 % des patients avaient une trajectoire d’OB stable et que les patients pouvaient être classés en 3 clusters. Ces trois clusters étaient prédictifs de la survie à 30 ans (p < 0,05) et de l’apparition d’une pneumopathie intersitielle diffuse (PID) (p < 0,05). Enfin, le modèle a identifié un groupe de 9,5 % de patients, caractérisés par une ScS cutanée diffuse (dcScS) (p < 0,05) et une OB à l’inclusion élevée (p < 0,05) mais décroissante sur 1 an qui présentent un sur-risque de PID (p < 0,0001) et de décès (p < 0,0001). L’OB, qui est une mesure simple et fiable, pourrait être utilisée pour prédire la gravité de la maladie et la survie dans la ScS. Bien que la mesure d’OB soit stable chez la plupart des patients atteints de ScS, les patients atteints de dcScS avec une OB élevée mais décroissante en un an présentent un risque de PID et de mortalité plus important.

Malgré des stratégies thérapeutiques plus efficaces dans la vascularite associée aux ANCA (VAA), il persiste une morbidité importante, principalement dû aux infections et aux maladies cardiovasculaires. L’épaisseur intima-média de la carotide (cIMT) est un marqueur d’athérosclérose infra-clinique associée aux facteurs de risque cardiovasculaire et elle est prédictive d’événements cardiovasculaires majeurs (ECVM). Nous avons émis l’hypothèse que les patients atteints de VAA pourraient bénéficier d’un traitement par statine en prévention primaire afin de réduire les marqueurs infra-cliniques de l’athérosclérose et l’incidence des ECVM. Cette étude de supériorité de phase 3, multicentrique, randomisée, contrôlée, en double aveugle, a comparé la rosuvastatine au placebo pour la réduction de la progression des marqueurs infra-cliniques d’athérosclérose. Les patients atteints de VAA en rémission après une première poussée ou une rechute ont été randomisés avec un ratio 1:1 pour recevoir la rosuvastatine 20 mg/jour ou un placebo pendant 24 mois. Le critère d’évaluation principal était le changement moyen de l’épaisseur intima-média (EIM) de la carotide (paroi distale des artères carotides primaires) à 24 mois. Au total, 111 participants ont été randomisés (55 % d’hommes, âge moyen 54,8 (13,3) ans, 63,1 % de GPA, 28,8 % de GEPA et 8,1 % de PAM), 54 dans le bras rosuvastatine et 57 dans le bras placebo. Le critère d’évaluation principal n’a pas été atteint. Le changement moyen de l’EIM au mois 24 n’était pas différent entre les deux groupes (différence −0,002 [−0,034 ; 0,030], p = 0,89). Le taux annuel de changement de l’EIM moyen était de 0,0110 (0,0617) mm/an dans le groupe rosuvastatine et de 0,0189 (0,0556) mm/an dans le groupe placebo (différence −0,0062 [−0,0318 ; 0,0193], p = 0,61). Des résultats similaires étaient observés pour la variation du nombre de plaques d’athérome dans les artères carotides et fémorales et dans l’aorte abdominale (différence 0,01 [−0,39 ; 0,42], p = 0,94). Les taux moyens de cholestérol LDL étaient significativement différents entre les deux groupes à tous les moments évalués (p < 0,001, p < 0,001 et p < 0,001 pour les réductions entre les groupes rosuvastatine et placebo aux mois 6, 12 et 24, respectivement). De même, les taux de CRP ultrasensible étaient significativement différents entre les deux groupes de l’étude au mois 24 (différence −3,16 [−5,58 ; 0,74], p = 0,011 pour les réductions entre les groupes rosuvastatine et placebo). Il n’y a eu qu’un seul ECVM dans le groupe rosuvastatine. La survie sans rechute de la vascularite ne différait pas entre les deux groupes (HR = 1,59, IC95 % = [0,81 ; 3,09], p = 0,18). Onze et dix-sept patients ont interrompu l’intervention dans les groupes rosuvastatine et placebo, respectivement. L’incidence des événements indésirables graves était similaire dans les deux groupes : 27,8 % dans le groupe rosuvastatine et 22,8 % dans le groupe placebo. Chez les patients atteints de vascularite associée aux ANCA, 24 mois de rosuvastatine réduisaient le taux de cholestérol LDL mais pas la progression des marqueurs infra-cliniques d’athérosclérose ou l’incidence des événements cardiovasculaires majeurs.

OBJECTIVE COVID-19 vaccines have a favorable safety profile in patients with autoimmune rheumatic diseases (AIRDs) such as idiopathic inflammatory myopathies (IIMs), however hesitancy continues to persist among these patients.Therefore, we studied the prevalence, predictors, and reasons for hesitancy in patients with IIMs, other AIRDs, non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs), using data from the two international COVID-19 Vaccination in Autoimmune Diseases (COVAD) e-surveys. METHODS The 1st and 2nd COVAD patient self-reported e-surveys were circulated from March to December 2021, and February to June 2022 (ongoing). We collected data on demographics, comorbidities, COVID-19 infection and vaccination history, reasons for hesitancy, and patient reported outcomes. Predictors of hesitancy were analyzed using regression models in different groups. RESULTS We analyzed data from 18,882 (COVAD-1) and 7666 (COVAD-2) respondents. Reassuringly, hesitancy decreased from 2021 (16.5%) to 2022 (5.1%) [OR 0.26; 95%CI: 0.24-0.30, p < 0.001]. However, concerns/fear over long-term safety had increased [OR 3.6;95% CI:2.9-4.6, p < 0.01].We noted with concern greater skepticism over vaccine science among patients with IIMs than AIRDs [OR:1.8; 95%CI: 1.08-3.2, p = 0.023] and HCs [OR: 4; 95%CI: 1.9-8.1, p < 0.001], as well as more long-term safety concerns/fear [IIMs vs AIRDs; OR: 1.9; 95%CI: 1.2-2.9, p = 0.001; IIMs vs HCs; OR: 5.4 95%CI: 3-9.6), p < 0.001].Caucasians [OR 4.2 (1.7-10.3)] were likely to be more hesitant, while those with better PROMIS physical health score were less hesitant [OR 0.9 (0.8-0.97)]. CONCLUSION Vaccine hesitancy has decreased from 2021 to 2022, long-term safety concerns remain among patients with IIMs, particularly in Caucasians and those with poor physical function.

Background COPA syndrome is a recently described monogenic autoimmune disease due to heterozygous mutations in COPA. COPA syndrome demonstrates considerable phenotypic overlap with SAVI (STING-associated vasculopathy with onset in infancy) due to gain-of-function mutations in STING. Interestingly, while both disorders are characterised by enhanced type I interferon signalling, neither disease is associated with systemic lupus erythematosus (SLE) – challenging classical dogma linking interferon upregulation and lupus. Objectives Our aim was to gather a European cohort of COPA patients to better delineate the clinical phenotype of this rare monogenic disorder. Methods Assessment of clinical, radiological, immunological and therapeutic data from 27 patients (13 families) with molecularly confirmed COPA syndrome. Results Twenty-seven individuals with pathogenic COPA mutations were included. Among them, 20 patients presented with at least one clinical manifestation evocative of COPA syndrome (clinical penetrance of 74.1%). Symptomatic patients were female in 13 (65%) cases with a median age at disease onset of 4 years (0-50). All COPA mutations were inherited in an autosomal dominant pattern except for one that occurred de novo. Pulmonary involvement was observed in 16 (80%) patients, with interstitial lung disease (ILD) in most cases (n=13, 65%), diffuse alveolar haemorrhage (DAH) in 5 (25%) individuals and the association of ILD and DAH in 3 (15%) patients. Twelve (60%) patients demonstrated joint involvement of variable severity: 4 (20%) individuals experiencing deforming arthritis including one requiring bilateral knee arthroplasty, 6 (30%) patients had polyarticular arthritis and two (10%) patients presented with isolated arthralgias. Renal disease was observed in three (15%) individuals, manifest as either proliferative glomerulonephritis (n=2) or membranous glomerulonephritis (n=1). Previously undescribed features were noted i.e. cutaneous involvement - acral ulcers, vitiligo and nasal perforation (n=3, 15%), cardiac disease (n=2, 10%), gastrointestinal dysfunction (n=2, 10%), and cytolytic hepatitis (n=1). When tested, 14 (93.9%) patients had positive autoantibodies. When assessed, immunophenotyping showed a mild T-cell lymphopenia, with an excess of naive T CD8+ cells and a defect of memory T CD8+ cells recorded in one patient. All patients explored exhibited elevated IFN alpha protein levels and high IFN signature scores. The IFN signature was mildly positive in half of the clinically asymptomatic individuals assessed. The majority (60%) of patients were treated with corticosteroids and immunosuppressants, ten (50%) received biotherapies and eight (40%) patients are currently under JAK1/2 inhibition. Conclusion We report the first European cohort of COPA patients. While confirming the core organ features (lung, joint and kidney) of COPA syndrome, our data expand the phenotype to include cardiac, skin and digestive features, further demonstrating the clinical overlap with SAVI and other type I interferonopathies, while also highlighting the possibility of isolated organ involvement. We confirm a high level of clinical non-penetrance, which can present a diagnostic challenge and indicates the need to better understand the underlying pathophysiology. In view of current (JAK inhibitors) and potential future targeted therapies, we suggest a requirement to assess IFN pathway status and/or perform sequencing in the case of suggestive features, even in the absence of a familial history. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.