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To describe the switch to biosimilar etanercept (bETN), evaluate factors associated with this switch, and evaluate the efficacy of this switch in a real-life setting We included patients, from October 2016 to April 2017, with rheumatoid arthritis (RA) and spondyloarthritis (SpA) who received innovator ETN (iETN) for at least 6 months. After receiving information on biosimilars, all physicians were invited to propose a switch from iETN to bETN. Factors associated with bETN discontinuation were explored by univariate and multivariate analyses. We estimated the proportion of patients still on bETN over time by Kaplan-Meier survival analysis. We assessed serum trough concentrations of iETN and bETN and anti-drug antibodies to ETN. Overall, 183 outpatients were eligible for a potential switch; 94 (51.6%) switched from iETN to bETN. The probability of a switch was greater with an older than younger aged physician (mean [SD] age 50.4 [14.3] with a switch vs 44.8 [11.3] with no switch, p = 0.005) and the physician having a full-time academic position than other position (56.4% with a switch vs 13.5% with no switch, p

BackgroundSome factors associated with severe COVID-19 outcomes have been identified in patients with psoriasis (PsO) and inflammatory/autoimmune rheumatic diseases, namely older age, male sex, comorbidity burden, higher disease activity, and certain medications such as rituximab. However, information about specificities of patients with PsO, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), including disease modifying anti-rheumatic drugs (DMARDs) specifically licensed for these conditions, such as IL-17 inhibitors (IL-17i), IL-23/IL-12 + 23 inhibitors (IL-23/IL-12 + 23i), and apremilast, is lacking.ObjectivesTo determine characteristics associated with severe COVID-19 outcomes in people with PsO, PsA and axSpA.MethodsThis study was a pooled analysis of data from two physician-reported registries: the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), comprising patients with PsO/PsA, and the COVID-19 Global Rheumatology Alliance (GRA) registry, comprising patients with PsA/axSpA. Data from the beginning of the pandemic up to 25 October, 2021 were included. An ordinal severity outcome was defined as: 1) not hospitalised, 2) hospitalised without death, and 3) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics (age, sex, time period of infection), comorbidities (hypertension, other cardiovascular disease [CVD], chronic obstructive lung disease [COPD], asthma, other chronic lung disease, chronic kidney disease, cancer, smoking, obesity, diabetes mellitus [DM]), rheumatic/skin disease (PsO, PsA, axSpA), physician-reported disease activity, and medication exposure (methotrexate, leflunomide, sulfasalazine, TNFi, IL17i, IL-23/IL-12 + 23i, Janus kinase inhibitors (JAKi), apremilast, glucocorticoids [GC] and NSAIDs). Age-adjustment was performed employing four-knot restricted cubic splines. Country-adjustment was performed using random effects.ResultsA total of 5008 individuals with PsO (n=921), PsA (n=2263) and axSpA (n=1824) were included. Mean age was 50 years (SD 13.5) and 51.8% were male. Hospitalisation (without death) was observed in 14.6% of cases and 1.8% died. In the multivariable model, the following variables were associated with severe COVID-19 outcomes: older age (Figure 1), male sex (OR 1.53, 95%CI 1.29-1.82), CVD (hypertension alone: 1.26, 1.02-1.56; other CVD alone: 1.89, 1.22-2.94; vs no hypertension and no other CVD), COPD or asthma (1.75, 1.32-2.32), other lung disease (2.56, 1.66-3.97), chronic kidney disease (2.32, 1.50-3.59), obesity and DM (obesity alone: 1.36, 1.07-1.71; DM alone: 1.85, 1.39-2.47; obesity and DM: 1.89, 1.34-2.67; vs no obesity and no DM), higher disease activity and GC intake (remission/low disease activity and GC intake: 1.96, 1.36-2.82; moderate/severe disease activity and no GC intake: 1.35, 1.05-1.72; moderate/severe disease activity and GC intake 2.30, 1.41-3.74; vs remission/low disease activity and no GC intake). Conversely, the following variables were associated with less severe COVID-19 outcomes: time period after 15 June 2020 (16 June 2020-31 December 2020: 0.42, 0.34-0.51; 1 January 2021 onwards: 0.52, 0.41-0.67; vs time period until 15 June 2020), a diagnosis of PsO (without arthritis) (0.49, 0.37-0.65; vs PsA), and exposure to TNFi (0.58, 0.45-0.75; vs no DMARDs), IL17i (0.63, 0.45-0.88; vs no DMARDs), IL-23/IL-12 + 23i (0.68, 0.46-0.997; vs no DMARDs) and NSAIDs (0.77, 0.60-0.98; vs no NSAIDs).ConclusionMore severe COVID-19 outcomes in PsO, PsA and axSpA are largely driven by demographic factors (age, sex), comorbidities, and active disease. None of the DMARDs typically used in PsO, PsA and axSpA, were associated with severe COVID-19 outcomes, including IL-17i, IL-23/IL-12 + 23i, JAKi and apremilast.AcknowledgementsWe thank all the contributors to the COVID-19 PsoProtect, GRA and EULAR Registries.Disclosure of InterestsNone declared

BackgroundRituximab (RTX) is associated with reduced humoral response to SARS-CoV-2 mRNA-based vaccine (1, 2). A recent study has shown that, despite their immunosuppression burden, kidney transplant recipients with previous exposure to SARS-CoV-2 showed a marked increase in antibody titer, even after a single dose of vaccine (3).ObjectivesTo describe the results of immunization after 1 to 3 doses of mRNA SARS-CoV-2 vaccine in RTX-treated patients with previous symptomatic COVID-19 infection.MethodsObservational prospective usual care study including consecutive patients with inflammatory rheumatic diseases in maintenance therapy with RTX. All patients received a 1 to 3-dose regimen of mRNA-based COVID-19 vaccination (BNT162b2 Pfizer/BioNTech or mRNA-1273, Moderna). Serum IgG antibody levels against SARS-CoV-2 spike proteins were measured at the time of the new RTX infusion. The SARS-CoV-2 S1/S2 IgG immunoassay (DiaSorin) was used for the quantitative determination of antibodies to the receptor-binding domain of the viral spike (S) protein. Seropositivity was defined by anti-S antibodies >15 UA/mL.ResultsWe included 69 patients (60 females, mean age 60±13 years) on maintenance therapy with RTX including 13 with previous symptomatic COVID-19, all proven by RT-PCR (10 females, mean age 58±12 years) (Table 1). SymptomaticCOVID-19 occurred between March 2020 and May 2021. The mean interval between the infection and vaccination was 8±3 months and the serological response was assessed after a mean of 74±58 days from the last dose of vaccination (3rd dose for 3 patients, 2nd dose for 6 patients and 1st dose for 4 patients). The 56 patients with no history of symptomatic COVID-19 infection all received 3 doses of vaccine and the serological response was assessed after a mean of 63±27 days from the 3rd dose of vaccination. The seropositivity rate was significantly higher in RTX-treated patients with previous symptomatic COVID-19 infection (11/13, 85% vs.15/56, 27%, pTable 1.Study populationPatients with previous symptomatic COVID-19 (n=13)Patients without symptomatic COVID-19 (n=56)Age (years), mean ± SD58±1260±11Females, n (%)10 (77)50 (89)Underlying disease: Rheumatoid arthritis10 (77)45 (80) Systemic sclerosis2 (15)5 (9) Systemic lupus erythematosus1 (8)1 (2) Sjögren syndrome0 (0)3 (5) Mixed connective tissue disease0 (0)2 (4)Disease duration (years), mean ± SD17±920±10Associated Methotrexate, n (%)9 (69)36 (64)Current treatment with corticosteroids, n (%)5 (38)21 (38)Corticosteroid dose >10 mg/day, n (%)0 (0)0 (0)CD19+ (/µL) (100-600), mean ± SD65±10645±51CD19 7 (54)33 (58)Figure 1.Distribution of SARS-CoV-2 spike antibody levels according to the history of proven symptomatic COVID-19. **** pConclusionRTX-treated patients with previous proven COVID-19 showed increased seropositivity and antibody titers after SARS-CoV-2 vaccination, even after a single-dose of vaccine. This response is strikingly different from that observed for SARS-CoV-2-naïve RTX treated patients who received 3 doses of SARS-CoV-2 mRNA-based vaccination. An “antigen dose phenomenon” may account for these discrepancies. A potential clinical implication might be to increase antibody response with an additional dose of vaccine following an exposure to SARS-CoV-2 in RTX-treated patients with absent or insufficient postvaccination antibody response.References[1]Avouac et al, Rheumatology 2021[2]Jyssum et al, Lancet Rheumatol 2021[3]Benotmane et al, Am J Transplant 2021Disclosure of InterestsNone declared

Objective.Inflammatory bowel disease (IBD) is a well-known extraarticular feature of spondyloarthritis (SpA). The aims of this study were to evaluate factors associated with IBD and incidence over 5 years of followup in the DESIR cohort.Methods.DESIR is a prospective observational cohort of patients with recent-onset inflammatory back pain suggestive of axial SpA. All available variables in the database were compared between patients with and without IBD at baseline and 5 years, and occurrence over 5 years of followup, with uni- and then multivariable analysis.Results.At baseline, of 708 patients, 35 had IBD (prevalence 4.94%, CI 95% 3.3–6.5). IBD was associated (multivariable) with history of uveitis, levels of Dickkopf-1, and tumor necrosis factor, but not with phenotypic presentation (peripheral arthritis, enthesitis, dactylitis, uveitis) or baseline serum levels of other cytokines. At 5 years, 480 patients were analyzed, 58 with IBD. IBD was associated (multivariable) with fulfillment of modified New York criteria, sick leave, Bath Ankylosing Spondylitis Disease Activity Index, and smoking. There was no association with magnetic resonance imaging scores, enthesitis, psoriasis, and bone mineral density. Twenty-three incident cases of IBD were recorded: estimated occurrence rate of 0.95/100 (95% CI 0.57–1.35) patient-years (PY). Incidence of IBD is associated (multivariable) with HLA-B27 (OR 0.36, 95% CI 0.22–0.59), fulfillment of modified New York criteria (OR 3.35, 95% CI 1.85–6.08), and familial history of IBD (OR 3.31, 95% CI 1.62–6.77).Conclusion.In early SpA, IBD occurs with an incidence of 1/100 PY, and is associated with poor outcome, familial history of IBD, absence of HLA-B27, and fulfillment of modified New York criteria.

Introduction Notre objectif était de décrire la prévalence de la séroconversion au SARS-CoV-2 par un dépistage sérologique systématique des patients atteints de rhumatisme inflammatoire chronique (RIC) et d’en étudier les facteurs associés. Matériels et méthodes COVID-RIC1 est une étude transversale multicentrique nationale menée dans 17 centres tertiaires en France. Critères d’inclusion : – ≥ 18 ans ; – diagnostic de polyarthrite rhumatoïde (PR), spondylarthrite axiale (axSpA) ou rhumatisme psoriasique (RPso) ; – traitement ≥ 1 mois par AINS, corticoïdes ou DMARD ; – accepter un test sérologique SARS-CoV-2. Données collectées par formulaire électronique centralisé et anonyme : démographiques, RIC, traitements symptomatiques et de fond, symptômes évocateurs de COVID-19. Les tests sérologiques pour le SARS-CoV-2 pouvaient être réalisés soit au centre tertiaire, soit dans le laboratoire habituel du patient. En cas de tests sérologiques antérieurs, les résultats ont également été recueillis. La séroprévalence était estimée comme le rapport du nombre de tests positifs sur le nombre de tests sérologiques SARS-CoV-2. Une régression logistique a été réalisée pour étudier l’impact des différentes covariables sur la séroconversion. Toutes les variables avec p

Introduction L’uveite est la manifestation extra-rhumatologique la plus frequente de la spondyloarthrite (SpA). Elle est principalement associee a l’antigene HLA-B27, neanmoins elle peut egalement survenir chez les patients HLA-B27 negatifs bien que leur profil specifique reste mal connu. Notre objectif etait de caracteriser le phenotype des patients ayant une uveite dans le cadre d’une SpA HLA-B27 negative, en le comparant a celui des patients ayant une uveite dans le cadre d’une SpA HLA-B27 positive. Patients et methodes Tous les patients de l’etude ASAS-PerSpA ayant une uveite ont ete inclus. Ceux ayant des donnees manquantes concernant le statut HLA-B27 ont ete exclus. Les phenotypes des groupes HLA-B27 positif et HLA-B27 negatif ont ete decrits d’apres leurs principales caracteristiques sociodemographiques, rhumatologiques et ophtalmologiques et compares a l’aide d’une regression logistique univariee puis multivariee (ajustement sur les variables associees au critere de jugement principal avec un p Resultats Parmi les 4 465 patients identifies dans l’etude ASAS-PerSpA, 621 ont ete inclus dans l’analyse (738 avaient un antecedent d’uveite, leur statut HLA-B27 n’etait connu que chez 621) : 89 (14 %) avec HLA-B27 negatif (âge moyen 45,3 ± 13,6 ans ; 48 % d’hommes) et 532 (86 %) avec HLA-B27 positif (âge moyen 43,7 ± 12,8 ans ; 70 % d’hommes). Les patients ayant une uveite HLA-B27 negative etaient plus frequemment de sexe feminin (52 % versus 30 % ; ORa = 2,29, IC95 % 1,37–3,84) et souffraient de maniere significativement plus frequente de maladies inflammatoires chroniques de l’intestin (MICI) (19 % versus 4 % ; ORa = 5,75, IC95 % 2,61–12,6). En revanche, ils etaient moins souvent d’origine asiatique (9 % versus 29 % ; ORa = 0,20, IC95 % 0,07–0,51) et avaient moins souvent d’antecedent familial de SpA (11 % versus 21 % ; ORa = 0,44, IC95 % 0,19–0,91). Le profil des patients avec uveite HLA-B27 negative etait egalement associe a une duree d’evolution de la SpA significativement moins longue (15 ± 12 ans versus 19 ± 12 ans ; ORa = 0,97, IC95 % 0,95–0,99) et a des rachialgies inflammatoires moins frequentes (79 % versus 91 % ; ORa = 0,42, IC95 % 0,22–0,83). Enfin, la prescription d’un biomedicament en raison de l’atteinte ophtalmologique etait moins frequente (11 % versus 19 % ; ORa = 0,41, IC95 % 0,18–0,85) pour les uveites HLA-B27 negatives que pour les uveites HLA-B27 positives. Conclusion Au total 14 % des uveites observees chez des patients avec SpA n’etaient pas associees a l’antigene HLA-B27. Les donnees de cette etude montrent que le diagnostic d’uveite ne doit pas etre ecarte chez les patients SpA HLA-B27 negatif, et ce tout particulierement chez les femmes, ayant une forme peripherique et/ou un antecedent de MICI. Ces uveites semblaient moins severes que celles survenant chez les patients HLA-B27 positif.

Introduction Il n’y a pas, à notre connaissance, de publication décrivant précisément la sévérité et l’évolution de l’infection à SARS-CoV-2 dans la spondyloarthrite (SpA). Les données sur la COVID-19 issues des cohortes de patients avec maladies inflammatoires à médiation immunitaire concernent de faibles effectifs de SpA. Notre objectif était de décrire la sévérité et l’évolution de la COVID-19 dans une large cohorte de patients atteints de SpA (SpA axiale et rhumatisme psoriasique) et d’identifier les facteurs associés aux formes sévères. Patients et méthodes Patients : spondyloarthrites (SpA) de la French RMD COVID-19 cohort (cohorte observationnelle, nationale, multicentrique) avec un diagnostic de COVID-19 (clinique, PCR, scanner ou sérologie). Données collectées : démographiques, type de SpA, comorbidités, traitements, gravité de la COVID-19. La gravité de la COVID-19 a été classée en fonction des soins nécessaires : bénin = soins ambulatoires ; modéré = traitement hospitalier non intensif ; sévère = admission en unité de soins intensifs ou décès ; grave = modéré ou sévère. Analyses statistiques : des modèles de régression logistique ont été utilisés pour identifier les facteurs associés à ces formes graves. Toutes les variables avec p

BackgroundAlthough it prevents severe forms of the disease, vaccination does not completely protect against the occurrence of COVID19 disease. If, DMARDs used have been associated with variable humoral response to SARS-CoV-2 vaccination, the impact of their use after SARS-CoV-2 natural infection have been poorly studied.ObjectivesTo characterize humoral response after SARS-CoV-2 infection and viral persistence in the nasopharyngeal sphere (NP), stools and blood of patients with rheumatic disease under DMARDs, and compared to healthy controls.MethodsProspective monocentric longitudinal study including patients with rheumatoid arthritis or spondyloarthritis under DMARDs and with a confirmed SARS-CoV-2 infection (positive NP PCR and/or positive serology and/or pathognomonic thoracic tomography (CT)) during the first or second wave of the COVID pandemic. Patients were followed up until one year after infection and humoral response was assessed before vaccination. Serum IgG and IgA antibodies against spike (S) and nucleocapsid (N) proteins were measured at every visit. Viral persistence was assessed at the early visit in the NP and stools using conventional RT-PCR and in the blood using a high sensitive technique (droplet digital PCR).ResultsBetween June 2020 and July 2021, we include 96 patients (50 SpA and 46 RA) with a mean age of 53 +/- 14 years and 20 healthy controls (mean age 49 ± 16 years) corresponding to relatives of patients (spouses, children) living together and infected at the same time. The immune responses were analyzed according to 6 treatment groups: methotrexate (MTX)/salazopyrine (SLZ) monotherapy (n=17/2); anti-TNF monotherapy (n=24), anti-TNF + MTX (n=23); rituximab (RTX) (n=11); anti-IL17 or -23 (n=8); others (n=11). Visits were made at 1 month (29 ±13 days; n=18), 3 months (110 ±23 days; n=67), 6 months (231 ±35 days; n=48) and 12 months (368 ± 19 days; n=19) after infection. The anti-S and anti-N IgG Ab titers were not significantly different in the 6 treatment groups and the control population at 3 months. A significant decrease in anti-S IgA Ab titers was noted in the group treated with RTX (p=0.007) and with molecules targeting the IL17/23 pathway (p=0.007). A similar but non-significant trend was observed in these same treatment groups for anti-N IgA Ab (p=0.07). The titers of anti-SARS-CoV-2 antibodies at M3, was not associated with a severe COVID disease. Detection of SARS-Cov-2 RNA in stools and serum was negative for all samples taken at 1 month or 3 months. 4 patients (2 RA treated with abatacept/RTX and 2 SpA treated with anti-TNF/secukinumab) had a positive RT-PCR NP with low to very low viral load at the 1-month visit (mean Ct 36). None of these 4 patients had had a severe form of COVID19 infection.ConclusionDMARDs - treated patients with previous proven COVID-19 did not seem to alter IgG Ab response but RTX and anti-IL17/-IL-23 might alter IgA humoral response. This lower immune response was not associated with a more severe disease. In these patients, new infection may not be considered as a full boost for the immune system. DMARDs did not induce viral persistence in the serum, the NP or in the stool.Acknowledgementsfinancial support from Société Française de Rhumatologie and ANR RA COVIDDisclosure of InterestsNone declared

BackgroundThe sudden emergence of SARS-CoV-2 onto the world stage has accelerated a major change in the management of patients with chronic rheumatic diseases and has catalyzed the rapid emergence of telemedicine.ObjectivesOur aim was to describe which parameters were used by rheumatologists to monitor patients with rheumatoid arthritis (RA) in teleconsultation during the first wave of the pandemic and identify the most relevant for decision making.MethodsRetrospective monocentric routine care cross-sectional study including RA patients seen in teleconsultation between March and September 2020. Available parameters assessing disease status were collected in teleconsultation files. Clinician intervention was defined by treatment escalation and/or the need for a rapid face-to-face consultation or day hospitalization.Results143 RA patients were included (117 females, mean age of 58±16 years, mean disease duration of 14±11 years). The presence or absence of patient self-reported RA flares was mentioned in all medical files, followed by the presence and/or the number of tender joints (76%), the duration of morning stiffness (66%), the number of pain-related nocturnal awakenings (66%) and the CRP value (54%).Patient self-reported RA flares concerned 43/143 patients (30%). The presence of self-reported RA flares was associated with a more detailed evaluation of patient in teleconsultation: The presence (or number) of tender joints and swollen joints were more significantly reported in patients who presented a flare (39/43, 91% vs. 70/100, 70%, p=0.008 and 25/43, 58% vs. 23/100, 23%, pTeleconsultation led to a clinician intervention in 22/143 patients (14%), representing 51% of patients with self-reported flares (22/43 patients). Therapeutic escalation was necessary in 13 patients: introduction or dose increase of corticosteroids in 8 patients, introduction or dose increase of methotrexate in 4 patients and introduction of hydroxychloroquine in 1 patient. Face-to-face consultation or day hospitalization were organized for 10 patients. Active disease was confirmed during this next face-to-face visit in 9 patients, with DAS28 ranging from 3.35 to 5.62, leading to therapeutic modification. The 133 other patients were seen in face-to-face consultation 6±2 months after the teleconsultation. No DMARD modification was recorded during this next face-to-face consultation.The following variables were associated with clinician intervention during the teleconsultation in univariate analysis: patient self-reported RA flares since the last visit (p10 mg/mL (p=0.012) and a morning stiffness > 30 minutes (p10 mg/L (OR: 3.32, 95% CI % 1.12-13.27) as the variables independently associated with clinician intervention.ConclusionOur study identified patient reported RA flares and increased CRP values as 2 red flags in teleconsultation, independently associated with therapeutic modification and/or the need for a rapid face-to-face consultation. These indicators may help clinician’s decision making in teleconsultation.Disclosure of InterestsJerôme Avouac Speakers bureau: Bristol Myers Squibb, SANOFI, galapagos, Lilly, Abbvie, Pfizer, Novartis, Biogen, Fresenius Kabi, Janssen, MSD, Roche-Chugai, Medac, Consultant of: galapagos, Abbvie, Pfizer, Bristol Myers Squibb, SANOFI, Nordic-Pharma, Grant/research support from: Bristol-Myers Squibb, Pfizer (Passerelle), Novartis (Dreamer), Fresenius Kabi, Anna Moltó: None declared, CAMELIA FRANTZ: None declared, Sarah Wanono: None declared, Elise Descamps: None declared, Olivier Fogel: None declared, Alice Combier: None declared, Lucile Poiroux: None declared, Corinne Miceli Richard: None declared, Yannick Allanore: None declared

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

BackgroundRecently, EULAR has proposed a definition of difficult-to-treat rheumatoid arthritis (D2TRA). However, descriptive data on D2TRA are scarce and only one Japanese publication details the D2TRA encountered in routine practice, no similar work has been done in Europe so far.ObjectivesTo describe D2TRA patients encountered in France according to two definitions and evaluate their therapeutic responses to different targeted therapies.MethodsWe reviewed all patients with RA treated in day hospital at Cochin University Hospital between 2020 and 2021. We divided our population into two groups of patients, a D2TRA group and a non-D2TRA group. This division was made on the same population according to two different definitions of D2TRA, resulting in four patient groups. The first definition is the one proposed by EULAR (EULAR D2TRA) defining D2TRAs as RAs with failure of ≥2 b/tsDMARDs (with different mechanisms of action) after failing csDMARD therapy. The second defined as D2TRA patients who have failed at least two targeted therapies, without prejudging the mechanism of action (non-EULAR D2TRA). We analyzed clinical characteristics and evaluated their response to different targeted therapies. Disease activity was assessed using the DAS for 28 joints (DAS28) at the latest visit.ResultsIn total, we included 320 patients, we identified 76 EULAR D2TRA patients (mean age 59 years, 87% female) with 244 of corresponding non-DTRA patients (mean age 60 years, 85% female) and 120 non-EULAR D2TRA patients (mean age 58.7 years, 87% female) with 200 of corresponding non-DTRA (mean age 61 years, 85% female). Compared to non-D2TRA patients, there were significantly more D2TRA patients from low socioeconomic backgrounds in both D2TRA groups. In the EULAR-D2TRA group, compared to the non-D2TRA, there were significantly more patients with diabetes (14% vs 6%, p=0.024). D2TRA patients in both groups had significantly more rheumatoid factor (RF), interstitial lung disease (ILD) and a higher DAS28 than non-D2TRA patients. No difference was noted regarding ACPA and erosions. We observed a lower proportion of remission in both D2TRA groups than in non-D2TRA group (21% in EULAR-D2TRA vs 34% in non-D2TRA, p=0.034 and 23% in non-EULAR D2TRA vs 36% in non-D2TRA, p=0.024). There were significantly fewer patients on Methotrexate in the non-EULAR D2TRA group compared to the non-D2TRA group (53% vs 64%, p=0.046). In the non-EULAR D2TRA group, there were significantly more patients in remission on Rituximab than on TNF inhibitors (41% vs 5%, p=0.0032). We did not observe a significant difference in achieving remission in patients on JAK inhibitors or IL-6 inhibitors in the two groups of D2TRA.Table 1.Clinical data of patients with D2TRANON D2T RA n=200NON-EULAR D2T RA n=120p-valueNON D2T RA n=244EULAR D2T RA n=76p-valueLow socioeconomic level69 (35)61 (51)0.00591 (37)39 (51)0.032TJC (0-28), mean (SD)3.4 (4.6)4.9 (5.8)0.01673.5 (4.5)5.6 (6.5)0.001SJC (0-28), mean (SD)2.4 (3.1)3.5 (4.3)0.00672.6 (3.3)3.5 (4.3)0.0503CRP in mg/dl, mean (SD)6 (9.5)7 .5 (12.1)0.21286.1 (9.9)7.9 (12.3)0.2060DAS28CRP, mean (SD)3.2 (1.2)3.6 (1.4)0.00443.2 (1.3)3.6 (1.4)0.0052Remission71 (36)28 (23)0.02483 (34)16 (21)0.034RF positive, n (%)156 (78)105 (88)0.037193 (79)68 (89)0.043Anti-CCP positive, n (%)152 (76)101 (84)0.099188 (77)66 (87)0.075Erosion, n (%)114 (57)69 (58)1138 (56)46 (60)0.596Interstitial Lung Disease, n (%)16 (8)19 (16)0.04117 (7)18 (24)Corticosteroids, n (%)84 (42)64 (53)0.064101 (41)46 (61)0.004 Dose (mg), mean ± SD6 (4.9)5.5 (3.4)0.4166 (4.6)5.3 (3.6)0.374Methotrexate, n (%)128 (64)63 (53)0.046149 (61)42 (55)0.422 Dose (mg), mean ± SD17.3 (4.25)17.5 (5.3)0.78617.2 (4.5)18.1 (5.1)0.291ConclusionThe complexity of managing RA patients can be explained by socio-economic status and the presence of comorbidities such as diabetes and ILD. Our work suggests that D2TRA patients have less Methotrexate and better response to Rituximab. These data need to be confirmed in prospective studies to allow personalized management of D2TRA.Disclosure of InterestsNone declared

BackgroundTo our knowledge, no published work has described precisely the severity and evolution of SARS-CoV-2 infection in patients with spondyloarthritis (SpA). Data on COVID-19 from cohorts of patients with immune-mediated inflammatory diseases concern small samples of SpA.ObjectivesOur objective was to describe the severity and course of COVID-19 in a large cohort of patients with SpA, including axial SpA (axSpA) and psoriatic arthritis (PsA), and to identify factors associated with severe forms.MethodsPatients: individuals with Spondyloarthritis (SpA) from the French RMD COVID-19 cohort (observational, national, multicenter cohort) with a diagnosis of COVID-19 (clinical, PCR, CT or serology) were included.Data collected: demographics, type of SpA, comorbidities, treatments, severity of COVID-19. Severity of COVID-19 was graded according to care needed: mild = outpatient care; moderate = non-intensive hospital treatment; severe = intensive care unit admission or death; severe = moderate or severe.Statistical analyses: Logistic regression models were used to identify factors associated with these severe forms. All variables with p ResultsBetween March 2020 and April 2021, 626 SpAs reported COVID-19 with a mild course in 508 cases (81.1%), moderate in 93 cases (14.8%), and severe in 25 cases (3.9%), including 6 deaths.The cohort analyzed included 349 women (55.8%), mean age 49.3 ± 14.1 years, mean BMI 27.1 ± 5.4 with 403 axSpA (64.4%), 187 PsA (29.9%) and 36 other SpA, duration of disease 11.3 ± 9.8 years; 352 (56.2%) had at least one comorbidity, of which obesity (23.6%), hypertension (15.5%), and smoking (10.4%) were the most frequent. Among them, 104 were treated with NSAIDs (16.6%), 186 with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) including 156 MTX, and 460 (73.5%) with biological DMARDs (379 TNFi, 57 IL-17i, 15 IL-23p19/p40i, 9 others).The following variables were associated with severe COVID-19 outcomes: age, body mass index, chronic obstructive lung disease, cardiovascular disease, diabetes, hypertension, interstitial lung disease, renal failure, and corticosteroids intake.The factors independently associated with severe COVID-19 outcomes were corticosteroid intake (3.15 [CI95%: 1.46-6.76], p 0.004), and age (OR=1.06 [CI95%: 1.04-1.08], p ConclusionThe course of COVID-19 was mild for the majority of SpA patients (81.1%). Corticosteroid intake was associated with more severe COVID-19 outcomes, whereas TNFi were found to be protective.Disclosure of InterestsNone declared

Introduction La prévalence des formes asymptomatiques d’infection COVID-19 en population générale est mal connue à ce jour (

Background Ankylosing spondylitis (AS) is a chronic inflammatory condition with pain, stiffness and fatigue reported as the most troubling symptoms. Early and sustained relief of these symptoms is essential for effective management. Secukinumab provided sustained relief from pain and fatigue in AS patients over 2 years in the MEASURE 2 study. We report the effect of subcutaneous secukinumab 150 mg on key clinical symptoms (pain, morning stiffness and fatigue) in AS patients over 208 weeks in MEASURE 2. Methods This post-hoc analysis of MEASURE 2 assessed mean change from baseline to Week 208 in total and nocturnal back pain scores (by VAS [0-100]; ASAS outcome component), overall level of spinal pain (neck, back or hip) from BASDAI scores, and morning stiffness (overall level; mean of question 5 and 6 of BASDAI score). Additionally, the SF-36 physical component summary score, overall level of fatigue (BASDAI question 1), FACIT-Fatigue score and patients meeting minimal clinically important difference (MCID) criteria across multiple clinical domains were assessed. Data are shown for patients originally randomised to secukinumab 150 mg and placebo. Data are reported as observed for the overall population and by prior TNF inhibitor (TNFi) therapy status (naive vs inadequate response [IR]). Results Baseline characteristics were comparable across secukinumab 150 mg (N = 72) and placebo (N = 74) groups; total mean back pain score was 67.7±17.79, nocturnal back pain score was 64.9±19.58 and morning stiffness was 6.5±2.11. Secukinumab 150 mg-treated patients reported rapid and early reductions in pain scores by Week 4, which were sustained through Week 208 (Table 1). Improvements with secukinumab 150 mg were reported for all key clinical symptoms by Week 4, which were sustained at Week 208. A higher proportion of secukinumab 150 mg-treated patients met MCID criteria at Week 16 vs placebo across multiple clinical domains, which was sustained or further improved through Week 208. Improvements were observed in TNFi-naive and -IR patients, with a greater magnitude of improvement in TNFi-naive patients. Conclusion Secukinumab 150 mg was associated with rapid and clinically meaningful improvements in total and nocturnal back pain, morning stiffness and fatigue, with improvements sustained over 4 years of treatment. Disclosures H. Marzo-Ortega: Consultancies; AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. Grants/research support; Janssen, Novartis. C. Miceli-Richard: Consultancies; Pfizer, Roche, UCB, Wyeth, Merck. Member of speakers’ bureau; Abbott, Bristol-Myers Squibb, Merck, Pfizer, Roche, Schering-Plough, Wyeth. Grants/research support; AbbVie, Bristol-Myers Squibb, Novartis, Merck, Pfizer, Wyeth. S. Gill: Consultancies; AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Amgen, Sanofi-Genzyme. Other; AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Amgen, Sanofi-Genzyme. M. Magery: Consultancies; Eli Lilly, Novartis. Grants/research support; AbbVie, UCB, Amgen. P.G.P. Machado: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. A. Shete: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. J. Wang: Other; Employee of Novartis. S. Rohrer: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. A. Deodhar: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GSK, Galapagos, Janssen, Novartis, Pfizer, UCB. Grants/research support; Eli Lilly, GSK, Novartis, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, UCB.

Resume Actualisation des recommandations de la Societe francaise de rhumatologie pour la prise en charge en pratique des patients atteints de spondyloarthrite (SpA). La SpA est prise en compte avec ses differentes expressions cliniques (axiale, peripherique, enthesitique) et ses manifestations associees et comprend le rhumatisme psoriasique. Procedures standardisees selon les recommandations EULAR pour l’elaboration des recommandations : analyse de la litterature depuis la version precedente (juin 2013), groupe de travail, elaboration de recommandations avec regroupement et synthese, vote et niveau d’accord. Quatre principes generaux et 15 recommandations sont proposes. Les 4 premieres recommandations concernent les objectifs du traitement et les considerations generales (outils d’evaluation, comorbidites). Les recommandations 5 et 6 s’interessent aux moyens non pharmacologiques. La recommandation 7 concerne les AINS, base du traitement, et les items 8 a 10 l’utilisation des antalgiques, de la corticotherapie et des traitements d’action lente conventionnels. Les recommandations 11 a 14 s’interessent a l’usage des biomedicaments, integrant les nouvelles classes, dans leurs indications (maladie active malgre le traitement conventionnel, et pour les formes axiales non radiographiques, presence de signes objectifs d’inflammation) et suivi, leur gestion en cas d’echec ou en remission. La recommandation 15 concerne le recours a la chirurgie. Cette actualisation, integrant les donnees recentes, offre des recommandations en nombre plus reduit et de formulation plus simple, dans le but d’une utilisation plus facile pour guider la prise en charge en pratique des patients atteints de spondyloarthrite.

Background:The bioequivalence between rituximab (RTX) originator and its biosimilar GP2013 has been demonstrated in rheumatoid arthritis (RA) (1). A recent randomized controlled trial suggested in a selected population a very low immunogenicity of GP2013 in RA (Objectives:To study in daily practice the risk of immunogenicity of patients treated with GP2013 for their chronic inflammatory rheumatic disorder.Methods:Prospective routine care study carried out between September 2018 and August 2020 in the Rheumatology department of Cochin Hospital. We consecutively included patients treated with the biosimilar RTX GP2013, systematically used in the department since March 2018. Samples were taken before each infusion in order to detect anti-RTX antibodies (Ab) and RTX residual concentrations by ELISA (Lisa Tracker Duo Rituximab, LTR005, Theradiag).Results:We included 159 consecutive patients treated with GP2013 (124 women, 78%) with a mean age of 59±13 years and a mean disease duration of 18±11 years. Among these 159 patients, 108 (68%) had RA and 51 had another disease (16 systemic sclerosis (SSc), 15 mixed connective tissue disease (MCTD), 5 systemic lupus (SLE), 5 inflammatory myopathies (MI), 5 undifferentiated polyarthritis, 2 juvenile idiopathic arthritis (JIA) and 3 primary Sjögren’s syndromes). 137 patients (86%) were receiving associated disease-modifying therapy (DMARD), mainly methotrexate (111/137 patients, 81%). 120 patients (75%) were in maintenance therapy with originator RTX (cumulative dose of RTX: 3.5±6g) before the switch to GP2013 in March 2018. Originator RTX was not re-established during the entire treatment period. The other 39 patients (25%) treated with GP2013 were naïve of originator RTX.The analysis of the first sample, performed before the second GP2013 infusion, identified 8 patients (5 RA, 1 SLE, 1 MCTD and 1 SSc) with positive anti-RTX antibodies (prevalence 5%), with rates varying between 6 and >100ng/mL and undetectable residual RTX concentrations. Among these 8 patients, 6 had previously received originator RTX and 2 were RTX-naïve patients. There was a trend for higher body mass index in patients with positive anti-RTX antibodies (28±7 vs. 25±6 kg/m2, p=0.12), and no association was observed between anti-RTX immunization and age, disease duration, combination with conventional DMARD, mean interval between infusions or cumulative RTX dose.Among the 8 immunized patients, two groups could be isolated: i) a group of 5 patients (3 RA, 1 SLE, 1 SSc) with low antibody levels (6-22 ng/mL) and no significant clinical consequences (absence of treatment discontinuation and loss of efficacy after 13±4 months of follow-up, only one minor allergic reaction) and ii) a group of 3 patients (2 RA, 1 MCTD) with a high antibody levels (≥100ng/mL) and meaningful clinical consequences: one severe allergic reaction during the second GP2013 infusion leading to treatment discontinuation, and a loss of efficacy with incomplete B depletion in 2 patients leading to RTX dose escalation from 500 mg to 1 g. Among the 151 patients not immunized at the time of the first sample, no severe allergic reaction and 6 minor allergic reactions were noted under GP2013.Conclusion:The immunogenicity of patients treated with RTX is a rare event with possible clinical and biological consequences, especially in patients with high antibody levels.References:[1]Smolen et al, Ann Rheum Dis 2017[2]Tony et al, Arthritis Care Res 2019Disclosure of Interests:None declared

Introduction La place centrale de l’IL-17A dans la physiopathologie de la spondyloarthrite axiale (AxSpA) a ete confirmee par le succes des anti-IL-17A. Cependant, la nature des populations cellulaires produisant cette importante cytokine pro-inflammatoire reste mal definie. Nous avons donc caracterise les principales populations cellulaires productrices d’IL-17A dans la AxSpA, et plus particulierement une population de lymphocytes T non conventionnels, les MAIT (Mucosal Associated Invariant T cells). Patients et methodes La production d’IL-17A de 5 populations de cellules sanguines peripheriques triees, a savoir les MAIT, les lymphocytes Tγ δ, les T CD4+, les T CD8+ et les neutrophiles a ete evaluee avant et apres stimulation par l’association de PMA, d’un ionophore calcique A23187 et de la B1,3 glucane. L’expression genique et proteique d’IL-17A etait respectivement determinee par la technologie nCounter et la technologie ultra-sensible SimoA. Les MAIT provenant d’entheses axiales de temoins sains (n = 5) etaient caracterises par cytometrie en flux, qPCR et leur production d’IL-17 evaluee apres stimulation. Resultats Dans le sang, a l’echelle cellulaire, les MAIT produisaient la plus grande quantite d’IL-17A par rapport aux T CD4+ (p Conclusion Les MAIT circulants et les MAIT residents dans les entheses axiales contribuent a la production d’IL-17 et pourraient jouer un role important dans la physiopathologie de l’AxSpA.

Introduction L’efficacité vaccinale anti-SARS-CoV-2 est réduite chez les patients traités par rituximab (RTX) [1]. L’objectif de ce travail a été d’identifier quels facteurs influencent la réponse humorale aux vaccins contre la COVID-19 chez les patients traités par RTX. Patients et méthodes Étude observationnelle prospective de soin courant incluant consécutivement des patients atteints de rhumatismes inflammatoires chroniques et de maladies systémiques hospitalisés pour réalisation d’une nouvelle perfusion de RTX entre avril 2021 et juin 2021. L’ensemble des patients avaient reçu deux doses de vaccins anti-COVID-19. Une sérologie COVID-19 était systématiquement réalisée le jour de l’hospitalisation, permettant la détection et la quantification des anticorps dirigés contre les protéines virales Spike (anti-S, seuil > 15 UA/mL, LIAISON® SARS-CoV-2 S1/S2 IgG immunoassay, DiaSorin). Un dosage systématique des CD19 était également effectué le jour de la perfusion (Aquios, Beckman Coulter). Résultats Quarante-cinq patients (39 femmes) ont été inclus, avec un âge moyen de 63 ± 11 ans et une durée moyenne d’évolution de la maladie de 19 ± 9 ans. La majorité des patients avaient une polyarthrite rhumatoïde (PR, 34 patients, 76 %) ; 5 avaient une sclérodermie systémique, 2 un lupus systémique, 2 une connectivite mixte et 2 un syndrome de Sjögren. La dose cumulée moyenne reçue de RTX était de 7 ± 5,5 g et 25/45 patients (56 %) avaient des CD19 indétectables ( 30, la maladie de fond, la dose cumulée de RTX, les CD19 > 18/mL, une durée entre la dernière perfusion de RTX et la vaccination > 6 mois, le taux de gammaglobulines, un traitement associé par méthotrexate et corticoïdes a identifié les CD19 > 18/mL comme l’unique variable associée à une sérologie positive (odds ratio : 35,2, IC95 % : 3,59–344,20). Conclusion La déplétion lymphocytaire B est le principal facteur de réponse humorale à la vaccination anti-SARS-CoV-2 chez les patients traités par RTX. La surveillance des CD19 pourrait être intéressante afin d’identifier la meilleure période pour effectuer la vaccination.

Introduction La pandémie de COVID-19 a catalysé l’émergence rapide de la télémédecine. Cet outil a été l’unique moyen de poursuivre l’activité de consultation pendant la première vague de la pandémie. Notre objectif a été de décrire sur quels paramètres les malades atteints de polyarthrite rhumatoïde (PR) vus en téléconsultation ont été évalués, et d’identifier les éléments sur lesquels les rhumatologues se sont appuyés pour prendre leur décision. Patients et méthodes Il s’agit d’une étude rétrospective monocentrique observationnelle. Nous avons inclus l’ensemble des patients atteints de PR, définie par le rhumatologue dans le « catalogue rhumatologique » du logiciel ORBIS, vus pour leur suivi entre mars et septembre 2020 en consultation téléphonique ou en téléconsultation réalisée à partir du système ORTIF. Les paramètres ayant permis l’évaluation du patient ont été recueillis dans le dossier médical. L’intervention du rhumatologue a été définie par une intensification thérapeutique et/ou une convocation pour une visite présentielle en consultation ou hospitalisation (de jour ou conventionnelle). Résultats 143 patients atteints de PR ont été inclus (117 femmes, 82 %) avec un âge moyen de 58 ± 16 ans et une durée de la maladie de 14 ± 11 ans. Les anti-CCP étaient positifs chez 104 patients (73 %), les facteurs rhumatoïdes chez 100 patients (70 %) et 75 patients présentaient des érosions (52 %). Sur le plan thérapeutique, 96 recevaient du méthotrexate (67 %), 67 une corticothérapie (47 %) et 69 un traitement biologique ou synthétique ciblé (48 %). La téléconsultation a eu lieu par téléphone pour 106 patients (74 %) et par visioconsultation pour 37 patients (26 %). La survenue de poussées de la maladie a été recherchée pour l’ensemble des patients et a été détectée chez 43 d’entre eux (30 %). Un seul patient avec poussée avait arrêté ses traitements par crainte de la pandémie. Les indices utilisés pour évaluer la PR ont été, par ordre décroissant : la présence et/ou le nombre d’articulations douloureuses (n = 109, 76 %), la durée de la raideur matinale (n = 95, 66 %), le nombre de réveils nocturnes (n = 95, 66 %), la valeur de la CRP (n = 77, 54 %), l’EVA globale évaluée par le patient (n = 68, 48 %), la valeur de la vitesse de sédimentation (n = 51, 36 %), la présence et/ou le nombre d’articulations gonflées (n = 48, 33,5 %), le score DAS28 (VS ou CRP) (n = 37, 26 %), l’EVA douleur (n = 33, 23 %) et l’EVA Asthénie (n = 24, 17 %). La téléconsultation a conduit à une intensification thérapeutique chez 13 patients (introduction ou augmentation de la corticothérapie chez 8 patients, introduction ou majoration du méthotrexate chez 4 patients et introduction de l’hydroxychloroquine chez 1 patient) et à une demande de visite présentielle pour 7 patients. Après analyse multivariée par régression logistique, la survenue d’une ou plusieurs poussées (Odds Ratio, OR : 15,6 ; IC95 % : 3,37–68,28) et une CRP > 5 mg/L (OR : 3,32, IC95 % : 1,12–13,27) étaient les seules variables indépendamment associées à une intervention du médecin. Conclusion La survenue de poussées, le nombre d’articulations douloureuses, la durée de la raideur matinale, le nombre de réveils nocturnes et la valeur de la CRP étaient les paramètres les plus fréquemment collectés au cours de la téléconsultation. La survenue d’une ou plusieurs poussées de PR et une valeur de CRP élevée ont été les éléments principaux ayant motivé une intervention du rhumatologue en téléconsultation. La validation de ces paramètres pour une utilisation en pratique courante de télémédecine est en cours dans une étude prospective.

Introduction L’impact des traitements immunomodulateurs utilisés dans les rhumatismes inflammatoires chroniques sur la réponse humorale anti-SARS-coV-2 et sur la persistance virale dans la sphère nasopharyngée (NP), les selles et le sang a été peu étudié à ce jour. L’objectif était de caractériser la réponse humorale anti-SARS-CoV-2 ainsi que la persistance virale NP, sérique et fécale de patients sous immunomodulateurs (DMARDs) pour un rhumatisme inflammatoire chronique, comparativement à une population témoin sans rhumatisme inflammatoire chronique et non immunodéprimée. Patients et méthodes Étude longitudinale prospective (inclusions de juin 2020 à maintenant) de patients sous DMARDs synthétiques et/ou biologiques pour une spondyloarthrite (SpA) ou une polyarthrite rhumatoïde (PR). Les titres d’Ac anti-Spike (S) et anti-Nucleocapside (N) en IgG et IgA ont été déterminés dans le sérum et sur l’écouvillonnage NP. La persistance virale NP, fécale et sérique a été déterminée par RT-PCR. L’ARNémie plasmatique du SARS-CoV-2 a été déterminée par RT-PCR numérique ultrasensible sur gouttelettes (BioRad®). Résultats Un total de 96 patients (50 SpA et 46 PR) d’âge moyen 53 ± 14 ans ont été inclus dans l’étude COVIRIC après une infection confirmée à SARS-CoV-2 (RT-PCR et/ou sérologie positive et/ou tomodensitométrie (TDM) thoracique compatible). 20 témoins (âge moyen 49 ± 16 ans) correspondant à des collatéraux de ces patients (conjoints, enfants majeurs) vivants sous le même toit et infectés au même moment ont été inclus comme population contrôle. Les réponses immunes ont été analysées selon 6 groupes de traitement : méthotrexate (MTX)/salazopyrine (SLZ) monothérapie (n = 17/2) ; anti-TNF monothérapie (n = 24), anti-TNF + MTX (n = 23) ; rituximab (RTX) (n = 11) ; traitements ciblant la voie IL17/23 (n = 8) ; autres (n = 11). Les visites étaient effectuées à 1 mois (29 ± 13 jours ; n = 18), 3 mois (110 ± 23 jours ; n = 67), 6 mois (231 ± 35 jours ; n = 48) et 12 mois (368 ± 19 jours ; n = 19) après l’infection. Aucune des visites n’était post-vaccinale. La distribution des titres d’Ac IgG anti-S et anti-N n’était pas significativement différente dans les 6 groupes de traitement et la population témoin à 3 mois. En revanche, on notait une diminution significative des IgA anti-S dans les groupes de traitement par RTX (p = 0,007) et par molécules ciblant la voie IL17/23 (p = 0,007). On observait une tendance similaire mais non significative dans ces mêmes groupes de traitement pour les IgA anti-N (p = 0,07) dans le sérum et pour la quantification des IgA anti-S anti-SARS-CoV-2 dans les prélèvements NP du groupe RTX comparativement aux témoins (p = 0,07). Les titres des Ac anti-SARS-CoV-2 à M3, quel que soit leur sous-type, ne conditionnaient pas la sévérité de l’infection COVID-19. La détection de l’ARN SARS-Cov-2 dans les selles et le sérum était négative pour l’ensemble des prélèvements réalisés à 1 mois et 3 mois. 4 patients (2 PR ; traitement par abatacept (ABA)/RTX ; 2 SpA traitement par ADA/sécukinumab) avaient une RT-PCR NP positive avec charge virale faible à très faible à la visite de 1 mois (Ct moyen 36). Aucun de ces 4 patients n’avaient eu une forme sévère d’infection COVID19. Conclusion Les traitements analysés dans cette étude n’ont pas eu d’impact significatif sur les titres d’IgG anti-N et anti-S. En revanche, les traitements par RTX et ceux ciblant la voie IL17/23 semblent impacter la réponse humorale IgA mais sans lien avec la sévérité de l’infection dans la population étudiée. Les différents traitements analysés n’induisaient pas de persistance virale sérique ou dans les selles.

Introduction La bioequivalence entre le rituximab (RTX) princeps et son biosimilaire GP2013 a ete demontree dans la polyarthrite rhumatoide (PR) [1] . Un essai randomise controle recent a suggere sur une population selectionnee une tres faible immunogenicite du GP2013 dans la PR ( [2] . Notre objectif a ete d’etudier en pratique courante le risque d’immunogenicite des patients traites par GP2013 pour leur rhumatisme inflammatoire chronique. Patients et methodes Etude prospective de soins courants realisee entre septembre 2018 et aout 2020 dans le service de Rhumatologie de l’hopital Cochin. Nous avons inclus consecutivement les patients traites par le biosimilaire du RTX GP2013, utilise dans le service de facon systematique depuis mars 2018. Des Prelevements systematiques ont ete effectues avant chaque perfusion afin de doser par technique ELISA les anticorps (Ac) anti-RTX et les concentrations residuelles de RTX (Lisa Tracker Duo Rituximab, LTR005, Theradiag). Resultats Nous avons inclus 159 patients consecutifs traites par GP2013 (124 femmes, 78 %) avec un âge moyen de 59 ± 13 ans et une duree moyenne de la maladie 18 ± 11 ans. Parmi ces 159 patients, 108 (68 %) avaient une PR et 51 une autre maladie (16 sclerodermies systemiques (SSc), 15 connectivite mixte (CM), 5 lupus systemiques (LES), 5 myopathies inflammatoires (MI), 5 rhumatismes inflammatoires inclasses, 2 arthrites juveniles idiopathiques (AJI) et 3 syndromes de Sjogren primitifs). 137 patients (86 %) recevaient un traitement de fond associe, principalement du methotrexate (111/137 patients, 81 %). 120 patients (75 %) etaient traites au long cours par RTX princeps (dose cumulee de RTX : 3,5 ± 6 g) avant le switch systematique vers le GP2013 en mars 2018. Aucun retour au princeps n’est survenu pendant toute la periode de suivi. Les 39 autres patients (25 %) traites par GP2013 etaient naifs du RTX princeps. L’analyse du premier prelevement, realise avant la seconde perfusion de GP2013 a identifie 8 patients (5 PR, 1 LES, 1 CM et 1 SSc) avec des Ac anti-RTX positifs (prevalence 5 %), avec des taux variant entre 6 et > 100 ng/mL et des concentrations residuelles de RTX indetectables. Parmi ces 8 patients, 6 patients avaient precedemment recu du RTX princeps et 2 patients etaient naifs de cette molecule. Il etait note une tendance a une association entre immunisation et indice de masse corporel plus eleve (n = 8 ; 28 ± 7 vs 25 ± 6, p = 0,118), mais il n’existait aucune association entre immunisation anti-RTX et l’âge, la duree de la maladie, la prise d’un traitement de fond conventionnel associe, l’intervalle moyen entre les perfusions ou la dose cumulee de RTX. Parmi les 8 patients immunises, deux groupes ont pu etre isoles : – un groupe de 5 patients (3 PR, 1 LES, 1 SSc) avec un faible taux d’Ac (6-22 ng/mL) sans consequence clinique observee (maintien du traitement, absence de perte d’efficacite apres 13 ± 4 mois de suivi, une seule reaction allergique mineure) ; – un groupe de 3 patients (2 PR, 1 CM) avec fort taux d’Ac (≥ 100 ng/mL) caracterise par une reaction allergique severe lors de la seconde perfusion de GP2013 ayant conduit a l’arret du traitement chez un des 3 patients et une perte d’efficacite clinique avec effet fin de dose et absence de depletion B chez les 2 autres, avec pour consequence l’augmentation des doses de RTX de 500 mg a 1 g. Parmi les 151 patients non immunises lors du premier prelevement, aucune reaction allergique severe et 6 reactions allergiques mineures ont ete notees sous GP2013. L’analyse des prelevements ulterieurs (pour l’instant 97 patients avec 2 prelevements, 27 patients avec 3 prelevements) est en cours. Conclusion L’immunogenicite des patients traites par RTX est un phenomene rare, mais avec de possibles consequences cliniques et biologiques lors d’une immunisation avec un taux eleve d’Ac.

Introduction La prise en charge de la spondyloarthrite (SpA) axiale est dans certains cas difficile, tant du point de vue de sa confirmation diagnostique que de la decision therapeutique. Chez certains patients, des pathologies autres que la SpA sont susceptibles d’influencer son evaluation clinique. La dysplasie acetabulaire (DA) constitue une anomalie frequente de l’architecture de la hanche, pour laquelle plusieurs etudes ont montre qu’elle peut etre responsable de symptomes douloureux. L’objectif de cette etude ancillaire de la cohorte DESIR etait de determiner si l’identification d’un phenotype de DA est associee a la presence d’une douleur de hanche a l’examen clinique chez les patients presentant une lombalgie inflammatoire recente evocatrice de SpA axiale, pouvant alors constituer une source de confusion lors de l’evaluation des patients. Patients et methodes Cette etude a ete conduite a partir des donnees de la cohorte prospective DESIR, dans laquelle ont ete inclus des patients âges de 18 a 50 ans, presentant une lombalgie inflammatoire recente evocatrice de SpA axiale. L’evaluation radiographique de la DA a ete realisee par l’intermediaire d’une double lecture (DG et GP), a partir des radiographies de bassin de face obtenues lors de la visite d’inclusion. Pour chaque parametre d’evaluation de la DA, la moyenne des mesures faites par chaque lecteur a ete prise pour reference. Les parametres qui ont ete mesures et les valeurs limites correspondantes retenues pour definir la DA etaient : l’angle de Tonnis (> 12°) ; l’angle acetabulaire (> 45°) ; l’angle VCE–Vertical Center Edge - ( Resultats La prevalence globale de la DA etait de 21,9 % (139/636). Elle etait de 26,4 % chez les femmes (90/341) et de 16,6 % (49/295) chez les hommes. A l’exception d’une proportion plus elevee de femmes, il n’a pas ete mis en evidence de difference significative entre les patients avec DA et les autres participants pour ce qui concerne leurs caracteristiques generales et celles relatives a la SpA axiale (activite de la maladie, impact fonctionnel, caracteristiques radiologiques). La presence d’une douleur de hanche etait rapportee chez 20,9 % (29/139) des patients avec DA versus 11,9 % (59/497) chez les autres participants (p = 0,007). En limitant la definition de la dysplasie a la presence d’un angle VCE anormal, la presence d’une douleur de hanche etait rapportee chez 23,6 % (17/72) des patients avec DA versus 12,6 % (71/564) des autres participants (p = 0,01). Conclusion Parmi les patients presentant une lombalgie inflammatoire recente compatible avec une SpA axiale, la presence d’un phenotype de DA (selon plusieurs definitions) est associee a la constatation clinique d’une douleur de hanche. L’existence d’une DA sous-jacente semble pouvoir constituer un facteur de confusion lors de l’evaluation de l’activite de la maladie et/ou d’une eventuelle atteinte inflammatoire de la hanche dans le contexte de la SpA axiale.

Background:Skeletal disorders affect the skeleton in different ways with some bones being very impaired while others less severely. In translational studies using murine models of human disorders, the bone phenotype is mainly evaluated at distal femur or proximal tibia. The sacroiliac joint (SIJ), which connects the spine to the pelvis, is involved in the balanced transfer of mechanical energy from the lumbar spine to the lower extremities. Its role in biomechanical stress makes it of particular interest in various bone diseases. For instance, patients with X-linked hypophosphatemia (XLH), who mainly display osteomalacia, are frequently affected with early osteoarthritis of the SIJ. Interestingly, we recently showed that the Hyp mouse, a murine model of XLH that greatly mimics the human disorder, displayed early and severe osteoarticular alterations of the SIJ [1].Objectives:Here, using the Hyp mouse as a model, we show that the SIJ constitutes a highly reliable joint to investigate in murine models of skeletal disorders.Methods:SIJ and distal femur were evaluated in 3-month-old Hyp mice compared to wild-type (WT) mice (n=10 per group). using high-resolution microCT. Measurements of trabecular and cortical bone parameters at sacral and iliac sides and trabecular bone parameters at distal femur were performed with the CTanalyzer software.Results:Hyp mice displayed a significant reduction in parameters of trabecular bone at distal femur, compared to WT mice (Figure 1A). Similarly, a reduction in trabecular bone was shown in Hyp SIJ compared to WT at sacral side (Figure 1B). There was a significant positive correlation between trabecular bone parameters of distal femur and sacral side of SIJ in Hyp mice (e.g. bone volume to total volume [BV/TV]: r = 0,763 p: 0,01). Bone parameters such as sacral BV/TV were higher in comparison to femoral parameters (Figure 1C). No difference was observed on trabecular bone parameters at iliac side of Hyp and WT mice. However, regarding the cortical bone of SIJ, significant alterations were noticed especially at iliac side of SIJ in Hyp mice compared to WT mice. An increase in open cortical porosity, and a decrease in cortical area fraction, as well as in average cortical thickness at iliac side of SIJ in Hyp mice were suggestive of osteo-articular lesions, characteristic for XLH.Conclusion:Trabecular bone parameters at the SIJ, in comparison to the femur, appear to be a relevant alternative to evaluate bone alterations in Hyp mice. Our study suggests that the SIJ represents a valuable tool to investigate both bone and local osteo-articular alterations for murine models of skeletal disorders.Figure 1.A) Bone to total volume ratio in the trabecular bone of distal femur, expressed in percent. B) Bone to total volume ratio in the trabecular bone of sacral slope of the SIJ, expressed in percent. C) Bone to total volume ratio in the trabecular bone of distal femur and sacral slope of the SIJ of Hyp mice, expressed in percent. *: p < 0,05; **: p < 0,01; ***: p< 0,001; ****: p< 0,0001.References:[1]Cauliez, Zhukouskaya et al. Impact of Early Conventional Treatment on Adult Bone and Joints in a Murine Model of X-Linked Hypophosphatemia. Front Cell Dev Biol.:doi: 10.3389/fcell.2020.591417Disclosure of Interests:None declared.

Introduction Chez les patients (pts) atteints de spondylarthrite ankylosante (SA), il est difficile de predire precocement l’evolution de la maladie en raison de l’heterogeneite des symptomes, de la severite de la maladie et des criteres d’evaluation qui, en dehors de la progression radiographique, sont principalement rapportes par les patients. L’objectif de cette analyse etait d’evaluer si les caracteristiques a l’initiation du traitement peuvent permettent de predire la reponse au secukinumab (SEC) chez les pts atteints de SA, afin d’optimiser la prise en charge et definir des objectifs individualises et realistes [1] , [2] . Patients et methodes Cette analyse post hoc a ete realisee en combinant les donnees de 4 etudes de phase 3 (MEASURE 1-4) [3] , [4] , [5] ayant inclus des pts atteints de SA traites par SEC 150 mg (n = 747) et 300 mg (n = 113). Une analyse par regression logistique univariee a ete appliquee pour rechercher les potentiels facteurs predictifs a l’inclusion (p Resultats Les facteurs a l’inclusion significativement associes en analyse multivariee (p Conclusion La presente analyse a identifie un jeune âge, un IMC bas, une hsCRP elevee, un statut naif d’anti-TNF, une distance occiput-mur et un score MASES faibles comme etant associes a une meilleure reponse au SEC. Ces facteurs pourraient permettent de predire le devenir des pts atteints de SA traites par SEC.

Introduction L’uveite est la manifestation extra rhumatologique la plus frequente de la spondylarthrite axiale (SpA). DESIR est une cohorte multicentrique prospective de patients presentant des douleurs rachidiennes inflammatoires recentes evocatrices de SpA. Nous avons precedemment rapporte une prevalence de base de 8,5 % d’uveite pour les patients inclus dans la cohorte ; l’uveite etait associee a une maladie inflammatoire de l’intestin (MICI) et a une infection anterieure [1] . L’objectif de l’etude etait d’evaluer la prevalence et l’incidence de l’uveite au cours des cinq premieres annees de suivi prospectif de la cohorte, et d’evaluer les facteurs qui y sont associes. Patients et methodes DESIR est une cohorte d’observation prospective de patients presentant des douleurs rachidiennes inflammatoires d’apparition recente (plus de 3 mois, moins de 3 ans), suggerant une SpA axiale. Tous les facteurs disponibles dans la base de donnees ont ete compares entre les patients avec et sans uveite a 5 ans, par analyse uni puis multivariee. Les facteurs de base associes aux nouveaux cas d’apparition d’uveite au cours des 5 ans ont egalement ete analyses. Signification : p inferieur a 0,05. Resultats Apres 5 ans, 91 patients (sur 480 avec un suivi complet) ont eu au moins un episode d’uveite, ce qui donne une prevalence estimee a 18,9 % [95 %CI : 15,4-22,4]. En analyse multivariee, l’uveite a ete associee a une dactylite (RC 2,92 [2,06–4,14] ; p = 0,002**), VS > 7 mm (valeur mediane) (RC 2,19 [1,57–3,06] ; p = 0,018*). De nouveaux cas incidents d’uveite sont apparus dans 31 cas sur 5 ans, ce qui donne un taux d’incidence estime a 1,29/100 patients-annees [0,84–1,74]. La nouvelle incidence de l’uveite a ete associee, dans l’analyse multivariee, aux facteurs de base suivants : diagnostic de SpA (RC 9,65 [3,21–28,96] ; p = 0,039*), score total de SPARCC inflammatoire en IRM sacro-iliaque (lecture centrale) sur la mediane (RC 3. 98 [2,26–7] ; p = 0,015*), dactylite (OR 4,7 [2,65–8,36] ; p = 0,007**), score de syndesmophyte par rapport a la mediane (lecture centrale) (OR 0,22 [0,1–0,45] ; p = 0,039*). Aucune association significative n’a ete trouvee avec HLA-B27, les DMARD cs ou b, BASDAI, ASDAS, BASFI. Conclusion Les donnees sur cinq ans de la cohorte DESIR ont permis d’estimer le taux d’incidence de l’uveite a 1,3/100p-an sur cinq ans, l’uveite a ete associee a une dactylite, a une inflammation biologique et sacro-iliaque par IRM.

Objectives:Secukinumab (SEC) is an interleukin-17 inhibitor used to treat patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Drug maintenance is often used as a proxy for treatment effectiveness and safety in real life settings. We aim to assess SEC maintenance in routine clinical practice and to identify survival predictors associated.Methods:We conducted a retrospective, longitudinal, observational, multicenter study including all patients (pts) with axSpA or PsA who received at least 1 injection of SEC between July 2016 and October 2019. We collected patient’s demographics and clinic characteristics, SEC date of initiation and dosage and dosage modification of SEC, previous biologic Disease-modifying antirheumatic drugs (bDMARDs) and concomitant treatments. Date and reasons of discontinuation – i.e., lack of efficacy, safety issue, sustained remission or others – were collected. Several potential maintenance predictors were tested: age, gender, disease (axSpA or PsA), smoking status, bDMARDs history and concomitant treatment. Among patients with non-radiographic axSpA (nr-axSpA), evidence of MRI sacroiliitis or elevated CRP were also assessed as potential maintenance predictors. Drug maintenance was analyzed by the Kaplan-Meier method and adjusted for baseline factors were estimated by log rank analysis.Results:The main characteristics of the 561 pts included were the following: 363 (64.7%) axSpA, 198 (35.3%) PsA, 329 (58.6%) female, mean age 45,6 +/- 12 years, 221 (39.4%) smokers, 175 (31.2%) radiographic sacroiliitis, 259 (46.2%) MRI sacroiliitis, 198 (35.3%) elevated CRP, 247 (44.0%) HLA B27 positive, mean BASDAI 48,3 +/- 26.8%. SEC was associated to methotrexate (MTX) in 139 pts (24.8%) and was the first line bDMARD in 55 pts (9.8%). The median drug maintenance (MDM) of SEC was 79 weeks (wk) [73-84]. At 52 wk, 245 pts (60%) SpA were still treated with SEC. During the 3-year follow-up, 264 pts discontinued SEC: 180 (68.2%) pts for lack of effectiveness, 47 (17.8%) for adverse events, 14 (5.3%) for others and 23 (8.7%). SEC prescription as first line bDMARD was associated with longer survival versus second line or more: 111 wk [83-138] vs. 69 wk [57-80] (p=0. 017) (figure 1). MDM was not significantly different depending on gender, MTX combo, elevated CRP, axSpA vs PsA and smoking status. Among the nr-axSpA pts, MRI sacroiliitis or elevated CRP did not modify SEC maintenance (p=0.68) (figure 2).Figure 1.Secukinumab maintenance according to therapeutic lineFigure 2.Secukinumab maintenance in nr-axSpA populationConclusion:In routine clinical practice, SEC median maintenance was 79 weeks. Fist line administration was the only independent factor associated with improved SEC retention. Lack of effectiveness was the most common reason of discontinuation.Disclosure of Interests:Benoît Flachaire: None declared, Jean-Guillaume Letarouilly Grant/research support from: Research grant from Pfizer, Céline Labadie: None declared, Nicolas Cohen Speakers bureau: Novartis, Janssen, Vincent Pradel: None declared, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Guy Baudens: None declared, Pascal Claudepierre Speakers bureau: Janssen, Novartis, Lilly, Corinne Miceli Richard: None declared, Philippe Dieudé: None declared, Jean-Hugues Salmon Speakers bureau: Novartis, Janssen, Jérémie SELLAM: None declared, Eric Houvenagel Speakers bureau: Janssen, Novartis, Marie-Hélène Guyot: None declared, Chi Duc Nguyen: None declared, Xavier Deprez Speakers bureau: Novartis, Janssen, Isabelle CHARY VALCKENAERE: None declared, Pierre Lafforgue Speakers bureau: Novartis, Janssen, Damien LOEUILLE: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly, Thao Pham Speakers bureau: Novartis, Janssen, Lilly

Background:Real-world data are missing for Ustekinumab (UST) and secukinumab (SEK) in psoriatic arthritis (PsA).Objectives:To evaluate the characteristics of the patients (pts) with PsA treated by UST or SEK and to assess real world persistence of UST and SEK in PsA.Methods:This is a retrospective, multicenter study of pts with PsA (CASPAR criteria or diagnosis confirmed by a rheumatologist) initiating UST or SEK with a follow-up ≥ 6 months from January 2011 to April 2019. The comparison of persistence between UST and SEK was analysed using a Cox model with an inverse probability of treatment weighting propensity score including 11 confounding factors. Subgroup analyses (age>65 years, gender, Body Mass Index (BMI), Charlson score>2, psoriasis, CRP>5mg/L, number (nb) of prior biotherapies, proportion of pts on maximum dose of UST or SEK, combination with methotrexate (MTX), enthesitic and axial forms of PsA) were also performed to test the heterogeneity of UST and SEK persistence. Finally, 2 sensitivity analyses were performed, first excluding the pts treated before the marketing authorization of SEK, and then excluding the pts that underwent a molecule switch. Causes of discontinuation were also collected.Results:406 pts were included: 245 with UST and 161 with SEK. At baseline before propensity score-matching, the UST group has a higher BMI (28.9 ± 6.4 kg/m2vs. 27.4 ± 6.0 kg/m2), more peripheral forms (98% vs. 90.8%), a higher nb of active smokers (27.1% vs. 19.9%), a higher frequency of psoriasis (96.3% vs. 83.2%), less MTX users (38.9% vs. 44.2%), a higher nb of pts with CRP >5mg/L (54.3% vs. 47%), a higher nb of pts naïve to biotherapies (22% vs. 13%) and a higher nb of pts with recommended dosing (97.3% vs 50.9%). The median persistence was 9.4 months and 14.7 months for UST and SEK, respectively. The persistence rate was lower in the UST group compared to the SEK group (40.9% vs. 59.1% % at 1 year; 26.4% vs. 38.0% at 2 years; weighted HR=1.42; 95% CI 1.07 to 1.92; p=0.015) (Fig 1). In subgroup analysis, combination with MTX was associated with a higher persistence rate in the patients with SEK compared to those receiving UST: 43.6% vs. 23.2% (HR=2.20; 95% CI 1.30 to 3.51; p=0.001), whereas no difference was observed in SEK and UST monotherapy: 33.8% vs 28.4%, respectively (HR=1.06; 95% CI 0.74 to 1.53; p=0.75) (Fig 2). A similar difference was found in the sensitivity analyses, with however a difference at the limit of significance for the analysis excluding pts with a molecule switch (adjusted HR=1.35; IC95% 0.96 to 1.92; p=0.085). The causes of discontinuation were due to inefficacy in 85% of cases and an adverse event in 12% of cases (19% in the SEK group and 9% in the UST group).Conclusion:In this first real-world study comparing UST and SEK persistence in PsA, the persistence of SEK was longer than that of UST. Subgroup analysis revealed this difference of persistence was restricted to patients treated in combination with MTX.Disclosure of Interests:Jean-Guillaume Letarouilly Grant/research support from: Research grant from Pfizer, Benoît Flachaire: None declared, Céline Labadie: None declared, Nicolas Cohen Speakers bureau: Novartis, Janssen, Maeva Kyheng: None declared, Jérémie SELLAM: None declared, Pascal Richette: None declared, Philippe Dieudé: None declared, Pascal Claudepierre Speakers bureau: Janssen, Novartis, Lilly, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Eric Houvenagel Speakers bureau: Janssen, Novartis, Chi Duc Nguyen: None declared, Marie-Hélène Guyot: None declared, Nicolas Segaud: None declared, Frederic Maury: None declared, Laurent Marguerie: None declared, Xavier Deprez Speakers bureau: Novartis, Janssen, Jean-Hugues Salmon Speakers bureau: Novartis, Janssen, Guy Baudens: None declared, Corinne Miceli Richard: None declared, Elisabeth Gervais Speakers bureau: Novartis, Janssen, Roche, Pfizer, BMS, Abbvie, Isabelle CHARY VALCKENAERE: None declared, Pierre Lafforgue Speakers bureau: Novartis, Janssen, Damien LOEUILLE: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Thao Pham Speakers bureau: Novartis, Janssen, Lilly, Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly

Background:It is currently not known if TNF or IL-17A inhibitors have an impact on immune cell frequencies in axial Spondyloarthritis (AxSpA). This question is important to understand the impact of biologics on the immune system. Data from clinical trials didn’t show significant modification on immune cells and especially on lymphocytes. But regarding the risk of infections linked to these treatments lymphocyte cell subsets are certainly disturbed. Moreover, biologics could affect subsets of cells with an unusual phenotype.Objectives:To identify the phenotype of cell subsets affected by biologics.Methods:We used an “unsupervised approach” to analyze CD4+ T cells and CD8+T cells subsets. Contrary to a “supervised approach”, this strategy takes advantages of the fluorescence emitted by all of the surface markers used to characterize the cells at the same time. The objective was on the one hand to overcome statistical problems related to the number of patients and the repetition of the tests and on the other hand to increase the sensitivity of the analysis by identifying and analyzing new cell populations. The first step was to cluster the cells based on a selection of 12 T cells markers characteristic of the classical cell subsets and the stage of maturation to obtain cell clusters with a phenotype based on the combination of these 12 markers. Then, we were able to describe “a posteriori” the change of frequency of the clusters identified. The second step was to create a visualization of the cells affected to confirm their existence in a classical flow cytometry gate. With this pipeline, we analyzed CD4 and CD8 T cells isolated from a group of AxSpA patients (n=7) before and after 3 months of TNF therapy and a group of patients (n=6) before and after 4 months of IL-17A therapy.Results:We observed that after biologics CD4 and CD8 T cells frequencies did not change but there was a redistribution of the different clusters analyzed. Specifically, we identified for CD4+T cells after anti TNF treatment an increase of 2 clusters (CD4+CD27+CD45RA+Va7.2intCD161int and CD4+CD27-CD45RA-CCR6+CD161int) and a decrease of 3 clusters (CD4+CD27+CD45RA+CRTH2intCD161int, CD4+ CD27+CD45RA+CXCR3+, CD4+CD27+CD45RA+gdint CD161int) and for CD8+T cells a decrease of 1 cluster after treatment (CD8+ CD27+CD45RA+CD161+CXCR3+) and an increase of 1 cluster (CD8+ CD27+CD45RA+). The clusters affected by anti-IL-17A therapy were different. For CD4+T cells, we identified a decrease of 2 clusters (CD4+CD27+CD45RA+CXCR5+ CD161+ and CD4+CD27+CD45RA- CXCR3+CCR6+CD161+) and an increase of 2 clusters (CD4+CD27+CD45RA+gdintCD161+, CD4+CD27+ CRTH2intCCR6+) and for CD8+T cells a decrease of 1 cluster (CD8+CD27+CD45RA+ CXCR3+CRTH2intCD161int) and an increase of 1 cluster (CD8+CD27+CD45RA+CXCR3intCD161-).Conclusion:We identified 5 different clusters in CD4+T cells affected by anti TNF and 4 by anti-IL-17A. We identified 2 clusters in CD8+T cells affected by anti TNF and 2 by anti-IL-17A. The phenotypes of these clusters were unexpected and raised new questions about the effect of biologics in AxSpA. We were also able to create a visualization of these cells affected by biologics in a “classic gating view” which will help us to perform scRNAseq. With this unique approach, we show an impact of biologics on the frequency of very specific subset of CD4+ and CD8+ T cells in AxSpAFigure 1.Disclosure of Interests:None declared

Background:Uveitis is the most frequent extra rheumatological manifestation in axial Spondyloarthritis (SpA). DESIR is a prospective multicenter cohort of patients with early inflammatory back pain suggestive of SpA. We reported previously a 8.5% baseline prevalence of uveitis for the patients included in the cohort; this history of uveitis at the first visit of the cohort was associated with inflammatory bowel disease (IBD) and preceding infection (1).Objectives:The aim of the study was to evaluate the prevalence and incidence of uveitis over the first five years of prospective follow-up of the cohort, and to evaluate its associated factors.Methods:DESIR is a prospective observational cohort of patients with recent onset inflammatory back pain (more than 3 months, less than 3 years), suggestive of axial SpA, All available factors in the database were compared between patients with and without uveitis at 5 years, by uni and then multivariate analysis. Baseline factors associated with new cases of uveitis occurrence over the 5 years were also analyzed. Significance: p less than 0.05.Results:After 5 years, 91 patients (out of 480 with complete follow-up) had at least one uveitis episode, giving an estimated prevalence of 18.9% [95%CI: 15.4-22.4]. In multivariate analysis, uveitis was associated with dactylitis (OR 2.92 [2.06 – 4.14]; p=0.002**), ESR > 7mm (median value) (OR 2.19 [1.57 – 3.06]; p=0.018*).New incident uveitis occurred in 31 cases over 5 years, giving an estimated incidence rate of 1.29 [0.84 – 1.74] / 100 patient-years. New incidence of uveitis was associated in multivariate analysis with the following baseline factors: diagnosis of SpA (OR 9.65 [3.21 – 28.96]; p=0.039*), total sacro iliac MRI inflammatory SPARCC score (central reading) over median (OR 3.98 [2.26 – 7]; p=0.015*), dactylitis (OR 4.7 [2.65 – 8.36]; p=0.007**), syndesmophyte score over median (central reading) (OR 0.22 [0.1 – 0.45]; p=0.039*).No significant association was found with HLA-B27, cs or b DMARDs, BASDAI, ASDAS, BASFI.Conclusion:Five-years data of the DESIR cohort allowed an estimation of incidence rate of uveitis of 1.3/100p-y; over five years, uveitis was associated with dactylitis, biologic and sacro iliac MRI inflammation.References:[1]Wendling D, et al.Arthritis Care Res(Hoboken). 2012 Jul;64(7):1089-93.Disclosure of Interests:Daniel Wendling: None declared, Clément Prati: None declared, Thierry Lequerre: None declared, Corinne Miceli Richard: None declared, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Anna Moltó Grant/research support from: Pfizer, UCB, Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, UCB, xavier guillot: None declared

Background Elevated baseline (BL) CRP levels is one of the predictors of treatment response in patients (pts) with active AS.1 The relationship between BL CRP levels and the treatment response to IL-17A inhibition has not been assessed in AS pts thus far. Objectives This post-hoc analysis assessed the response to secukinumab (SEC) treatment in AS pts with normal or elevated BL CRP from the phase 3 MEASURE 1 and MEASURE 2 studies over 3 years. Methods The study designs of MEASURE 1 and 2 have been reported.2 This analysis pooled data from all pts with available BL CRP levels who received subcutaneous (s.c.) SEC 150 mg (approved dose; n=197) or placebo (PBO; n=195). Efficacy endpoints included ASAS20/40, BASDAI, BASDAI50, ASDAS inactive disease, and ASAS partial remission (PR) stratified by normal ( 5–10,>10–15,>15 mg/L. Data are presented as non-responder imputation (NRI) at Week (Wk)16 and multiple imputation (MI) at Wk156 for binary variables and mixed-effect model repeated measure (MMRM) at Wks 16 and 156 for continuous variables. Results Overall, 36.5% (143/392) of pts with normal CRP and 63.5% (249/392) of pts with elevated BL CRP were included in the pooled analysis. BL characteristics were balanced across normal and elevated BL CRP groups.3 At Wk16, efficacy endpoints were improved with SEC 150 mg vs PBO in pts with normal or elevated BL CRP.3 Results were consistent across all levels of elevated BL CRP with a trend for greater improvement in pts with more elevated CRP (Table). Improvements were sustained or further improved at Wk156 in all groups (Table). Conclusions SEC 150 mg demonstrated sustained efficacy through 3 years in AS patients with both normal and elevated CRP levels, with an increased effect in elevated CRP patients. References [1] Davis JC Jr, et al. J Rheumatol. 2005;32:1751–4. [2] Baeten D, et al. N Engl J Med 2015;373:2534–48. [3] et al. Arthritis Rheumatol 2017;69 [4] Braun J, et al. Arthritis Rheumatol 2017;69(suppl 10). Acknowledgements The study was sponsored by Novartis Pharma AG Disclosure of Interest J. Braun Grant/research support from: AbbVie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB, Consultant for: AbbVie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB, Speakers bureau: AbbVie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB, J. Sieper Grant/research support from: AbbVie Inc., Pfizer Inc., and Merck, Consultant for: AbbVie Inc., Pfizer Inc., Merck, UCB, and Novartis, Speakers bureau: AbbVie Inc., Pfier Inc., Merck, and UCB, R. Landewe Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, Wyeth, Consultant for: Abbott/AbbVie, Ablynx, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Centocor, GlaxoSmithKline, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB, Wyeth, Speakers bureau: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB, Wyeth, X. Baraliakos Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Werfen, Consultant for: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Werfen, C. Miceli-Richard Grant/research support from: Abbott/AbbVie, Bristol-Myers Squibb, Novartis, Merck, Pfizer, Wyeth, Consultant for: Pfizer, Roche, UCB, Wyeth, Merck, Speakers bureau: Abbott, Bristol-Myers Squibb, Merck, Pfizer, Roche, Schering-Plough, Wyeth, E. Quebe-Fehling Employee of: Novartis, B. Porter Shareholder of: Novartis Pharmaceutical Corporation, Employee of: Novartis Pharmaceutical Corporation, K. Gandhi Shareholder of: Novartis Pharmaceutical Corporation, Employee of: Novartis Pharmaceutical Corporation, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB

Background Inflammatory bowel disease (IBD) is a well-known extra articular feature of spondyloarthritis (SpA), with increasing evidence of a pathophysiological relationship. Objectives The aims of this study were to evaluate in the DESIR cohort a) the prevalence of IBD at baseline and M60, and b) the incidence of IBD over the first 5 years of follow-up, c) factors (epidemiological, clinical, imaging, biological data available in the database) associated with IBD, a on the prevalent cases at baseline and at year 5 and also on the incident cases. Methods DESIR is a prospective observational cohort of patients with recent onset ( Results At baseline, 706 patients were analysed, 35 had a past history or a concomitant IBD: prevalence 4.94% [CI 95%: 3.3–6.5]. IBD was significantly associated (univariate) with family history of IBD, DMARD use, steroid use, history of uveitis, elevated ESR and negatively associated with psoriasis, HLA-B27 and NSAID score. In multivariate analysis IBD was positively and independently associated with history of uveitis; OR 3.62 [1.95–6.74], levels of DKK-1: OR 1.03 [1.02–1.05] and TNF serum levels: OR 1.17 [1.08–1.26]. IBD was not associated with phenotypic presentation (peripheral arthritis, enthesitis, dactylitis, uveitis) or baseline serum levels of other cytokines (IL-6, IL-17 A, IL-17 F, IL-23, IL-23). At M60, 480 patients were analysed, 58 with IBD: prevalence 12.1% [9.17–14.99]. In univariate analysis on prevalent cases, IBD was associated with lower NSAID score, worse activity and function indexes (ASDAS-CRP, BASFI, SF-36, HAQ, ASQoL), use of DMARD anti TNF, more sick leave. In multivariate analysis, IBD was associated with fulfilment of modified New York criteria: OR 4.85 [2.23–10.57], sick leave: OR 1.01 [1.005–1.014], BASDAI: OR 1.10 [1.05–1.16], and with smoking: OR 2.79 [1.53–5.07]. No association with MRI scores, enthesitis, psoriasis, BMD. After a 5 year follow-up period, 23 new incident cases of IBD were recorded, giving an estimated occurrence rate of 0.95/100 [0.57–1.35] patient-years in this population. Incidence of IBD was independently associated (multivariate) with: HLA B27: OR 0.36 [0.22–0.59], fulfilment of modified New York criteria at M0: OR 3.35 [1.85–6.08], family history of IBD: OR 3.31 [1.62–6.77]. Conclusions In early SpA, IBD occurs with an incidence of around 1/100 patient-years, and is associated with poor outcome at 5 years, family history of IBD, absence of HLA-B27, fulfilment of modified New York criteria. Disclosure of Interest None declared

Background Uveitis, a common extra-articular manifestation of SpA, has an estimated prevalence in patients (pts) with ankylosing spondylitis (AS) of 33.2%, which increases with disease duration and positive HLA-B27 status.1 Uveitis occurs in 10%–50% of SpA pts.1 The exposure-adjusted incidence rate [EAIR] of uveitis (combined new-onset and flares) reported in AS pts treated with TNF inhibitors is 2.6–3.5 per 100 patient-years (pt-yrs).2–5 Objectives To assess the incidence of uveitis in secukinumab-treated AS pts in long-term pooled clinical data from three phase 3 trials (MEASURE 1–3 [NCT01358175, NCT01649375, NCT02008916]) and from post-marketing analyses. Methods Analysis included pooled pt-level data from all pts in MEASURE 1 who received any dose (≥1) of secukinumab up to the last pt attending Week 156 study visit, and up to visit Week 156 in MEASURE 2 and visit Week 104 in MEASURE 3 for each patient, respectively. Post-marketing data were from the most recent periodic safety surveillance report. Incidence of uveitis is reported as EAIR per 100 pt-yrs of secukinumab exposure. Results In the phase 3 AS clinical trials, 135 (17%) pts reported pre-existing (but not active or ongoing) uveitis at baseline and 589 (74.2%) pts were HLA-B27 positive. The EAIR for uveitis was 1.4 per 100 pt-yrs over the entire treatment period (n=794). Among all cases of uveitis (n=26), 14 (54%) were flares in pts with a history of uveitis at baseline (Table). The EAIR of uveitis in the post-marketing data (based on cumulative secukinumab exposure of 96 054 pt-yrs) was 0.03 per 100 pt-yrs. Conclusions: In secukinumab-treated pts with active AS, a low incidence of uveitis was observed, including new-onset cases and flares, in both clinical trials and post-marketing analyses. References [1] Zeboulon, et al. Ann Rheum Dis2008;67:955–59. [2] Wendling, et al. Curr Med Res Opin2014;30:2515–21. [3] Van der Heijde, et al. Rheumatology (Oxford)2017;56:1498–509. [4] Sieper, et al. Arthritis Rheum2014;66:S242. [5] Heldmann, et al. Clin Exp Rheumatol2011;29:672–80. Disclosure of Interest A. Deodhar Grant/research support from: AbbVie Inc., Eli Lilly, GSK, Janssen, Novartis, Pfizer Inc., UCB, Consultant for: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, C. Miceli-Richard Grant/research support from: Pfizer, Roche, UCB, Wyeth, Merck, Consultant for: Abbott/AbbVie, Bristol-Myers Squibb, Novartis, Merck, Pfizer, Wyeth, Speakers bureau: Abbott, Bristol-Myers Squibb, Merck, Pfizer, Roche, Schering-Plough, Wyeth., X. Baraliakos Grant/research support from: AbbVie, BMS, Celgene, Chugai, MSD, Novartis, Pfizer, UCB, Consultant for: AbbVie, BMS, Celgene, Chugai, MSD, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, BMS, Celgene, Chugai, MSD, Novartis, Pfizer, UCB, H. Marzo-Ortega Grant/research support from: Janssen and Pfizer, Consultant for: AbbVie, Celgene, Janssen, Novartis and UCB, Speakers bureau: AbbVie, Celgene, Janssen and UCB, D. Gladman Grant/research support from: Amgen, AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB., Consultant for: Amgen, AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB., R. Martin Shareholder of: Novartis, Employee of: Novartis, J. Safi Jr Shareholder of: Novartis, Employee of: Novartis, B. Porter Shareholder of: Novartis, Employee of: Novartis, A. Shete Shareholder of: Novartis, Employee of: Novartis

Background MicroRNAs have been shown to play a crucial role during innate or adaptive immune response. Dysregulation of miRNAs has been described in several autoimmune or rheumatic diseases including rheumatoid arthritis, inflammatory bowel disease or psoriasis. In spondyloarthritis (SpA), only few studies on miR expression have been reported with highly diverse methodologies and involving small samples of patients. Objectives Because T CD4 lymphocytes and monocytes are important cells in SpA pathophysiology, we wanted to assess the miR expression profile in these two cell types sorted from axial SpA (AxSpA) patients. Methods Eighty one AxSpA patients were included in this study. Among these patients, 74 fulfilled the ASAS classification criteria (imaging arm) with sacro-iliitis on X-rays (n=56) or objective signs of inflammation on MRI (n=18). Two independent cohorts of 22 and 59 SpA patients were compared to 17 and 38 age and sex-matched controls. Both SpA patients and controls were recruited from October 2014 to July 2017 in the department of rheumatology at Cochin Hospital in Paris, France. All SpA patients had an active disease despite NSAIDs intake (mean BASDAI score of 49±19 and mean ASDAS score of 3±0.9), were free of any biologic treatment and were eligible for a TNF-blocker treatment. Seventy-seven percent were HLA-B27 positive. T lymphocytes and monocytes were isolated from PBMC by direct isolation with magnetic microbeads (CD4 +and CD14+). Three-hundred seventy two miRs were screened by q-RT-PCR on the exploratory cohort and only MiRs showing a significant differential expression in the first cohort were analysed in the validation cohort. An unpaired T-test was used for comparison of miR expression level. Results In the exploratory cohort, 51 (CD14+) and 70 miRs (CD4+) were found to be differentially expressed between patients and controls. Among these, 15 miRs (in CD14+), and 12 miRs (in CD4+) were also found dysregulated in the validation cohort. These validated miRNAs were found to play a key role in physiological pathways such as NFkB or TGFb, Wnt signalling and monocyte differentiation that have been involved in the pathophysiology of the disease. Neither clinical subphenotypes nor biological parameters were associated with different profiles of miR expression after adjusting for multiple tests. We found a negative correlation between miR-146a-5p level and BASDAI (r=-0.28, p=0.011) and ASDAS (r=-0.38, p=5.9 10–4) in monocytes. Conclusions We found a dysregulation of miR expression in monocytes and T CD4 lymphocytes from patients with axial spondyloarthritis, whose consequences could contribute to the pathophysiology of the disease and be of interest for therapeutic perspective. Moreover, identifying biomarkers with the potential of diagnostic signature should help the clinician in daily practice. Disclosure of Interest None declared

Background: Etanercept biosimilar (bETN) is available for treatment of spondyloarthritis (SpA) and rheumatoid arthritis (RA) since 2016 in France. Data showing effectiveness and safety of bETN are still limited. Objectives: 1/To evaluate the RA and SpA patients’ and treating rheumatologists’ characteristics associated with the switch 2/To evaluate the safety and efficiency of bETN. Methods: Patients: All the patients receiving innovator etanercept for at least 3 months on October 2016 and monitored in the department of rheumatology B of Cochin hospital. Physicians: All the 9 physicians in charge of at least one patient. Study design: After information (one hour session) on the biosimilars, all the physicians were invited to propose a switch from innovator etanercept to bETN. Data collected: physicians’ characteristics, patients’ characteristics (demographics, diagnosis of the rheumatic disease, disease activity parameters). Results: Of the 435 outpatients who had received etanercept; 304 were receiving etanercept in 2016 and 183 were eligible for a potential switch (the remaining 121 patients did not attend any out-patient-clinic between October 1st 2016 and April 1st 2017). The percentage of patients who switched to bETN was 51.6% (94 patients). This switch was more frequently performed in patients monitored by older physicians (mean age: 50.4±14.3 vs 44.8±11.3, p=0.005) and by physicians with a full-time academical position (56.4 % vs 13.5 %, p The patients’ characteristics were similar: % RA (51.1% vs 44.9%), age (52.1±15 vs 50.5±15), female gender (57.4% vs 51.6%), disease duration (16.8±11.9 vs 14.8±11.3) except for the NSAID intake (28.3 % vs 12.3 %, p=0.014) and the global evaluation (25.2±19.4 vs 19.1±21.8, p=0.02) in the switchers vs non-switchers, respectively. However, no independent factors were associated with the switch in the multivariate analysis. The bETN retention rate was 83 % [0.76–0.92] after a 6 month follow-up period. The bETN was discontinued in 26 patients with the following reasons: inefficiency 13 patients, adverse event 13 patients (painful injection site n = 4, fatigue = 2, pruritus n = 2, “allergic reaction” n =1, headache n = 1, pollakiuria n = 1, dizziness n = 1, supply problem n = 1). The univariate analysis aimed at evaluating the baseline predisposing factors of bETN discontinuation overtime picked up the baseline objective sign of inflammation (defined by CRP≥6 mg/L or ESA ≥28 mm) (OR=4.18 [1.19 – 14.66] p=0.0256), p=0.002) and global disease activity score (OR = 1.57 [1.04 – 2.36], p=0.03). Nevertheless, no independent factors were associated with the switch in the multivariate analysis. There was no difference in the changes in the disease activity parameters in both the completer and ITT population. Conclusions: This study suggests that: 1/The probability to switch from etanercept innovator to bETN was mainly related to physicians’ behavior 2/Using an open design, the percentage of patients complaining of a lower efficiency and/or a worse safety profile of the biosimilar was high 3/There was no objective parameter permitting to conclude at a lower efficiency and/or a worse safety profile of the bETN in comparison to the innovator etanercept. Disclosure of Interest: None declared

Background The response to TNF-blockers in axial spondyloarthritis (AxSpA) is at least partially influenced by HLA-B27 through a still poorly understood mechanism.Objectives Given that HLA-B27 regulates the gut microbiota composition in rats1,2, we seek to evaluate the predictive value of the gut microbiota composition in AxSpA patients on their responsiveness to TNF-blockers.Methods A total of 58 patients was monocentrically recruited between October 2014 and May 2015. At baseline, these patients had an active disease despite NSAIDs intake and were eligible for treatment with a TNF-blocker, while having no history of inflammatory bowel disease (IBD). The mean BASDAI (̑extpm}SD) was 45.6{̑extpm}21.4; ASDAS 2.8{̑extpm}0.9 and CRP 9.7{̑extpm11.4 mg/L. Among these patients, 56 fulfilled the ASAS classification criteria (imaging arm) with sacro-iliitis on X-rays (n=37) or objective signs of inflammation on MRI (n=48). Two patients fulfilled the clinical arm. These patients were not subjected to antibiotics within 3 months before stool sample collection. Bacterial 16S rRNA gene sequencing of the V3-V4 region was performed on stools samples before and 3 months after TNF-blocker treatment. Beta diversity metrics were calculated on the abundance of operational taxonomic units (OTU) after their taxonomic assignment on quality-filtered sequences.Results Principal component analysis (PCA) ordination of Bray-Curtis similarity revealed that current smoking (compared with never or ever smokers) and HLA-B27 genotype were significantly associated with the overall composition of the microbiota at baseline. Meanwhile, the abundance of eleven bacterial OTUs was influenced by HLA-B27 genotype at baseline but not after 3 month of treatment. In contrast, we identified a bacterial signature that was linked to the smoking behaviour independently of TNF-blocker treatment, whereas the BASDAI and ASDAS indices were significantly associated to the general composition of the gut microbiota after the 3 month treatment. In line with a previous report3, the abundance of Ruminococcus gnavus was not associated with disease activity in the absence of IBD. Interestingly, the abundance of 5 and 7 bacterial OTUs at baseline was associated with the response to TNF-blockers assessed by BASDAI and ASDAS, respectively. Among these candidates, the abundance of one bacterial OTUs belonging to the Clostridiales order was associated with a better response to the treatment and with the HLA-B27 genotype.Conclusions Anti-TNF treatment was found to modulate the HLA-B27-induced variations of the intestinal microbiota of AxSpA patients. Moreover, the abundance of a subset of OTUs at baseline was found to predict the responsiveness to TNF-blockers. Further functional studies will be conducted to assess how these taxa can be use as predictors of the treatment outcome.References [1] Gill, et al. Effects of HLA-B27 on Gut Microbiota in Experimental Spondyloarthritis Implicate an Ecological Model of Dysbiosis. Arthritis Rheumatol2017.[2] Lin, et al. HLA-B27 and human β2-microglobulin affect the gut microbiota of transgenic rats. PLoS One2014.[3] Breban, et al. Faecal microbiota study reveals specific dysbiosis in spondyloarthritis.Annal Rheum Dis2017.Disclosure of Interest None declared

Objective To update French Society for Rheumatology recommendations about the management in clinical practice of patients with spondyloarthritis (SpA). SpA is considered across the range of clinical phenotypes (axial, peripheral, and entheseal) and concomitant manifestations. Psoriatic arthritis is included among the SpA phenotypes. Methods According to the standard procedure advocated by the EULAR for developing recommendations, we first reviewed the literature published since the previous version of the recommendations issued in June 2013. A task force used the results to develop practice guidelines, which were then revised and graded using AGREE II. Results Four general principles and 15 recommendations were developed. The first four recommendations deal with treatment goals and general considerations (assessment tools and comorbidities). Recommendations 5 and 6 are on non-pharmacological treatments. Recommendation 7 is about nonsteroidal anti-inflammatory drugs, which are the cornerstone of the treatment, and recommendations 8 to 10 are on analgesics, glucocorticoid therapy, and conventional disease-modifying antirheumatic drugs. Biologics are the focus of recommendations 11 through 14, which deal with newly introduced drug classes, including their indications (active disease despite conventional therapy and, for nonradiographic axial SpA, objective evidence of inflammation) and monitoring, and with patient management in the event of treatment failure or disease remission. Finally, recommendation 15 is about surgical treatments. Conclusion This update incorporates recent data into a smaller number of more simply formulated recommendations, with the goal of facilitating their use for guiding the management of patients with SpA.

The effects of inflammatory disease activity (DA) on radiographic progression in patients with axial spondyloarthritis (axSpA) are worse in men and smokers, but an explanation for this is lacking.1 Recently, we have found a relationship between inflammatory lesions in the sacroiliac joints (SIJs) detected by MRI and clinical DA measures in male patients, which was absent in female patients.2 Here, we investigate whether this gender-specific association between MRI-lesions and clinical DA extends to the spine. The objectives of this study were: (i) to explore the relationship between inflammatory lesions of the spine on MRI and DA in patients with axSpA; (ii) to investigate if such a relationship is gender specific and (iii) to explore the influence of other patient-related factors on the relationship between MRI of the spine and DA. Two-year follow-up data from 164 patients fulfilling Assessment of SpondyloArthritis international Society (ASAS) axSpA criteria in the DEvenir des Spondylarthopathies Indifferenciees Recentes (DESIR) cohort with at least two spine MRIs available during this period were analysed.3 ,4 The relationship between MRI-spine and DA (Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), patient’s global DA, night pain, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) was analysed by generalised estimating equations (GEEs) on absolute MRI-spine scores (Berlin …

Background One of the most effective strategies to prevent infections is vaccination, especially in patients treated with biologics and immunosuppressive (IS) agents. Nevertheless, the effectiveness of the resulting immune response in these patients has been questioned. Objectives To perform a systematic literature review aiming to assess evidence available regarding immune response efficiency (IRE) and the ideal schedule for vaccination in RA and SpA patients treated with Methotrexate (MTX), TNF inhibitors (TNFi), anti-CD20 (rituximab, RTX), anti-CTLA4 (abatacept, ABA) or anti-IL6 (tocilizumab, TCZ). Methods A systematic literature review was conducted by searching in PubMed all studies with the MeSH terms “[Rheumatoid Arthritis” OR “Spondyloarthritis”] AND [“vaccination” OR “vaccines”] AND [“Methotrexate” OR “Abatacept” OR “Tocilizumab” OR “Rituximab” OR “Adalimumab” OR “Certolizumab” OR “Etanercept” OR “Golimumab” OR “Infliximab”], with no limitation regarding time of publication. Only studies evaluating the IRE were included. Case reports, general reviews and meta-analysis were excluded. Results After exclusion criteria, 35 studies (out of 60 studies retrieved) assessing IRE in RA or SpA patients were selected, under MTX (n=35), TNFi (n=18), RTX (n=8), ABA (n=4) or TCZ (n=5). The studied vaccines were mostly the trivalent seasonal Influenza (n=20), the anti-pneumococcal vaccine (n=16), and few studies regarding the tetanus toxoid vaccine (TTV) (n=2), Hepatitis A vaccine (n=1) and accidental revaccination against yellow fever (n=2). Most studies (32/35) evaluated the IRE using the antibody (Ab) titer. When studying the anti-pneumococcal and influenza vaccination, the primary outcome was mainly the seroresponse 3 to 6 weeks after vaccination (i.e. Ab ratio post/pre-vaccine) but some studies (15/35) also assessed the seroprotection rate (i.e. patients with an effective titer of protective Ab), and some (3/35) the effectiveness of seroresponse using the opsonization index rate. Regarding the anti-pneumococcal and influenza vaccination, MTX, RTX, and ABA were reported to impair the immune response; neither TNFi nor TCZ were shown to decrease seroresponse. Regarding TTV, one study showed persistent seroresponse in patients treated with TNFi; a second study showed no difference between MTX and RTX in response to T-cell dependant protein Ag TTV. Two studies reported no significant difference in efficiency or tolerance in patients accidentally revaccinated against yellow fever under TNFi. Conclusions These observations highly suggest that an effective vaccination for patients treated with MTX, RTX, and ABA should necessitate a therapeutic window or a scheduled treatment spacing, in order to offer the best protection against Influenza and Pneumococcal infection. This might not be necessary in patients under TNFi or TCZ; nevertheless, further studies are necessary to optimize the vaccination modalities. Disclosure of Interest None declared

Background Blau Syndrome (BS) is a rare autosomal dominant inflammatory disease characterized by early-onset granulomatous arthritis, dermatitis and recurrent uveitis (1). Mutations in the nucleotide-binding domain (NBD) of CARD15/NOD2 gene (mainly R334W, R334Q and L469F) have been identified in Blau syndrome (2). Despite advances in BS knowledge, patients9 functional prognosis remains uncertain, BS potentially leading to visual impairment or joint deformities. Optimal treatments have not been determinated yet. Objectives To assess the efficacy of several biologic agents in this affection Methods We conduct an observational, international, retrospective cohort of BS collecting clinical, biological and histological data. Results Among the twenty-three patients included in the cohort, 14 patients were treated by one or several lines of biologic agents, mostly by TNF blockers (80%), IL1 blockers (16%) or treatment targeting CTLA-4 (4%). Fifty-seven percent of patients achieved remission after almost two lines of treatment (1.75 lines; [0.8–2.7]). Association with csDMARDs did not significantly improved response to biologics. Considering the 3 mains symptoms independently, TNF blockers were associated with a better response in case of articular or skin features but less effective in case of ocular involvement, a clinical situation in which IL-1 targeting should be preferentially chosen. Conclusions Biologic treatments appeared to be effective in BS but additional data prospectively collected are still needed in order to define their place in the therapeutic strategy in order to minimize functional consequences. References Blau EB. Familial granulomatous arthritis, iritis, and rash. The Journal of pediatrics. 1985 Nov;107(5):689–93. PubMed PMID: 4056967. Epub 1985/11/01. eng. Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Hafner R, et al. CARD15 mutations in Blau syndrome. Nature genetics. 2001 Sep;29(1):19–20. PubMed PMID: 11528384. Epub 2001/08/31. eng. Disclosure of Interest None declared