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To determine whether leukocyte esterase reagent strip test (LERST) analysis could help distinguish inflammatory arthritis from mechanical joint effusion. We analyzed synovial fluid (SF) from consecutive patients with a non-traumatic joint effusion during a 6-month period. Inflammatory SF was defined by white blood cell (WBC) count ≥ 2000/mm3. The LERST was performed with both semi-quantitative visual analysis (VA) and automated colorimetric reader (ACR) analysis. Leukocytes ≥ 1+ was considered a positive LERST result and WBC count was the reference. We obtained 100 SF samples (87 knees, 7 ankles, 5 hips, and 1 elbow) from 100 patients (mean ± SD age 61 ± 17 years, 59% men). The laboratory analyzed 88 SF samples (37 mechanical and 51 inflammatory). The remaining 12 SF samples were 10 hemarthrosis not allowing LERST analysis and 2 samples with coagulum not allowing WBC count. As compared with the laboratory analysis, the LERST had sensitivity and specificity 55% and 89% with VA and 47% and 92% with ACR analysis. The positive and negative predictive values were 87.5% and 59% with VA and 89% and 55% with ACR analysis. We found almost perfect agreement between VA and ACR results (kappa 0.70 [95% CI 0.50–0.90]). The WBC count increased with number of + observed after VA. Our results confirm that the LERST is able to detect inflammation in SF of native joints, thereby representing a useful and cheap tool in primary care. Its low sensitivity limits its use for ruling out inflammatory disorders.

International audience; Objectives: To determine whether changes in ultrasonography (US) features of monosodium urate crystal deposition is associated with the number of gouty flares after stopping gout flare prophylaxis.Methods: We performed a 1-year multicentre prospective study including patients with proven gout and US features of gout. The first phase of the study was a 6-month US follow-up after starting urate-lowering therapy (ULT) with gout flare prophylaxis. After 6 months of ULT, gout flare prophylaxis was stopped, followed by a clinical follow-up (M6 to 12) and ULT was maintained. Outcomes were the proportion of relapsing patients between M6 and M12 according to changes of US features of gout and determining a threshold decrease in tophus size according to the probability of relapse.Results: We included 79 gouty patients [mean (±SD) age 61.8±14 years, 91% males, median disease duration 4 (IQR 1.5;10) years]. Among the 49 completers at M12, 23 (47%) experienced relapse. Decrease in tophus size ≥50% at M6 was more frequent without than with relapse (54% vs. 26%, P=0.049). On ROC curve analysis, a threshold decrease of 50.8% in tophus size had the best sensitivity/specificity ratio to predict relapse [AUC 0.649 (95% confidence interval 0.488; 0.809)]. Probability of relapse was increased for patients with a decrease in tophus size

Introduction Les atteintes cutanees sont habituelles au cours du syndrome de Gougerot-Sjogren primitif (SSp), mais leur prevalence et leurs caracteristiques sont difficiles a etablir precisement en raison du nombre limite de patients etudies dans la plupart des cohortes, de la variabilite des signes fonctionnels et cliniques evalues dans chaque cohorte, de la rarete de certains de ces signes et de l’heterogeneite des evaluations des etudes precedentes. L’objectif principal de cette etude etait de determiner, a partir de 3 groupes francais de patients souffrant de SSp (TEARS, ASSESS, DiapSS) dans lesquels differents criteres d’evaluation ont ete utilises, la prevalence des atteintes dermatologiques, les parametres cliniques et paracliniques qui leur sont associes. Materiel et methodes Nous avons utilise les donnees de deux cohortes francaises (ASSESS, qui a evalue la prevalence des atteintes cutanes chez 395 patients atteints de SSp, et DiapSS, qui comprend 139 patients atteints du syndrome de Gougerot-Sjogren diagnostique selon les criteres ACR-EULAR de 2016 parmi 325 patients suspectes d’etre atteints du SSp) et les donnees de base de l’essai randomise TEARS (110 patients atteints de SSp recent ou actif traites par rituximab ou placebo, evalues pour la secheresse cutanee a l’aide d’une echelle visuelle analogique sur 100). Resultats Les manifestations cutanees incluses dans l’indice EULAR d’activite du syndrome de Gougerot-Sjogren (ESSDAI) etaient rares dans la cohorte ASSESS (n = 16/395, 4,1 %), mais elles etaient associees a une activite dans les autres domaines de l’ESSDAI. L’etude TEARS a montre une forte prevalence de la secheresse cutanee (EVA > 50 ; 48,2 %) et a constate que les patients ayant la peau seche presentaient des scores EVA de douleur et de secheresse globale plus eleves (p = 0,003 et p Discussion Les signes dermatologiques inclus dans l’ESSDAI sont rares. Ces atteintes cutanees actives sont associees a l’activite de l’ESSDAI dans divers domaines. Un examen systematique par un dermatologue permettrait de mieux estimer les manifestations cutanees specifiques et non specifiques du syndrome de Gougerot-Sjogren. L’atteinte cutanee la plus courante est la secheresse cutanee mais elle n’est pas incluse dans les criteres d’evaluation de la maladie. Elle devrait donc etre evaluee par une EVA specifique.

To determine the prevalence and significance of dermatological disorders in primary Sjögren syndrome (pSS).We used 2 pSS French cohorts (ASSESS, in which prevalence of skin disorders in 395 patients was evaluated; and diapSS, in which 76 on 139 pSS patients had an examination by a dermatologist) and baseline data of the TEARS randomized trial (110 patients with recent or active pSS treated with rituximab or placebo and evaluated for skin dryness using a visual analogue scale (VAS) out of 100).Skin manifestations included in the EULAR Sjögren syndrome disease activity index (ESSDAI) were rare in the ASSESS cohort (n=16/395, 4.1%, mainly purpuras; only 3 had high activity), but they were associated with activity in the other ESSDAI domains (peripheral neurological (P0.001), muscular (P0.01), haematological (P0.05), biological (P0.05), history of arthritis (P0.01), splenomegaly (P0.05) and higher gamma globulin levels (P0.01)). In the diapSS cohort, compared to pSS patients not receiving a dermatological consultation, the pSS patients who had a dermatological consultation had significantly more dermatological involvement outside the ESSDAI score [38.2% (29/76) versus 15.9% (10/63); P0.01]. The TEARS study showed a high prevalence of cutaneous dryness (VAS50; 48.2%) and found that patients with dry skin had higher VAS pain (P0.01) and drought (P0.01) scores.ESSDAI skin activity is rare and associated with hypergammaglobulinemia and ESSDAI activity. Systematic dermatological examination is informative for non-specific lesions. The most common skin disorder is skin dryness, which is associated with a higher pain and overall subjective dryness.

Background Rheumatoid arthritis (RA) is associated with increased risk of infections. Screening for oral (dental and/or sinus) infection could be proposed before biologic disease-modifying antirheumatic drugs (bDMARDs) initiation but is not systematically recommended. The aim of our study was to assess the prevalence of oral infection in RA patients requiring bDMARDs. Materials and methods This was a monocentric retrospective study. We included patients with RA and active disease requiring bDMARDs. Dental infection and sinusitis were assessed by a stomatologist and otorhinolaryngologist after clinical, panoramic dental X-ray and sinus CT evaluation. Factors associated with oral infections were analysed in uni- and multivariate models, estimating odds ratios (ORs) and 95% confidence intervals (CIs). Results We included 223 RA patients (79.4% women, mean disease duration 8.9 ± 8.6 years). The mean age was 54.4 ± 10.9 years and mean Disease Activity Score in 28 joints 5.5 ± 2.6. Systematic dental screening revealed infection requiring treatment before bDMARDs initiation in 46 (20.9%) patients. Sinusitis was diagnosed by the otorhinolaryngologist in 33 (14.8%) patients. Among the 223 patients, 69 (30.9%) had dental and/or sinus infection. On univariate analysis, active smoking was associated with increased probability of oral infection (OR = 2.16 [95% CI 1.02-4.57], P = .038) and methotrexate with reduced probability (OR = 0.43 [95% CI 0.23-0.81], P = .006). On multivariate analysis, no RA variables were associated with oral infection. Conclusion In our study, asymptomatic oral infection was confirmed in one third of RA patients.

AIM To determine whether findings from lung ultrasound and chest high-resolution computed tomography (HRCT) correlate when evaluating COVID-19 pulmonary involvement. MATERIALS AND METHODS The present prospective single-centre study included consecutive symptomatic patients with reverse transcription polymerase chain reaction (RT-PCR)-proven COVID-19 who were not in the intensive care unit. All patients were assessed using HRCT and ultrasound of the lungs by distinct operators blinded to each other's findings. The number of areas (0–12) with B-lines and/or consolidations was evaluated using ultrasound and compared to the percentage and classification (absent or limited, 75%) of lung involvement on chest HRCT. RESULTS Data were analysed for 21 patients with COVID-19 (median [range] age 65 [37–90] years, 76% male) and excellent correlation was found between the ultrasound score for B-lines and the classification (p, Highlights • Ultrasonography is correlated with chest CT in COVID-19 patients. • Lung ultrasonography could be a relevant alternative to chest CT. • Lung ultrasonography is correlated with oxygen parameters.

Objective To evaluate the clinical course of and risk factors for arterial thrombotic events in adult inpatients with coronavirus disease 2019 (COVID-19). Methods All consecutive adult patients admitted for COVID-19 infection in a referral center in France and discharged from the hospital between April 1 and April 30, 2020, were included. All arterial thrombotic events that occurred through discharge were considered for analysis. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records with use of a standardized data collection form. Results Overall, 531 COVID-19+ patients were analyzed. Among them, 30 (5.6%) experienced arterial thrombotic events. Arterial thrombotic events in the setting of COVID-19 infection happened at a median of 11 (5-20) days after the first symptoms of infection; occurred in high-risk patients according to traditional cardiovascular risk factors; had an atypical pattern, such as thrombosis of the aorta, upper limb, or renal arteries or cerebral microvasculopathy in 7 (23.3%) cases; and were associated with an in-hospital mortality rate of 40%. Arterial thrombotic events increased the risk of death by 3-fold in COVID-19+ patients (hazard ratio, 2.96; 95% CI, 1.4 to 4.7; P=.002). A subdistribution survival hazard model showed that a concentration of D-dimer above 1250 ng/mL increased the risk of arterial thrombotic events in COVID-19+ patients by more than 7 (subdistribution hazard ratio, 7.68; 95% CI, 2.9 to 20.6; P Conclusion A dramatically high rate of in-hospital death was observed in patients who suffered arterial thrombotic events in the setting of COVID-19 infection. A D-dimer level above 1250 ng/mL at entry may identify COVID-19+ patients at risk for arterial thrombotic events.

Highlights • The SFR selected the most critical questions Rheumatologists must contend in the management of their patients with rheumatic diseases during COVID-19 pandemic • A group of 10 experts from SFR and CRI boards proposed responses based on the current knowledge of May 2020. • In most circumstances, there is no contraindication to the initiation or continuation of anti-inflammatory drugs as well as DMARDs. • If signs suggestive of infection (coronavirus or other) occurs, treatments should be discontinued and resumed, if necessary, after 2 weeks without any symptoms., Background: Rheumatologists must contend with COVID-19 pandemic in the management of their patients and many questions have been raised on the use of both anti-inflammatory drugs and disease-modifying anti-rheumatic drugs (DMARD). The French Society of Rheumatology (SFR) selected the most critical ones to the daily practice of a rheumatologist and a group of 10 experts from SFR and Club Rheumatism and Inflammation (CRI) boards proposed responses based on the current knowledge of May 2020. Basic procedure: Following the availability of the first 18 questions and statements, 1400 individuals consulted the frequently asked questions between the March 31, 2020 and April 12, 2020. As a result, 16 additional questions were forwarded to the SFR, and answered by the board. An additional round of review by email and video conference was organized, which included updates of the previous statements. The scientific relevance of 5 of the questions led to their inclusion in this document. Each response received a final assessment on a scale of 0–10 with 0 meaning no agreement whatsoever and 10 being in complete agreement. The mean values of these votes for each question are presented as the levels of agreement (LoA) at the end of each response. This document was last updated on April 17, 2020. Main findings: Based on current scientific literature already published, in most circumstances, there is no contraindication to the initiation or continuation of anti-inflammatory drugs as well as DMARDs. If signs suggestive of infection (coronavirus or other) occurs, treatments should be discontinued and resumed, if necessary, after 2 weeks without any symptoms. Only, some signals suggest that people taking an immunosuppressive dose of corticosteroid therapy are at greater risk of developing severe COVID-19. Intra-articular injections of glucocorticoids are allowed when there is no reasonable therapeutic alternative, and providing that precautions to protect the patient and the practitioner from viral contamination are adopted, included appropriate information to the patient. Principal conclusions: Currently available data on managing patients with rheumatic diseases during the COVID-19 pandemic are reassuring and support continuing or initiating symptomatic as well as specific treatments of these diseases, the main target of their management remaining their appropriate control, even during this pandemic.

Background: Telomere-related genes (TRG) mutations are detected in 30% of familial pulmonary fibrosis (FPF) and are also associated with personal/familial extra-pulmonary disease suggestive of short telomere syndrome (STS). Aim: to evaluate the prevalence of TRG mutations in a national cohort of interstitial lung disease (ILD) with suspected genetic predisposition in Greece and to define patients’ characteristics and impact on outcome.Methods: Genetic diagnoses made between December 2014-September 2019 in patients with FPF, pulmonary fibrosis at young age or personal and/or family extra-pulmonary disease suggestive of STS were analyzed. Results: 150 ILD patients, 73% male, age-at-diagnosis 67 years old, 33% non-smokers, 75% with definite/probable UIP or CPFE, 93% with dyspnea/cough, FVC% pred 75%, DLCO% pred 49% were tested; FPF was 65%, 19% young age, 21% personal and 17% family extra-pulmonary disease suggestive of STS; 21% were tested for more than 1 indication. TRG pathogenic variations were detected in 19 (13%): 13 in a familial, 3 in young age and 3 in extra-pulmonary disease suggestive of STS context as follows: TERT, TERC, RTEL1, PARN, NOP10, NHP2 in 8,5,2,2,1 and 1 respectively. No difference was detected in epidemiological-clinical-radiologic-functional characteristics between patients without and with mutations apart from age-at-diagnosis [69 vs 62 years, p

Objectives To refine the prevalence, characteristics and response to treatment of myositis in primary SS (pSS). Methods The multicentre prospective Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome (ASSESS) cohort of 395 pSS patients with ≥60 months’ follow-up was screened by the 2017 EULAR/ACR criteria for myositis. Extra-muscular complications, disease activity and patient-reported scores were analysed. Results Before enrolment and during the 5-year follow-up, myositis was suspected in 38 pSS patients and confirmed in 4 [1.0% (95% CI: 0.40, 2.6)]. Patients with suspected but not confirmed myositis had higher patient-reported scores and more frequent articular and peripheral nervous involvement than others. By contrast, disease duration in patients with confirmed myositis was 3-fold longer than without myositis. Two of the four myositis patients fulfilled criteria for sporadic IBM. Despite receiving three or more lines of treatment, they showed no muscle improvement, which further supported the sporadic IBM diagnosis. The two other patients did not feature characteristics of a myositis subtype, which suggested ‘pure’ pSS myositis. Steroids plus MTX was then efficient in achieving remission. Conclusions Myositis, frequently suspected, occurs in 1% of pSS patients. Especially when there is resistance to treatment, sporadic IBM should be considered and might be regarded as a late complication of this disease.

Purpose of review To provide an overview of recent studies that could be helpful in a better understanding of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and to facilitate the clinical management of this severe complication of RA. Recent findings The advances in deciphering the genetic architecture of RA-ILD support the hypothesis of RA-ILD as a complex disease with a complex phenotype encompassing at least the usual interstitial pneumonia (UIP) high-resolution CT pattern and non-UIP. Genetics studies have provided evidence for a shared genetic background in idiopathic pulmonary fibrosis (IPF) and RA-ILD, and more specifically RA-UIP, a disease with high morbidity and mortality. These findings support the rationale for common pathogenic pathways opening new avenues for future intervention in RA-ILD, notably with - drugs that proved active in IPF. In agreement, a recent controlled trial suggests efficacy of nintedanib, an antifibrotic drug, in patients with progressive lung fibrosis, including RA-ILD. However, there is a substantial gap in RA-ILD treatment, notably evaluating the effect of the RA treatments on the ILD course because of no controlled trial yet. Summary The phenotypical, environmental, and genetic similarities between IPF and RA-ILD have led to a better understanding of the underlying pathogenesis of RA-ILD. Despite the identification of several biomarkers and useful screening tools, several questions remain unanswered regarding the identification of patients with RA at increased risk of ILD and risk of progression. Other substantial gaps are the lack of recommendations for how high-risk patients should be screened and which specific therapeutic strategy should be initiated. International collaborative efforts are needed to address these issues and develop specific recommendations for RA-ILD.

Objective To study the profile of type-2 diabetes (T2D) in patients with RA or OA. Methods This observational, multicentre, cross-sectional study included, over a 24-month period, consecutive patients with adult-onset diabetes and RA or OA. We collected demographics, disease activity and severity indices, current treatments for RA and diabetes, history and complications of diabetes. A systematic blood test was performed, assessing inflammatory, immunological and metabolic parameters. The homoeostasis model assessment (HOMA)2-S was used to assess insulin resistance. Results We included 167 patients with T2D, 118 with RA and 49 with OA. RA and OA patients had severe T2D with suboptimal metabolic control and a biological profile of insulin resistance. Insulin resistance was significantly higher in RA than in OA patients after stratification on age, BMI and CS use [HOMA2-S: 63.5 (35.6) vs 98.4 (69.2), P Conclusion RA patients display severe T2D with inflammation-associated insulin resistance. These findings may have therapeutic implications, with the potential targeting of insulin resistance through the treatment of joint and systemic inflammation.

Objectives The aim of this study was to determine the prevalence and clinical significance of extra-articular manifestations (EAMs) at inclusion into a cohort of patients with recent-onset arthritis consistent with rheumatoid arthritis (RA). Methods The ESPOIR cohort included patients aged 18 to 70 years who had a definitive or probable diagnosis of RA. Symptoms consistent with EAMs were collected at baseline. We divided the patients into two groups, with vs. without baseline EAMs. We looked for associations linking the presence of EAMs at baseline to patient and disease characteristics at baseline and 5 years later, as well as to diagnostic certainty after 2 years. The analyses were adjusted for multiple comparisons using the Benjamini–Hochberg procedure to control the false discovery rate. Results Of 798 patients, 330 (41.4%) had at least one symptom consistent with EAM at baseline, with the most common being sicca syndrome (28.4%) and Raynaud's phenomenon (17.3%). The EAM+ group had a higher mean baseline DAS-28 value (5.3 ± 1.3 versus 5.0 ± 1.3; corrected p value = 0.005) compared to the EAM- group. The final diagnosis did not differ between the two groups. After 5 years, the EAM+ group had significantly higher values for the tender joint count (3.9 ± 6.4 versus 1.8 ± 3.3, corrected p value = 0.005) and swollen joint count (1.3 ± 2.8 versus 1.1 ± 2.3, corrected p value =0.0005) compared to the EAM- group. Conclusion EAMs, particularly sicca syndrome and Raynaud's phenomenon, are very common in patients with early arthritis consistent with RA. In this population, several parameters reflecting disease activity were higher among patients with EAMs, at baseline and after 5 years.

Objectives Interleukin (IL)-1β blocking is effective for the treatment of gout flares and is recommended in patients with contraindications to the standard of care, such as stage 4–5 chronic kidney disease (CKD) patients. However, efficacy and safety data regarding these agents are lacking in this population. We aimed to investigate the efficacy and safety of anakinra for the treatment of gout flares in patients with stage 4–5 CKD or renal transplantation. Methods This retrospective study encompassing 3 academic centres included consecutive patients with stage 4–5 CKD or kidney transplantation who received anakinra for the treatment of acute gouty arthritis and completed at least one follow-up visit. Efficacy, occurrence of infection, and renal function variations were recorded. Results Of the 31 included patients (24 men, mean age 72 ± 11 years), 25 were non-transplant subjects with stage 4–5 CKD (mean estimated glomerular filtration rate, MDRD formula (eGFR) 22.7 ± 6.5 mL/min/1.73 m 2 ), and six had undergone kidney transplantation (mean eGFR 41.5 ± 22.8 mL/min/1.73 m 2 ). Median gout duration was 3.5 years, and the mean serum urate (SUA) level was 8.7 mg/dL. Twenty-one (68%) patients had tophi, and 21 had gout arthropathy. Anakinra was efficacious in all patients (final VAS 10 and CRP level 10 mg/L). Ten patients (32%) were anakinra dependent (i.e., required prolonged treatment with anakinra). A serious infection was recorded in only one patient, occurring 3 months after starting anakinra. No significant variation in renal function was observed. Conclusion Anakinra may be a safe therapeutic option for gout patients with advanced CKD. Further randomized controlled studies are required to confirm our results.

Rituximab (RTX) is an anti-CD20 monoclonal antibody that selectively depletes B-cell population. Thus, it presents a potential risk for the development of hypogammaglobulinemia and related infectious events. Our aim was to identify predictors of hypogammaglobulinemia in RA patients long-term treated with RTX.Multicenter observational usual care study of patients with RA on RTX maintenance therapy (minimal exposition of 30 months). Serum protein electrophoresis was performed before each RTX infusion. Hypogammaglobulinemia and severe hypogammaglobulinemia were defined as total gammaglobulin6g/L and4g/L, respectively. The primary outcome was the occurrence within the follow-up period of hypogammaglobulinemia.134 patients met inclusion criteria and were followed-up for 79.5 ± 24.6 months. Hypogammaglobulinemia occurred during the follow-up period in 23 patients (2.7 events per 100 pt-yrs). The mean time to development of hypogammaglobulinemia was 64 ± 23 months. Patients who developed hypogammaglobulinemia were more likely to experience severe infections (26.1% vs. 6.3%, P = 0.033). Multivariate Cox analysis identified gammaglobulin levels8g/L at baseline as an independent predictor of hypogammaglobulinemia (HR 7.34 [95% CI: 2.00-26.90], P = 0.003). Concomitant methotrexate (MTX) intake was also predictive of a reduced risk of hypogammaglobulinemia occurrence (HR 0.26 [95% CI: 0.08-0.87], P = 0.03).Our results show that gammaglobulin levels of less than 8g/L at baseline is a strong independent risk factor for developing subsequent hypogammaglobulinemia, whereas concomitant MTX therapy seems to be a protective factor in RA patients treated long-term with RTX.

Background:ESPOIR is a longitudinal prospective cohort of adults with possible early RA (ClinicalTrials.gov: NCT03666091). Patients were referred by rheumatologists and general practitioners to one of the 14 regional centers in France. The objective and design of the cohort are described elsewhere (1). Patients received standard of care by their rheumatologists and were followed without predefined therapeutic strategiesObjectives:To report the current 10-year outcome of patients with early rheumatoid arthritis (RA) in the ESPOIR cohort, and predictors of outcome.Methods:From 2003 to 2005, 813 patients were included if they had early arthritis (< 6 months) with a high probability of RA developing and had never been prescribed disease modifying anti-rheumatic drugs (DMARDs). Multivariate logistic regression analysis was used to evaluate predictors of outcome.Results:In total, 521 (64.1%) RA patients were followed up for 10 years and 35 (4.3%) died, which appears similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174/521 (33.4%) received at least one biologic DMARD, 13.6 and 23.4% within 2 and 5 years. At year 10 (Table), mean DAS28 ESR was 2.5 ± 1.3; 273 (52.4%) patients were in DAS28 remission, 39.7% in CDAI remission, 40.1% in DAS28 sustained remission, and 14.1% in drug-free remission. Disability was well controlled overtime (Figure) and half of the patients achieved a HAQ Disability Index < 0.5; the SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 ± 17.9. A total of 82 (16.5%) patients required joint surgery including arthroplasty or arthrodesis in only 6.5% of the cases. A substantial number of patients showed new comorbidities, mainly cardiovascular or metabolic diseases over 10 years. Finally, positivity for anti-citrullinated protein antibodies was confirmed as a robust predictor of long-term outcome in patients with early RA.Table 1.Outcome in ESPOIR cohort and 1993 cohort at 10 yearsESPOIR cohort n=5211993 cohort n=112DAS28 ESR2.5 ± 1.3DAS44-2.2 ± 0.9SDAI7.5 ± 8.7CDAI6.8 ±8.3DAS28 ESR remission (n (%)273 (52.4)CDAI remission207 (39.7)DAS28 sustained remission, n (%)209 (40.1)DAS28 drug-free remission, n (%)75 (14.1)DAS28 ESR LDA336 (64.5)Rheumatoid nodules39 (7.5)Sicca syndrome314 (60.3)Patient global assessment24.0 ± 24.0HAQ DI score0.5 ± 0.60.75 ± 0.71HAQ DI < 0.5, n (%)280 (54.5)SF36 MCS46.7 ± 10.5SF36 PCS44.6 ± 9.2Pain (mm, VAS)16.6 ± 20.6Fatigue (mm, VAS)31.4 ± 27.023.2 ± 23.0ESR (mm/hr)14.4 ± 13.818.4 ± 16.5CRP level (mg/l)6.4 ± 16.59.3 ± 11.7Normal CRP (< 5 mg/l), n (%)336 (67.6)Total mSharp score*13.8 ± 19.635.4 ± 46.1Erosion score4.9 ± 9.418.4 ± 26.5)Joint narrowing score8.9 ± 12.132.1 ±23.2Joint surgery82 (16.5)26 (23.2)Joint arthroplasty/arthrodesis34 (6.5)20 (17.9)Data are mean (SD)DAS28, disease activity in 28 joints; HAQ DI, Health Assessment Questionnaire Disability Index; SF36 MCS, Medial Outcomes Study 36-item Short Form mental component summary; SF36 PCS, Medical Outcomes Study 36-item Short Form physical component summary; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; VAS, visual analog scale; CDAI, Clinical Disease Activity Index; SDAI, Simple Disease Activity Index; *van der Heijde-modified Total Sharp scoreFigure 1.Health Assessment Questionnaire Disability Index (HAQ-DI) over 10 years Data are mean (SD).Conclusion:We report a very mild 10-year outcome of a large inception cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of early RA patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients than previously.References:[1]Combe B et al. Jt Bone Spine Rev Rhum. 2007;74:440–5Acknowledgements:We thank MC Boissier, G Falgaronne and F. Lioté for help in patient recruitment. An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years of the cohort study. Two additional grants from INSERM supported part of the biological database. The French Society of Rheumatology, Abbvie, Pfizer, Lilly and more recently Fresenius and Biogen supported the ESPOIR cohort.Disclosure of Interests:Bernard Combe Speakers bureau: AbbVie; BMS; Gilead; Lilly; Merck; Pfizer; Roche-Chugai;, Consultant of: AbbVie; BMS; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Grant/research support from: Fresenius, Novartis, Pfizer, and Roche-Chugai., Nathalie Rincheval: None declared, Francis Berenbaum Speakers bureau: Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4Moving Biotech, 4P Pharma, Consultant of: Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4Moving Biotech, 4P Pharma, Patrick BOUMIER: None declared, Alain Cantagrel Speakers bureau: AbbVie; Amgen, Bristol-Myers Squibb; Grunenthal; Lilly; Medac; MSD France; Novartis; Pfizer; Roche-Chugai; Sanofi;, Consultant of: AbbVie; Amgen, Bristol-Myers Squibb; Grunenthal; Lilly; Medac; MSD France; Novartis; Pfizer; Roche-Chugai; Sanofi;, Grant/research support from: Abbvie, Fresenius, MSD France, Novartis, Pfizer, and UCB, Philippe Dieudé Speakers bureau: Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Lilly, Medac, Novartis Roche-Genentech, Sanofi, Consultant of: Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Lilly, Medac, Novartis Roche-Genentech, Sanofi, Grant/research support from: Bristol-Myers Squibb, GlaxoSmithKline, Pfizer., Maxime Dougados Speakers bureau: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Consultant of: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Grant/research support from: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Bruno Fautrel Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Grant/research support from: AbbVie, Lilly, MSD and Pfizer, René-Marc Flipo Speakers bureau: Abbvie, Biogen, BMS, Janssen, MSD, Nordic, Novartis, Pfizer, Roche-Chugai and Sanofi-Genzyme, Consultant of: Abbvie, Biogen, BMS, Janssen, MSD, Nordic, Novartis, Pfizer, Roche-Chugai and Sanofi-Genzyme, Grant/research support from: Abbvie, Janssen, Novartis, Pfizer and Roche-Chugai, Philippe Goupille Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB., Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB., Grant/research support from: Abbvie, Biogen, MSD, Pfizer, Xavier Mariette Speakers bureau: BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Servier, and UCB., Consultant of: BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Servier, and UCB., Grant/research support from: Servier, Alain Saraux Speakers bureau: AbbVie, Bristol-Myers Squibb, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB, Grant/research support from: Roche-Chugai, Thierry Schaeverbeke Speakers bureau: AbbVie, BMS, Lilly, Novartis, Nordic Pharma, Pfizer, Roche, UCB, Consultant of: AbbVie, BMS, Lilly, Novartis, Nordic Pharma, Pfizer, Roche, UCB, Grant/research support from: Pfizer, AbbVie, BMS, Roche, UCB, Astra, MSD, Rigel, AB-sciences, Jean Sibilia Speakers bureau: AbbVie, Lilly, MSD, Amgen, Pfizer, BMS, Janssen, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Novartis., Consultant of: AbbVie, Lilly, MSD, Amgen, Pfizer, BMS, Janssen, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Novartis., Grant/research support from: AbbVie, Lilly, Pfizer, Roche, Olivier VITTECOQ Speakers bureau: AbbVie, Bristol-Myers Squibb, Gilead, Lilly, Merck, Novartis, Pfizer; Roche-Chugai, Mylan and Sanofi, Consultant of: AbbVie, Bristol-Myers Squibb, Gilead, Lilly, Merck, Novartis, Pfizer; Roche-Chugai, Mylan and Sanofi, Grant/research support from: Novartis, Pfizer, Merck, and Bristol-Myers Squibb, Jean-Pierre Daures: None declared

Objectives To study the characteristics of B-cell non-Hodgkin’s lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence. Methods A multicentre case–control study was performed in France. Cases were patients with RA fulfilling ACR-EULAR 2010 criteria in whom B-cell NHL or Hodgkin lymphoma developed after the diagnosis of RA. For each case, 2 controls were assigned at random from the ESPOIR cohort and were matched on age at lymphoma diagnosis (cases)/age at the 10-year follow-up visit in the cohort (controls). Case and control characteristics were compared to identify parameters associated with the occurrence of lymphoma. Results 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphoma (DLBCL, n=27, 50.0%). On immunochemistry, 4 of 27 (14.8%) lymphoma cases were positive for Epstein-Barr virus. On univariate analysis, factors associated with the occurrence of lymphoma were male sex (OR 3.3, 95% CI 1.7 to 6.7), positivity for ACPA (OR 5.1, 95% CI 2.0 to 15.7) and rheumatoid factor (OR 3.9, 95% CI 1.6 to 12.2), and erosions on radiographs (OR 3.8, 95% CI 1.7 to 8.3) and DAS28 (OR 2.0, 95% CI 1.5 to 2.7), both at the time of matching. Methotrexate, TNF blockers and a number of previous biologics were not associated with the occurrence of lymphoma. On multivariable analysis, erosions and DAS28 remained significantly associated with increased risk of lymphoma. Conclusion Lymphomas complicating RA are mostly DLBCL. Risk of lymphoma in patients with RA was increased with markers of disease activity and severity, which supports the paradigm of a continuum between autoimmunity and lymphomagenesis in RA.

Resume Objectif L’objectif de cette etude etait de comparer la prevalence des ASCA chez les patients atteints de spondyloarthrite (SpA) et d’explorer le lien entre statut ASCA et phenotype de la maladie. Methodes Nous avons realise une etude cas-temoin incluant des patients atteints de SpA selon les criteres du Groupe europeen d’etude des spondyloarthropathies (ESSG, European Spondyloarthropathy Study Group) pour la SpA. Ont ete collectees aux fins d’analyse les donnees relatives au sexe, a l’âge, a la duree de la maladie, aux caracteristiques cliniques ou associees de la SpA, aux traitements et au statut HLA-B27 et ASCA. Un groupe de patients temoins sans SpA a egalement ete analyse. Resultats Au total, 235 patients atteints de SpA et 54 patients temoins ont ete etudies. L’âge median des patients atteints de SpA (53,6 % d’hommes, 52,2 % porteurs de HLA-B27) etait de 46,0 ans (IQR 35,0–57,0). La duree de la maladie etait de 60,0 mois (IQR 24,0–156,0). Une maladie inflammatoire chronique de l’intestin (MICI) a ete observee chez 11 % des patients atteints de SpA. La presence d’ASCA etait significativement plus importante chez les patients atteints de SpA que chez les temoins (25,5 % [IC 95 % 20,1–31,6] [IgG : 9,8 % ; IgA : 21,7 %] contre 7,4 % [IC 95 % 2,1–17,9], p = 0,004). L’analyse multivariee a montre que la presence d’ASCA etait associee a une atteinte peripherique (OR : 3,30 [1,26–8,62], p = 0,015), a l’existence d’une MICI (OR : 3,43 [1,15–10,20], p = 0,026), a une uveite passee ou actuelle (OR : 4,36 [1,08–17,64], p = 0,039) et a une arthrite (OR : 3,78 [1,57–9,15], p = 0,003). Conclusion Nos resultats ont apporte la preuve que les patients atteints de SpA avaient une prevalence d’ASCA superieure et que la presence d’ASCA pouvait etre associee a un phenotype particulier, notamment l’atteinte peripherique et l’uveite.

Resume Malgre sa severite, l’atteinte pulmonaire interstitielle de la polyarthrite rhumatoide reste encore souvent sous-diagnostiquee. L’utilisation recente d’examens d’imagerie performants, telle que la tomodensitometrie thoracique a haute resolution, a permis d’evaluer a la hausse la prevalence de cette complication chez les patients atteints de polyarthrite rhumatoide. L’atteinte pulmonaire interstitielle de la polyarthrite rhumatoide est particuliere et differe de celle rencontree dans les autres connectivites notamment par son aspect volontiers fibrosant, sa mauvaise reponse therapeutique et son mauvais pronostic. Compte tenu d’une morbi-mortalite associee importante, cette atteinte extra-articulaire necessite une attention particuliere. Alors qu’un depistage precoce pourrait permettre un meilleur suivi et une meilleure prise en charge pneumologique, les premiers signes fonctionnels pulmonaires apparaissent souvent tardivement a un stade radiologique deja evolue. Enfin, les etudes concernant l’impact des differents traitements utilises dans le traitement de la polyarthrite rhumatoide sur l’atteinte pulmonaire interstitielle restent contradictoires. Cette revue a donc pour objectif de rapporter les donnees actuelles de la litterature sur les caracteristiques de cette complication mais egalement sur l’influence des traitements de la polyarthrite rhumatoide dans la survenue et l’evolution de la pneumopathie interstitielle diffuse.

Resume Introduction Plusieurs etudes ont suggere que l’obesite pouvait avoir une influence negative sur la reponse aux anti-TNFα mais il n’existe aucune donnee sur la reponse au rituximab (RTX). Nous avons voulu determiner si l’indice de masse corporelle (IMC) pouvait affecter la reponse au RTX dans la PR. Methodes Nous avons analyse de maniere retrospective les donnees de 114 patients atteints de PR et traites par RTX. La variation a 6 mois du Disease Activity Score (DAS28), du score douleur sur l’echelle visuelle analogique (EVA), de la vitesse de sedimentation (VS), du taux de proteine C-reactive (CRP), du nombre d’articulations douloureuses (NAD) et du nombre d’articulations gonflees (NAG) par rapport aux valeurs initiales etait analysee. Le critere principal de jugement etait la diminution du DAS28 ≥ 1,2. Les criteres secondaires etaient la bonne reponse EULAR et la remission EULAR. Resultats L’IMC median initial (intervalle interquartile) etait de 26,8 (1,8–23,23–31) kg/m 2 . Le nombre de patients avec un IMC normal, en surpoids et obeses etait respectivement de 38, 41 et 35. A 6 mois, le nombre de patients atteints de PR qui rapportaient une diminution du DAS28 ≥ 1,2 ainsi qu’une bonne reponse therapeutique EULAR et une remission EULAR etait respectivement de 44 (38,6 %), 27 (23,7 %) et 24 (21,1 %). En analyse univariee, l’IMC median etait similaire chez les sujets repondeurs et non repondeurs pour une diminution du DAS28 ≥ 1,2 (26,9 [1,1–24,24–30] vs. 26,8 [2–6,6–23,23–31], p = 0,78), une bonne reponse EULAR (27,7 [3–7,7–24,24–30] vs. 26,7 [3–5,5–22,22–31], p = 0,57) et une remission EULAR (26,9 [1–8,8–24,24–30] vs. 26,8 [2–5,5–23,23–31], p = 0,94). L’analyse multivariee ajustee confirmait l’absence de correlation entre l’IMC et les differents criteres de reponse au RTX. L’IMC etait seulement negativement correle a une baisse du ΔNAG ( p = 0,0276) et du ΔNAD ( p = 0,0233). Conclusion L’IMC n’avait aucun impact negatif sur la reponse au RTX dans la PR. Ces donnees constituent une aide dans le choix d’une biotherapie pour les patients obeses atteints de PR.

Introduction L’essai francais ToLEDO (Towards the Lowest Efficacious Dose) cherchait a comparer une strategie de decroissance des bDMARDs (tocilizumab (TCZ) ou abatacept (ABA)) a une strategie de maintien a pleine dose chez des patients ayant une polyarthrite rhumatoide (PR) en remission prolongee. La non inferiorite n’a pas ete demontree pour le critere principal (evolution du DAS44). Un des objectifs secondaires de cet essai etait d’evaluer l’impact de cette strategie de decroissance en termes de progression radiographique a 2 ans. Patients et methodes ToLEDo est un essai randomise controle ouvert multicentrique de non-inferiorite (NI). Les patients devaient presenter une PR selon les criteres ACR-EULAR 2010, etre traites depuis au moins 1 an par ABA ou TCZ (seul ou en association) sans ou avec une corticotherapie a une dose ≤ 5 mg/j, et en remission depuis au moins 6 mois (DAS28 ans , et la progression structurale etait evaluee a l’aide du score de Sharp modifie par van der Heijde (vSHS) par 2 lecteurs entraines et en insu du groupe de randomisation. Les criteres de jugement pour cette analyse secondaire etaient : l’evolution vSHS sur 2 ans (compares entre les deux groupes au moyen d’un modele lineaire mixte), et le taux de progresseurs a 2 ans avec ΔvSHS > 0 et avec ΔvSHS > plus petit changement detectable (SDC = 6,9). Les analyses ont ete realisees en per protocol (PP). Resultats 80 sujets avaient un vSHS renseigne a l’inclusion et a au moins un des deux temps de lecture (44 bras M et 36 bras S) et ont ete consideres pour l’analyse de l’evolution du vSHS. La difference d’evolution du vSHS entre le bras M et le bras S sur 2 ans etait non significative, de 2,47 [IC95 % : -0,34 ;5,28]. Parmi les 80 sujets, 62 (34 bras M et 28 bras S) ont ete consideres pour l’analyse du taux de progresseurs (vSHS renseigne a l’inclusion et a 2 ans). Le taux de progresseurs a 2 ans avec ΔvSHS > 0 n’etait pas significativement plus eleve dans le bras S compare au bras M : 75 % contre 68 %, soit une difference de 7 % [IC95 % de precision : -15 % ; 30 %]. De meme, le taux de progresseurs a 2 ans avec ΔvSHS > SDC n’etait pas significativement plus eleve dans le bras S compare au bras M : 29 % contre 15 %, soit une difference de 14 % [IC95 % de precision : -07 % ; 34 %]. Discussion Cet essai a pu etre penalise par un manque de puissance, un nombre consequent de deviations au protocole ainsi que par l’anciennete et la severite de la PR chez les patients etudies. Conclusion Les resultats sur ces criteres de jugement secondaires radiographique sont coherents avec la conclusion sur le critere de jugement principal : bien que non statistiquement significative, la difference entre les deux groupes, en defaveur du groupe espacement, conduisent a ne pas recommander l’espacement des injections de TCZ et d’ABA chez des patients avec une PR tres erosive ou a risque de progression structurale.

Background:Rheumatoid arthritis (RA) is associated with an increased risk of non-Hodgkin B-cell lymphoma (B-cell NHL).Objectives:1)To study the characteristics of B-cell NHL complicating RA2)To identify the factors associated with their occurrence.Methods:A multi-centre case-control study was performed in France. Cases were patients with RA fulfilling the ACR-EULAR 2010 criteria, who developed a B-cell NHL after the diagnosis of RA. Cases were reported following a call for observations by the “Club Rhumatismes et Inflammation” network, registries from the French society of Rheumatology (AIR, ORA and REGATE) and the ESPOIR cohort. For each case, 2 control patients were drawn at random from patients in the ESPOIR cohort with RA fulfilling the ACR-EULAR 2010 criteria; cases and controls were matched on age (age at lymphoma diagnosis for cases and age at the 10-year ESPOIR visit for controls). Patients with associated Sjögren’s syndrome were excluded. Cases and controls characteristics were compared for parameters associated with the occurrence of lymphoma.Results:A total of 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphomas (n=26, 48.2%)(Figure 1). EBV positivity was found in 4 cases among 27 tested (14.8%). Cases had a mean age of 63.5 years (SD=10.9), and had a mean RA duration of 12.4 years (SD=10.5) at the time of diagnosis of lymphoma; there was no significant difference with controls (p=0.47 and p=0.40 respectively). The mean duration of follow-up after the diagnosis of lymphoma was 5.2 years (SD=5.8). In univariate analysis, factors associated with occurrence of B-cell NHL were: male gender (OR=3.3, 95%CI: 1.7-6.7), positive ACPA (OR=5.1, 95%CI: 2.0-15.7), positive Rheumatoid Factor (RF) (OR=3.9, 95%CI=1.6-12.2), erosions on X-rays (OR=15.4, 95%CI: 6.9-37.7) and DAS28 (OR=2.0, 95%CI: 1.5-2.7). Methotrexate, TNF-blockers and the number of previous biologics were not associated with the occurrence of B-cell NHL. Hydroxychloroquine and sulfasalazine were more frequent in cases versus control, which could be linked to a date bias. Erosions and DAS28 remained significant in multivariate analysis(Table 1).Conclusion:This study revealed an association between markers of activity (DAS28), severity (erosions) and autoimmune B-cell activation (RF and ACPA) and the risk of B-cell NHL in patients with RA, supporting the continuum between autoimmunity and lymphomagenesis in RA.Figure 1.lymphomas histologyTable 1.association between RA characteristics and B-cell NHL in univariate and multivariate analysisVariablesCases (N=54)Controls (N=108)Univariate analysisMultivariate analysisOR (95%CI)p-valueOR (95%CI)p-valueMale gender, N (%)27 (50.0)25 (23.2)3.3(1.7-6.7)0.00062.2(0.8-6.1)0.13Positive ACPA, N (%)49 (90.7)71 (65.7)5.1(2.0-15.7)0.0006--Positive RF, N (%)49 (90.7)77 (71.3)3.9(1.6-12.2)0.005--Positive RF or ACPA, N (%)49 (90.7)80 (74.1)3.4(1.3-10.6)0.012.9(0.7-15.0)0.16Erosions on X-rays, N (%)44 (81.5)26 (24.1)15.4(6.9-37.7)< 0.00019.8(3.8-28.2)< 0.0001DAS28 at B-cell NHL diagnosis/at the 10th year visit*, mean(SD)4.1 (1.6)2.6 (1.4)2.0(1.5-2.7)< 0.00011.9(1.3-2.8)0.0007*B-cell NHL diagnosis for cases, 10thyear visit for controlsDisclosure of Interests:Joanna KEDRA: None declared, Raphaèle Seror Consultant of: BMS UCB Pfizer Roche, Philippe Dieudé: None declared, Arnaud Constantin: None declared, ERIC TOUSSIROT: None declared, Elias Kfoury: None declared, Charles Masson: None declared, Divi Cornec: None declared, Jean-Jacques Dubost: None declared, Laurent Marguerie: None declared, Sebastien Ottaviani: None declared, Franck Grados: None declared, Rakiba Belkhir: None declared, olivier fain: None declared, Philippe Goupille Grant/research support from: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Christelle Sordet: 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, Peggy Philippe: None declared, Muriel PIPERNO: None declared, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, Olivier Lambotte Consultant of: BMS France, MSD, Astra Zeneca, Incyte, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Jérémie SELLAM: None declared, Thomas Sene: None declared, Guillaume Denis: None declared, Thierry Lequerre: None declared, Xavier Mariette Consultant of: BMS, Gilead, Medimmune, Novartis, Pfizer, Servier, UCB, Gaetane Nocturne: None declared

Background Recent studies showed that ultrasonography (US) could be useful for managing urate-lowering therapy (ULT) in gouty patients. In the first phase of the present study (USEFUL-1), we suggested that US was an accurate tool to follow monosodium urate (MSU) crystal dissolution under efficient ULT. For gout flare after starting ULT, prophylaxis is recommended during the first 6 months of ULT. The duration of gout flare prophylaxis over the 6 months is consensual with a grade B recommendation. However, little is known about the probability of relapse according to the urate load modification. Objectives To determine whether a modification of US features of MSU crystal deposition is associated with reduced number of flares after stopping gout flare prophylaxis. Methods We performed a 1-year multicentre prospective study including patients with proven gout and US features of gout. The first phase of the study was a 6-month US follow-up after starting (ULT) with gout flare prophylaxis. After 6 months of ULT, gout flare prophylaxis was stopped, followed by a clinical follow-up (month [M] 6 to 12). Outcomes were the proportion of patients with relapse between M6 and M12 according to the modification of US features of gout and determining a threshold decrease in tophus size according to the probability of relapse. Results We included 79 patients with gout (mean [± SD] age 61.8 ± 14 years, 91% males, disease duration 6.3 ± 6.1 years). Among the 49 completers at M12, 23 (47%) experienced relapse. Decrease in tophus size ≥ 50% at M6 was more frequent without than with relapse (54% vs 26%, P= 0.049). On ROC curve analysis, a threshold decrease of 50.8% in tophus size had the best sensitivity/specificity ratio to predict relapse. Probability of relapse was increased for patients with a decrease in tophus size Conclusion A high reduction in US tophus size is associated with low probability of relapse after stopping gout prophylaxis. US follow-up may be useful for managing ULT and gout flare prophylaxis. Disclosure of Interests Esther Ebstein: None declared, Marine Forien: None declared, Eleonora Norkuviene: None declared, Pascal Richette Consultant for: Grunenthal, Horizon, Speakers bureau: AstraZeneca, Grunenthal, Gael Mouterde: None declared, Claire Daien: None declared, Hang Korng Ea: None declared, Claire Briere: None declared, Frederic Liote Grant/research support from: institutional grants from Grunenthal, Ipsen Pharma/Menarini, Novartis, SOBI for the European Crystal Network Workshops, Consultant for: Grunenthal, Novartis, Mykolas Petraitis: None declared, Thomas Bardin Consultant for: Astrazeneca, Grunenthal, Horizon, Novartis, Speakers bureau: Astella, AstraZeneca, Grunenthal., Jeremy Ora: None declared, Philippe Dieude: None declared, Sebastien Ottaviani: None declared

Background Bone sarcoidosis: usefulness of 18F-FDG PET/CT Objectives Bone sarcoidosis is usually rare but more sensitive imaging procedures such as 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) allow a better characterization of such lesions. We aimed to describe bone sarcoidosis involvement using 18F-FDG PET/CT. Methods We performed an observational retrospective study of patients with pulmonary sarcoidosis having a 18F-FDG PET/CT. As stated by ATS/ERS/WASOG criteria, diagnosis of sarcoidosis was established on the presence of clinical symptoms and/or imaging features of sarcoidosis, and evidence of non-caseating epithelioid granuloma in a biopsy sample after exclusion of other known etiology of granuloma. We assessed clinical and 18F-FDG PET/CT characteristics. Results A total of 85 patients (56.5% of female, median age 47 years) with sarcoidosis were analyzed. The median of disease follow-up was 4 years. Sarcoidosis occurred in more than three organs among 66% of cases. Using ATS/ERS/WASOG criteria, bone sarcoidosis was diagnosed in 12 (14%) patients. Spine was the most commonly affected bone (92%), followed by pelvis (67%), sternum (33%), humerus (25%) and fingers (17%). Only peripheral adenopathy was associated with bone lesions (p=0.04). Seven patients have benefited from a follow-up 18F-FDG PET/CT, which in 100% of cases showed an improvement of lesions. Conclusion Bone sarcoidosis occurred in 14% of patients, affecting multiple bones and mostly the axial skeleton. 18F-FDG PET/CT appears to be a sensitive imaging for diagnosis and follow-up of bone sarcoidosis. References [1] Aberg C, and al. AJR Am J Roentgenol. avr 2004 [2] Baldini S, and al. Br. J. Haematol. nov 2008 [3] Bechman K, and al. Rheumatology 1 mai 2018 [4] ClarenCon F, and al. Spine. 15 sept 2007 [5] Conte G, and al. Ecancermedicalscience. 7 mai 2015 [6] Costabel U, and al. European Respiratory Society. World Association for Sarcoidosis and Other [7] Granulomatous Disorders. European Respiratory Journal. 1 oct 1999 [8] Glaudemans AWJM, and al. Journal of Immunology Research. 2013 [9] Grozdic Milojevic I, and al. Sarcoidosis Vasc Diffuse Lung Dis. 29 mars 2016 [10] James DG, and al. Ann. N. Y. Acad. Sci. 1976 [11] Judson MA, and al. Sarcoidosis Vasc Diffuse Lung Dis. 18 avr 2014 [12] Kaira K, and al. Chest. avr 2007 [13] Lefere M, and al. Clin Nucl Med. mars 2003 [14] Mostard RL, and al. Clin Nucl Med. janv 2012 [15] Prost N de, and al. RES. 2010 [16] Sparks JA, and al. Seminars in Arthritis and Rheumatism. 1 dec 2014 [17] Thelier N, and al.J. Rheumatol. aout 2008 [18] Wilcox A, and al. Current Opinion in Rheumatology. juill 2000 [ [19] Zhou Y, and al. Seminars in Arthritis and Rheumatism. 1 fevr 2017 [20] Zisman DA, and al. Semin Respir Crit Care Med. dec 2002 Disclosure of Interests None declared

Background Osteoporosis is common among patients with end-stage heart disease. A rapid decrease of bone mineral density (BMD) is usually observed after heart transplantation. Bone loss is probably linked to glucocorticoids and calcineurin inhibitors use and vitamin D deficiency. Objectives The aim of this study was to evaluate the interest of a systematic screening of osteoporosis in heart transplant patients. Methods We performed a prospective monocentric study including patients, who had of heart transplantation in our hospital, from December 2016 to January 2019.The following parameters were systematically assesses: history of cardiac disease, immunosuppressive therapies, glucocorticoids, previous history of low trauma fracture, known risk factors of osteoporosis, treatment received for bone disease management (calcium, vitamin D and bisphosphonates). Blood tests with creatinine clearance, calcium and vitamin D levels, were assessed. Bone densitometry and spine radiographs (to search asymptomatic vertebral fractures) were assessed in all patients. Osteoporosis was defined respectively for patients ≥50 years and Results A total of 42 patients were included (76.7% male), mean age was 58.1±10.6 years, mean duration after transplantation was 2.6±3.1 years. Past or active smoking statues were observed in 26 patients (mean 23.9 pack-years). Calcium, vitamin D and bisphosphonates were administered in 13 (30.9%), 10 (23.8%) and one patients, respectively. All patients received prednisone (mean dose: 10.7±4.9 per day). Mean lumbar spine BMD was 1.03±0.25 g/cm2 and left femoral neck BMD 0.85±0.15g/cm2. Osteoporosis was observed in 18 (45%) patients. Only one hip fracture was known before heart transplantation. Incidental low trauma fractures after transplantation were diagnosed in 14 patients (33.3%): 11 patients with vertebral fractures (mean 2 vertebral fractures per patient) including 4 patients with asymptomatic vertebral fractures. Others low trauma fractures were hip fracture, proximal humerus and fibula for one patient each. Mean duration between transplantation and the first low trauma fracture was 7.5±3.7 months. Low level of calcemia was found in 20 patients (47.6%) and low level of vitamin D (≤30mg/l) in 32 patients (76.2%) associated with secondary hyperparathyroidism in 21 patients (51.2%), mean creatinine clearance was 51.7±19.9ml/min. After evaluation, specific treatment of osteoporosis was started for 33 patients (78.6%): zoledronic acid (n=20), denosumab (n=8), alendronate (n=4) and teriparatide (n=1). Conclusion Systematic screening of osteoporosis seems to be useful in heart transplant patients. Osteoporosis was observed in half of these patients with a high frequency of low trauma fracture after heart transplantation, particularly in the first year. Disclosure of Interests None declared

Background Ustekinumab (UST) and secukinumab (SEK) are new Biologic Disease-modifying antiRheumatic Drugs (bDMARDs) available in psoriatic arthritis (PsA), targeting respectively IL12-23 and IL 17. Real-world data are missing for these drugs, despite the wide use. There is only one previous published study including 160 patients (1) receiving UST, but not SEK. Objectives To evaluate the characteristics of the patients with PsA treated by UST or SEK and to assess real life drug survival and efficacy of UST and SEK in PsA. Methods This is a national, retrospective, multicentric study from patients suffering from PsA (CASPAR criteria) from July 2011 to april 2018. Drug survival was defined as the time from initiation to discontinuation (stop/switch) of bDMARDs. Kaplan-Meier survival curves and Cox-regression analyses [hazard ratios (HR) and 95% confidence intervals (CIs)] were used adjusting for patient demographics, disease characteristics, co-therapy with methotrexate, and line of treatment with ustekinumab. For peripheral involvement, treatment was considered to be effective for patients with a combined favorable expert opinion and/or > 30% clinical improvement of swollen and tender joint counts. For axial involvement, efficacy criteria were: improvement of BASDAI by at least 2 points on a scale from 0 to 10 or 50% improvement and/or expert opinion. Results 186 patients were included with a mean follow-up ≥ 6 months: 111 patients under UST and 75 under SEK. The mean age was 51.5 (12.9) years old, 55% of patients were women and the body mass index was 27.3 (5.8) kg/m². The disease duration was 10.8 (8.1) years. Patients were bDMARDs-naive in 15%. The median drug survivals for UST and SEK were respectively 12 and 14 months (Fig1). A propensity score cannot be used to compare the two bDMARDs, since the number of patients was too small. Smoking was associated with an unfavourable drug survival for SEK (HR= 0.22, 95%CI 0.91), whereas CRP levels were associated with a favorable one for UST (HR=1.009, 95%CI 1.003–1.016). Nine patients under SEK and 2 under UST stopped their treatments due to side effects. Conclusion This is the first real-world study for drug survival on PsA for SEK and one with the largest number of patients for UST. Drug survival of UST and SEK seems similar to TNF inhibitors’ (2). References [1] Iannone F, et al. Drug survival and effectiveness of ustekinumab in patients with psoriatic arthritis. Real-life data from the biologic apulian registry (BIOPURE). Clin Rheumatol. 2018;37:667–75. [2] Walsh JA, et al. Care Spec Pharm. 2018;24:623-631 Disclosure of interests Jean-Guillaume Letarouilly: None declared, Jeremie Sellam: None declared, Pascal Richette Consultant for: Grunenthal, Horizon, Speakers bureau: astraZeneca, Grunenthal, Philippe Dieude: None declared, Pascal Claudepierre Consultant for: Honoraria from Novartis as steering committe of this survey, Corinne Miceli Richard Grant/research support from: MSD, Pfizer, abbVie, Biogen, UCB, Novartis, Consultant for: abbvie, Novartis, BMS, Eric Houvenagel Speakers bureau: Lilly, Novartis, Janssen, Chi Duc Nguyen: None declared, Marie-Helene Guyot: None declared, Nicolas Segaud: None declared, Laurent Marguerie: None declared, Xavier Deprez Speakers bureau: Novartis Janssen, Jean-Hugues Salmon Speakers bureau: Janssen Novartis, Guy Baudens Grant/research support from: Financial Grant from NordicPharma, Consultant for: Roche SAS, Maeva Kyheng: None declared, Julien Paccou Speakers bureau: Novartis Janssen, Elisabeth Gervais Grant/research support from: Roche, Pfizer, Consultant for: Bristol-Myers Squibb, UCB, Rene-Marc Flipo Consultant for: Honoraria from Novartis as steering committe of this survey

Background: Biologic Disease Modifying Anti-Rheumatic Drugs (bDMARD) tapering is possible in rheumatoid arthritis (RA) patients in sustained remission. However, only minimal data are available on progressive tapering of non-TNF bDMARD such as tocilizumab (TCZ) or abatacept (ABA). Objectives: The TOLEDO (Towards the Lowest Efficacious Dose) trial aimed to assess the impact on disease activity of progressive spacing of TCZ or ABA in RA patients in sustained remission compared to their maintenance at full dose. Methods: In this multicenter open-label non-inferiority randomized controlled trial, patients fulfilling ACR-EULAR 2010 criteria for RA were included if they were 1) treated with ABA or TCZ for ≥ 1 year (monotherapy or in combination with csDMARD, corticosteroid allowed at a dose ≤ 5 mg/day), 2) in DAS28VS remission (DAS28 3.2, and DAS28 >3.2 not recovered at the following visit despite bDMARD escalation at previous step) were also compared between the 2 arms. Analysis were done per protocol (PP) according to a non-inferiority hypothesis (non-inferiority margin at 0.25 for DAS44 and 0.07 for relapse rates). Results: 117 patients were randomized in Spacing arm and 116 in Maintenance arm (90 and 112 respectively for PP analysis). 165 (72.4%) patients were treated with TCZ and 63 (27.6%) with ABA. At the end of the follow-up in the Spacing arm, 12.4% of patients were able to discontinue their bDMARD (step 4), 38.9% had tapered them (step 1 to 3) and 23.9% needed to go back to initial step (step 0). In terms of disease activity, the non-inferiority of the Spacing strategy in terms of disease activity (DAS44) was not demonstrated for the whole population and the ABA subgroups: slope difference of 11% (95% CI: -9%, 32%) and 37% (95% CI: -4%, 77%) respectively. However, it was satisfied for the TCZ subgroup: slope difference 3% (95% CI: -21%, 27%) (Figure 1). Relapses (Figure 2) were more frequent in the Spacing arm: +45% (95% CI: 32%, 57%), +48% (95% CI: 24%, 71%) and +43% (95%CI: 29%, 58%) in the whole population, ABA and TCZ subgroups respectively. Durable relapses were more frequent in the Spacing arm: +10% (95%CI: 0%, 19%), 16% (95%CI: -5%, 37%) and 7% (95%CI: -3%, 16%) in the whole population, ABA and TCZ subgroups respectively, compared with Maintenance arm. Conclusion: The TOLEDO trial generally failed to demonstrate the non-inferiority of the proposed tapering strategy in comparison to maintenance at full dose. However, the non-inferiority was satisfied in terms of disease activity for the TCZ subgroup. Disclosure of Interests: Joanna KEDRA: None declared, Philippe Dieude: None declared, Hubert MAROTTE: None declared, Alexandre Lafourcade: None declared, Emilie Ducourau Speakers bureau: BMS and Abbvie, Thierry Schaeverbeke: None declared, Aleth Perdriger: None declared, Martin SOUBRIER: None declared, Jacques Morel: None declared, Arnaud Constantin: None declared, Emmanuelle Dernis: None declared, Valerie Royant: None declared, Jean-Hugues Salmon Speakers bureau: Janssen Novartis, Thao Pham Speakers bureau: Lilly, Novartis, Jacques-Eric Gottenberg Grant/research support from: Bristol-Myers Squibb, Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Lilly, Pfizer, Sanofi-Genzyme, UCB Pharma, Consultant for: Bristol-Myers Squibb, Eli Lilly, UCB, Sanofi-Genzyme, Pfizer, Edouard Pertuiset: None declared, maxime dougados Grant/research support from: Eli Lilly and Company, Pfizer, AbbVie, and UCB Pharma, Consultant for: Eli Lilly and Company, Pfizer, AbbVie, and UCB Pharma, Valerie Devauchelle-Pensec Grant/research support from: Roche-Chugai, Speakers bureau: MSD, BMS, UCB, Roche, Philippe Gaudin Speakers bureau: Roche, Chugai, BMS, Abbvie, Servier, Pfizer, MSD, UCB, ESAOTE, Genevrier, Janssen, Novartis, Lilly, Biogen, Amge, Gregoire CORMIER: None declared, Philippe Goupille: None declared, Xavier Mariette Grant/research support from: Servier, Consultant for: AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, UCB Pharma, Francis Berenbaum: None declared, Didier Alcaix: None declared, SID AHMED ROUIDI: None declared, Jean-Marie Berthelot: None declared, Agnes Monnier: None declared, Christine Piroth: None declared, Frederic Liote Grant/research support from: institutional grants from Grunenthal, Ipsen Pharma/Menarini, Novartis, SOBI for the European Crystal Network Workshops, Consultant for: Grunenthal, Novartis, Vincent Goeb: None declared, Cecile Gaujoux-Viala Consultant for: Speaking and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Merck-Serono, Medac, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB Pharma., Speakers bureau: Speaking and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Merck-Serono, Medac, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB Pharma., Isabelle CHARY VALCKENAERE: None declared, David Hajage: None declared, Florence Tubach Grant/research support from: Financial compensation received from MSD on a pro-rota basis for participation in Scientific Committee meetings and functions for this study, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant for: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, Sanofi Genzyme, SOBI, UCB

Resume Objectif Nous avons souhaite comparer la prevalence de l’enthesopathie observee a l’echographie chez des patients atteints de spondyloarthrite (SpA) et de polyarthrite rhumatoide (PR) et chez des temoins sains (TS). Methodes Une evaluation clinique et echographique des entheses a ete realisee sur sept sites (tendon quadricipital, tendon patellaire proximal et distal, tendon d’Achille, aponevrose plantaire, tendon du triceps et epicondyliens lateraux) chez tous les patients atteints de PR (criteres 2010 de l’ACR/EULAR) et de SpA (criteres de l’ASAS) ainsi que chez les temoins. Les scores d’evaluation echographique des entheses de Glasgow (GUESS) et de Madrid (MASEI) ont ete determines par deux echographistes en aveugle des donnees cliniques. Resultats Nous avons inclus 30 patients atteints de PR (âge moyen 55,7 ± 14,8 ans, duree moyenne de la maladie 10,5 ± 7,9 ans), 41 patients atteints de SpA (âge moyen 45,3 ± 15,4 ans, duree moyenne de la maladie 9,2 ± 8,7 ans) et 26 temoins (âge moyen 50,4 ± 17,3 ans). La prevalence des entheses douloureuses sur les sites examines etait similaire dans les groupes SpA et PR (17 % contre 14 %, non significatif [ns]) mais superieure a celle observee chez les temoins (3 %, p Conclusion Il n’y avait pas de differences entre les patients atteints de PR et de SpA concernant les anomalies des entheses visibles a l’echographie. La specificite de ces caracteristiques echographiques peut etre faible dans les affections inflammatoires touchant les articulations et les entheses, comme la SpA ou la PR.

ObjectiveTo evaluate the prevalence and performance as axial Spondyloarthritis (axSpA) diagnostic feature of radiographic and MRI lesions ‘typical’ of axSpA of the sacroiliac joint (SIJ) and spine in a mechanical chronic back pain (CBP) population and in an axSpA cohort.MethodsCross-sectional multicentre study. Patients: (1) recent onset axSpA (DESIR cohort) and (2) mechanical non-axSpA CBP matched for age and gender (ILOS study). Imaging: radiographs and MR scans were performed identically in both groups. All images were centrally read, blinded for diagnosis and for other imaging findings in the same patient. Statistical analysis: prevalence of lesions ‘typical of axSpA’ were compared in both groups. Sensitivity, specificity and positive likelihood ratios (LR+) of each lesion (and combination of lesions) were calculated.ResultsA total of 98 patients with CBP were included, and compared with 100 patients with recent onset axSpA. SIJ lesions were consistently more frequent in the axSpA group (35.0% vs 11.8% pConclusionOur study confirms that ‘typical’ lesions can also be observed in patients with non-axSpA CBP but that SIJ lesions by all modalities remain the most valuable for diagnosis, including structural lesions of the SIJ. This suggests the potential interest of adding MRI SIJ structural lesions in the definition of MRI abnormalities for axSpA classification.

Resume Objectif L’echographie apparait comme un outil d’interet dans le diagnostic d’arthropathie a depots de pyrophosphate de calcium dihydrate (PPCD). Nous avions pour objectif de comparer la performance de l’echographie du poignet avec celle de la radiographie conventionnelle pour le diagnostic d’arthropathie a PPCD. Methodes Des patients avec presence de cristaux de PPCD dans le liquide synovial (genou, hanche, epaule, cheville ou poignet) ont ete inclus de maniere consecutive et compares a des sujets temoins sans cristaux de PPCD dans le liquide articulaire. Selon les recommandations publiees, nous avons utilise le terme de chondrocalcinose articulaire (CCA) pour les signes evocateurs d’arthropathie a PPCD retrouves a l’imagerie. Chez tous les patients, l’analyse echographique et radiographique des poignets a la recherche d’une CCA a ete realisee en insu par deux operateurs differents (un operateur pour chaque modalite d’imagerie). Les deux examinateurs etaient en insu pour les donnees cliniques, l’analyse du liquide articulaire et les resultats de l’echographie ou de la radiographie. Resultats Un total de 32 patients ayant une arthropathie a PPCD et 26 temoins ont ete inclus. Parmi les patients atteints d’une arthropathie a PPCD, 30 (93,7 %) ont presente des signes echographiques de CCA et 17 (53,1 %) des signes radiographiques de CCA (p Conclusion Notre etude souligne l’interet diagnostique de l’echographie du poignet dans le depistage de l’arthropathie a PPCD, avec une sensibilite superieure a celle de la radiographie pour l’identification des depots de cristaux de PPCD.

International audience; OBJECTIVES:We aimed to determine the ability of ultrasonography (US) to show disappearance of urate deposits in gouty patients requiring urate-lowering therapy (ULT).METHODS:We performed a 6-month multicentre prospective study including patients with: proven gout; presence of US features of gout (tophus and/or double contour sign) at the knee and/or first metatarsophalangeal joints; and no current ULT. US evaluations were performed at baseline and at months 3 and 6 (M3, M6) after starting ULT. Outcomes were: the change in US features of gout at M6 according to final (M6) serum urate (SU) level (high, > 360 μmol/l, i.e. > 6 mg/dl; low, 300-360 μmol/l, i.e. 5-6 mg/dl; very low, < 300 μmol/l, i.e. < 5 mg/dl); and correlation between changed US features and final SU level.RESULTS:We included 79 gouty patients (mean ± s.d., age 61.8 (14) years, 91% males, disease duration 6.3 (6.1) years). Baseline SU level was 530 ± 97 µmol/l (i.e. 8.9 mg/dl ± 1.6mg/dl). At least one US tophus and double contour sign was observed in 74 (94%) and 68 (86%) patients, respectively. Among the 67 completers at M6, 18 and 39 achieved a very low and low SU level, respectively. We found a significant decrease in US features of gout among patients with the lowest SU level (P < 0.001). Final M6 SU level was positively correlated with decreased size of tophus (r = 0.54 [95% CI: 0.34, 0.70], P < 0.0001), and inversely correlated with proportion of double contour sign disappearance (r=-0.59 [-0.74, -0.40]).CONCLUSION:US can show decreased urate deposition after ULT, which is correlated with decreased SU level. The responsiveness of US in gout is demonstrated and can be useful for gout follow-up and adherence to ULT.

Regulator of telomere length 1 (RTEL1) mutations have been evidenced in 5–9% of familial pulmonary fibrosis; however, the phenotype of patients with interstitial lung disease (ILD) and RTEL1 mutations is poorly understood.Whole exome sequencing was performed in 252 probands with ILD and we included all patients with ILD and RTEL1 mutation. RTEL1 expression was evaluated by immunochemistry in the lungs of controls, as well as in RTEL1 and telomerase reverse transcriptase (TERT) mutation carriers.We identified 35 subjects from 17 families. Median age at diagnosis of ILD was 53.1 years (range 28.0–80.6). The most frequent pulmonary diagnoses were idiopathic pulmonary fibrosis (n=20, 57%), secondary ILD (n=7, 20%) and unclassifiable fibrosis or interstitial pneumonia with autoimmune features (n=7, 20%). The median transplant-free and overall survival periods were 39.2 months and 45.3 months, respectively. Forced vital capacity at diagnosis was the only factor associated with decreased transplant-free survival. Extra-pulmonary manifestations were less frequent as compared to other telomere-related gene mutation carriers. A systematic analysis of the literature identified 110 patients with ILD and RTEL1 mutations (including this series) and confirmed the heterogeneity of the pulmonary phenotype, the prevalence of non-idiopathic diseases and the low prevalence of extra-pulmonary manifestations.Immunohistochemistry showed that RTEL1 was expressed by bronchial and alveolar epithelial cells, as well as by alveolar macrophages and lymphocytes, but not by fibroblasts.

Objective To describe the disease course of patients with early arthritis without rheumatoid factor (RF) and anti-citrullinated protein auto-antibodies (ACPA) in an inception cohort. To determine baseline predictors of fulfilling 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) for these patients within 3 years. Method Patients included in the multicenter ESPOIR cohort were compared at baseline and 3 years by whether they were negative for RF and ACPA (“seronegative”) or positive for RF and/or ACPA (“seropositive”). Univariate analysis was used to determine the association between baseline variables in seronegative patients and RA classification. Stepwise multiple logistic regression was used to identify predictors of RA classification within 3 years, estimating odds ratios (ORs). Results Among 354 seronegative patients, 224/340 with available data (65.9%) fulfilled RA classification at baseline and 189/233 (81.1%) at 3 years. As compared with seropositive patients, seronegative patients had lower DAS28 (p = 0.002) and lower modified total Sharp score (mTSS; p = 0.026) at baseline; DAS28 remission was similar (p = 0.634), but radiographic progression rate was lower in seronegative patients (p

Background:Interstitial lung disease (ILD) is a common extra-articular manifestation of RA and is associated with increased morbidity and mortality.1-3 Studies have shown variability in the prevalence and mortality rate of patients with RA-associated ILD (RA-ILD).4 Further studies are needed to better characterise the epidemiology of RA-ILD.Objectives:To estimate the prevalence and incidence of clinical RA-ILD in France and to compare mortality rates between patients with RA-ILD and patients with RA without clinical ILD (RA-noILD).Methods:A historical cohort study was conducted using data from the French national claims database (SNDS) between 1 January 2013 and 31 December 2018. Adults with an RA diagnosis (International Classification of Diseases, Tenth revision [ICD-10] codes M05, M06.0, M06.8 and M06.9) and ≥2 distinct dates of DMARD delivery were included. Onset of RA was defined as the first date of occurrence between RA codes and the first known DMARD reimbursement. ILD diagnosis was defined as having ICD-10 code J84 and ≥1 computed tomography scan after, but within 1 year of, the first date of ILD occurrence. All patients had ≥6 months’ reimbursement after RA-ILD onset. The prevalence and incidence (2014–2018) of RA-ILD were estimated. The mortality rate was calculated, comparing patients with RA-ILD and patients with RA-noILD, matched 1:1 for age, sex, age at RA-ILD onset, duration of RA and presence of diabetes, arterial disease, dyslipidaemia and cardiac disease. Mortality was compared between patients with RA with and without clinical ILD in the matched population using Cox proportional hazards regression.Results:The prevalence of RA-ILD was 6.52 per 100,000 inhabitants (incidence=1.04 per 100,000 person-years). Of the 173,138 patients with RA included in the overall population, 4330 (2.5%) had clinical ILD. Patients with RA-ILD were older at RA diagnosis (mean [SD] age: 63.3 [13.7] vs 56.9 [15.2] years) and were more likely to be male (39.8% vs 27.0%) compared with patients with RA-noILD. Patients with RA-ILD were more likely to have cardiac disease (84.9% vs 63.1%), arterial disease (38.0% vs 19.3%), diabetes (21.4% vs 12.5%) and dyslipidaemia (44.7% vs 32.9%) compared with those with RA-noILD. The mortality rate in patients with clinical RA-ILD was 1.71 per 100,000 inhabitants. The mortality rate increased according to age (0.28 per 100,000 inhabitants for patients aged Conclusion:This is the largest epidemiological study of RA-ILD in France. The prevalence of clinical RA-ILD in this population was towards the lower end of previous estimates (1–58%),3 possibly due to under-reporting of claims data. However, the occurrence of clinical ILD was associated with a strong increase in mortality compared with patients with RA-noILD.References:[1]Bodolay E, et al. Rheumatology (Oxford) 2005;44:656–661.[2]Duarte AC, et al. Rheumatology (Oxford) 2019;58:2031–2038.[3]Hyldgaard C, et al. Ann Rheum Dis 2017;76:1700–1706.[4]Spagnolo P, et al. Arthritis Rheumatol 2018;70:1544–1554.Acknowledgements:This study was funded by Bristol Myers Squibb. Claire Line, PhD of Caudex provided medical writing support, funded by Bristol Myers Squibb.Disclosure of Interests:Pierre-Antoine Juge Consultant of: Bristol Myers Squibb, Lidwine Wemeau Stervinou Consultant of: Boehringer Ingelheim, Bristol Myers Squibb, Roche, Sanofi, Sebastien Ottaviani Consultant of: AbbVie, Bristol Myers Squibb, Lilly, Merck Sharp & Dohme, Novartis, Roche-Chugai, SOBI, UCB, Guillaume Desjeux: None declared, Joe Zhuo Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Bruno Bregman Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Virginie Vannier-Moreau Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Rene-Marc Flipo Speakers bureau: AbbVie, Bristol Myers Squibb, Janssen, Lilly, Medac, Merck Sharp & Dohme, Novartis, Pfizer, Roche-Chugai, Grant/research support from: Amgen, Janssen, Novartis, Pfizer, Bruno Crestani: None declared, Philippe Dieudé Consultant of: Boehringer Ingelheim, Bristol Myers Squibb, Chugaï, Lilly, Medac, Novartis, Pfizer, Sanofi, Grant/research support from: Bristol Myers Squibb, GlaxoSmithKline, Pfizer

Background:Interstitial lung disease (ILD) is an extra-articular manifestation of rheumatoid arthritis (RA) detected in 20% to 60% of patients with RA on high-resolution computed-tomography (HRCT) chest scan and is clinically significant in near 10%. Despite a high morbi-mortality rate, a definite strategy for preclinical ILD screening in patients with RA remains to be determined. To date, several factors have been reported to increase the risk of RA-ILD occurrence (i.e. older age at RA onset, ACPA positivity, male sex, RA disease activity, the MUC5B rs35705950 promoter variant...). However, none of these risk factors has been validated in a prospective cohort of patients with RA. The ESPOIR prospective cohort includes patients aged 18 to 70 years with recent arthritis (less than 6 months) and a definite or probable diagnosis of RA.Objectives:To identify in the ESPOIR cohort factors associated with ILD after at least 10 years of RA duration in order to develop a predictive score to identify patients with preclinical RA-ILD.Methods:An ILD detection by chest HRCT scan was systematically offered to every patient with definite RA after at least 10 years-follow-up. Chest HRCT scans were centrally reviewed by an experienced radiologist. Potential predictors of ILD were prospectively collected from baseline to the date of the HRCT scan, and all included patients were genotyped for MUC5B rs35705950. To take into account repeated measures, trajectories were determined for disease activity, C reactive protein, smoking, treatment exposure (i.e. prednisone, methotrexate [MTX] and biological disease modifying anti-rheumatic drugs [bDMARDs]). A logistic model was used to identify independent predictors for the occurrence of ILD on HRCT scans. Confidence intervals were estimated using sampling methods. A predictive score for preclinical ILD occurrence was developed based on the identified predictors.Results:163 RA patients according to 2010 ACR/EULAR classification criteria, none of whom had pulmonary symptoms, were investigated with a chest HRCT scan (128 women (78.5%), mean RA duration 13.7 ± 1.1 years, age at inclusion 47.6 y/o ± 10.4, mean disease activity score [DAS]-28 during follow up was 3.1 ± 1.0). ILD was detected in 31 patients (19.0%). The MUC5B rs35705950 minor allele frequency (MAF) was 22.2% and 10.0% in the RA-ILD and RA-noILD populations, respectively (OR univariate=2.6 CI95% [1.2-5.5], P=0.01). After logistic regression, independent predictors for preclinical RA-ILD were male sex (OR=3.9 CI95% [1.4-11.4]), older age at RA onset (OR=1.1 per year CI95% [1.0-1.2]), mean DAS-28 score during the follow-up (OR=2.0 CI95% [1.2-3.4]) and MUC5B rs35705950 T risk allele (OR=3.7 CI95% [1.4-10.4]) (Figure 1). No influence of the use of RA-related drugs (prednisone, MTX or bDMARDs) was identified as risk factor. The logistic model could predict preclinical ILD occurrence after 13 years of RA duration with an AUC=0.82 CI95% (0.72-0.91). A predictive score for preclinical RA-ILD based on the 4 identified predictive risk factors was developed (Sensitivity 80%, Specificity 56%).Figure 1.Factors independently associated with preclinical ILD after 13 years of RA durationConclusion:In this cross-sectional study of the prospective ESPOIR cohort, we identified clinical and genetic predictors for ILD after 13 years of RA duration. We developed a predictive score that could improve risk stratification for preclinical RA-ILD and help physicians identify patients with RA in whom a HRCT scan should be performed.Disclosure of Interests:Pierre-Antoine Juge Consultant of: BMS, Benjamin Granger: None declared, Marie-Pierre Debray: None declared, Esther Ebstein: None declared, Fabienne Louis Sidney: None declared, Joanna KEDRA: None declared, Raphael Borie: None declared, Arnaud Constantin Consultant of: Bristol-Meyers Squibb, Chugai, Roche, Abbvie, MSD, Pfizer, and UCB, Bernard Combe Consultant of: Abbvie, Bristol-Meyers Squibb, Lilly, MSD, Janssen, Pfizer, Roche, Chigai, and Sanofi, Grant/research support from: Abbvie, Bristol-Meyers Squibb, Lilly, MSD, Janssen, Pfizer, Roche, Chugai, and Sanofi, René-Marc Flipo Consultant of: Bristol-Meyers Squibb, Roche, Chugai, Abbvie, and Pfizer, Grant/research support from: Roche, Chugai, Abbvie, and Pfizer, Xavier Mariette Consultant of: Bristol-Meyers Squibb, GSK, Janssen, Pfizer, and UCB, Olivier VITTECOQ Consultant of: Bristol Myers Squibb, Roche, Chugai, MSD, Novartis, Pfizer, Abbvie, and Lilly, Alain Saraux Consultant of: Roche, Chugai, and Bristol-Meyers Squibb, Grant/research support from: Roche, Chugai, and Bristol-Meyers Squibb, Guillermo CARVAJAL ALEGRIA: None declared, Jean Sibilia Consultant of: Roche, Chugai, Bristol-Meyers Squibb, UCB, GSK, LFB, Actelion, Pfizer, MSD, Novartis, Amgen, Hospira, AbbVie, Sandoz, Gilead, Lilly, Sanofi, Janssen, and Mylan, Francis Berenbaum Consultant of: Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Elli Lilly, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4P Pharma, Caroline Kannengiesser: None declared, Catherine Boileau: None declared, Bruno Crestani Consultant of: Boehringer Ingelheim, Roche, Sanofi, Apellis, Astra-Zeneca, Grant/research support from: MedImmune, Boehringer Ingelheim, Bruno Fautrel Consultant of: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, SOBI, UCB, Grant/research support from: AbbVie, MSD, Pfizer, Philippe Dieudé: None declared

Background:COVID19 due to SARS-CoV-2 infection implies an important anti-viral immune response leading to a major inflammatory syndrome with increased pro-inflammatory cytokine levels (i.e. the cytokine storm paradigm). The impact of a preexisting interstitial lung disease (ILD) on the morbi-mortality of COVID-19 is unclear. An increased mortality rate has been identified in studies that included a limited number of patients with ILD from various etiologies. To date, no studies have investigated the severity of COVID-19 in patients with preexisting ILD in a large population of rheumatic and musculoskeletal diseases (RMD-ILD). Since March 18th, 2020, the French RMD COVID19 dataset (NCT04353609) includes patients with an RMD and SARS-Cov-2 infection.Objectives:To assess the impact of a preexisting ILD on COVID-19 morbi-mortality within the French RMD COVID-19 dataset.Methods:Patients from the French RMD COVID-19 dataset were included in the analysis. COVID-19 diagnosis was established by a positive SARS-CoV-2 PCR test and/or typical symptoms or chest CT scans pattern during the period of the pandemic. Baseline phenotypic characteristics of the RMD including pre-existing ILD prior to the SARS-CoV-2 infection were collected. COVID-19 evolution was characterized as benign (ambulatory care), moderate (hospitalization outside intensive care unit [ICU]) and severe (hospitalization in ICU). Association between the ILD status and the severity and mortality rate of COVID-19 was assessed using multivariable logistic regression adjusted on sex, age, body mass index and diabetes.Results:By June 26, 2020, 897 patients were included. Pre-existing ILD was reported in 27 patients (3%): 11 patients with systemic sclerosis, 8 with rheumatoid arthritis, 2 with auto-immune myositis, 2 with mixed connective tissue disease and 4 with other RMD. Among these 27 patients (11 male, mean age 63.1 ± 16.4 y/o, 56.5% having a usual interstitial pneumonia HRCT pattern), 22 had severe infection. Death related to COVID-19, was observed in 58 patients with RMD without ILD (7.1%) and in 10 patients with RMD-ILD (37%). Having a preexisting ILD was found to be independently associated with an increased risk of severe COVID-19 (adjusted OR=7.6 [2.9 – 20.2], PConclusion:In RMD patients with SARS-CoV-2 infection, preexisting ILD was associated with an increased risk to severe COVID-19 and related mortality. Our findings suggest that RMD-ILD patients should be prioritized for COVID-19 vaccination according to the high morbi-mortality rate during SARS-CoV-2 infection.Disclosure of Interests:Pierre-Antoine Juge Consultant of: BMS, Eric Hachulla Consultant of: Actelion, Bayer, GSK and Pfizer, Grant/research support from: Actelion, Bayer, GSK and Pfizer, Christophe Richez: None declared, Elodie Drumez: None declared, Alain Duhamel: None declared, Raphael Borie: None declared, Philippe Dieudé: None declared

Background Previous studies suggested that obesity could negatively affect the response to antitumour necrosis factor-α (TNFα) agents in rheumatoid arthritis (RA). However, data are lacking on whether obesity affects the response to abatacept (ABA). We aimed to determine whether body mass index (BMI) affects the response to ABA in RA. Materials and methods In this multicenter retrospective study, we included RA patients who received ABA. BMI was calculated at the initiation of treatment. After 6 months of treatment, change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate and C-reactive protein level, tender and swollen joint count were analysed. The primary endpoint was decrease in DAS28 ≥ 1·2. Secondary outcomes were good response and remission by EULAR criteria. Results At baseline, among 141 RA patients included, the median [interquartile range] BMI was 26·0 [22·9–30·8] kg/m². The number of patients with normal weight, overweight and obesity was 64 (45·4%), 38 (27%) and 39 (27·6%), respectively. Baseline characteristics did not differ among the three BMI subgroups. Univariate analysis revealed no difference in BMI between responders and nonresponders: DAS28 decrease ≥ 1·2 (25·0 [23·4–31·3] vs. 26·3 [22·9–30·2], P = 0·95), EULAR good response (26·4 [23·5–30·9] vs. 26·0 [22·9–30·6], P = 0·96) and remission (26·7 [21·7–30·3] vs. 26·0 [23·0–30·1], P = 0·83). Conclusion In our real-life study, BMI did not affect the response to ABA in RA. If confirmed, these results suggest that obesity is not a limitation of ABA use in RA.