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BackgroundA Treat-to-Target approach (T2T) is broadly considered to lead to better clinical outcomes and recommended in patients with RA. However, very few studies have analyzed the effect of T2T on radiographic progression, and any such studies have provided inconsistent results.ObjectivesTo investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice leads to lower radiographic progression in RA.MethodsPatients from the multicenter RA-BIODAM cohort with ≥2 consecutive visits with radiographs available were included. In RA-BIODAM patients were enrolled as they were initiating a new csDMARD/bDMARD treatment were followed-up with the intention to benchmark and intensify treatment. The primary outcome of this analysis was the change in Sharp-van der Heijde score (SvdH, 0-448), assessed every 6 months, using average scores from 2 readers (scores with known chronological order). Following a DAS44-T2T remission strategy, which was defined at each 3-month visit, was the main variable of interest. Patients were categorized based on the proportion of visits in which T2T was followed according to our definition: very low (≤40% of the visits, low (>40%, 75%). Radiographic progression at 2 years was visualized across groups by cumulative probability plots. Per 3-month interval T2T could be followed zero, one or two times (in a total of 2 visits). Associations between the number of visits with T2T in an interval and radiographic progression, both in the same and in the subsequent 6-month interval, were analysed by generalised estimating equations, adjusted for age, gender, disease duration and country.ResultsIn total, 511 patients were included (mean (SD) age: 56 (13) years; 76% female). After 2 years, patients showed on average 2.2 (4.1) units progression (median:1 unit). Mean (SD) 2-year progression was not significantly different across categories of T2T: very low: 2.1 (2.7)-units; low: 2.8 (6.0); high: 2.4 (4.5), very high: 1.6 (2.2) (Figure 1). Meticulously following-up T2T in a 3-month interval neither reduced progression in the same 6-month interval (parameter estimates (for yes vs no): +0.15 units (95%CI: -0.04 to 0.33) for 2 vs 0 visits; and +0.08 units (-0.06;0.22) for 1 vs 0 visits) nor did it reduce progression in the subsequent 6-month interval (Table 1).Table 1.Effect of following DAS44-remission-T2T strategy on 6-month radiographic progression over 2 yearsChange in radiographic damage(regression coefficient (95% CI))N=506T2T during 3 months on radiographic progression in the same 6-month period 2 visits vs 0 followed0.15 (-0.04; 0.33) 1 visit vs 0 followed0.08 (-0.06; 0.22)T2T during 3 months on radiographic progression in the subsequent 6-month period 2 visits vs 0 followed-0.09 (-0.28; 0.10) 1 visit vs 0 followed-0.10 (-0.24; 0.05)Figure 1.Cumulative probability plot with 2-year radiographic progression according to the proportion of 3-monthly visits with T2T followedConclusionIn this daily practice cohort, more meticulously following T2T principles did not result in more reduction of radiographic progression than a somewhat more liberal attitude toward T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.AcknowledgementsBIODAM was financially supported by an unrestricted grant from AbbVieDisclosure of InterestsSofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB, Robert B.M. Landewé Speakers bureau: AbbVie, BMS, Gilead, Galapagos, GSK,Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Gilead, Galapagos, GSK,Janssen, Lilly, Novartis, Pfizer, UCBDr Landewé owns Rheumatology Consultancy BV, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma. Director of Imaging Rheumatology bv., Alexandre Sepriano Speakers bureau: Novartis, Consultant of: UCB, Oliver FitzGerald Speakers bureau: Biogen, Novartis, AbbVie, BMS, Pfizer, Grant/research support from: BMS, Novartis, UCB, Pfizer, Lilly, Janssen, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Orion, Pfizer, Roche and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, Amgen, BMS, Merck, Celgene and Novartis, Joanne Homik: None declared, Ori Elkayam Speakers bureau: Pfizer, Lilly, Novartis, Abbvie, BI, Janssen, Consultant of: Pfizer, Lilly, Novartis, Abbvie, BI, Janssen, Grant/research support from: Pfizer, Abbvie, Janssen, Carter Thorne Consultant of: Abbvie, Organon, Pfizer, Sandoz, Maggie Larché Speakers bureau: AbbVie, Actelion, Amgen, BMS, Boehringer-Ingelheim, Fresenius-Kabi, Gilead, Janssen, Mallinckrodt, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, Sobi, UCB, Grant/research support from: Abbvie, BMS, Gianfranco Ferraccioli Speakers bureau: SOBI, Consultant of: Abbivie, Marina Backhaus: None declared, Gilles Boire Speakers bureau: Abbvie Canada, BMS Canada, Lilly Canada, Janssen Canada, Merck Canada, Pfizer Canada, Viatris, Consultant of: Abbvie Canada, Amgen Canada, BMS Canada, Celgene, GileadSciences, Janssen Canada, Lilly Canada, Merck Canada, Mylan Canada, Novartis Canada, Pfizer Canada, Roche Canada, Samsung Bioepis, Sanofi Canada, Teva, Grant/research support from: Lilly Canada, BMS Canada, Pfizer, Sandoz Canada, UCB Canada, Merck Canada, Novartis Canada, Roche Canada, Bernard Combe Speakers bureau: Abbvie, BMS,Celltrion,Galapgos-Gilead, Janssen, Lilly, MERCK, Pfizer,Roche-Chugai, Consultant of: Abbvie, Celltrion,Galapgos-Gilead, Janssen, Lilly, MERCK, Roche-Chugai, Grant/research support from: Pfizer, Roche-chugai, Thierry Schaeverbeke: None declared, Alain Saraux Speakers bureau: Abbvie, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, Sanofi, UCB, Consultant of: Abbvie, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Novartis, Fresenius, Lilly, Maxime Dougados Consultant of: Pfizer, AbbVie, UCB, Merck, Lilly, Novartis, BMS, Galapagos, Biogen, Roche, Grant/research support from: Pfizer, AbbVie, UCB, Merck, Lilly, Novartis, BMS, Galapagos, Biogen, Roche, Maurizio Rossini Speakers bureau: Amgen, Abbvie, BMS, Eli-Lilly, Galapagos,MSD, Novartis, Pfizer, Sandoz, Theramex, UCB, Marcello Govoni Speakers bureau: Abbvie, Pfizer, Galapagos, BMS, Eli-Lilly, Paid instructor for: Pfizer, Consultant of: Abbvie, BMS, Novartis, Astrazeneca, Pfizer, Luigi Sinigaglia: None declared, Alain Cantagrel Speakers bureau: Abbvie, Amgen, Biogen, BMS, Janssen, Lilly France, Médac, MSD France, Nordic-Pharma, Novartis, Pfizer, Sanofi Aventis, UCB, Consultant of: BMS, Janssen, Lilly France, MSD France, Sandoz, Grant/research support from: MSD France, Novartis, Pfizer, Cornelia Allaart: None declared, Cheryl Barnabe Speakers bureau: Sanofi Genzyme, Pfizer, Fresenius Kabi, Janssen, Consultant of: Gilead, Celltrion Healthcare, Clifton Bingham Consultant of: AbbVie, BMS, Eli Lilly, Janssen, Moderna, Pfizer, Sanofi, Grant/research support from: BMS, Dirkjan van Schaardenburg: None declared, Hilde Berner Hammer Speakers bureau: AbbVie, Novartis, Lilly, Rana Dadashova: None declared, Edna Hutchings: None declared, Joel Paschke: None declared, Walter P Maksymowych Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, UCB, Consultant of: Abbvie, Boehringer Ingelheim, Celgene, Eli-Lilly, Galapagos, Novartis, Pfizer, UCB, Grant/research support from: Abbvie, Novartis, Pfizer

To investigate the evolution of bone metastases in patients receiving immune checkpoint inhibitors (ICI).A single-center retrospective study included cancer patients with bone metastases treated with ICI at our institution between January 2014 and September 2019. Clinical and biological data were collected from medical records and independent expert review of imaging was performed. Target and non-target lesions were identified and followed up to 1 year. Patients were then classified as bone responder or non-responder. Comparisons between groups were performed with Student's t test or Mann-Whitney test.Among 1108 patients screened, 192 patients had bone metastases and 48 patients were included in the final analysis, with lung cancer, renal carcinoma and melanoma as most represented cancer type. Half of the patients experienced stability, condensation or peripheral sclerosis of bone lesions. Initial progression before stabilization with or without sclerosis of bone lesion occurred for 19% of patients (pseudoprogression). There was an association between bone response and global oncological outcomes. Bone responder patients had a significant decrease in morphine and co-analgesic prescription as well as a significant decrease in alkaline phosphatases compared to non-responder patients.Bone response was observed in half of patients with available imaging and follow-up after 3 months of ICI treatment, with sclerosis observed in one-third of bone lesions at month 3, in all tumor types. Up to 20% of patients experienced a pseudoprogression of bone lesions such as previously described in primary tumor and other metastatic sites. Bone response was associated with improvement of pain and survival.

BackgroundMonoclonal Gammopathy of Undetermined Significance (MGUS) is common in patients with inflammatory rheumatic diseases but there are scarce data regarding the effect of disease-modifying antirheumatic drugs (DMARDs) on this pre-malignant condition. Recently, preclinical data and phase I trial have shown efficacy of JAK inhibitors (JAKi) in multiple myeloma.ObjectivesWe aimed to evaluate the impact of JAKi on MGUS when initiated for an active rheumatic disease.MethodsPatients with monoclonal abnormality prior to JAKi initiation for an active rheumatic disease were identified through the MAJIK-SFR Registry, a french multicentre prospective study, and a call for observation via the “Club Rhumatismes et Inflammations”. Clinical and biological data were collected using a standardised case report form.ResultsNineteen patients were identified, 10 women and 9 men, with a mean age of 65 years and a diagnosis of rheumatoid arthritis (n=14), psoriatic arthritis (n=3) or spondyloarthritis (n=2). The JAKi prescribed was baricitinib (n=8), tofacitinib (n=6) or upadacitinib (n=5), with a mean duration of 13 months.Sixteen patients had individualized serum monoclonal protein (IgG Kappa n=9; IgG Lambda n=6; IgM Kappa n=3; IgA Lambda n=1) ranging from 0,16g/dL to 2,3g/dL. With a follow-up of 2 to 47 months, 8 of 16 patients experienced a decrease in serum monoclonal protein level and 8 had a stable serum monoclonal protein level. The maximal decrease observed was an initial IgG Kappa of 2.3g/dL decreasing to 0.2g/dL at month 14. During follow-up, two patients did not have any detectable serum monoclonal protein on serum electrophoresis (initial value of 5.2g/l and 1.6g/l), but still a positive immunofixation. One patient had bone marrow aspirate with 8% of plasma cells before JAKi introduction and 3% after 4 months of treatment.Three patients did not have initial measurable spike but a positive immunofixation that became negative at month 8 and 11 (IgG Lambda, n=2) or stable (IgG Kappa, n=1).ConclusionThis study brings reassuring and promising data on the MGUS evolution in patients treated with JAKi for rheumatic diseases, which may guide the choice of treatment in patients with both conditions.References[1]Berenson JR, To J, Spektor TM, et al. A Phase I Study of Ruxolitinib, Lenalidomide, and Steroids for Patients with Relapsed/Refractory Multiple MyelomaClin Cancer Res. 2020 May 15;26(10):2346-2353.AcknowledgementsMAJIK-SFR Registry and Club Rhumatismes et InflammationsDisclosure of InterestsNone declared

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

Introduction Alors que l’immunotherapie prend une place de plus en importante en cancerologie, il y a tres peu de donnees rapportees concernant son effet sur les metastases osseuses. Notre objectif etait d’etudier l’evolution des metastases osseuses chez les patients atteints de cancer et traites par inhibiteurs de checkpoint immunitaire (ICI). Patients et methodes Dans le cadre d’une etude retrospective monocentrique, tous les patients atteints de cancer avec metastases osseuses et traites par ICI entre Janvier 2014 et Septembre 2019 ont ete inclus, si les imageries etaient disponibles. Les donnees cliniques et biologiques ont ete collectees a partir du dossier medical informatise et une relecture des imageries a ete realisee de facon independante par un radiologue specialise en imagerie osteo-articulaire. Des lesions cibles et non-cibles ont ete identifiees lors de la mise sous ICI puis suivies a 3, 6 et 12 mois. Des comparaisons entre les patients avec ou sans reponse osseuse ont ete realisees avec test de Mann-Whitney ou test t de Student. Resultats 48 patients ont pu etre inclus dans les analyses. Pour la moitie des patients, on retrouvait une stabilite des lesions osseuses, avec condensation et/ou apparition d’une sclerose peripherique. Il existait une progression initiale en taille avant d’avoir une stabilite avec ou sans sclerose de la lesion osseuse pour 19 % des patients, phenomene classiquement decrit comme « pseudoprogression ». On retrouvait une correlation entre reponse osseuse et evolution oncologique globale (reponse tumorale evaluee par les criteres RECIST, survie globale et survie sans progression). Pour les patients avec une reponse osseuse, on notait une diminution significative de la consommation en morphine et en co-analgesiques, mais egalement une diminution significative et precoce des phosphatases alcalines en comparaison avec les patients non repondeurs sur leur metastase(s) osseuse(s). En revanche, il n’y avait pas de difference notable sur la survenue d’evenement osseux. Discussion L’evolution des metastases osseuses etait favorable pour la moitie des patients traites par ICI, avec souvent une sclerose peripherique observee des le 3eme mois de traitement, mais possiblement un phenomene de pseudoprogression comme decrit prealablement avec les tumeurs primitives. Cette reponse osseuse s’associait a une meilleure qualite de vie et survie. La relecture specialisee apportait une reelle plus-value comparativement aux comptes-rendus initiaux. Conclusion Les metastases osseuses ont un profil de reponse particulier sous ICI, comme decrit dans les tumeurs primitives, avec une frequente sclerose et possible pseudoprogression.

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:Considering the potential role of the gut microbiota in the pathophysiology of spondyloarthritis (SpA) as in the therapeutic response to biologics (1), we evaluated the hypothesis that co-medications known to interfere with the gut microbiota could impair the therapeutic response to TNF-inhibitors (TNF-i) in SpA patients. This was first suggested by the results of a retrospective cohort showing that a co-medication with proton pump inhibitors (PPIs), non-steroidal anti-inflammatory drugs (NSAIDs) or antibiotics was significantly associated with a decreased chance to respond to a first TNF-I, independently of each other (2).Objectives:To validate in a replication cohort the potential negative association between therapeutic response to TNF-i and co-medication with commonly used drugs.Methods:Demographic information and disease characteristics were retrospectively collected. Patients were classified as responder (R) or non-responder (NR) according to the BASDAI (< 40/100) value at month 6 or to the clinician judgment (when BASDAI was not available). We collected all drugs known to interfere with the gut microbiota that were administered 1 month before and during the first 3 months of the TNF-i treatment. We only considered drugs given to more than 5% of patients. Univariate and multivariate analyses were performed to evaluate the relationship between co-medications, predictors of response known from literature and TNF-i response. All analyses were computed on STATA 13.1 with a statistically significant threshold of 0.05.Results:We included from 4 different centres 185 patients having axial SpA with radiographic or magnetic sacroiliitis in 75% and 73% of cases, respectively. One third of them had peripheral involvement. 73% were B27 positive. TNF-i administrated were infliximab (8%), etanercept (22%), adalimumab (44%) golimumab (19%), certolizumab (7%). 127 patients (69%) were considered as R. 59.4% of patients who received NSAIDs were R, compared to 81% not treated with NSAIDs (p< 0.0001). 43,3% of patients receiving PPIs were R compared to 83% of patients PPI free (p< 0.0001). Differences were not significant for antibiotics, methotrexate (MTX), psychotic drugs and corticosteroids. Considering known predictors of response, a magnetic sacroiliitis and the age at TNF-i initiation were significantly associated with a higher proportion of R patients (p=0.048 and 0.018 respectively). In multivariate analysis, PPIs intake remained associated with a poorer response to a first TNF-i (pUnivariate analysisMultivariate analysisOdd Ratio (95% Confidence Interval)Gender1.43 (0.76; 2.72)Disease duration1.02 (0.99; 1.06)Age at TNF-I initiation0.97 (0.95; 0.995) 0.97 (0.94; 0.999)Magnetic sacroiliitis0.46 (0.21; 0.99)0.63 (0.26; 1.52)Baseline BASDAI1.02 (0.99;1.04)Baseline CRP0.99 (0.98; 1.02)Positive B270.81 (0.4;1.68)Peripheral involvement0.79 (0.4; 1.56)NSAIDs2.91 (1.47; 5.77)1.08 (0.41; 2.79)PPIs6.4 (3.25; 12.7)6.9 (2.8;17)Antibiotics1.87 (0.84; 4.16)Psychotics1.94 (0.75; 4.97)Corticosteroids1.11 (0.39; 3.11)Methotrexate2.29 (0.97; 5.38)Conclusion:Co-medication with PPIs was considered as an independent factor associated with TNF-i failure. The hypothesis that this effect is due to their interference with the gut microbiota is only speculative but, regardless of the reason for this interaction, clinicians should be aware of the potential negative effect on TNF-i response.References:[1]Bazin, T., Hooks, K.B., Barnetche, T. et al. Microbiota Composition May Predict Anti-Tnf Alpha Response in Spondyloarthritis Patients: an Exploratory Study. Sci Rep8, 5446 (2018). https://doi.org/10.1038/s41598-018-23571-4[2]Masson M, Kostine M, Barnetche T, Truchetet ME, Richez C, Schaeverbeke T. Ab0661 Co-Medications May Alter the Response to Tnf-Inhibitors in Spondyloarthritis Patients: A Pharmacomicrobiomic Effect? Annals of the Rheumatic Diseases. 1 juin 2020;79(Suppl 1):1625–6.Disclosure of Interests:None declared.

Introduction Sarilumab, un anticorps monoclonal inhibiteur du recepteur a l’IL-6 indique dans le traitement de la PR active moderee a severe, a montre une efficacite sur l’activite de la maladie et sur certains parametres rapportes par les patients (PRO). L’etude francaise SariPRO (effet de sarilumab sur les PRO chez les patients atteints de PR active) ( NCT03449758 ) visait a evaluer l’effet du sarilumab 200 mg toutes les 2 semaines (S) sur les PROs. Patients et methodes L’etude SariPRO est une etude multicentrique, en ouvert, non controlee, de phase IV incluant des adultes atteints d’une PR moderee a severe (DAS28-ESR > 3,2) avec une reponse inadequate ou une intolerance aux csDMARD ou aux inhibiteurs du TNF. Critere d’evaluation primaire : modification du score RAID (evalue la qualite de vie associee a la PR) entre l’inclusion et la semaine 24 (S24). Principaux criteres secondaires d’evaluation : modification entre l’inclusion et chaque visite (S4, 12, 24) pour plusieurs PROs, y compris le RAID, l’HADS (mesure l’anxiete et la depression), le MAThys (evalue les troubles de l’humeur a l’aide d’une echelle analogique visuelle avec cinq dimensions allant de l’inhibition a l’excitation), le FACIT-F (mesure la fatigue), l’HAQ-DI (mesure la capacite fonctionnelle), l’IPAQ (mesure l’activite physique), l’EVA de l’activite de la maladie, la duree de la raideur matinale et l’activite de la maladie. Criteres de tolerance : incidence et gravite des EI. Pour les variables continues, le nombre de donnees disponibles, la moyenne, l’ecart-type, la mediane et la fourchette (min, max) ont ete fournis avec l’IC de 95 %. Resultats Quatre-vingt-quatre patients au total (31 centres) ont ete inclus dans cette etude. La mise sous sarilumab est associee a une reduction du score total du RAID (moyenne [ecart-type]) de l’inclusion (5,8 [1,9]) a S4 (4,6 [2,1]), S12 (3,9 [2,3]) et S24 (3,3 [2,5]) ; la variation du score moyen entre l’inclusion et S24 etait de −2,4 [IC a 95 % : −3,0 a −1,8]. De meme, chaque domaine du RAID score a ete diminue. Les scores d’anxiete et de depression (HAD), la fatigue (FACIT-F), l’EVA de l’activite de la maladie et la duree du derouillage matinal ont tous diminue, de l’inclusion a chacune des visites suivantes. La capacite fonctionnelle (HAQ-DI) et l’activite physique (IPAQ) ont augmente. En revanche, les troubles de l’humeur (echelle MAThyS) sont restes stables lors du traitement ( Tableau 1 ). La VS, le nombre d’articulations douloureuses et gonflees, le DAS28 et le CDAI ont tous diminue entre l’inclusion et chaque visite. Le profil de tolerance du sarilumab est comparable a celui rapporte dans les essais cliniques precedents. Conclusion Dans cette etude proche de la « vraie vie » chez les patients atteints de PR en France, le traitement par sarilumab a ete associe a une amelioration clinique de la maladie ressentie par le patient observee a travers le score RAID et la plupart des autres PROs, ainsi qu’a une amelioration de l’activite de la maladie a S24. Les troubles de l’humeur n’ont pas ete modifies.

Background:Description and initial management of rheumatic immune-related adverse-events (irAEs) from cancer immunotherapies have been reported by several groups but to date, few studies have evaluated the long-term outcomes and management of rheumatic irAEs (1).Objectives:To describe the long-term management and assess the one-year outcomes of patients who experienced rheumatic immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI).Methods:This was a single-centre prospective observational study including patients referred for musculoskeletal symptoms while treated with ICI. After baseline rheumatological evaluation defining the clinical entity presented, follow-up visits were organised according to the type and severity of irAE. At one year, persistence of irAE, ongoing treatment, as well as cancer outcomes were assessed.Results:63 patients were included between September 2015 and June 2018. 24 patients (38%) presented with non-inflammatory musculoskeletal conditions managed with short-term symptomatic treatment and did not require specific follow-up. 39 patients (62%) experienced inflammatory manifestations, mimicking either rheumatoid arthritis (RA, n=19), polymyalgia rheumatica (PMR, n=16), psoriatic arthritis (PsA, n=3) and one flare of a preexisting axial spondyloarthritis. Overall, 32 patients (82%) received systemic glucocorticoids, with a median rheumatic dosage of 15mg/day (range: 5-60mg/day). None of the patients had to permanently discontinue ICI therapy for rheumatic irAE. 20 patients (67%) were still receiving glucocorticoids at one year, with a median dosage of 5mg/day (range: 2-20mg/day). Glucocorticoids were more frequently discontinued for patients with RA-like condition (44%) than PMR-like condition (23%), but no other predictive factor of glucocorticoids withdrawal could be identified. At one year, overall survival and progression-free survival were comparable between patients who were still receiving glucocorticoids for rheumatic irAE and patients who have discontinued. Eight patients required csDMARDs.Conclusion:At one year, a majority of patients required long-term low-dose glucocorticoids for chronic rheumatic irAE, which seems not altering oncological control.References:[1]Braaten TJ, Brahmer JR, Forde PM, et al. Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation. Ann Rheum Dis. 2019 Sep 20.Disclosure of Interests:None declared

Background:Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Its use has been associated with hypersensitivity pneumonitis and diffuse lung disease. Whether MTX exposure increases the risk of interstitial lung disease (ILD) in patients with RA is disputed.Objectives:We aimed to evaluate the association of antecedent MTX use with development of RA-ILD.Methods:Through a case-control study design with derivation and international validation samples, we examined the association of MTX exposure with ILD in 482 patients with RA-ILD and 741 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques.Results:Analysis of the derivation sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.25 to 0.92; P=0.028), which was confirmed in the validation samples (pooled adjusted OR, 0.39; 95% CI, 0.23 to 0.68; PConclusion:Our results suggest that MTX is not a risk factor for RA-ILD and support a possible disease modifying effect of MTX on development of RA-ILD.Disclosure of Interests:Pierre-Antoine Juge: None declared, Joyce S. Lee Consultant of: Celgene, Genentech, Boehringer Ingelheim, Jessica Lau: None declared, Leticia Kawano: None declared, Jorge Rojas-Serrano: None declared, Marco Sebastiani: None declared, Gouri Koduri: None declared, Eric Matteson Grant/research support from: Pfizer, Consultant of: Boehringer Ingelheim, Gilead, TympoBio, Arena Pharmaceuticals, Speakers bureau: Simply Speaking, Karina Bonfiglioli Consultant of: Roche, Abbvie, Pfizer, Janssen and BMS, Marcio Sawamura: None declared, Ronaldo Kairalla: None declared, Lorenzo Cavagna: None declared, Emanuele Bozzalla Cassione: None declared, Andreina Manfredi: None declared, Mayra Mejia: None declared, Pedro Rodríguez Henríquez: None declared, Montserrat I. Gonzalez-Perez: None declared, Ramcés Falfan-Valencia: None declared, Ivette Buendia-Roldan: None declared, Glora Perez-Rubio: None declared, Esther Ebstein Consultant of: BMS, Employee of: BMS, Steven Gazal: None declared, Raphael Borie Consultant of: Roche, Boehringer Ingelheim, Sebastien Ottaviani: None declared, Caroline Kannengiesser: None declared, Benoît Wallaert Consultant of: Roche, Boehringer Ingelheim, Yurdagul Uzunhan Consultant of: Roche, Boehringer Ingelheim,, Hilario Nunes: None declared, Dominique Valeyre Consultant of: Astra Zeneca, Roche, Boehringer Ingelheim, Nathalie Saidenberg Kermanac’h: None declared, marie-Christophe Boissier: None declared, Lidwine Wemeau Stervinou Consultant of: Roche, Janssen, BMS, Boehringer Ingelheim, Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly, Sylvain Marchand-Adam Consultant of: Roche, Novartis, Boehringer Ingelheim, Pascal Richette: None declared, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi, Claire Dromer: None declared, Marie-Elise Truchetet: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Thierry Schaeverbeke: None declared, Huguette Lioté: None declared, Gabriel Thabut Employee of: Astra Zeneca, Kevin Deane Grant/research support from: Janssen, Consultant of: Inova, ThermoFisher, Janseen, BMS and Microdrop, Joshua Solomon: None declared, Tracy Doyle: None declared, Jay H. Ryu: None declared, Ivan O. Rosas Consultant of: Boehringer Ingelheim, Gerentech, Three Lakes Partners, V. Michael Holers Grant/research support from: Janssen, Celgene, and BMS, Catherine Boileau: None declared, Marie-Pierre Debray: None declared, Raphaël Porcher: None declared, David A. Schwartz Consultant of: NuMedii, Robert Vassallo Shareholder of: Pfizer, BMS, SunPharma, Bruno Crestani Shareholder of: Apellis, Boehringer Inghelheim, Medillune, Roche, Consultant of: Boehringer Ingelhiem, Astra Zeneca, Roche, Sanofi, Philippe Dieudé: None declared

Background:Overlap between systemic sclerosis (SSc) and another auto-immune systemic disease (AISD) in the same patient seems to be more frequent than each disease’s prevalence would explain.Objectives:Our aim was to investigate for overlap syndrome from 2 French cohorts of SSc patients and to compare their characteristics with non-overlap SSc.Methods:Our study was retrospective observational and bicentric. Patients responding to the 2013 ACR-EULAR scleroderma classification criteria for SSc were screened for concomitant AISD. Patients satisfying 2010 ACR-EULAR diagnostic criteria for rheumatoid arthritis (RA) and/or 2016 ACR-EULAR classification criteria for Sjögren’s syndrome (SgS) and/or 2012 SLICC systemic lupus erythematosus (SLE) classification criteria were included in our study. Patient, disease, and treatment characteristics were retrospectively retrieved from medical records and were compared to a SSc cohort.Results:A population of 534 SSc patients was studied. Thirty-four (6.4%) patients were identified as having overlap syndrome. There was 21 (3.9%) patients with RA, 14 (2.6%) with GSS and 4 (0.7%) with SLE (5 patients had 2 AISD). Diagnosis of RA, SLE or SgS was made after diagnosis of SSc for 22 (65%) patients, concomitantly for 10 patients (29%), and before for 2 (6%) patients. Interestingly, two patients with SSc/RA overlap were tested ACPA-positive 2 and 5 years before the first arthritis, respectively. Patients with SSc/RA were severe with 81% of them having erosive disease and despite treatment, only 48% (10/21) patients achieved RA remission (DAS28-CRP < 2.6) at the time of their last visit. Disease duration was longer in patients with SSc overlap syndrome compared to non-overlap patients (15.5 ± 10.6 yearsvs.9.5 ± 8, p < 0.001). Proportion of limited cutaneous SSc was similar in overlap and non-overlap groups (70.6%vs.75.5%, respectively, p = NS), as was the positivity for anti-centromeres antibodies (50%vs.43.2%, respectively, p = NS). The disease phenotype of SSc overlap syndrome was similar to the one of non-overlap SSc in terms of prevalence of pulmonary arterial hypertension, interstitial lung disease, digital ulcer and mortality. With respect to treatments, patients with overlap were more likely to receive glucocorticoids (85.3%vs.45%, p < 0.001), immunosuppressive drugs (82.4%vs.49.2%, p < 0.001) and biologic DMARD (bDMARD, 52.9 %vs.3.8%, p < 0.001). The most prescribed bDMARDs in the overlap population was tocilizumab (40.6%), TNF-alpha inhibitor (29.4%) and rituximab (26.5%) (p < 0.001 for all comparisonvs.non-overlap SSc).Conclusion:We found a prevalence of overlap syndrome higher than 5% among SSc patients. While SSc overlap and non-overlap share common characteristics, overlap patients are more likely to receive glucocorticoids and biologics such as anti-TNF. These overlap should be searched actively (eg, screening for ACPA) since some treatment used for other autoimmune diseases such as glucocorticoids or TNF-alpha inhibitor may be harmful in SSc.Disclosure of Interests:Marc SCHERLINGER Consultant of: Amgen, Mylan, Fresenius Kabi, Johanna Lutz: None declared, Jean Sibilia: None declared, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Thierry Schaeverbeke: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Emmanuel Chatelus: None declared, Marie-Elise Truchetet: None declared

Background:The reason why some spondyloarthritis (SA) patients fail to respond to TNF inhibitors (TNF-i) remains unclear. Recently, it has been shown in cancer immunotherapy that the therapeutic response may be strongly altered by co-medication with drugs interfering with the gut microbiota, such as antibiotics, proton pump inhibitors (PPI), non-steroidal anti-inflammatory drugs (NSAIDs), psychotropic or antidiabetic drugs.Objectives:Considering the potential role of the gut microbiota in the pathophysiology of SA as in the therapeutic response, the aim was to study the influence of co-medications known to interfere with the microbiota with the therapeutic response to TNF-i in SA patients.Methods:We retrospectively reviewed the charts of all patients treated in our department with a first TNF-i from 2009 to 2018. Data collected were demographic information, HLA-B27 status, disease characteristics… Patients were classified as responder (R) or non-responder (NR) according to the BASDAI (< 40/100) value at M6 or to the clinician judgment (when BASDAI was not available). Regarding co-medications, we collected all drugs known to interfere with the gut microbiota that were administered 1 month before and during the first 3 months of the TNF-i treatment. We only considered drugs given to more than 5% of patients. Quantitative data were expressed as mean ± standard deviation, and qualitative variables as percentages. Univariate and multivariate analyses were performed to evaluate the relationship between co-medications and TNF-i. All analyses were computed on STATA 13.1 software with a statistically significant threshold of 0.05.Results:We included 188 patients suffering from ankylosing spondylitis (n=89) or peripheral SA (n=99). They were 68 women and 120 men, mean aged 46.6 ± 13; 53% were B27 positive. TNF-i were infliximab (19%), etanercept (44%), adalimumab (34%) golimumab (2%), certolizumab (1%), combined with MTX in 51 patients. 135 patients (72%) were R and 53 (28%) NR. In univariate analysis, 59.1% of patients who received NSAIDs were R, compared to 88.2% of patients not treated with NSAIDs (p< 0.0001); 42.2% of patients receiving PPIs were R compared to 86.3% of patients PPI free (p< 0.0001); 55.8% of patients who were given antibiotics were R, compared to 75.7% of patients who did not (p=0,02); 27.8% of patients treated with psychotropic drugs were R, compared to 75.9% of patients not receiving such treatment (p< 0.0001) (Figure 1). Differences were not statistically significant for corticosteroids, MTX, angiotensin-converting enzyme inhibitors and statins. Although 91% of patients taken PPIs were also given NSAIDs, NSAIDs, PPIs and antibiotics intake were considered as independent factors associated with TNF-i failure in multivariate analysis.Conclusion:Co-medication with NSAIDs, PPIs, antibiotics and psychotropic drugs were significantly associated with a decreased chance to respond to TNF-i. The hypothesis that this effect is due to their interference with the gut microbiota is only speculative but, regardless the reason of this interaction, clinician should be aware of the potential negative effect of these co-medication on TNF-i.Figure 1.Disclosure of Interests:Maéva Masson: None declared, Marie Kostine: None declared, Thomas Barnetche: None declared, Marie-Elise Truchetet: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Thierry Schaeverbeke: None declared

Background Immune checkpoint inhibitors (ICI) represent a new standard of care for the treatment of selected advanced cancers and are still being investigated in many other tumour types. By enhancing the T-cell activation, a unique spectrum of inflammatory side effects has emerged, also known as immune-related adverse events (irAEs), including various well-described rheumatic manifestations. Data regarding the association between irAEs and patient outcomes are conflicting. Objectives To evaluate the incidence and characteristics of irAEs in patients receiving ICI, as well as the correlation with tumour response and patient survival. Methods This was a single-centre prospective observational study including all cancer patients receiving ICIs. The occurrence of irAEs, tumour response and patient outcomes were assessed on a regular basis. Overall survival has been considered from the start of ICI. Results From May 2015 to September 2017, 636 patients (70% male, mean age 64 years) have been included in this cohort while receiving anti PD-1 (n=435), anti PD-L1 (n=66) or anti CTLA-4 (n=3) as single agent or as sequential (n=100) or combined (n=32) therapies. Cancer types were mainly melanoma (n=293), non-small cell lung cancer (n=150) and renal carcinoma (n=83). Overall, 274/633 patients (43%) experienced irAEs, either 1 irAE (n=162), 2 irAEs (n=78) or ≥3 irAEs (n=34), with a median exposure time of 52 days30–91 for the first irAE. Dermatological irAEs were by far the most frequent (n=160), followed by digestive (n=80), endocrine irAEs (n=67), rheumatic (n=49) and pulmonary irAEs (n=17). So far, evaluation of tumour response was available for 551 patients, including 190 responders (complete response n=36 and partial response n=154), 192 patients with stable disease and 169 with progressive disease. 122/189 responders (65%) and 107/192 with stable disease (56%) experienced at least one irAE while reported only in 40/169 non responders (24%). Patients experiencing at least one irAE had an increased overall survival (median of 1169 days versus 224 days, p Conclusions Although irAE occurrence is not required for treatment benefit, it strongly associates with overall survival. Optimal multidisciplinary management of irAEs, including rheumatologists when needed, is worthwhile to maintain beneficial responses. Disclosure of Interest None declared

Introduction L’efficacite du tocilizumab (TCZ) dans l’arterite a cellules geantes (ACG) est demontree dans deux essais randomises, permettant de reduire le risque de rechute et de diminuer les doses de corticoides (CS). Il est recommande en cas de corticoresistance, de rechute ou d’epargne cortisonique necessaire [1] . Il n’existe neanmoins aucune recommandation concernant la duree de traitement et les modalites d’arret. D’autre part, la toxicite du TCZ chez les patients atteints d’ACG pourrait etre plus importante que dans la polyarthrite rhumatoide. L’objectif de notre etude etait d’evaluer, en vraie vie, dans une cohorte retrospective multicentrique de patients traites par TCZ pour une ACG ou une aortite primitive (AP), le risque de rechute sous traitement et apres interruption, l’evolution des doses de CS et la survenue d’effets secondaires. Patients et methodes Les patients pour lesquels un traitement par TCZ a ete initie dans le cadre d’une ACG et/ou d’une AP depuis le 01/01/2012 ont ete identifies. Ils devaient etre âges de plus de 50 ans et repondre aux criteres de l’American College of Rhumatology definissant l’ACG, ou presenter une AP. Le recueil d’informations a ete realise a partir d’une fiche informatisee preetablie avant le debut de l’etude. Les donnees ont ete recueillies au diagnostic initial, lors de la premiere phase therapeutique sous CS, a l’introduction du TCZ et lors de la deuxieme phase therapeutique apres introduction du TCZ. La rechute etait definie par la survenue d’une manifestation clinique ou d’un syndrome inflammatoire en lien avec la maladie justifiant une intensification therapeutique. Resultats Trente-sept ACG dont 22/29 (76 %) presentaient une BAT positive et 6 AP etaient inclues dans l’etude, ou les diagnostics s’echelonnaient de mai 2007 a janvier 2019. La moyenne d’âge etait de 74 ans [IQR : 67–81]. La duree mediane sous CS avant TCZ etait de 511 jours [IQR : 143–1292] et la dose cumulee mediane de CS de 9,6 g [IQR : 8,3–13,2]. Respectivement 26, 21 et 11 patients sur 43 recevaient des doses de CS Conclusion Bien que nos resultats confirment une capacite d’epargne cortisonique notable du TCZ, il ne permet une remission prolongee apres arret du traitement que chez moins de un patient sur deux. Une attention doit etre portee quant a la tolerance de ce traitement dans cette population âgee et lourdement pretraitee.

Background Comorbidities including cardiovascular (CV) risk, cancer and osteoporosis are frequent in RA.[1] Objectives To quantify at baseline and 3 years later, the prevalence (at baseline) and incidence (over 3 years) of some selected comorbidities. Methods This was an open long term (3 years) extension of the COMEDRA 6-month randomized controlled trial in which patients with definite, stable RA were visiting a nurse for comorbidity counselling.[2] Comorbidity status was assessed through face-to-face interviews and nurses provided advice on screening and management, at baseline and 3 years later. The frequency of comorbidities was assessed at both timepoints and incidence of new cases was assessed as overall % of patients and as relative increase in the given comorbidity. Results Of the 970 recruited patients, 776 (80%) were followed up at 2–4 years (15, 1.5%, had died) and 769 (79%) had available data for comorbidities at both timepoints: at baseline, mean (±SD) age 58 (±11) years, mean disease duration 14 (±10) years; 614 (80%) were women and 538 (70%) were receiving a biologic with a mean DAS28 of 3.1±1.3. At baseline, the most frequent comorbidities were history of fracture (31.9%) and high blood pressure (30.9%) and at 3 years the comorbidity which had most increased (i.e., incidence) in this population aged around 60 years, was high blood pressure (4%) whereas smoking had decreased (Table). Conclusions Comorbidities are frequent in RA though screening does not always address the most frequent or severe comorbidities. Efforts must be pursued to improve comorbidity screening and prevention. References Ref 1. Baillet A, Gossec L et al. Ann Rheum Dis. 2016;75(6):965–73. Ref 2. Dougados M, Soubrier M, et al. Ann Rheum Dis. 2015;74(9):1725–33. Acknowledgements grant from Roche France and from the French National Research Program (PHRC AOM 12072). Disclosure of Interest None declared

Background Despite its high prevalence and mortality, little is known about the pathogenesis of RA–associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA–ILD frequently share the usual interstitial pneumonia pattern and common environmental risk factors, we hypothesized that the two diseases may share additional risk factors including FPF-linked genes. Objectives Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD. Methods We used whole-exome sequencing (WES) followed by restricted analysis of a discrete number of FPF-linked genes and performed a Burden test to assess the excess number of mutations in RA–ILD patients compared to controls. Results Among the 101 RA–ILD patients included, 12 (11.9%) had 13 WESidentified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA–ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations for RA–ILD patients (p=9.45’10-4, odds ratio [OR] 3.17 95% CI 1.53 – 6.12). Telomeres were shorter for RA-ILD patients with a TERT, RTEL1 or PARN mutation than controls (p=2.87x10-2). Conclusions Our results support the contribution of FPF-linked genes to RA–ILD susceptibility. Disclosure of Interest None declared

Background Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) axis have been a major advance in cancer immunotherapy. By enhancing T cell activity, unprecedented long-lasting tumour responses are observed in selected cancers but some patients experience immune related adverse events (irAE). Objectives To evaluate the prevalence and type of rheumatic and musculoskeletal disorders in patients receiving ICI at a single institution (University Hospital of Bordeaux, France). Methods All cancer patients with musculoskeletal disorders while receiving ICI were referred to our rheumatology department. For each referred patient, an experienced rheumatologist performed a comprehensive clinical evaluation. Blood tests (inflammatory markers, serum creatine kinase, autoantibodies) and imaging (X-rays, ultrasound) were obtained according to clinical findings. HLA-DR phenotyping was also performed for some patients to search for shared epitope. Results From September 2015 to December 2016, 329 patients received ICI (anti CTLA-4: n=38; anti PD-1: n=251; anti PD-L1: n=29; combination anti CTLA-4/anti PD-1: n=11) and 21 patients were referred to our rheumatology department (6.4%). Mean age was 65 years and cancer types included melanoma (n=10), non small cell lung cancer (n=9), Merkel carcinoma (n=1) and renal carcinoma (n=1). All musculoskeletal disorders occurred in patients receiving anti PD-1 (nivolumab: n=12; pembrolizumab: n=6) or anti PD-L1 (avelumab: n=2; atezolizumab: n=1), with a median exposure time of 90 days (range: 1–650 days). There were two distinct clinical presentations: 1) inflammatory arthritis (IA) mimicking either rheumatoid arthritis (n=5) or polymyalgia rheumatica (n=8) and, 2) non-inflammatory musculoskeletal conditions (n=8). Of note, one patient was anti-CCP positive but negative for RF. Shared epitope HLA-DRB1 *01:01 was present in 4 patients. Eleven patients required corticosteroid therapy with a median dose of 15mg/day (range: 7–30 mg/day). Non-inflammatory disorders were easily managed with NSAIDs, analgesics and/or physiotherapy. ICI treatment was temporarily discontinued in one patient only, in line with the clinical trial protocol. To date, there was a partial or complete tumour response to ICI in 10 patients whereas 3 had stable disease and 7 had progressive disease. Tumour response or stable disease was observed in 11 of 12 patients with IA but only in 2 of 8 patients with non-inflammatory conditions. Conclusions In our series, patients with immune-related IA mimicking rheumatoid arthritis and polymyalgia rheumatica were responsive to low-to-moderate dose of prednisone and did not require ICI discontinuation. Furthermore, tumour response was frequently observed in such patients. Disclosure of Interest None declared

Background After the two global pivotal studies, which evaluated the safety and efficacy of subcutaneous tocilizumab (TCZ-SC) in combination (combo) with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), it was important to understand the efficacy and safety profile of TCZ-SC both as monotherapy (mono) and in combo with csDMARDs in patients (pts) managed in conditions less strict than those of pivotal clinical trials. Objectives To evaluate the efficacy and safety of TCZ-SC 162 mg once weekly (qw) as mono and in combo with csDMARDs over 24 weeks in adult pts with moderate to severe RA. The primary efficacy criterion was the change in DAS28-ESR from baseline to week 24 (W24). Methods TOSCA is a national, multicenter, open-label phase IIIb study, part of the international umbrella study (TOZURA). It aimed to enroll TCZ-naive pts who were csdMARDs inadequate responders (IR) and/or biological DMARD-IR. Pts received TCZ-SC 162 mg qw for 24 weeks, administered at the investigator9s discretion as mono or in combo with a csDMARD. Stable oral corticosteroids (CCS), ≤10 mg/day prednisone or equivalent (eq.pred), were allowed. Results The baseline characteristics of the 139 included patients were: mean age 57.3 years (±13.8), 74.1% female, mean RA disease duration 10.8 years (±9.2), immunopositivity 85.5%, structural joint damage 65.6%, mean DAS28 5.8 (±1.1). 52.5% of patients were bDMARD-IR. TCZ-SC was initiated in mono TCZ in 30.9% of pts and in combo in 69.1% (79.1% MTX). Oral CCS were used by 56.8% of pts (mean 7.4 mg/d/eq.pred.±2.7). In comparison with combo pts, the mono pts were older (58.7 vs 56.7 years), with a higher mean DAS28 (6.1 vs 5.7), a longer disease duration (11.5 vs 10.6 years), and a higher CCS mean dose (8.3 vs 6.9 mg/d/eq.pred.). At W24, the mean DAS28 score variation vs baseline was -3.1 overall (p 5 mg CCS at baseline decreased the daily dose ≤5 mg/d/eq.pred. (30.1% in mono TCZ and 26.7% in combo). Out of the 23 pts (16.5%) who withdrew, 13.0% did so for lack of efficacy and 52.1% for safety reasons; one death occurred following a septic shock after surgery for gastric volvulus, not related to TCZ. At W24 95.7% of patients had experienced at least one adverse event (AE) and 10.1% at least one serious AE with similar rates between groups. Conclusions TCZ-SC demonstrated at 6 months comparable efficacy, safety and steroid sparing results in mono- and combo therapy consistent with the known profile of TCZ-IV. Disclosure of Interest B. Fautrel: None declared, E. Senbel: None declared, O. Vittecoq: None declared, S. Rist: None declared, B. Combe: None declared, T. Schaeverbeke: None declared, F. Liote: None declared, R.-M. Flipo: None declared, C. Baffie Employee of: Altizem on behalf of Roche, D. Pau Employee of: Roche, E. Conde Da Silva Fraga Employee of: Roche, A. Pinta Employee of: Roche, P. Gaudin: None declared

Background Patients with RA are either more at risk of, or less well screened for, several comorbidities including cardiovascular (CV) risk, cancer, infections and osteoporosis.[1] Recommendations have been developed on how and at what frequency to screen for comorbidities in RA patients.[2] Objectives to characterise patients who are being screened correctly (i.e., in accordance with recommendations). Methods Study design: This was an open long-term (3 years) extension of the COMEDRA 6 month randomized controlled trial in which patients with definite, stable RA were visiting a nurse for comorbidity assessment and screening counselling.[3] For this analysis, only the final visit data were used cross-sectionally. Assessment of comorbidity screening: A score was developed to quantify comorbidity screening procedures in accordance with guidelines:[4] this score gives 50 points to CV risk screening, 20 points to cancer screening, 20 points to pneumococcus and influenza vaccination and 10 points to osteoporosis screening. The score ranges 0–100 and 0 indicates optimal screening. Factors associated with optimal screening: demographic and disease characteristics were compared between patients considered well-screened (lowest tertile for screening score) versus other patients. Statistical analysis: Variables with p Results 769 patients were assessed: mean (±SD) age 62 (±11) years, mean disease duration 17 (±10) years; 614 (80%) were women and 535 (70%) were receiving a biologic. Disease was well-controlled (mean DAS28 2.8±1.3). The mean comorbidity screening score was 24.3 (±17.8) (range, 0–100). The 316 patients (41% of all patients) in the lowest tertile for this score (i.e., with a score ≤15) were less often smokers: odds ratio [95% confidence interval] 0.45 [0.28 – 0.72], were more often treated for hyperlipidemia (2.58 [1.85 – 3.61]), and were more often treated with a biologic (1.97 [1.4 – 2.76]). Conclusions Comorbidity screening is suboptimal in RA. Patients who were better screened were more frequently already followed-up for hyperlipidemia and were more frequently receiving biologics but more less frequently smokers. Thus it seems getting optimal screening may reflect both patient characteristics but also physician attention to comorbidity in certain situations. Empowering patients to be responsible for the comorbidity screening reminders should be explored. References Ref 1. Baillet A, Gossec L et al. Ann Rheum Dis. 2016;75(6):965–73. Ref 2. Gossec L et al. Joint Bone Spine. 2016;83(5):501–9. Ref 3. Dougados M, Soubrier M et al. Ann Rheum Dis. 2015;74(9):1725–33. Ref 4. Gossec L et al. Arthritis Rheumatol. 2016; 68 (suppl 10): abstract. http://acrabstracts.org/abstract/screening-for-and-management-of-comorbidities-after-a-nurse-led-program-results-of-a-3-year-longitudinal-study-in-776-established-ra-patients/. Acknowledgements grant from Roche France and from the French National Research Program (PHRC AOM 12072). Disclosure of Interest None declared

Background Rheumatic immune-related adverse events (irAEs) are increasingly recognized musculoskeletal manifestations in cancer patients receiving immune checkpoint targeted immunotherapy. Since they represent a spectrum of new clinical entities and a robust evidence base is lacking, a task force was convened to harmonize expert consensus regarding their identification and management due to the lack of dedicated clinical trials. Our aim was to develop EULAR recommendations for the diagnosis and the management of rheumatic irAEs due to cancer immunotherapy, based on literature and expert opinion. Methods Recommendations were developed according to the 2014 EULAR Standard Operating Procedures. The task force consisted of 19 clinical experts from Europe and North America (14 rheumatologists, 2 internists and 3 oncologists), 1 clinical epidemiologist, 1 allied health professional and 2 patient representatives. During the first meeting, the group defined the focus of the task force, the target population, and formulated research questions. A systematic literature research was performed by one fellow (MK) with the help of a librarian. Based on available evidence and using a consensus procedure, recommendations were developed during a second meeting. The level of agreement was determined by an anonymous voting process. Results 4 overarching principles and 10 recommendations were developed. The overarching principles define the role of rheumatologists and highlight the shared decision-making process between patients, oncologists and rheumatologists. One recommendation addresses the referral process, two address the diagnosis, and five address the therapeutic strategy of cancer patients experiencing rheumatic, musculoskeletal, and systemic signs or symptoms while receiving immunotherapy. An additional recommendation was included to address pre-existing rheumatic conditions and the last focuses on the diagnostic approach before immunotherapy. Conclusions These recommendations provide the basis of a EULAR consensus on the diagnosis and the management of rheumatic irAEs, worthwhile for rheumatologists, internists and oncologists. Legal entity responsible for the study EULAR, European League Against Rheumatism. Funding EULAR, European League Against Rheumatism. Disclosure All authors have declared no conflicts of interest.

Objective We used data from the AutoImmunity and Rituximab (AIR) registry to investigate the safety of surgery for patients with rheumatoid arthritis receiving rituximab (RTX) in routine care. Methods Data for patients included in the AIR registry and undergoing surgery during the year following an infusion of RTX were reviewed to describe the frequency of postsurgical complications, compare patients with and without complications, and identify factors associated with complications. Results We examined data for 133 patients with a known date of surgery and at least 1 followup visit, corresponding to 140 procedures, including 94 orthopedic surgeries (67%) and 23 abdominal surgeries (16.5%). The median delay between surgery and the last RTX infusion was 6.4 months (interquartile range 4.3–8.7 months), without any difference between patients with and without complications. Nine patients (6.7%) experienced 12 complications (8.5%), including 8 surgical site infections (5.7%) and 1 death due to septic shock. Postoperative complications occurred after 4.3% of abdominal surgeries (1 of 23) and 7.4% of orthopedic surgeries (7 of 95). On univariate analysis, spine surgery was associated with postoperative complications (P = 0.048). Conclusion In common practice, the risk of complications may be more important in case of spine surgery, but does not seem to be linked to the time between the last RTX infusion and surgery.

ObjectivesLittle data are available regarding the rate and predicting factors of serious infections in patients with rheumatoid arthritis (RA) treated with abatacept (ABA) in daily practice. We therefore addressed this issue using real-life data from the Orencia and Rheumatoid Arthritis (ORA) registry.MethodsORA is an independent 5-year prospective registry promoted by the French Society of Rheumatology that includes patients with RA treated with ABA. At baseline, 3 months, 6 months and every 6 months or at disease relapse, during 5 years, standardised information is prospectively collected by trained clinical nurses. A serious infection was defined as an infection occurring during treatment with ABA or during the 3 months following withdrawal of ABA without any initiation of a new biologic and requiring hospitalisation and/or intravenous antibiotics and/or resulting in death.ResultsBaseline characteristics and comorbidities: among the 976 patients included with a follow-up of at least 3 months (total follow-up of 1903 patient-years), 78 serious infections occurred in 69 patients (4.1/100 patient-years). Predicting factors of serious infections: on univariate analysis, an older age, history of previous serious or recurrent infections, diabetes and a lower number of previous anti-tumour necrosis factor were associated with a higher risk of serious infections. On multivariate analysis, only age (HR per 10-year increase 1.44, 95% CI 1.17 to 1.76, p=0.001) and history of previous serious or recurrent infections (HR 1.94, 95% CI 1.18 to 3.20, p=0.009) were significantly associated with a higher risk of serious infections.ConclusionsIn common practice, patients treated with ABA had more comorbidities than in clinical trials and serious infections were slightly more frequently observed. In the ORA registry, predictive risk factors of serious infections include age and history of serious infections.

We appreciate the very clever analysis by Moura and Moura1 of the numerous questions addressed by the management of immune-related adverse events (irAEs) occurring in patients treated with checkpoint inhibitors, and their citation of a French proverb, although the exact meaning of the proverb « en medecine comme en amour, ni jamais ni toujours » is not that medicine is unpredictable, but that there are always exceptions. Medical doctors must be aware of these exceptions and constantly remain vigilant. The two first questions addressed by Moura and Moura concern the value of a rheumatologist’s collaboration while guidelines have recently been published to help oncologists in the management of irAEs.2–4 We definitely agree with these authors to consider the strong value added by the rheumatologist’s analysis of musculoskeletal symptoms occurring in patients treated with immune checkpoint inhiboitors (ICIs). To illustrate this point, we will shortly report on three recent patients referred to our rheumatology unit by their oncologist for a suspicion of irAE. The first patient, an 80-year-old woman, was given nivolumab since 5 …

We read with genuine interest the original case reported by Chan and Bass1 in response to our paper describing musculoskeletal immune-related adverse events (irAE) related to cancer immunotherapy.2 Immune checkpoint inhibitors (ICI) represent an exciting new standard of care in selected advanced cancers and are being actively investigated in others. Unfortunately, only a subset of patients benefit from ICI and the current challenge is to transform the majority of non-responders to responders.3 This will likely be improved by combining ICI with other treatment strategies such as small molecules. Two MEK inhibitors, trametinib and cobimetinib, are …

In their correspondence, Cantini and Benucci1 express their concern about the lack of real-life data supporting the switch from originator to biosimilar biological disease-modifying antirheumatic drugs, as recommended in the recently issued consensus-based recommendations.2 They argue that the Danish Nationwide Biologic (DANBIO) registry reporting real-life data showed a lower than expected retention rate after the switch to biosimilar infliximab (bio-IFX) and etanercept.3 4 Concerning bio-IFX, several other real-life studies have been published so far. One Dutch and one French open studies have examined real-life outcomes of the switch from originator to bio-IFX in patients with inflammatory rheumatic diseases.5 6 Both …

International audience; OBJECTIVES: In France, the prevalence of gout is currently unknown. We aimed to design a questionnaire to detect gout that would be suitable for use in a telephone survey by non-physicians and assessed its performance. METHODS: We designed a 62-item questionnaire covering comorbidities, clinical features and treatment of gout. In a case-control study, we enrolled patients with a history of arthritis who had undergone arthrocentesis for synovial fluid analysis and crystal detection. Cases were patients with crystal-proven gout and controls were patients who had arthritis and effusion with no monosodium urate crystals in synovial fluid. The questionnaire was administered by phone to cases and controls by non-physicians who were unaware of the patient diagnosis. Logistic regression analysis and classification and regression trees were used to select items discriminating cases and controls. RESULTS: We interviewed 246 patients (102 cases and 142 controls). Two logistic regression models (sensitivity 88.0% and 87.5%; specificity 93.0% and 89.8%, respectively) and one classification and regression tree model (sensitivity 81.4%, specificity 93.7%) revealed 11 informative items that allowed for classifying 90.0%, 88.8% and 88.5% of patients, respectively. CONCLUSIONS: We developed a questionnaire to detect gout containing 11 items that is fast and suitable for use in a telephone survey by non-physicians. The questionnaire demonstrated good properties for discriminating patients with and without gout. It will be administered in a large sample of the general population to estimate the prevalence of gout in France

OBJECTIVE: (1) To determine the prevalence of gastrointestinal (Gl) symptoms in patients with and without Helicobacter pylori infection and treated with non-steroidal anti-inflammatory drugs (NSAIDs) and (2) to estimate the impact of H. pylori eradication on these symptoms. METHODS: This was a multicentric, community-based, randomized, case-control study. Patients presenting with a rheumatic disorder motivating the prescription of an NSAID for at least 2 wks were stratified in two groups (H. pylori-positive and H. pylori-negative) by a serological doctor test and H. pylori-positive patients divided further into two subgroups, receiving either an eradication treatment (group 1) or a placebo (group 2).The main outcome measure was the prevalence of Gl symptoms estimated in groups 1 and 2 and in noninfected patients (group 3) at weeks 2, 6, and 12. RESULTS: Among H. pylori-negative patients (n = 145), Gl symptoms were present in 42.6%, 21.4%, and 10.0% at weeks 2, 6, and 12, respectively. In groups 1 and 2, Gl symptoms were present in 57.7% and 40.7%, respectively, at week 2 (p = 0.03); 24.7% and 23% at week 6 (p = 0.85); and 9.4% and 17.3% at week 12 (p = 0.13). The prevalence of Gl symptoms at week 2 was similar in group 2 and in the H. pylori-negative group (p = 0.77). The highest prevalence of symptoms at week 2 in group 1 was essentially due to diarrhea. The prevalence of Gl symptoms was the same for groups 1 and 3 at week 12, and higher in group 2, but the difference did not reach statistical significance. CONCLUSIONS: The short-term (6 wks) Gl tolerance of conventional NSAIDs does not differ whether or not the patients are infected by H. pylori. The tendency observed for the medium term (12 wks) deserves to be confirmed.

Introduction La pneumopathie interstitielle diffuse (PID) est l’une des causes majeure de mortalite chez les patients atteints de polyarthrite rhumatoide (PR). Malgre une prevalence et une mortalite importante, la physiopathologie de la PID associee a la PR (PR-PID) reste meconnue. La PR-PID partage plusieurs caracteristiques phenotypiques avec la fibrose pulmonaire idiopathique (FPI) telles que l’aspect de pneumopathie interstitielle commune sur le scanner et un pronostic tres severe. Enfin, les similitudes entre PR-PID et FPI concernent egalement les facteurs environnementaux (tabac,…) suggerant que ces deux pathologies pourraient egalement partager des facteurs de risques genetiques tels que ceux predisposant a la FPI familiale (FPF). Methodes Nous avons utilise des donnees d’exome obtenue par whole-exome sequencing (WES) de patients atteints de PR-PID provenant de differents centres de rhumatologie et de pneumologie francais. L’ensemble des patients PR-PID+ repondaient aux criteres ACR/EULAR 2010. Le diagnostic de PID etait realise apres analyse de scanner thoracique de haute resolution. Apres une analyse restrictive de 9 genes rapportes comme etant associes aux FPF, nous avons compare le nombre de mutations retrouvees parmi les patients PR-PID au nombre de mutations retrouvees chez des individus temoins. Un burden test a ete effectue pour definir l’exces de mutations chez les patients PR-PID au sein de ces 9 genes d’interet. Resultats Parmi les 101 patients PR-PID inclus, 12 (11,9 %) presentaient des mutations au sein des regions codantes des genes TERT, RTEL1, PARN et SFTPC. Le burden test comparant 81 patients PR-PID a 1010 individus temoins caucasiens europeens a confirme un exces de mutations parmi ces genes chez les patients PR-PID (P = 9,45 × 10−4 ; OR = 3,17 ; IC 95 % 1,53–6,12). Chez les patients PR-PID porteurs de mutations des genes TERT, RTEL1 et PARN, appartenant au complexe telomerase, la taille des telomeres etait significativement plus petite que celle observees chez les temoins (P = 2,87 × 10−2). Conclusion Ces resultats sont en faveur d’un fond genetique commun entre FPI et PR-PID, suggerant une physiopathologie commune entre ces deux pathologies. En cas de confirmation de ces resultats, les avancees therapeutiques realisees dans la prise en charge des FPI pourraient alors beneficier aux patients atteints de PR-PID.