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Resumen Los progresos de la inmunopatologia han dado lugar al auge de los tratamientos «dirigidos» que se utilizan en muchas especialidades medicas para las enfermedades inflamatorias inmunomediadas (IMID, immune-mediated inflammatory diseases). Estos tratamientos engloban los biofarmacos (anticuerpos monoclonales y proteinas de fusion) o de inmunoterapias dirigidas quimicas, como los inhibidores de JAK, que actuan sobre la via de senalizacion intracelular. Los biofarmacos son anticitocinas (factor de necrosis tumoral [TNF]-α; IL-6; IL-1; IL-17; IL-12/23), anti-linfocitos B o inhibidores de la coestimulacion del linfocito T. El objetivo de esta actualizacion es presentar estos nuevos inmunosupresores disponibles en el mercado en distintas enfermedades sistemicas, como la artritis reumatoide, las espondiloartritis, el lupus sistemico, etcetera. Para cada tratamiento dirigido, la descripcion del mecanismo de accion, de las indicaciones, de los efectos adversos y de las contraindicaciones graves permite disponer de informacion sobre una utilizacion adecuada. La descripcion de la evaluacion preterapeutica, asi como los consejos sobre las situaciones particulares, como la sospecha de una tuberculosis, la aparicion de una alergia, de una hemopatia, de una patologia neoplasica o de una reaccion paradojica, un deseo de gestacion, la preparacion de un viaje, asi como la realizacion de una vacunacion o de cuidados dentales constituyen una ayuda practica en el tratamiento de nuestros pacientes.

BackgroundThe preferential Janus kinase-1 inhibitor FIL is approved for treatment of moderate to severe active RA in Europe and Japan.ObjectivesEfficacy and safety of FIL were assessed in patients (pts) with IR to bDMARDs in a LTE trial (NCT03025308) enrolled from a Phase 3 PS (NCT02873936).1MethodsbDMARD-IR pts received FIL 200 mg (FIL200), FIL 100 mg (FIL100), or placebo (PBO), all with stable conventional synthetic (cs)DMARDs up to 24 weeks (W). At W14 of the PS, pts with IR to FIL or PBO (ResultsThe PS included 147, 153, and 148 pts on FIL200, FIL100, and PBO. Pts continuing on LTE FIL200 and FIL100 at data cutoff: 80/121 (66%) and 76/110 (69%) from PS FIL200 and FIL100; 35/47 (75%) and 32/46 (70%) from PS PBO, and 13/23 (57%) and 13/22 (59%) from PS SOC. LTE baseline (BL) characteristics were similar in FIL200 and FIL100 pts. During LTE, PS FIL ACR20/50/70 response rates decreased modestly by W48 (Figure 1). Among PS PBO pts, response rates were lower at LTE BL, reaching similar levels to PS FIL pts by W48; rates increased to W48 in PS SOC pts on either FIL dose but not to levels of other groups. Percentages of pts attaining DAS28(CRP) ≤3.2, DAS28(CRP) Table 1.EAIRs of TEAEs in LTE, as of June 1, 2020EAIR (95% CI)FIL200+csD → FIL200+csD n=121PYE 228.4PBO+csD → FIL200+csD n=47PYE 98.1SOC+csD → FIL200+csD n=23PYE 42.1FIL100+csD → FIL100+csD n=110PYE 223.3PBO+csD → FIL100+csD n=46PYE 91.1SOC+csD → FIL100+csD n=22PYE 38.2TEAE46.9 (38.8, 56.6)38.7 (28.2, 53.2)52.2 (34.4, 79.3)40.3 (32.8, 49.5)40.6 (29.4, 56.1)49.8 (31.8, 78.0)TEAE Grade ≥310.5 (7.0, 15.7)10.2 (5.5, 18.9)19.0 (9.5, 38.0)10.3 (6.8, 15.5)13.2 (7.5, 23.2)18.3 (8.7, 38.5)TE serious AE12.3 (8.5, 17.8)12.2 (6.9, 21.5)21.4 (11.1, 41.1)8.1 (5.1, 12.8)13.2 (7.5, 23.2)21.0 (10.5, 41.9)Death1.3 (0.4, 4.1)1.0 (0, 5.7)0 (0, 8.8)0.4 (0.1, 3.2)0 (0, 4.0)0 (0, 9.7)TE infections34.2 (27.4, 42.6)22.4 (14.8, 34.1)35.6 (21.5, 59.1)22.4 (17.0, 29.5)26.3 (17.7, 39.3)39.3 (23.7, 65.2)TE serious infections3.5 (1.8, 7.0)2.0 (0.5, 8.2)7.1 (2.3, 22.1)0.9 (0.2, 3.6)2.2 (0.5, 8.8)7.9 (2.5, 24.4)Opportunistic infections0 (0, 1.6)0 (0, 3.8)0 (0, 8.8)0 (0, 1.7)0 (0, 4.0)0 (0, 9.7)TE herpes zoster2.2 (0.7, 5.1)1.0 (0.1, 7.2)0 (0, 8.8)0 (0, 1.7)2.2 (0.5, 8.8)2.6 (0.1, 14.6)TE MACE (adjudicated)1.3 (0.4, 4.1)1.0 (0.1, 7.2)0 (0, 8.8)0.9 (0.2, 3.6)1.1 (0.2, 7.8)0 (0, 9.7)TE DVT/PE (adjudicated)0.9 (0.2, 3.5)0 (0, 3.8)2.4 (0.1, 13.2)0.4 (0.1, 3.2)0 (0, 4.0)0 (0, 9.7)Malignancies (excluding NMSC)1.3 (0.4, 4.1)3.1 (1.0, 9.5)4.7 (0.6, 17.2)1.8 (0.7, 4.8)3.3 (1.1, 10.2)0 (0, 9.7)NMSC0 (0, 1.6)0 (0, 3.8)4.7 (0.6, 17.2)0 (0, 1.7)0 (0, 4.0)0 (0, 9.7)DVT, deep vein thrombosis; MACE, major adverse cardiovascular event; NMSC, nonmelanoma skin cancer; PE, pulmonary embolism; TE, treatment-emergentConclusionEfficacy was mostly maintained in PS FIL pts up to W48. Response among PS PBO and SOC pts increased from BL to W48, but response in PS SOC pts continued to be lower than in other groups; these pts may represent a refractory population. FIL safety was largely consistent between PS and LTE.References[1]Genovese MC et al. JAMA 2019;322:315–25.AcknowledgementsThis study was funded by Gilead Sciences, Inc., Foster City, CA. Medical writing support was provided by Claudine Bitel, PhD, of AlphaScientia, LLC, San Francisco, CA; and funded by Gilead Sciences, Inc., Foster City, CA.Disclosure of InterestsMaya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Galapagos, Gilead, and Pfizer, Grant/research support from: Gilead and Pfizer, Tsutomu Takeuchi Speakers bureau: AbbVie, AYUMI, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Eli Lilly Japan, Gilead Sciences, Mitsubishi-Tanabe, Novartis, Pfizer Japan, and Sanofi, Consultant of: Astellas, Chugai, and Eli Lilly Japan, Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi Sankyo, Eisai, Mitsubishi-Tanabe, Shionogi, Takeda, and UCB Japan, Vijay Rajendran Shareholder of: Galapagos, Employee of: Galapagos, Jacques-Eric Gottenberg Speakers bureau: AbbVie, Eli Lilly and Co., Galapagos, Gilead Sciences, Inc., Roche, Sanofi Genzyme, and UCB, Consultant of: Bristol Myers Squibb, Sanofi Genzyme, and UCB, Grant/research support from: Bristol Myers Squibb and Pfizer, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., YingMeei Tan Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Qi Gong Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Katrien Van Beneden Shareholder of: Galapagos, Employee of: Galapagos, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, and UCB, Consultant of: AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Lilly, Fresenius-Kabi, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB

BackgroundNo immunomodulatory drug has ever demonstrated its efficacy in primary Sjögren’s Syndrome (pSS). Drug repurposing, or drug repositioning, refers to the use in another disease of an existing drug, originally approved or evaluated in a different disease.ObjectivesThe objective of our study was to repurpose existing therapeutic drugs in pSS using a transcriptomic approach.MethodsWe generated pSS transcriptomic signatures from peripheral blood samples of patients with pSS compared to healthy controls in two cohorts (ASSESS and a Norwegian cohort) and data mined available pSS transcriptomic signatures in public databases. We compared each disease signature to transcriptomic signatures, obtained from the biological action of 2837 drugs, 2160 knock-in and 3799 knock-down genes, available in the Connectivity Map database. A median similarity score with regard to disease signatures was computed for each candidate drug/gene. Drugs and genes were selected if p│80│. If this score is sufficiently high and statistically significant (>80, pFigure 1.Methods of drug-repurposing transcriptomic analysis (adapted from Toro-Dominguez et al, Arthritis Res Ther 2017;19:54)Results1091 peripheral blood transcriptomes were analyzed from 6 independent studies (906 patients with pSS and 185 healthy controls). Our analysis identified 11 transcriptomic drug signatures significantly associated with pSS signature. We identified 72 transcriptomic knock-in (11) or knock-down (61) gene signatures significantly associated with that of pSS, including 21 with a negative similarity score (Table 1).Table 1.Knock-down and knock-in genes significantly associated with the pSS transcriptomic signaturesType ofexperimentSimilarity scoreGenesNumber of genesKnock-in+IFNG, DUSP28, IFNB1, LYN, BCL2L2, TNFRSF1A, CD40, BCL10, NLK, ZNF39810-SLC52A2111Knock-down+SLC25A14, GOLIM4, DTYMK, DCXR, RRM2, IMPA1, CLTB, F12, CAB39, ID1, ISOC1, UBAP1, HIGD2A, UFD1L, SOD2, BTG1, PRKCI, HIST2H2BE, NISCH, TEAD4, MTX2, TYK2, GTF2B, NDUFS7, NNT, ACADSB, GSTP1, HOMER2, SORBS3, PCK2, PHB2, PDXK, TES, TM9SF2, TBX2, HOXA6, KIF2C, MED1, NR2F6, CD14, BECN141-TM9SF3, E2F3, PRMT3, KD, PKN2, SUCLA2, CD44, GRN, SP3, ATP5S, MYCBP2, TRAF7, POLA2, ADRB2, PSMG1, PPP2R3C, PMAIP1, ETFA, ANKRD37, SPECC1L2061Type I and II interferons were highly ranked (similarity score >99), and their overexpression mimicked the disease signature. CD40 appeared also as a very relevant target (similarity score = 98.8). Three drugs had a significant negative similarity score: ampicillin (-88.69, p=0.0019), amylocaine (-88.28, p=0.0026), and droxinostat (-85.42, p=0.0027). Droxinostat is a HDAC inhibitor. HDAC activity has been shown to be an essential element of the coactivation system for IFN-induced gene regulation and the IFN-induced innate immune response.ConclusionThis first drug repositioning transcriptomic approach in Sjögren’s syndrome confirms the interest of targeting interferons and identifies histone deacetylases as potential therapeutic targets.AcknowledgementsInvestigators of the ASSESS cohort: Emmanuelle Dernis, Valerie Devauchelle-Pensec, Philippe Dieude, Jean-Jacques Dubost, Anne-Laure Fauchais, Vincent Goeb, Eric Hachulla, Pierre Yves Hatron, Claire Larroche, Véronique Le Guern, Jacques Morel, Aleth Perdriger, Carinne Salliot, Stephanie Rist, Alain Saraux, Jean Sibilia, Olivier Vittecoq, Gaétane Nocturne, Philippe Ravaud, Raphaèle SerorCentre de Ressources Biologiques de l’Hôpital Bichat: Sarah TubianaJohan G. Brun for contributing to the Norwegian cohort.Funding SourcesThis work was supported by the Innovative Medicines Initiative 2 Joint Undertaking (IMI 2 JU) (NECESSITY grant 806975). The Joint Undertaking received support from the European Union’s Horizon 2020 Research and Innovation Program and from the European Federation of Pharmaceutical Industries and Associations. This work was also supported by R01 AR065953 Beth the NIH, United States. The contents are the sole responsibility of the authors and do not necessarily the official views of the NIH.JEG received an unrestricted grant from Bristol-Myer-Squibbs to do the transcriptomic analysis of the ASSESS and Norwegian cohorts. JEG received a grant from Geneviève Garnier (Association Française du Syndrome de Gougerot-Sjögren et des syndromes secs).The ASSESS cohort is promoted by the French Society of Rheumatology and received two research grants from the French Society of Rheumatology.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Disclosure of InterestsRenaud FELTEN: None declared, Tao Ye: None declared, Cédric Schleiss: None declared, Benno Schwikowski: None declared, Jean Sibilia: None declared, Fanny Monneaux: None declared, Hélène Dumortier: None declared, Roland Jonsson: None declared, Christopher Lessard: None declared, Wan Fai Ng: None declared, Tsutomu Takeuchi: None declared, Xavier Mariette: None declared, Jacques-Eric Gottenberg Grant/research support from: JEG received an unrestricted grant from Bristol-Myer-Squibbs to do the transcriptomic analysis of the ASSESS and Norwegian cohorts.

BackgroundFilgotinib (FIL) is a Janus kinase 1 preferential inhibitor approved for the treatment of moderate to severe rheumatoid arthritis (RA) in patients (pts) with an inadequate response to disease-modifying antirheumatic drugs.1 In a pooled analysis of Phase 3 FINCH 1–3 studies of FIL in RA, median lymphocyte levels were relatively stable over 1 year with lymphocyte decreases observed in individual FIL-treated pts. Lymphocyte levels should be monitored.1ObjectivesTo assess the effect of FIL on lymphocyte levels and lymphopenia in the FINCH 4 long-term extension (LTE) study in RA.MethodsSafety data of FIL 100 mg (FIL100) and 200 mg (FIL200) from LTE baseline to data cut off (01 June 2020) are reported overall and by prior FIL exposure for pts who received ≥1 FIL dose in FINCH 4 (NCT03025308; adults with RA who had completed FINCH 1/2/3). Adverse events (AEs) of lymphopenia were graded based on clinical severity; laboratory abnormalities (decreased lymphocytes) were graded per Common Terminology Criteria for Adverse Events v4.03 (CTCAE). Frequencies of both measures and exposure-adjusted incidence rates (EAIRs) of AEs are reported. Median lymphocyte levels are reported to LTE Week 48.ResultsThe safety analysis set included 2729 pts (FIL200: n=1530; FIL100: n=1199). Of these, 75.4% (n=2058) had prior FIL exposure in FINCH 1/2/3. Median FIL exposure to LTE Week 48 was 600 (FIL200: 696; FIL100: 533) days.In both treatment groups, median laboratory lymphocyte levels remained relatively stable to LTE Week 48 for pts with prior FIL exposure. Pts without prior exposure had numerically higher median lymphocyte levels at LTE baseline vs pts with prior exposure (Figure 1). These decreased over time, but medians remained within normal range. The frequency and EAIR of graded decreases in laboratory lymphocyte levels were higher with FIL200 vs FIL100 (Table 1); incidence was slightly higher in pts with vs without prior FIL exposure, with the difference most apparent for Grade 2 decreases.Table 1.Frequencies of treatment-emergent laboratory decreases in lymphocytesPrior FIL exposureNo prior FIL exposureOverallTotalFIL200FIL100FIL200FIL100FIL200FIL100(N=2729)(n=1195)(n=863)(n=335)(n=336)(n=1530)(n=1199)Decreased lymphocytes228 (19.1)125 (14.5)41 (12.3)40 (12.0)269 (17.6)165 (13.8)434 (16.0)(any grade), n (%)Grade 148 (4.0)35 (4.1)14 (4.2)7 (2.1)62 (4.1)42 (3.5)104 (3.8)Grade 2159 (13.3)82 (9.5)21 (6.3)26 (7.8)180 (11.8)108 (9.1)288 (10.6)Grade 321 (1.8)8 (0.9)6 (1.8)7 (2.1)27 (1.8)15 (1.3)42 (1.5)Grade 40000000A treatment-emergent laboratory decrease in lymphocytes was defined as an increase of ≥1 toxicity grade from baseline at any time post-baseline up to and including the date of last study drug dose + 30 days. Severity grades were defined per CTCAE (lower limit of normal: 9/L [Grade 1]; 9/L [2]; 9/L [3]; 9/L [4]).Figure 1.Of all pts receiving FIL, 43 (1.6%) reported a lymphopenia AE; frequencies and EAIRs of lymphopenia AEs were slightly higher with FIL200 (1.9%; EAIR [95% CI]: 1.2 [0.9–1.8]) vs FIL100 (1.2%; 0.8 [0.4–1.3]). Most were Grade 1 or 2 in severity. Grade 3 lymphopenia AEs occurred in 4 (0.3%) vs 1 (No serious AEs of lymphopenia or treatment discontinuations due to lymphopenia were reported. In total, 8 (0.3%) pts interrupted study treatment due to lymphopenia. Infection rates, but not serious infections, were slightly higher for pts with lymphopenia, however no relationship between lymphopenia severity and infection AE grade was seen.ConclusionIn FINCH 4, lymphopenia AEs were infrequent but numerically greater with FIL200 vs FIL100, suggesting a dose–response relationship. While exposure at either dose may be associated with decreased lymphocytes, median lymphocyte levels were comparable in both groups and all remained within normal range at LTE Week 48, similar to observations in FINCH 1–3.References[1]Filgotinib SmPC and Jyseleca EPAR, 2020. Available at: https://www.ema.europa.eu/enAcknowledgementsThe authors would like to acknowledge Nadia Verbruggen and Pieter-Jan Stiers for providing statistical analysis support. This study was co-funded by Galapagos NV (Mechelen, Belgium) and Gilead Sciences, Inc. (Foster City, CA, USA). Medical writing support was provided by Kristian Clausen, MPH, CMPP (Aspire Scientific Ltd, Bollington, UK), and funded by Galapagos NV.Disclosure of InterestsJacques-Eric Gottenberg Consultant of: AbbVie, Bristol Myers Squibb, Galapagos, Gilead, Lilly, and Pfizer, Grant/research support from: Bristol Myers Squibb, and Pfizer, Gerd Rüdiger Burmester Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Lilly, MSD, Pfizer, Roche, and Sanofi, Katrien Van Beneden Shareholder of: Galapagos NV, Employee of: Galapagos NV, Chris Watson Shareholder of: Galapagos Biotech Ltd, Employee of: Galapagos Biotech Ltd, Ineke Seghers Employee of: Galapagos NV, Vijay Rajendran Employee of: Galapagos NV, Lorenzo Dagna Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Boehringer-Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Janssen, Kiniksa Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and Swedish Orphan Biovitrium (SOBI), Grant/research support from: Bristol Myers Squibb, Celltrion, Kiniksa Pharmaceuticals, Pfizer, and Swedish Orphan Biovitrium (SOBI), Maya H Buch Speakers bureau: Speaker fees paid to host institution by AbbVie, Consultant of: Consultant honoraria paid to host institution by AbbVie, Galapagos, Gilead, and Pfizer, Grant/research support from: Gilead and Pfizer.

BackgroundThe preferential Janus kinase-1 inhibitor FIL significantly improved signs and symptoms of RA in Phase 2 and 3 trials.1–5 FIL is approved for treatment of moderate to severe active RA in Europe and Japan. Integrated safety analysis of FIL with patient data through 2019 was presented at the 2020 ACR virtual meeting.6ObjectivesTo report updated, as-treated data from the FIL integrated safety analysis with increased study drug exposure.MethodsData were integrated from 2 Phase 2 (NCT01668641, NCT01894516), 3 Phase 3 (NCT02889796, NCT02873936, NCT02886728), and 2 long-term extension (LTE) (NCT02065700, NCT03025308) trials. Phase 2 and 3 LTE data were through Nov 2020 and Jan 2021, respectively. The as-treated analysis set included all available data for pts receiving ≥1 dose FIL 200 (FIL200) or 100 mg (FIL100), including those rerandomized to FIL for LTE. Exposure-adjusted incidence rates (EAIR)/100 patient-y exposure (PYE) of treatment-emergent adverse events (TEAEs; onset after first dose and no later than 30 days after last dose or new drug first dose date −1 day) and TEAEs of special interest (AESIs) are presented.Results3691 pts received FIL200 or FIL100 for 8085.1 PYE (median 2.2, maximum 6.8 y). In the as-treated set, 61% of FIL200 and 45% of FIL100 pts received FIL for ≥2 y, 19% and 5% for ≥3 y, and 11% and 0.5% for ≥4.5 y, respectively. EAIR for TEAEs was higher with FIL100 than FIL200; EAIRs for deaths were 0.5 and 0.3 for FIL200 and FIL100 (Figure 1). Incidences of infections and serious infections were numerically greater for FIL100 vs FIL200, while EAIRs for other AESIs were comparable between doses (Table 1). EAIRs for AESIs tended to decrease since the previous update, except for venous thromboembolism (total FIL 0.1 to 0.2) and malignancies excluding NMSC (total FIL 0.5 to 0.6).Table 1.TEAEs of special interest, as-treated setTEAE, n (%) and EAIR per 100 PYE (95% CI)FIL 200 mgn=2267PYE=5302.5FIL 100 mgn=1647PYE=2782.6Total FILN=3691PYE=8085.1Infectious AEs1206 (53.2)747 (45.4)1927 (52.2)EAIR21.1 (19.7, 22.5)30.2 (26.8, 34.0)21.0 (19.9, 22.3)Serious infectious AEs80 (3.5)57 (3.5)137 (3.7)EAIR1.5 (1.1, 1.9)2.7 (1.9, 3.9)1.6 (1.3, 2.0)Opportunistic infections5 (0.2)4 (0.2)9 (0.2)EAIR0.1 (0, 0.2)*0.1 (0.1, 0.4)*0.1 (0.1, 0.2)*Active tuberculosis03 (0.2)3 (EAIR00.1 (0, 0.3)*0 (0, 0.1)*Herpes zoster84 (3.7)30 (1.8)114 (3.1)EAIR1.6 (1.2, 2.0)1.1 (0.8, 1.5)*1.4 (1.1, 1.7)Major adverse cardiovascular eventsa19 (0.8)14 (0.9)33 (0.9)EAIR0.3 (0.2, 0.5)0.5 (0.3, 0.8)*0.4 (0.2, 0.6)Venous thromboembolismb11 (0.5)4 (0.2)15 (0.4)EAIR0.2 (0.1, 0.4)*0.1 (0.1, 0.4)*0.2 (0.1, 0.3)*Atrial systemic thrombotic eventsa1 (1 (2 (EAIR0 (0, 0.1)0 (0, 0.3)0 (0, 0.1)Malignancy excluding NMSC32 (1.4)17 (1.0)49 (1.3)EAIR0.6 (0.4, 0.9)0.6 (0.4, 1.0)*0.6 (0.4, 0.8)NMSC15 (0.7)5 (0.3)20 (0.5)EAIR0.3 (0.2, 0.5)*0.2 (0.1, 0.4)*0.2 (0.2, 0.4)*Gastrointestinal perforations3 (0.1)1 (4 (0.1)EAIR0.1 (0, 0.2)*0 (0, 0.3)*0 (0, 0.1)**Except when any study had 0 event within the treatment, the Poisson model was not adjusted by study. PYE was defined as (last dose date − first dose date + 1)/365.25.aPositively adjudicated.bAdjudicated as deep vein thrombosis or pulmonary embolism.NMSC, nonmelanoma skin cancerConclusionWith 1 additional year of exposure since the 2020 report, FIL continues to be well tolerated with no new safety concerns emerging. EAIRs of TEAEs, including deaths, and AESIs remained stable or decreased since the 2020 report, except for slight increases in rates of NMSC and malignancies excluding NMSC. In the context of demonstrated efficacy, both FIL doses had an acceptable risk/benefit profile.References[1]Westhovens R et al. Ann Rheum Dis 2017;76:998–1008.[2]Kavanaugh A et al. Ann Rheum Dis 2017;76:1009–19.[3]Combe B et al. Ann Rheum Dis 2021;80:848–58.[4]Genovese MC et al. JAMA 2019;322:315–25.[5]Westhovens R et al. Ann Rheum Dis 2021;80:727–38.[6]Winthrop K et al. Arthritis Rheumatol 2020;72(suppl 10); abstract 0229.AcknowledgementsFunding for DARWIN 1 and 2 was provided by Galapagos NV, and funding for DARWIN 3, FINCH 1, 2, 3, and 4 was provided by Gilead Sciences, Inc., Foster City, CA. Funding for this analysis was provided by Gilead Sciences, Inc. The sponsors participated in the planning, execution, and interpretation of the research. Medical writing support was provided by Gregory Bezkorovainy, MA, of AlphaScientia, LLC, San Francisco, CA; and funded by Gilead Sciences, Inc., Foster City, CA.Disclosure of InterestsKevin Winthrop Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly and Co., Galapagos NV, Gilead Sciences, Inc., GlaxoSmithKline, Pfizer, Roche, Regeneron, Sanofi, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, and Pfizer, Yoshiya Tanaka Speakers bureau: Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol Myers Squibb, Eisai, Chugai, AbbVie, Astellas, Pfizer, Sanofi, Asahi-Kasei, GSK, Mitsubishi-Tanabe, Gilead Sciences, Inc., and Janssen, Consultant of: AbbVie, Ayumi, Daiichi-Sankyo, Eli Lilly, GSK, Taisho, and Sanofi, Grant/research support from: AbbVie, Asahi-Kasei, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, and Takeda, Tsutomu Takeuchi Speakers bureau: AbbVie, AYUMI, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Eli Lilly Japan, Gilead Sciences, Inc., Mitsubishi-Tanabe, Novartis, Pfizer Japan, and Sanofi, Consultant of: Astellas, Chugai, and Eli Lilly Japan, Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi Sankyo, Eisai, Mitsubishi-Tanabe, Shionogi, Takeda, and UCB Japan, Alan Kivitz Shareholder of: Amgen, Gilead Sciences, Inc., GlaxoSmithKline, Pfizer, and Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, and Sanofi, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, and Sanofi, Consultant of: AbbVie, Boehringer Ingelheim, Flexion, Genzyme, Gilead Sciences, Inc., Janssen, Novartis, Pfizer, Regeneron, Sanofi, and SUN Pharma Advanced Research, Mark C. Genovese Shareholder of: Gilead Sciences, Inc., Consultant of: AbbVie, Amgen, Beigene, Eli Lilly and Co., Genentech, Inc., Gilead Sciences, Inc., Sanofi Genzyme, RPharm, and SetPoint, Employee of: Gilead Sciences, Inc., Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Franziska Matzkies Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Beatrix Bartok Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Kun Chen Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Deyuan Jiang Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Iyabode Tiamiyu Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos BV, Employee of: Galapagos BV, Sander Strengholt Shareholder of: Galapagos BV, Employee of: Galapagos BV, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Eli Lilly and Co., Galapagos, Gilead Sciences, Inc., and Pfizer, Consultant of: AbbVie, Eli Lilly and Co., Galapagos, Gilead Sciences, Inc., and Pfizer, Jacques-Eric Gottenberg Speakers bureau: AbbVie, Eli Lilly and Co., Galapagos BV, Gilead Sciences, Inc., Roche, Sanofi Genzyme, and UCB, Consultant of: Bristol Myers Squibb, Sanofi Genzyme, and UCB, Grant/research support from: Bristol Myers Squibb and Pfizer

BackgroundIn cancer immunotherapy, T-lymphocyte activation can lead to secondary autoimmune diseases named OASI for Opportunistic Autoimmunity Secondary to cancer Immunotherapy [1]. The epidemiology of OASI deserves to be further studied due to the unadapted reporting of clinical trials and the lack of prospective studies. Moreover, literature focuses on the most severe OASI and/or on specific OASI (myocarditis, colitis, arthritis).ObjectivesOur goal was to determine incidence, severity of all grade OASI using a multicentric prospective patient cohort starting treatment with cancer immunotherapy.MethodsWe present a multicentric, prospective, observational, longitudinal, real life, French e-cohort. 900 patients treated with ipilimumumab and/or nivolumab will be included. Data is collected from the patient and the oncologist at inclusion, then patients report directly any symptom that could be suggestive of OASI with the help of monthly digital questionaries. In case an OASI is suspected, further confirmation is made with the practician in charge and by a paired analysis with the Système National De Santé (SNDS), the French health insurance registry.ResultsOn the 19/01/2022, 439 patients were included, 310 males (70.6%) and 129 females (29.4%). Mean age is 66 years old with a median follow up of 192 days. 354 patients (80.6%) are treated with Nivolumab alone, 7 (1.6%) with Ipilimumab alone and 76 (17.8 %) with combined Nivolumab + Ipilimumab. 136 patients (31.6%) are treated for a non-small cell lung carcinoma, 107 patients (24.9%) for a clear cell renal carcinoma, 91 patients (21.2%) for a skin melanoma, 49 patients (11.4%) for a head or neck epidermoid carcinoma, 24 patients (5.6%) for another lung cancer sub-type, and 32 patients (5.3%) for another histological cancer type. The mean follow-up is 294 days (+/- 192). 83 patients (18.9%) died since the beginning of the follow up.47 patients (10.7%) developed 63 OASI. The mean delay between the beginning of cancer immunotherapy and the OASI is 134.7 days (+/- 103.4).Approximately, one third of the OASI were musculoskeletal diseases. The OASI included polymyalgia rheumatica (3 patients), psoriatic arthritis (1 patient), polyarthritis (1 patient) systemic lupus (1 patient), arthralgias and myalgias (8 patients), colitis (11 patients), dysthyroïditis (6 patients), hepatitis (4 patients), nephritis (3 patients), pneumonitis (2 patients), hypophysitis (2 patients), adrenal insufficiency (4 patients), myocarditis (1 patient), hemophagocytic lympho-histiocytosis (1 patient), and other types of OASI (15 patients).26 patients (55% of patients with OASI, 5,9% of all patients) had to stop cancer immunotherapy due to an OASI, one because of a rheumatic disease (systemic lupus). 52 patients were treated with corticosteroids, 1 patient with methotrexate (psoriatic arthritis), 3 patients with infliximab (colitis) and 1 patient with abatacept (myocarditis). 1 patient died after an OASI (colitis).ConclusionThe first results of this prospective study, using an original patient-centered methodology, confirm the expected incidence of autoimmune events secondary to cancer immunotherapy and the role of rheumatologists in their therapeutic management.References[1]Kostine M, Chiche L, Lazaro E, et al. Opportunistic autoimmunity secondary to cancer immunotherapy (OASI): An emerging challenge. Rev Med Interne. 2017;38(8):513-525. doi:10.1016/j.revmed.2017.01.004AcknowledgementsBMS funded the study (unrestricted grant) but had no role in study design, data collection, analysis or decision to publish.Disclosure of InterestsEden Sebbag: None declared, Nicolas Cloarec: None declared, Philippe Barthelemy: None declared, Nathanaël Sedmak: None declared, Naima Hamamouche Consultant of: Work for Sanoia Digital CRO, Hervé Servy Consultant of: Work for Sanoia Digital CRO, Guillaume Desjeux Consultant of: Work for Sanoia Digital CRO, Isabelle Monnet: None declared, Abeer Najem: None declared, Marc Porneuf: None declared, Laetitia-Shanna Rajpar: None declared, Jérôme Meunier: None declared, Tévy San: None declared, Laure Chauvenet: None declared, Ariane DARUT JOUVE: None declared, Sabrina FALKOWSKI: None declared, Claudia Rizzo: None declared, Noémie Litrowski: None declared, Anthony Canellas: None declared, Jean-François Paitel: None declared, Marc Pracht: None declared, Jacques Cadranel: None declared, Laurence Weiss: None declared, Christos Chouaid: None declared, Thomas Aparicio: None declared, Stephane Nancey: None declared, Cécile Arnold: None declared, Erik Sauleau: None declared, Jaqcues-Eric Gottenberg: None declared

To study the impact of hyperuricemia on clinical presentation, severity, and associated comorbidities of psoriatic arthritis (PsA).Retrospective bicentric case-control study performed in Strasbourg and Colmar, France, from 2009 to 2019. Patients with PsA (according to ICD-10 coding) and at least one available serum urate (SU) measurement were included. Demographic, comorbidities, clinical, and radiographic data were collected. Hyperuricemia was defined as SU level ≥ 360 µmol/L.We included 242 patients: 73 (30.2%) had hyperuricemia and 15 (6.2%) met 2015 ACR/EULAR criteria for gout. On univariate analysis, as compared with normo-uricemic patients, hyperuricemic patients were more frequently male (72.6% vs 39.1%, p = 1.6 × 10Patients with hyperuricemic PsA show poorer response to PsA treatment and have more peripheral and destructive joint damage than normo-uricemic patients. Key Points • Gout and psoriatic arthritis (PsA) can co-exist in the same patient. • Monosodium urate crystals might have a deleterious impact on PsA. • Hyperuricemic PsA is more polyarticular, less frequently axial, and more destructive than normo-uricemic PsA. • PsA with hyperuricemia should lead to more personalized medicine.

Introduction La réponse vaccinale chez les patients atteints de maladies auto-immunes et inflammatoires peut être fortement impactée sous certains traitements de fond, tels que le RTX. À ce jour, peu de données sont disponibles concernant les JAK inhibiteurs (JAKi), et aucune en lien avec la vaccination anti-SARS-CoV-2. L’objectif de cette étude était d’étudier la réponse vaccinale anti-SARS-CoV-2 chez des patients sous JAKi. Patients et méthodes Dans cette étude ancillaire du registre MAJIK-SFR (NCT04602091), les patients toujours sous anti-JAKi au moment de la vaccination et ayant eu une sérologie anti-SARS-CoV-2 effectuée au moins 2 semaines après un schéma vaccinal complet (2 injections du vaccin Pfizer, Moderna ou AstraZeneca, ou 1 injection du vaccin Janssen, ou infection COVID-19 suivi d’une injection de n’importe quel vaccin). Les taux d’anticorps IgG ou totaux anti-protéine spike (S1, S1/S2 ou RBD) ont été détectés à l’aide de kits commerciaux utilisant majoritairement la technique d’immunoanalyse par chimiluminescence, ou dans 4 cas par ELISA ou enzyme linked fluorescence assay (ELFA). Le patient était considéré répondeur si le taux d’anticorps détecté était ≥ au seuil de positivé du kit. Les caractéristiques des patients ont été comparées entre les répondeurs et non-répondeurs afin d’identifier les facteurs associés a la non-réponse. Résultats Cent treize patients ont été inclus (98 [86,7 %] atteints de PR, 15 [13,4 %] de PsA) dont 56 (49,6 %) sous baricitinib, 30 (26,5 %) sous tofacitinib et 27 (23,9 %) sous upadacitinib. Quatre-vingt-dix-sept (85,8 %) patients ont reçu une vaccination par vaccin à ARNm (Pfizer ou Moderna). Neuf patients avaient eu une infection COVID avant la vaccination. Cinq patients ont reçu une 3e dose. La réponse vaccinale a été évaluée en moyenne 8,7 semaines (±5,2) après la dernière injection. Le taux de séroconversion était de 88,5 %. Le taux de non-réponse était plus élevé sous upadacitinib (n = 7/27, 25,9 %, p = 0,013) comparé au baricitinib (n = 5/56, 8,9 %) ou tofacitinib (n = 1/30, 3,3 %). Les non-répondeurs étaient plus âgés que les répondeurs (p = 0,02), mais l’âge moyen à la vaccination était similaire pour chaque JAKi. Sous barictinib et tofacitinib les non-répondeurs avaient tous ≥ 65 ans ; 4 des 7 non-répondeurs sous upadacitinib avaient moins de 65 ans. L’intervalle entre la dernière injection et la sérologie était légèrement plus long chez les non-répondeurs (11,25 ± 5,94 vs 8,32 ± 5,01, p = 0,099). Aucun autre paramètre (utilisation concomitante de MTX ou corticostéroïdes, dose de JAKi, activité de la maladie, type de vaccin) n’était associé à une non-réponse. Un antécédent de traitement par RTX (n = 18, 15,9 %) n’avait pas non plus d’impact sur la réponse vaccinale ; néanmoins, la dernière injection datait de ≥ 6 mois avant la vaccination chez tous les patients. Conclusion Le taux de séroconversion après vaccination anti-SARS-CoV-2 chez les patients traités par JAKi reste élevé (88,5 %). Cependant, la non-réponse peut survenir principalement chez les patients âgés ≥ 65 ans. De plus, l’upadacitinib était associé à un taux de non-réponse plus élevé (25,9 %). Ces résultats doivent être confirmés mais suggèrent que chez les patients sous JAKi de ≥ 65 ans ou traités par upadacitinib, une évaluation sérologique pourrait être discuter pour guider la décision clinique (3e dose de vaccin et/ou vaccination familiale). L’évaluation de la réponse immunitaire cellulaire chez les non-répondeurs sera également intéressante pour déterminer si une autre forme d’immunité peut avoir été acquise.

BackgroundPrimary Sjögren’s syndrome (pSS) is a rare systemic autoimmune disease with no specific treatment at present. To better assess patient symptoms, we have developed a web application (WebApp) to collect patient symptom intensity on a regular basis.ObjectivesTo measure the daily variability of symptoms using the WebApp. We also evaluated its ease of use.Methods45 consecutive patients with pSS were included in 3 referral centers. Symptoms were assessed during the baseline and 3 month visits. We collected the VAS relating to fatigue, dryness and pain as well as the ESSPRI score. Patients used the WebApp daily for 3 months. The variability of symptoms over time was assessed by the predicted median error. This value was determined using a linear regression model, in order to predict the value at the 3rd month, then this value was compared to the actual value collected at the 3rd month during the clinical visit. The ease of use of the WebApp was assessed using a satisfaction score (SUS score).ResultsOf the 45 patients included, 91.1% were women with an average age of 57 years, and low systemic disease activity (84.4% had an ESSDAI score below 5). The intensity of the symptoms collected during the clinical visits was similar at baseline and at 3 months. The values ​​of the median error for each measurement are between 0.5 and 0.8. The 3-month predicted median error values ​​ranged from 2 to -3. The patients all used the web application for 3 months with good attendance (80% of data completion) and were satisfied with this tool (median SUS score = 90).ConclusionSymptoms of pSS fluctuate from day to day in the majority of patients, making a point measurement imprecise. The developed WebApp is easy to use, and could allow more sensitive detection of the effect of a therapeutic intervention. This tool will soon be evaluated during prospective interventional clinical trials.AcknowledgementsI would like to thanks all people who have helped and were directly or indirectly involved in this study.Disclosure of InterestsNone declared

BackgroundHyperuricemia (HU) is a metabolic abnormality associated with psoriasis (PsO) and psoriatic arthritis (PsA)1. The prevalence of HU is 2–13% in general population, 19–20% in PsO patients (pts), and 27–32% in PsA pts1,2. Pts with PsO/PsA are at significantly increased risk of HU and development of gout1. The pathogenic role of chronic HU in the development and maintenance of PsA is based on epidemiological, clinical, and fundamental arguments and hence does not appear fortuitous. These processes can influence each other3. Moreover, PsA with HU has been shown to be more peripheral, destructive, and challenging to treat4.ObjectivesTo evaluate the impact of HU on PsA in terms of clinical presentation, severity, comorbidities, and response to secukinumab (SEC) over 1-year.MethodsThis post hoc analysis included pooled data from PsA pts enrolled in the FUTURE 2–5 and MAXIMISE phase 3 trials. Pts were stratified into 2 groups based on baseline (BL) serum uric acid (SUA) level (HU: ≥360 µmol/L; without HU: ResultsOverall, 2504 PsA pts were included in the analysis, of which 822 (32.8%) had HU (62 [2.5%] with gout; 49 [2.0%] treated with ULT). At BL, pts with HU were mostly male (76.0% vs 34.2%) and had a higher body mass index (30.9 vs 28.3 kg/m2) with more comorbidities, such as hypertension (43.8% vs 31.3%), compared to pts without HU. A higher proportion of pts with HU had dactylitis (34.5% vs 25.9%), and PsO (48.3% vs 36.3%) with a greater mean PASI score (13.6 vs 10.2), compared to pts without HU (Table 1). The proportion of pts achieving ACR50, resolution of enthesitis/dactylitis, and mean change in HAQ-DI score were comparable up to Week 52 irrespective of BL HU status. The PASI90 response rate was higher in pts without HU with SEC 150 mg (with and without load) and similar in SEC 300 mg group irrespective of BL HU status (Figure 1).Table 1.Demographics and baseline characteristicsParameters, mean ± SD unless specifiedWith hyperuricemia (N=822)Without hyperuricemia (N=1682)Age (Years)48.5 ± 12.4148.3 ± 12.19Gender (Male), n (%)625 (76.0)576 (34.2)Weight (kg)92.71 ± 18.6279.59 ± 17.55BMI (kg/m2)30.90 ± 5.8628.33 ± 5.91History of hypertension, n (%)360 (43.8)526 (31.3)History of diabetes mellitus, n (%)85 (10.3)144 (8.6)TJC20.6 ± 15.5221.3 ± 16.25SJC10.9 ± 9.3110.8 ± 9.13Enthesitis, n (%)412 (50.1)852 (50.7)Dactylitis, n (%)284 (34.5)436 (25.9)Evidence of current psoriasis; n (%)397 (48.3)611 (36.3)Mean PASI score*13.61 ± 11.0310.16 ± 9.13TNFi naїve, n (%)477 (58.0)938 (55.8)MTX use at randomization, n (%)321 (39.1)685 (40.7)Serum uric acid (µmol/L)420.7 ± 57.11274.9 ± 51.98CRP (mg/L)11.6 ± 18.6610.7 ± 23.36*not collected in MAXMISEBMI, body mass index; CRP, C-reactive protein; MTX, methotrexate; SJC, swollen joint count; TJC, tender joint count; TNFi, tumor necrosis factor inhibitorConclusionIn this pooled analysis of SEC PsA studies, pts with HU reported a higher prevalence of hypertension, with more clinical dactylitis, and more PsO, with higher PASI score compared to pts without HU. Efficacy across all musculoskeletal manifestations was similar with SEC 150 and 300 mg; while PASI90 response rate was slightly better in patients without HU with SEC 150 mg, and similar with SEC 300 mg irrespective of HU status, at 1-year.References[1]Tripolino C, et al. Front Med. 2021;8:737573[2]AlJohani R, et al. J Rheumatol. 2018;45(2):213–7[3]Felten R, et al. Clin Rheumatol. 2020;39:1405–13[4]Widawski L, et al. Clin Rheumatol. 2022. https://doi.org/10.1007/s10067-022-06061-xDisclosure of InterestsRenaud FELTEN Consultant of: Novartis (Advisory board), Laura Widawski: None declared, Lionel Spielmann: None declared, Corine Gaillez Shareholder of: Novartis, Employee of: Novartis, Weibin Bao Shareholder of: Novartis, Employee of: Novartis, Jacques-Eric Gottenberg Consultant of: Novartis (Advisory board), Pierre-Marie Duret: None declared, Laurent Messer: None declared

BackgroundThe COVID-19 pandemic has taken a toll on the mental health of the general population. Patients with systemic lupus erythematosus (SLE) were particularly exposed due to many uncertainties linked to the virus and their immunosuppression as well as difficulties to access medical care and their treatment (eg, hydroxychloroquine) during the early pandemic.ObjectivesTo evaluate the difficulties encountered by SLE patients during the early COVID-19 pandemic, and evaluate their impact on patient mental health.MethodsWe conducted a nationwide survey including SLE patients from France metropolitan and overseas territories, recruited by their treating specialist or through a patient association (AFL+). The survey was administered online or in paper form between November 2020 and April 2021, and included questions aiming at evaluating the difficulties encountered during the early COVID-19 pandemic (March to August 2020). The impact on mental health was evaluated using Hospital Anxiety and depression scale (HADS) and post-traumatic stress disorder (PTSD) Checklist for DSM-5 (PCL-5).Results536 SLE patients (91.9% women) of mean age 50 (±14.1) years responded to the survey. The main reported difficulties were issues to access medical care (n = 136, 25.4%) or to obtain hydroxychloroquine treatment (n = 98/389, 25.2%), the loss of employment (n = 85/349, 24.4%) and financial difficulties (n = 75/536, 11%). Hydroxychloroquine shortage was responsible for difficulties in obtaining the drug for 25.2% (98/389) of HCQ-treated patients, and 57 had to interrupt HCQ treatment for a median of 7 days (IQR: 3-17). In the 342 patients with complete assessment, 161 (47.2%) screened positive for anxiety, 141 (41.2%) for depressive syndrome and 128 (38.7%) for PTSD. Multivariate analysis showed that female sex (OR=4.29 [95%CI: 1.39-13.24]), financial issues (OR=2.57 [1.27-5.22]), difficulties to access medical care (OR=2.15 [1.26-3.69]), or to obtain hydroxychloroquine treatment (OR=1.90 [1.06-3.40]) were independently associated with a positive screening for PTSD.ConclusionThe COVID-19 pandemic resulted in a severe burden in SLE patients, including difficulties in access to care and treatment along with high psychological distress. Better understanding these difficulties will allow better prevention and care in times of crisis.Table 1.Factors associated with the development of anxiety, depression or PTSD. Odds ratio (CI95%) using multivariate logistic regression are shown.Patient and pandemic-associated factorsOdds ratio (95%CI) for anxietyOdds ratio (95%CI) for depressionOdds ratio (95%CI) for PTSDFemale sex2.25 (0.97-5.25), p = 0.058ns4.29 (1.39-13.24)p = 0.01Financial difficultiesns2.59 (1.31-5.11)p = 0.0062.57 (1.27-5.22)p = 0.009Difficulties to obtain HCQ1.70 (0.97-2.98)p = 0.065ns1.90 (1.06-3.40)p = 0.03Difficulties to access medical care1.94 (1.15 3.25)p = 0.0122.57 (1.53-4.33)p < 0.00012.15 (1.26-3.69)p = 0.005AcknowledgementsAntonin Folliasson for his help.Disclosure of InterestsMarc SCHERLINGER: None declared, naimah zein: None declared, Jacques-Eric Gottenberg: None declared, Marianne Riviere: None declared, Jean François Kleinmann: None declared, Jean Sibilia: None declared, Laurent Arnaud Speakers bureau: Alexion, Amgen, Astra-Zeneca, Abbvie, Biogen, BMS, Boehringer-Ingelheim, Cêmka, Kezar, GSK, Grifols, Janssen, LFB, Lilly, Menarini France, Medac, Novartis, Oséus, Pfizer, Roche-Chugaï, Sêmeia, UCB., Consultant of: consultant for Alexion, Amgen, Astra-Zeneca, Abbvie, Biogen, BMS, Boehringer-Ingelheim, Cêmka, Kezar, GSK, Grifols, Janssen, LFB, Lilly, Menarini France, Medac, Novartis, Oséus, Pfizer, Roche-Chugaï, Sêmeia, UCB.

BackgroundFilgotinib (FIL) is a Janus kinase 1 preferential inhibitor for the treatment of moderate to severe rheumatoid arthritis (RA)1. The recommended dose for adults with RA is 200 mg (FIL200); however, a starting dose of 100 mg (FIL100) is recommended for those aged ≥75 years (y) in view of limited clinical experience1. An important consideration is the generally higher incidence of adverse events (AEs) in the elderly due to comorbidities.ObjectivesTo evaluate the efficacy and safety of FIL100 and FIL200 in patients with RA aged ≥75 y.MethodsFINCH 4 (NCT03025308) is an ongoing phase 3 open-label LTE study of FIL100 and FIL200 for RA. Eligible patients completed a prior phase 3 randomized double-blind study of FIL lasting 52 weeks (FINCH 1 or 3) or 24 weeks (FINCH 2). In this post hoc analysis, safety and efficacy were assessed in patients aged ResultsAt LTE Week 48, 52% and 44% of patients aged Figure 1.The exposure-adjusted incidence rate (EAIR) of serious AEs and AEs of special interest (AESI) was generally higher in patients aged ≥75 y than Table 1.Exposure-adjusted incidence rate (95% CI) of AEs at Week 48 as events per 100 years of exposureFIL200FIL100Age, years≥75≥75n=1469n=61n=1136n=63(PYE 2253.9)(PYE 92.2)(PYE 1753.7)(PYE 98.4)With prior FIL exposure, n (%)1142 (77.7)53 (86.9)830 (73.1)33 (52.4)TEAE48.3 (45.5, 51.3)55.3 (42.1, 72.8)48.7 (45.5, 52.1)42.7 (31.6, 57.8)Serious TEAE6.8 (5.8, 8.0)17.4 (10.6, 28.3)7.4 (6.2, 8.7)14.2 (8.4, 24.0)AE leading to premature study discontinuation2.9 (2.3, 3.7)9.8 (5.1, 18.8)3.9 (3.1, 5.0)4.1 (1.5, 10.8)AE leading to death0.5 (0.3, 0.9)3.3 (0.7, 9.5)*0.3 (0.2, 0.8)0.0 (0.0, 3.8)Infections28.8 (26.6, 31.1)29.3 (20.1, 42.7)27.4 (25.0, 29.9)26.4 (18.0, 38.8)Serious infections1.6 (1.2, 2.2)2.2 (0.5, 8.7)1.7 (1.1, 2.4)3.1 (1.0, 9.5)Herpes zoster1.6 (1.2, 2.3)2.2 (0.5, 8.7)1.0 (0.6, 1.6)3.1 (1.0, 9.5)Adjudicated major adverse cardiovascular event0.4 (0.2, 0.7)2.2 (0.5, 8.7)0.5 (0.2, 0.9)1.0 (0.1, 7.2)Venous thrombotic and embolic events0.3 (0.1, 0.6)2.2 (0.5, 8.7)0.2 (0.1, 0.5)1.0 (0.1, 7.2)Malignancy excluding NMSC0.7 (0.4, 1.2)4.3 (1.6, 11.6)0.7 (0.4, 1.2)3.1 (1.0, 9.5)NMSC0.4 (0.2, 0.8)1.1 (0.0, 6.0)0.2 (0.1, 0.6)0.0 (0.0, 3.8)*Cause of death: esophageal carcinoma; cardiovascular; unknown. FIL(100/200), filgotinib (100/200 mg); NMSC, nonmelanoma skin cancer; PYE, patient years of exposure; (TE)AE, (treatment-emergent) adverse eventConclusionIn the ≥75 y group, response rates for key efficacy measures remained stable to Week 48 and were generally higher with FIL200 vs FIL100. The incidence of serious AEs and AESI was higher in those aged ≥75 than References[1]Filgotinib SmPCAcknowledgementsThe FINCH studies were funded by Gilead Sciences (Foster City, CA, United States). We thank the physicians and patients who participated in the studies. Medical writing support was provided by Debbie Sherwood, BSc (Aspire Scientific Ltd, Bollington, UK) and funded by Galapagos NV (Mechelen, Belgium).Disclosure of InterestsDaniel Aletaha Speakers bureau: AbbVie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, and Sandoz, Consultant of: AbbVie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, and Sandoz, Grant/research support from: AbbVie, Amgen, Lilly, Novartis, Roche, SoBi, and Sanofi, Rene Westhovens Speakers bureau: Celltrion, Galapagos, and Gilead, Consultant of: Celltrion, Galapagos, and Gilead, Bernard Combe Speakers bureau: AbbVie, BMS, Celltrion, Eli Lilly, Gilead-Galapagos, Janssen, MSD, Novartis, Pfizer, and Roche-Chugai, Consultant of: AbbVie, Celltrion, Eli Lilly, Gilead-Galapagos, Janssen, and Roche-Chugai, Jacques-Eric Gottenberg Consultant of: AbbVie, BMS, Galapagos, Gilead, Lilly, and Pfizer, Grant/research support from: BMS and Pfizer, Maya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Galapagos, Gilead, and Pfizer, Grant/research support from: Gilead and Pfizer, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, and UCB, Consultant of: AbbVie, Amgen, BMS, Celltrion, Fresenius-Kabi, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB, José A Gómez-Puerta Speakers bureau: AbbVie, BMS, Galapagos, GSK, Lilly, MSD, Novartis, Pfizer, Roche, and Sanofi, Consultant of: GSK, Roche, and Sanofi, Paul Van Hoek Employee of: Galapagos, Vijay Rajendran Employee of: Galapagos, Pieter-Jan Stiers Shareholder of: Galapagos, Employee of: Galapagos, Thijs Hendrikx Employee of: Galapagos, Gerd Rüdiger Burmester Consultant of: AbbVie, Amgen, BMS, Galapagos, Lilly, MSD, Pfizer, Roche, and Sanofi, Yoshiya Tanaka Speakers bureau: AbbVie, Amgen, Astellas, Astra-Zeneca, Boehringer-Ingelheim, BMS, Chugai, Eisai, Eli Lilly, Gilead, Mitsubishi-Tanabe, and YL Biologics, Consultant of: AbbVie, Ayumi, Daiichi-Sankyo, Eli Lilly, GSK, Sanofi, and Taisho, Grant/research support from: AbbVie, Asahi-Kasei, Boehringer-Ingelheim, Chugai, Corrona, Daiichi-Sankyo, Eisai, Kowa, Mitsubishi-Tanabe, and Takeda

BackgroundThe low prevalence of systemic autoimmune diseases and the diversity of their clinical manifestations make complex to conduct randomised clinical trials to assess the potential efficacy of targeted treatments.ObjectivesTo assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory autoimmune diseases.MethodsThe TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age > 18 years; rare systemic autoimmune disease (systemic lupus erythematosus, Sjögren’s syndrome, systemic scleroderma, inflammatory myopathy, vasculitis) or other refractory rheumatism treated with off-label drugs started after 1st January 2019.ResultsHundred (100) patients (79 females) were enrolled. The median age was 52.5 years [49;56], the median disease duration before enrolment was 5 years [3;7]. The targeted therapies at enrolment were as follows: JAK/STAT inhibitors (44%), anti-IL6R (22%), anti-IL12/23, anti-IL23 and anti-IL17 (9%), anti-BAFF (5%), abatacept (5%), other targeted treatments (9%), and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months [8;10].Safety: 11 serious infections (incidence rate of 14.8 /100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: The targeted treatment was considered effective by the clinician in 56% of patients and allowed in responders a median reduction of oral corticosteroids of 15 [9-21] mg/day.ConclusionThese initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.References[1]B. Terrier et al., Safety and efficacy of rituximab in systemic lupus erythematosus: results from 136 patients from the French AutoImmunity and Rituximab registry. Arthritis Rheum 62, 2458-2466 (2010).[2]J. E. Gottenberg et al., Efficacy of rituximab in systemic manifestations of primary Sjogren’s syndrome: results in 78 patients of the AutoImmune and Rituximab registry. Ann Rheum Dis 72, 1026-1031 (2013).[3]J. E. Gottenberg et al., Risk factors for severe infections in patients with rheumatoid arthritis treated with rituximab in the autoimmunity and rituximab registry. Arthritis Rheum 62, 2625-2632 (2010).[4]F. R. S. S. S. C. I. consortium, contributors, Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients. Ann Rheum Dis, (2020).[5]R. Felten et al., B-cell targeted therapy is associated with severe COVID-19 among patients with inflammatory arthritides: a 1-year multicentre study in 1116 successive patients receiving intravenous biologics. Ann Rheum Dis 81, 143-145 (2022).[6]D. J. Wallace et al., Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet 392, 222-231 (2018).[7]J. J. Paik et al., Study of Tofacitinib in Refractory Dermatomyositis: An Open-Label Pilot Study of Ten Patients. Arthritis Rheumatol 73, 858-865 (2021).[8]S. Cole et al., Integrative analysis reveals CD38 as a therapeutic target for plasma cell-rich pre-disease and established rheumatoid arthritis and systemic lupus erythematosus. Arthritis Res Ther 20, 85 (2018).[9]S. J. Bowman et al., Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjogren’s syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial. Lancet 399, 161-171 (2022).AcknowledgementsFrench networks (FAI2R, CRI, IMIDIATE, SFR, SNFMI) focused on rare systemic autoimmune diseases contributed this work by the contribution of network-affiliated physicians.Disclosure of InterestsJacques-Eric Gottenberg Consultant of: Abbvie, BMS, Gilead, Galapagos, Novartis, Lilly Roche Chugai, Sanofi, Janssen, Pfizer, Grant/research support from: BMS.Lilly and Pfizer for this register (with no access to data)., Aurore Chaudier: None declared, Yves Allenbach: None declared, Arsene Mekinian: None declared, Zahir Amoura: None declared, Patrice cacoub: None declared, Divi Cornec: None declared, Eric Hachulla: None declared, Pierre Quartier: None declared, isabelle melki: None declared, Christophe Richez: None declared, Raphaèle Seror: None declared, Benjamin Terrier: None declared, Valerie Devauchelle-Pensec: None declared, Julien Henry: None declared, MARC GATFOSSE: None declared, LAURENCE BOUILLET: None declared, Emeline GAIGNEUX: None declared, Vincent ANDRE: None declared, Gildas BAULIER: None declared, Aurélie SAUNIER: None declared, Marie Desmurs: None declared, Antoine POULET: None declared, Mathieu ETE: None declared, Marie-Elise Truchetet: None declared, Martin Michaud: None declared, Claire Larroche: None declared, AZEDDINE DELLAL: None declared, Amelie LEURS: None declared, Sebastien Ottaviani: None declared, Hubert NIELLY: None declared, Guillaume VIAL: None declared, Roland JAUSSAUD: None declared, Benedicte ROUVIERE: None declared, Pierre-Yves JEANDEL: None declared, Aurelien GUFFROY: None declared, Anne-Sophie Korganow: None declared, Mathieu JOUVRAY: None declared, alain meyer: None declared, Emmanuel Chatelus: None declared, Christelle Sordet: None declared, Renaud FELTEN: None declared, Jean Sibilia: None declared, Samira AHMED YAHIA: None declared, Jean François Kleinmann: None declared, Xavier Mariette Consultant of: BMS, Galapagos, GSK, Janssen, Novartis, Pfizer, Sanofi, UCB

BackgroundVaccination against SARS-CoV-2 is effective in preventing severe forms of COVID-19, but there remain concerns about a reduced vaccine response in patients suffering from inflammatory arthritides who are treated by immunosuppressive therapies.ObjectivesWe analysed the impact of bDMARDs on the humoral anti-SARS-CoV-2 vaccine response of patients followed in day hospitals.MethodsWe studied the vaccine response after a complete vaccine regimen followed in day hospital in 5 French hospitals and treated with an intravenous bDMARD between September 2019 and August 2021. After obtaining their informed consent, we included patients with an anti-SARS-CoV-2 serology. They were considered non-responders if the antibody level detected was inferior to the threshold of positivity of the kit used.Results205 patients were included (148 females/57 males). The median age was 64 years (Interquartile Range [IQR] 56-71). 25 were treated with tocilizumab (TCZ), 36 with abatacept (ABA), 53 with infliximab (IFX) and 91 with rituximab (RTX). When considering both patients after a complete vaccination schema (2 doses, or 1 dose in case of prior COVID-19) and those with 1 booster dose, 34 patients (16.6%) were non-responders (2 [5.9%] treated by IFX, none treated by TCZ, 9 [26.5%] treated by ABA and 23 [67.7%] treated by RTX). In multivariate analysis, the only characteristics that significantly and independently differed between responders and non-responders were last bDMARD and corticosteroid therapy at the time of 1st vaccination (Table 1). In RTX-treated patients, the delay from last infusion to 1st vaccine dose was significantly shorter in non-responders (median 4.3 IQR [2.9-6.1] months in non-responders versus 8.4 IQR [5.7-14.5] in responders, p=0.0007). Median survival, i.e. achieving a vaccine response in 50% of RTX-treated subjects, was achieved after 277 days (95CI [209-310]) in patients vaccinated with 2 or 3 doses (Figure 1). In ABA-treated patients, the delay from last infusion to 1st vaccine dose was not different between non-responders and responders.Table 1.Patients’ characteristics and comparisons between responders and non-responders.All patients (n=205)Responders (n=171)Non responders (n=34)Univariate p valueMultivariatep valueAge (median [IQR]), in years64 [56-71]64 [54-70]69 [57-75.5]0.070.40Female sex, n (%)148 (72.2)125 [73.1)23 (67.7)0.53Inflammatory arthritides, n (%)0.16**0.24 Rheumatoid Arthritis156 (78.0)128 (74.9)28 (82.4)0.51 Spondyloarthritis33 (16.1)31 (18.1)2 (5.9)0.12 Others*16 (7.8)12 (5.9)4 (1.9)0.31Last bDMARDs at time of 1st vaccination, n (%)0.0004ABA/RTX versus IFX/TCZ < 0.00010.00024 Infliximab53 (25.9)51 (29.8)2 (5.9) Tocilizumab25 (12.2)25 (14.6)0 Abatacept36 (17.6)27 (15.8)9 (26.5) Rituximab91 (44.4)68 (39.8)23 (67.7)Associated treatments at time of 1st vaccination CsDMARDs, n (%)126 (61.5)107 (62.6)19(55.9)0.56 Methotrexate91 (44.4)78 (45.6)13 (38.2)0.46 Median dose in users (mg /week) [IQR]15 [10-17.5]13.8 [10-15.6]15 [13.8-20]0.07 Corticosteroids, n (%)25 (12.2)19 (11.1)6 (17.6)0.29 Median dose (mg /day) [IQR]0 [0-0]0 [0-0]0 [0-2]0.0350.016Previous COVID-19 infection, n (%)23 (11.2)21 (12.3)2 (5.9)0.38Type of vaccine, n (%)0.62 Pfizer169 (82.4)142 (83.0)27 (79.4)0.62 Moderna14 (68.3)11 (6.4)3 (8.8)0.71 Astra-Zeneca17 (8.3)15 (8.8)2 (5.9)0.74 Janssen5 (2.4)3 (1.8)2 (5.9)0.19Vaccination, n (%) Complete167 (81.5)141 (82.5)28 (16.8)0.47 Complete + 1 booster dose56 (27.3)43 (25.1)13 (38.2)0.14Figure 1.Cumulative seropositive rate according to the interval (days) between the last course of rituximab administration and vaccinationConclusionABA and RTX alter the anti-SARS-CoV-2 vaccine response and were associated with nearly all vaccine non-responses in the present study. Corticosteroid therapy was associated with a lower vaccine response regardless of its indication or the concomitant use of bMARD.Disclosure of InterestsNone declared

BackgroundIt has been shown that smoking could be negatively associated with the risk of developing primary Sjögren’s Syndrome (pSS), and that amongst smoking pSS patients, seropositivity for anti SSA antibodies and frequency of focal sialadenitis were lower. However, data are scarce concerning the impact of smoking on disease activity, glandular features, patient reported outcomes (PROs) and disease progression.ObjectivesTo describe the impact on smoking on pSS disease characteristics and outcome.MethodsASSESS (Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome) is a French prospective multicenter, longitudinal cohort involving 395 patients with pSS enrolled in 15 French centers between 2006 and 2009 and followed since then. In these patients, we compared baseline characteristics and outcome (change in activity and PROs) during the first 5 years of follow-up, according to their smoking status (ever/never). For change during follow-up, any change of ≥ 3 points of ESSDAI or ≥ 1 point of ESSPRI or individual VAS, ≥ 25% of unstimulated salivary flow (UWSF) were considered.ResultsData on smoking at inclusion were available for 394 patients, 106 (26.9%) of them were ever-smokers. Compared to never smokers, ever-smokers were significantly younger (54.0 ± 11.3 vs 59.2 ± 12.2, p < 0.001), and more frequently men (14 (13.2%) vs 12 (4.2%), p = 0.0013). The mean ESSDAI did not differ according to smoking status, (5.0 ± 4.9 vs 5.5 ± 5.8, p = 0.436).There were no significant differences regarding the use of corticosteroids (49 (46.2%) vs 159 (55.2%), p = 0.113), immunosuppressive drugs (21 (19.8%) vs 77 (26.7%), p = 0.158), or hydroxychloroquine (49 (46.2%) vs 165 (57.3%), p = 0.05), even though numerically less smokers were taking these treatments. Smokers tended to have a lower dryness VAS and were less likely to use treatment for dry mouth (64 (60.4%) vs 210 (73%), p = 0.016).No difference was observed in PROs (ESSPRI 5.2 ± 2.2 vs 5.5 ± 2.1, p = 0.259), and in UWSF (0.5 ± 0.75 vs 0.4 ± 1.0, p = 0.672) between smokers and non-smokers.After five years, no difference in change of disease activity (ESSDAI change ≥ 3 points: 12/77 (15.6%) vs 30/207 (14.5%), p = 0.818), or in PROs (ESSPRI change ≥ 1: 30/70 (42.9%) vs 91/198 (46%) p = 0.654) was observed according smoking status, as well as no change in dryness (p = 0.968), pain (p = 0.280), fatigue (p = 0.605) or in UWSF (p = 0.132).Table 1.Baseline characteristics and change in patient-reported outcomes at 5 yearsBaselineSmokers n = 106Non smokers n = 288p-valueAge (years)54.0 ± 11.359.2 ± 12.20.00008Sex, females92 (86.0)276 (95,8)0.0013Disease duration (years) median [IQR]3.9 [1.1; 8.7]5.5 [2.6; 9.7]0.257ESSPRI5.2 ± 2.2 (n = 97)5.5 ± 2.1 (n = 267)0.259 Dryness4.9 ± 2.5 (n = 98)5.5 ± 2.2 (n = 270)0.053 Fatigue5.9 ± 2.8 (n =101)6.0 ± 2.6 (n = 275)0.924 Pain4.6 ± 2.8 (n = 101)4.9 ± 2.9 (n = 274)0.359Unstimuled salivary flow (mL/min)0.5 ± 0.75 (n = 89)0.4 ± 1.0 (n = 241)0.672Treatment for dry mouth64 (60.4)210 (73.0)0.016ESSDAI5.0 ± 4.9 (n = 104)5.5 ± 5.8 (n = 281)0.436Corticosteroids49 (46.2)159 (55.2)0.113Hydroxychloroguine49 (46.2)165 (57.3)0.050Immunosuppresive drugs21 (19.8)77 (26.7)0.158Lymphocytes count (/mm3)1661.1 ± 919.31492.1 ± 1072.0 (n = 280)0.128After five yearsChange in ESSDAI ≥ 312 (15.6) (n = 77)30 (14.5) (n = 207)0.818Change in ESSPRI ≥ 130 (42.9) (n = 70)91 (46.0) (n = 198)0.654Change in salivary flow ≥ 25%29 (44.6) (n = 65)55 (34.0) (n = 162)0.132Data are given as mean ± SD or n (%) unless otherwise specified. SD, standard deviation; IQR, interquartile range; ESSPRI, EULAR Sjögren’s Syndrome Patient Reported Index; ESSDAI, EULAR Sjögren’s Syndrome Disease Activity Index.Continuous variables were compared using student t test and qualitative variable using chi-squareConclusionSmokers pSS patients are more likely to be men and younger than non-smokers. Ever smokers tended to have less dryness, and take less frequently treatment for dryness, corticosteroids, hydroxychloroquine or immunosuppressants. After five years, no difference was observed, according to smoking status, in terms of change in disease activity or PROs.Disclosure of InterestsNone declared

BackgroundToday, there are still no DMARDs licensed for primary Sjögren Syndrome (pSS) patients. Among the explanations, are the limitations of current outcome measures used as primary endpoints: e.g; high placebo response rate, evaluation of either symptoms or systemic activity, and important features not being assessed. The NECESSITY consortium (https://www.necessity-h2020.eu/), including pSS experts from academia, pharmaceutical industry and patient groups formed to develop a new composite responder index, the Sjögren’s Tool for Assessing Response (STAR) that solve the issues of current outcome measures in pSS and is intended for use in clinical trials as an efficacy endpoint.ObjectivesTo develop a composite responder index in primary Sjögren’s syndrome (pSS): the STAR.MethodsTo develop the STAR, the NECESSITY consortium used data-driven methods, based on 9 randomized controlled trials (RCTs), and consensus techniques, involving 78 experts and 20 patients. Based on reanalysis of rituximab trials (TRACTISS and TEARS) and literature review, the Delphi panel identified a core set of domains to include in the STAR, with their respective outcome measures. STAR options combining these domains were designed and proposed to the panel to select and improve them. For each STAR option, sensitivity to change was estimated by the C-index (derived from Effect size) in all 9 RCTs. Delphi rounds were run for selecting STAR among these options. The Delphi panel also voted to classify trials as positive, negative or “in between” in regards to primary but also key secondary endpoints. For the options remaining before the final vote, meta-analyses of the RCTs were performed separately for positive and “in between” trials together, and for negative trials.ResultsThe Delphi panel identified 5 core domains (systemic activity, patient symptoms, lachrymal gland function, salivary gland function and biological parameters), and 227 STAR options, combining these domains, were selected to be tested for sensitivity to change. After two Delphi rounds, meta-analyses of the 20 remaining options were performed. The candidate STAR was selected by a final vote based on metrological properties and clinical relevance. In positive/in between trials, candidate STAR detected a difference between arms (OR 3.29, 95%-CI [2.07;5.22], whereas it did not in negative trials (OR 1.53, 95%-CI [0.81;2.91]).ConclusionThe candidate STAR is a composite responder index, including in a single tool all main disease features, and is designed for use as a primary endpoint in pSS RCTs. Its rigorous and consensual development process ensures its face and content validity. The candidate STAR showed good sensitivity and specificity to change. The candidate STAR will be prospectively validated in a dedicated three arms RCT of the NECESSITY consortium that will evaluate combination of synthetic DMARDs (hydroxychloroquine + lefunomide or hydroxychloroquine + mycophenolate vs placebo). We encourage the use of STAR in any ongoing and future trials.Table 1.Candidate STARDomainPointDefinition of responseSystemic activity3Decrease of clinESSDAI ≥ 3Patient reported outcome3Decrease of ESSPRI ≥ 1 point or ≥ 15%Lachrymal gland function1Schirmer:If abnormal score at baseline: increase ≥ 5 mm from baselineIf normal score at baseline: no change to abnormalOrOcular Staining Score:If abnormal score at baseline: decrease ≥ 2 points from baselineIf normal score at baseline: no change to abnormalSalivary gland function1Unstimulated Whole Salivary Flow:If score > 0 at baseline: increase ≥ 25% from baselineIf score is 0 at baseline: any increase from baselineorUltrasound:Decrease ≥ 25% in total Hocevar score from baselineBiological1Serum IgG levels: decrease ≥ 10%orRheumatoid Factor levels: decrease ≥ 25%Candidate STAR responder≥ 5 pointsESSDAI: EULAR Sjögren syndrome disease activity index; ESSPRI: EULAR Sjögren syndrome patient reported index; IgG: Immunoglobulin G;AcknowledgementsNECESSITY WP5 STAR development participants: Suzanne Arends (University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen 9700 RB, Netherlands), Francesca Barone (Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK), Albin Björk (Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden), Coralie Bouillot (Association Française du Gougerot Sjögren et des Syndromes Secs, France), Guillermo Carvajal Alegria (University of Brest, Inserm, CHU de Brest, LBAI, UMR1227, Brest, France; Service de Rhumatologie, Centre de Référence Maladies Autoimmunes Rares CERAINO, CHU Cavale Blanche, Brest, France), Wen-Hung Chen (GlaxoSmithKline, Research Triangle Park, North Carolina, USA), Kenneth Clark (GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom), Konstantina Delli (Department of Oral and Maxillofacial Surgery, University Medical Center Groningen (UMCG), University of Groningen, The Netherlands), Salvatore de Vita (Rheumatology Clinic, University Hospital of Udine, Italy), Liseth de Wolff (University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen 9700 RB, Netherlands), Jennifer Evans (Novartis Pharmaceuticals corporation USA), Stéphanie Galtier (Institut de Recherches Internationales Servier (IRIS), Suresnes Cedex, France), Saviana Gandolfo (Rheumatology Clinic, Department of Medical area, University of Udine, ASUFC, 33100 Udine, Italy), Mickael Guedj (Institut de Recherches Internationales Servier (IRIS), Suresnes Cedex, France), Dewi Guellec (CHU de Brest, Service de Rhumatologie, Inserm, CIC 1412, Brest, France), Safae Hamkour (Center of Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht 3584 GA, Netherlands), Dominik Hartl (Novartis Institutes for BioMedical Research, Basel, Switzerland), Malin Jonsson (Section for Oral and Maxillofacial Radiology, Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Norway), Roland Jonsson (Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Department of Rheumatology, Haukeland University Hospital, Bergen, Norway), Frans Kroese (University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen 9700 RB, Netherlands), Aike Albert Kruize (University Medical Center Utrecht, Department Rheumatology and Clinical Immunology, Utrecht, Netherlands), Laurence Laigle (Institut de Recherches Internationales Servier (IRIS), Suresnes Cedex, France), Véronique Le Guern (AP-HP, Hôpital Cochin, Centre de référence maladies auto-immunes et systémiques rares, service de médecine interne, Paris, France), Wen-Lin Luo (Department of Biometrics and Statistical Science, Novartis Pharmaceuticals, East Hanover, New Jersey), Esther Mossel (University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen 9700 RB, Netherlands), Wan-Fai Ng (Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK), Gaëtane Nocturne (Department of Rheumatology, Université Paris-Saclay, INSERM U1184: Centre for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicêtre, Paris, France), Marleen Nys (Global Biometric Sciences, Bristol Myers Squibb, Braine L’Alleud, Belgium), Roald Omdal (Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, PO Box 8100, 4068, Stavanger, Norway), Jacques-Olivier Pers (LBAI, UMR1227, University of Brest, Inserm, Brest, France and CHU de Brest, Brest, France), Maggy Pincemin (Association Française du Gougerot Sjögren et des Syndromes Secs, France), Manel Ramos-Casals (Department of Autoimmune Diseases, Hospital Clinic de Barcelona Institut Clinic de Medicinai Dermatologia, Barcelona, Catalunya, Spain), Philippe Ravaud (Centre d’Epidémiologie Clinique, Hôpital Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris, Paris, France), Neelanjana Ray (Global Drug Development - Immunology, Bristol Myers Squibb Company, Princeton, New Jersey, USA), Alain Saraux (HU de Brest, Service de Rhumatologie, Univ Brest, Inserm, UMR1227, Lymphocytes B et Autoimmunité, Univ Brest, Inserm, LabEx IGO, Brest, France), Athanasios Tzioufas (Rheumatology Clinic, Department of Medical area, University of Udine, ASUFC, 33100 Udine, Italy), Gwenny Verstappen (University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen 9700 RB, Netherlands), Arjan Vissink, Marie Wahren-Herlenius (Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden). We thank the following experts: Esen Karamursel Akpek, Alan Baer, Chiara Baldini, Elena Bartoloni, Marí-Alfonso Begona, Johan Brun, Vatinee Bunya, Laurent Chiche, Troy Daniels, Paul Emery, Robert Fox, Roberto Giacomelli, John Gonzales, John Greenspan, Robert Moots, Susumu Nishiyama, Elizabeth Price, Christophe Richez, Caroline Shiboski, Roser Solans Laque, Muthiah Srinivasan, Peter Olsson, Tsutomu Takeuchi, Frederick Vivino, Paraskevi Voulgari, Daniel Wallace, Ava Wu, Wen Zhang. We thank the anonymous patients from the NECESSITY Patient Advisory Group and the Sjögren Foundation for their valuable contribution to the Delphi process. We thank EW StClair and AN Baer who generated the baminercept data and made them publicly available.Disclosure of InterestsRaphaèle Seror Consultant of: GlaxoSmithKline, Boehringer, Janssen and Novartis, Grant/research support from: GlaxoSmithKline and Amgen, Gabriel Baron: None declared, Marine Camus: None declared, Divi Cornec Consultant of: GlaxoSmithKline, Bristol Myers Squibb, Janssen, Amgen, Pfizer and Roche, Elodie Perrodeau: None declared, Simon J. Bowman Consultant of: Abbvie, Astra Zeneca, Galapagos and Novartis Pharmaceuticals, Michele Bombardieri Consultant of: UCB, Amgen/Medimmune, Janssen, and GlaxoSmithKline, Grant/research support from: Amgen/Medimmune, Janssen, and GlaxoSmithKline, Hendrika Bootsma: None declared, Jacques-Eric Gottenberg Consultant of: AbbVie, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Pfizer, Roche, Sanofi, Novartis, MSD, CSL-Behring and Genzyme, Grant/research support from: Bristol Myers Squibb, Benjamin Fisher Speakers bureau: Bristol Myers Squibb and Novartis, Consultant of: Novartis, Bristol Myers Squibb, Janssen and Servier, Grant/research support from: Servier, Galapagos and Janssen, Wolfgang Hueber Shareholder of: Novartis Pharma, Employee of: Novartis Pharma, Joel van Roon: None declared, Valerie Devauchelle-Pensec: None declared, Peter Gergely Shareholder of: Novartis Pharma, Employee of: Novartis Pharma, Xavier Mariette Consultant of: Bristol Myers Squibb, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB, Grant/research support from: Ose Pharmaceuticals, Raphaël Porcher: None declared

BackgroundThe Fibrosis-4 (FIB4) score, including age, transaminases and platelets, can detect severe fibrosis (F3-F4) in patients with Non Alcoolic Steato Hepatitis (NASH) and could be of interest in the follow-up of patients with RA. Indeed, platelets contribute to the pathophysiology of RA, transaminases are used in the liver monitoring of our treatments. In addition, retrospective data suggested the association between FIB4 and mortality in RA (1).ObjectivesWe aimed to evaluate the value of the FIB4 score as a prognostic factor in RA in the prospective ESPOIR cohort.MethodsPatients of the ESPOIR cohort diagnosed with RA according to ACR-EULAR criteria were included in our analysis. The formula for the FIB-4 score is as follows: [Age (years) × ASAT (U/L)] / [Platelet count (10^9/L) × ALT (U/L)1/2]. The analyses were based on linear mixed-effects models with a random effect on the subject to account for repeated measures throughout time.Results633 of the 813 patients included met the ACR/EULAR criteria for RA and had a calculable FIB4 score. Median FIB4 was 0.75 IQR (0.53-0.99) and 61 patients (9.6%) had a high FIB4 score at baseline. Baseline FIB4 was significantly higher in patients with a chronic alcohol consumption (p=0.021) or viral hepatitis (pTable 1.Associations of FIB4 score with DAS28 and modified Sharp score evolutions in multivariate analysesVariableVariables included in modelp-valueDAS28TimeAge0.97Baseline number of swollen jointsBaseline Rheumatoid Factor0.51evolution over timeBaseline ACPA (presence)0.97Baseline CRPBaseline modified Sharp score > 00.15Baseline FIB40.26Modified Sharp scoreTime0.052Age0.0005Baseline number of swollen joints0.38Baseline Rheumatoid Factor0.61evolution over timeBaseline ACPA (presence)0.012Baseline CRP0.84Baseline FIB40.25ConclusionOur study was the first to evaluate the value of FIB4 in a prospective cohort of RA patients. The present prospective cohort study with a 10-year follow-up did not find a prognostic role of FIB4 in RA, in contrast to previous retrospective studies. Reassuringly, FIB4 score was not increased by DMARD treatment after 10 years of follow-up, confirming the absence of long-term DMARD-related hepatotoxicity.References[1]Seung Up Kim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Yong-Beom Park, Kwang-Hyub Han & Sang-Won Lee (2018): Fibrosis-4 index at diagnosis can predict all-cause mortality in patients with rheumatoid arthritis: A retrospective monocentric study, Modern Rheumatology, DOI: 10.1080/14397595.2018.1558760Figure 1.Impact of baseline FIB4 score on DAS28, HAQ and total modified-Sharp score over time.AcknowledgementsAn unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. The French Society of Rheumatology, Pfizer, Abbvie, Lilly, Sanofi also supported the ESPOIR cohort study.We also wish to thank Nathalie Rincheval (CHU Montpellier and EA 2415) who did expert monitoring and data management and all the investigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine, MC. Boissier, Paris-Bobigny, A. Cantagrel, Toulouse, B. Combe, Montpellier, M. Dougados, Paris-Cochin, P. Fardellone et P. Boumier Amiens, B. Fautrel, Paris-La Pitié, RM. Flipo, Lille, Ph. Goupille, Tours, F. Liote, Paris- Lariboisière, O. Vittecoq, Rouen, X. Mariette, Paris Bicetre, P. Dieude, Paris Bichat, A. Saraux, Brest, T. Schaeverbeke, Bordeaux, J. Sibilia, Strasbourg) V. Devauchelle and C Lukas for expert X-ray reading.Disclosure of InterestsNone declared.

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.

Introduction L’epidemie a COVID-19 a bouleverse le systeme sanitaire francais au mois de mars 2020. La meconnaissance de cette nouvelle maladie et la difficulte d’acces aux professionnels de sante pendant le confinement ont potentiellement abouti a des modifications, parfois inadaptees, de la prise en charge des patients suivis pour des pathologies chroniques. L’objectif de cette etude etait d’evaluer l’impact de l’epidemie COVID-19 sur la prise charge de la polyarthrite rhumatoide (PR) par une enquete transversale realisee au mois de juin 2020 chez les patients suivis dans la e-cohorte du registre ART-SFR. Patients et methodes Le registre national multicentrique francais ART-SFR inclut des PR initiant un traitement par anti-TNF depuis septembre 2016 avec un suivi prospectif prevu sur 5 ans. Lors de l’inclusion dans le registre, il est systematiquement propose au patient de participer a la e-cohorte qui consiste a recevoir des questionnaires mensuels en ligne portant sur leurs comorbidites, les traitements pris, la tolerance des traitements, le handicap fonctionnel, les vaccins. En juin 2020 un questionnaire supplementaire a ete envoye a tous les patients participant a la e-cohorte portant sur leurs traitements en cours et sur l’impact de l’epidemie COVID-19 sur la prise en charge habituelle de leur PR. Resultats En juin 2020, sur les 1155 patients inclus dans le registre ART, 455 avaient accepte de participer a la e-cohorte. Parmi eux, 169 (37 %), (72 % de femmes, âge moyen 54 ans, 86 % sous bDMARD ou anti-JAK) ont repondu au questionnaire portant sur l’impact du COVID-19 sur la prise en charge de leur maladie. Parmi ces patients, 16 (2,7 %) d’entre eux ont eu des symptomes compatibles avec une COVID-19, mais aucun d’entre eux n’a ete teste positif (test non fait, n = 11, ou negatif, n = 5). Aucun de ces patients n’a ete hospitalise pour une forme severe de COVID-19. Parmi les 145 patients sous bDMARD ou anti-JAK en mars 2020, 27 (18,6 %) d’entre eux ont eu un changement therapeutique entre mars et juin, dont la majorite (n = 18, 78 %) a la demande du rhumatologue pour une raison sans lien avec l’epidemie, 6 pour une suspicion d’infection a COVID-19. Seuls 6 patients ont interrompu d‘eux meme leur traitement par crainte d’une infection a COVID-19. Par ailleurs, 79 patients (47 %) ont declare avoir eu des poussees pendant la periode de confinement motivant un changement therapeutique pour 23 d’entre eux (29 %). Sur les 110 patients qui devaient avoir un rendez-vous pour le suivi de leur PR pendant la periode de confinement, 66 (60 %) ont note des modifications avec un report de la consultation ou une teleconsultation. Pendant la periode de confinement, 40 patients (24 %) ont ete mis en arret de travail ou chomage partiel, 32 (19 %) ont poursuivi leur activite en teletravail et 94 (57 %) ont poursuivi leur activite a la fois en teletravail et en presentiel, 12 patients (7 %) ont uniquement travailles en presentiel, parmi eux seuls 2 patients n’ont pas eu les moyens de respecter les gestes barriere pendant l’exercice de leur travail. Enfin, 3 patients (2 %) ont perdu leur travail. Conclusion Ces resultats rassurants sur le suivi pendant le confinement des patients PR majoritairement sous bDMARD ou anti-JAK doivent etre pris avec precautions. En effet, les patients inclus dans la e-cohorte du registre ART-SFR ne sont probablement pas representatifs des tous les patients suivis pour une PR sous traitement cible en France.

Background:The consequences of the COVID-19 outbreak are unprecedented and have been felt by everyone around the world, including people with rheumatic and musculoskeletal diseases (RMDs). With the development of vaccines, the future is becoming brighter. Vaccines are a key pillar of public health and have been proven to prevent many serious diseases. However, vaccination also raises questions, especially for patients with inflammatory RMDs and/or treated with drugs that influence their immune system.Objectives:Our aim was to collect safety data among RMD patients receiving COVID-19 vaccines.Methods:The EULAR COVID-19 Vaccination (COVAX) Registry is an observational registry launched on 5 February 2021. Data are entered voluntarily by clinicians or associated healthcare staff; patients are eligible for inclusion if they have an RMD and have been vaccinated against SARS-CoV-2. Descriptive statistics are presented.Results:As of 27 April 2021, 1519 patients were reported to the registry. The majority were female (68%) and above the age of 60 (57%). Mean age was 63 years (SD 16), ranging from 15 to 97 years. A total of 28 countries contributed to the registry, with France (60%) and Italy (13%) as the highest contributors. The majority (91%) had inflammatory RMDs. Inflammatory joint diseases accounted for 51% of cases, connective tissue diseases 19%, vasculitis 16%, other immune mediated inflammatory diseases 4%, and non-inflammatory/mechanical RMDs 9%. The most frequent individual diagnoses were rheumatoid arthritis (30%), axial spondyloarthritis (8%), psoriatic arthritis (8%), systemic lupus erythematosus (SLE, 7%) and polymyalgia rheumatica (6%). At the time of vaccination, 45% were taking conventional synthetic DMARDs, 36% biological DMARDs, 31% systemic glucocorticoids, 6% other immunosuppressants (azathioprine; mycophenolate; cyclosporine; cyclophosphamide; tacrolimus), and 3% targeted synthetic DMARDs. The most frequent individual DMARDs were methotrexate (29%), TNF-inhibitors (18%), antimalarials (10%) and rituximab (6%). The vaccines administered were: 78% Pfizer, 16% AstraZeneca, 5% Moderna and 1% other/unknown; 66% of cases received two doses and 34% one dose. Mean time from 1st and 2nd dose to case report was 41 days (SD 26) and 26 days (SD 23), respectively. COVID-19 diagnosis after vaccination was reported in 1% (18/1519) of cases. Mean time from first vaccination until COVID-19 diagnosis was 24 days (SD 17). Disease flares were reported by 5% (73/1375) of patients with inflammatory RMDs, with 1.2% (17/1375) classified as severe flares. Mean time from closest vaccination date to inflammatory RMD flare was 5 days (SD 5). The most common flare types were arthritis (35/1375=2.5%), arthralgia (29/1375=2.1%), cutaneous flare (11/1375=0.8%) and increase in fatigue (11/1375=0.8%). Potential vaccine side effects were reported by 31% of patients (467/1519). The majority were typical early adverse events within 7 days of vaccination, namely pain at the site of injection (281/1519=19%), fatigue (171/1519=11%) and headache (103/1519=7%). Organ/system adverse events were reported by 2% (33/1519) but only 0.1% (2/1519) reported severe adverse events, namely a case of hemiparesis in a patient with systemic sclerosis/SLE overlap syndrome (ongoing at the time of reporting), and a case of giant cell arteritis in a patient with osteoarthritis (recovered/resolved without sequelae).Conclusion:The safety profiles for COVID-19 vaccines in RMD patients was reassuring. Most adverse events were the same as in the general population, they were non-serious and involved short term local and systemic symptoms. The overwhelming majority of patients tolerated their vaccination well with rare reports of inflammatory RMD flare (5%; 1.2% severe) and very rare reports of severe adverse events (0.1%). These initial findings should provide reassurance to rheumatologists and vaccine recipients, and promote confidence in COVID-19 vaccine safety in RMD patients, namely those with inflammatory RMDs and/or taking treatments that influence their immune system.Acknowledgements:EULAR COVID-19 Task Force; European Reference Network on rare and Complex Connective Tissue and Musculoskeletal Diseases; European Reference Network on Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases Network; all rheumatologists contributing to the EULAR COVAX Registry.Disclosure of Interests:Pedro M Machado Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript., Grant/research support from: Orphazyme, unrelated to this manuscript., Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript., Saskia Lawson-Tovey: None declared, Kimme Hyrich Grant/research support from: BMS, UCB, and Pfizer, all unrelated to this manuscript., Speakers bureau: Abbvie, Loreto Carmona Consultant of: her institute works by contract for laboratories among other institutions, such as Abbvie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, S.A., Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal GmbH, and UCB Pharma, all unrelated to this manuscript., Laure Gossec Grant/research support from: AbbVie, Amgen, BMS, Biogen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, all unrelated to this manuscript., Speakers bureau: Amgen, Lilly, Janssen, Pfizer, Sandoz, Sanofi, Galapagos, all unrelated to this manuscript., Elsa Mateus Grant/research support from: LPCDR received support for specific activities: grants from Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal S.A., MSD, Celgene, Medac, Pharmakern, GAfPA; grants and non-financial support from Pfizer; non-financial support from Grünenthal GmbH, outside the submitted work., Anja Strangfeld Speakers bureau: AbbVie, MSD, Roche, BMS, and Pfizer, all unrelated with this manuscript., BERND RAFFEINER: None declared, Tiphaine Goulenok: None declared, Olilvier Brocq: None declared, Martina Cornalba: None declared, José A Gómez-Puerta Speakers bureau: AbbVie, BMS, GSK, Janssen, Lilly, MSD, Roche and Sanofi., Eric Veillard: None declared, Ludovic Trefond: None declared, Jacques-Eric Gottenberg: None declared, Julien Henry: None declared, Patrick Durez: None declared, Gerd Rüdiger Burmester: None declared, Marta Mosca: None declared, Eric Hachulla: None declared, Hans Bijlsma: None declared, Iain McInnes: None declared, Xavier Mariette Consultant of: BMS, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sanofi-Aventis, UCB, and grant from Ose, all unrelated to this manuscript.

Introduction Les études vaccinales de grande ampleur et les registres apportent des résultats précieux mais souvent de manière retardée par rapport à l’urgence pandémique. Les perfusions de biologiques intraveineux en hôpital de jour (HDJ) permettent de garantir un recueil de données fiables en temps réel. C’est ainsi que nous avions mis en évidence le surrisque d’une forme grave de COVID-19 sous rituximab. Nous avons souhaité étudier l’impact des bDMARDs sur la réponse vaccinale humorale des patients suivis en HDJ. Patients et méthodes Nous avons étudié la réponse vaccinale après un schéma vaccinale complet, 2 ou 3 doses de vaccin, suivis en hôpital de jour dans 5 centres hospitaliers français et traités par un biomédicament intraveineux entre septembre 2019 et août 2021. Après information et consentement des patients, nous avons inclus ceux disposant ou acceptant de réaliser une sérologie anti-SARS-CoV-2. Les patients étaient considérés comme non-répondeurs si le taux d’anticorps détecté était inférieur au seuil de positivé du kit utilisé. Résultats Sur les 925 patients suivis en HDJ dans les 5 centres, les données préliminaires de 205 patients sont disponibles (148 F/57 H). L’âge médian était de 64 ans (Interquartile Range [IQR] 56–71). 25 étaient traités par tocilizumab (TCZ), 36 par abatacept (ABA), 53 par infliximab (IFX) et 91 par rituximab (RTX). 156 étaient traités pour une PR, 33 pour une spondyloarthrite et 16 pour une autre pathologie (connectivite n = 5, myosite n = 3, vascularite n = 2, arthrite juvénile idiopathique n = 2, autres n = 4). 25 patients étaient co-traités par corticoïdes, 126 par csDMARDs et 2 par d’autres immunossuppresseurs (aziathioprine). Trois quarts des patients traités par RTX ont débuté leur schéma vaccinal plus de 4 mois après leur dernier cycle de traitement. Un total de 23 patients avaient un antécédent de COVID-19 confirmé (par PCR ou sérologie). Un total de 169 patients ont été vaccinés par Pfizer, 16 par Astra-Zeneca, 14 par Moderna, 5 par Janssen et un par Astra-Zeneca puis Pfizer. Un total de 167 patients ont bénéficié d’une sérologie après 2 doses de vaccin (ou un schéma vaccinal complet en cas de COVID-19 préalable). Parmi eux, 28 (16,8 %) étaient non-répondeurs. Il n’y avait pas de différence en fonction de l’âge (p = 0,24) ou du sexe des patients (p = 0,51), du type de pathologie ou du co-traitement par corticoïdes ou csDMARD. La réponse vaccinale était différente en fonction du bDMARD utilisé (p = 0,0003) : aucun patient traité par IFX (0/42) n’était non-répondeur, un seul sous TCZ (1/25, 4 %) contre 25 % sous ABA (8/32) et 27,9 % sous RTX (19/68). Un total de 94 % des non répondeurs après 2 ou 3 doses de vaccin avaient été traités par RTX ou ABA. Chez les patients traités par rituximab, le délai entre la dernière perfusion et la première dose de vaccin était significativement plus courte chez les non-répondeurs (médiane 4,3 IQR [2,9–6,1] mois chez les non-répondeurs versus 8,4 IQR [5,7–14,5] chez les répondeurs, p = 0,0007). La diminution de réponse vaccinale post-ABA ou RTX étaient similaires après 3 doses de vaccin (56 patients), 25 % de non répondeurs sous ABA (1/4), 25 % sous RTX (10/40) contre 19 % sous IFX (9/11) et aucun sous TCZ (0/1). 18 des 56 patients ont bénéficié d’une sérologie après 2 doses et également après 3 doses de vaccin. 7 étaient non-répondeurs après 2 doses (6 RTX et 1 TCZ). Parmi eux, 5 sont restés non-répondeurs après leur 3e dose, tous traités par RTX. Conclusion L’ABA et le RTX altèrent la réponse vaccinale anti-SARS-CoV-2 : associés à 94 % des non-réponses vaccinales. La réponse vaccinale est altérée si un délai suffisant n’est pas respecté entre la perfusion de RTX, permettant une repopulation lymphocytaire B, et la vaccination.

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The arrival of new drugs and new therapeutic strategies allowed to reach sustained remission in an increasing number of patients with rheumatoid arthritis. The study of biologic disease-modifying anti-rheumatic drugs (bDMARDs) adaptation strategies is a need to optimize the benefit/risk balance and cost/effectiveness ratio of these molecules. Current recommendations such as EULAR 2016 propose tapering bDMARDs, especially when combined with a csDMARD, when the patient is in remission after stopping persistent glucocorticoids. The analysis of literature comprising 22 studies shows that a bDMARD adaptation is possible in established rheumatoid arthritis when clinico-biological and ultrasound remission is maintained over six months. Priority should be given to a progressive tapering strategy doses controlled by disease activity while maintaining "tight control" to identify and effectively treat a relapse, a retreatment being usually favorable.

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.

Introduction De nombreux patients (pts) atteints de polyarthrite rhumatoide (PR) presentent une reponse inadequate aux bDMARDs. L’objectif de cette analyse est de determiner si la prise prealable d’un bDMARD affecte l’efficacite du FIL, inhibiteur selectif per os de JAK1. Patients et methodes L’etude internationale de phase 3 FINCH2 (NCT02873936) a inclus 448 pts atteints de PR active prealablement traites par bDMARD 1. Les pts ont ete randomises 1:1:1 pour recevoir FIL 200 ou 100 mg ou un placebo (PBO), 1×/j pendant 24 semaines. Le pourcentage de pts atteignant une faible activite de la maladie (LDA) ou une remission, mesures par le CDAI et le DAS28-CRP, a ete evalue a S24. Les resultats ont ete stratifies selon le nombre et le type de bDMARD prealablement recus. Resultats Sur les 448 pts inclus dans l’etude, 106 (23,7 %) avaient deja pris ≥ 3 bDMARDs. A S24, plus de pts recevant FIL ont atteint une LDA vs PBO, quel que soit le nombre et le type de bDMARD prealable. Pour les patients du bras FIL 200 (vs PBO), un score DAS28-CRP ≤ 3,2 a ete atteint a S24 respectivement par 52 % vs 26 %, 50 % vs 22 % et 40 % vs 9 % des pts ayant prealablement recu 1, 2 ou ≥ 3 bDMARD, et par respectivement 49 % vs 21 % et 46 % vs 16 % des pts ayant prealablement recu un anti-TNF ou un anti-IL6. A S24, les taux de remission etaient superieurs dans les bras FIL vs PBO. Pour le bras FIL 200 (vs PBO), un score DAS28-CRP Fig. 1 ). Les effets indesirables apparus sous traitement dans les sous-groupes etaient concordants avec ceux observes dans la population totale. Conclusion FIL a permis d’atteindre des taux de LDA et de remission plus eleves vs PBO chez les pts ayant prealablement recu un anti-IL-6 ou un anti-TNF ou 1, 2 ou ≥ 3 bDMARD, avec un profil de tolerance similaire a celui observe dans la population globale. La superiorite du FIL vs PBO chez des patients en echec de bDMARDs montre l’interet de l’inhibition selective de JAK1.

Background:Despite effective treatments, many patients (pts) with rheumatoid arthritis (RA) have inadequate responses to biologic DMARDs (bDMARD-IR), highlighting an unmet need. It is unclear whether prior bDMARD use affects efficacy of the oral, selective JAK-1 inhibitor filgotinib (FIL).Objectives:To explore clinical response to FIL in bDMARD-IR pts stratified by mode of action (MOA) and number of prior bDMARDs.Methods:The global, phase 3 FINCH-2 (NCT02873936) study treated 448 bDMARD-IR pts with active RA.1Pts were randomised 1:1:1 to once-daily FIL 200 mg, FIL 100 mg, or placebo (PBO) for 24 weeks. Efficacy was assessed by percent of pts achieving low disease activity (LDA) or remission at week (W)24 as measured by CDAI and DAS28(CRP) stratified by number and MOA of prior bDMARDs. Comparisons were not adjusted for multiplicity. Nonresponder imputation was used.Results:In total, 448 bDMARD-IR pts were included, 105 with prior experience with ≥3 bDMARDs (Table). At W24, pts receiving FIL were in LDA at a higher proportion vs PBO, irrespective of number of prior bDMARDs or MOA (Figure 1). For pts receiving FIL 200 vs PBO, DAS28(CRP) ≤3.2 was achieved at W24 by 52% vs 26%, 51% vs 22%, and 38% vs 9% of pts with 1, 2, or ≥3 prior bDMARDs, respectively, and 49% vs 21% and 50% vs 13% of pts exposed to TNF or IL-6 inhibitors; for all subgroups, rates were significantly higher vs PBO (Figure 1). Delta between FIL 200 mg and PBO was maintained irrespective of number or type of prior bDMARDs. At W24, pts receiving FIL achieved remission at numerically higher rates vs PBO (Figure 2). For pts receiving FIL 200 mg vs PBO, DAS28(CRP) Table.Number and MOA of prior bDMARDsFIL 200 mgn = 147FIL 100 mgn = 153PBOn = 148TotalN = 448Prior bDMARDs 173 (49.7)86 (56.2)77 (52.0)236 (52.7) 237 (25.2)33 (21.6)36 (24.3)106 (23.7) ≥337 (25.2)34 (22.2)34 (23.0)105 (23.4)LOE ≥1 bDMARD125 (85.0)129 (84.3)126 (85.1)380 (84.8)Intolerance ≥1 bDMARD36 (24.5)34 (22.2)32 (21.6)102 (22.8)Prior TNFi121 (82.3)134 (87.6)124 (83.8)379 (84.6) LOE ≥1 TNFi97 (66.0)113 (73.9)103 (69.6)313 (69.9) Intolerance ≥1 TNFi25 (17.0)24 (15.7)24 (16.2)73 (16.3)Prior non-TNFi73 (49.7)62 (40.5)75 (50.7)210 (46.9) LOE ≥1 non-TNFi52 (35.4)43 (28.1)56 (37.8)151 (33.7) Intolerance ≥1 non-TNFi13 (8.8)13 (8.5)11 (7.4)37 (8.3)Prior IL-6i34 (23.1)35 (22.9)32 (21.6)101 (22.5) LOE ≥1 IL-6i25 (17.0)22 (14.4)21 (14.2)68 (15.2) Intolerance ≥1 IL-6i5 (3.4)10 (6.5)5 (3.4)20 (4.5)Data presented as n (%).i, inhibitor; LOE, lack of efficacy.Conclusion:Treatment with FIL vs PBO led to higher rates of LDA and remission in pts with IR to IL-6 or TNF inhibition, or to 1, 2, or ≥3 prior bDMARDs, with a similar safety profile to the overall study population. A significantly higher proportion of pts overall receiving FIL 200 mg vs PBO were in LDA at W24. Improved efficacy of FIL vs PBO in pts who previously failed multiple bDMARDs indicates distinct benefits of selective JAK-1 inhibition with FIL.References:[1]Genovese, et al.JAMA2019;322(4):315–25.Disclosure of Interests: :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, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Grace C. Wright Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Exagen, Eli Lilly, Myriad Autoimmune, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, UCB, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Exagen, Eli Lilly, Myriad Autoimmune, Novartis, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, UCB, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd., Kenneth Kalunian Grant/research support from: Pfizer, Lupus Research Alliance, Sanford Consortium, Consultant of: Genentech, Nektar, BMS, Janssen, AstraZeneca, Biogen, Vielabio, Equillium, Eli Lilly, ILTOO, Abbvie, Amgen, Roche, Gilead, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Ying Guo Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Shangbang Rao Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., YingMeei Tan Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme

Background:EULAR guidelines recommend a treat-to-target approach focusing on reducing inflammation to prevent joint damage, physical disability, and mortality.1However, patients consider reduction in pain and fatigue, along with maintenance of physical function, and improvement in health-related quality of life (HRQoL) important areas for improvement with RA treatment.2In the FINCH 2 study, filgotinib (FIL)—a potent, selective, oral small molecule Janus kinase 1 inhibitor—in combination with conventional synthetic (cs)DMARD therapy significantly improved the signs and symptoms of rheumatoid arthritis (RA) in patients with an inadequate response to a biologic (b)DMARD compared with placebo (PBO).3In addition, patients experienced significant improvements in HAQ-DI at week (W)12 and W24 with FIL 100 mg (p 3Objectives:To evaluate the rate and magnitude of change in patient-reported outcomes (PROs) from FINCH 2 assessing pain, HRQoL, and fatigue.Methods:Patients in this double-blind, randomised study (NCT02873936) received FIL 200 mg, FIL 100 mg, or PBO while continuing csDMARD therapy. PROs were collected prospectively on day 1 and at the W2, W4, W8, W12, W14, W16, W20, and W24 visits for assessment of pain (VAS pain scale) and on day 1 and at W4, W12, and W24 for assessment of fatigue (FACIT-Fatigue) and HRQoL (SF-36). Changes from baseline for each PRO at each time point up to W24 were analysed longitudinally using a mixed-effects model for repeated measures. P values for the difference between each FIL arm and PBO at each time point were calculated.Results:Among the 448 patients randomised and treated (FIL 200 mg, n = 147; FIL 100 mg, n = 153; PBO, n = 148) 381 (85.0%) completed the study. Baseline mean (SD) VAS pain scale was 67 (21.0), SF-36 physical component summary (PCS) was 31.1 (7.89), SF-36 mental component summary (MCS) was 44.3 (11.6), and FACIT-Fatigue score was 24.4 (11.6); baseline values did not vary between treatment groups. Significantly greater improvements in VAS pain scores began at W2 and were maintained through W24 for patients who received either dose of FIL vs PBO (Fig 1A). FIL also significantly improved patients’ fatigue at W4, W12, and W24 compared with PBO for those receiving 200 mg doses, and at W4 and W12 for those receiving 100 mg doses (Fig 1B). HRQoL related to physical functioning (SF-36 PCS) was significantly enhanced at W4, W12, and W24 with both doses of FIL as compared with PBO (Fig 2A). Improvements to mental-health-related QoL (SF-36 MCS) were reported for FIL as early as W4 and maintained through W24, with statistically significant improvements at W4 and W12 for FIL 200 mg vs PBO (Fig 2B).Conclusion:In a patient population with refractory disease that had inadequate response to prior bDMARDs and had significant disease at baseline, FIL treatment—coadministered with csDMARD therapy—was able to provide rapid and sustained improvements in key measures of pain, HRQoL, and fatigue as reported by patients.References:[1]Smolen, et al.Ann Rheum Dis. 2017;76:960–77.[2]Fautrel, et al.Rheumatol Int.2018;38:935–47.[3]Genovese, et al.JAMA. 2019;322(4):315–25.Disclosure of Interests:David Walker Grant/research support from: Gilead, Consultant of: Gilead, Lilly, Pfizer, Roche, Speakers bureau: Lilly, Pfizer, Roche, Tsutomu Takeuchi Grant/research support from: AbbVie, Asahikasei Pharma Corp., Astellas Pharma, Inc., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Nipponkayaku Co. Ltd., Shionogi & Co., Ltd., Takeda Pharmaceutical Co., Ltd., UCB Japan, Consultant of: Astellas Pharma, Inc., Chugai Pharmaceutical Co, Ltd., Eli Lilly Japan,, Speakers bureau: Abbvie, AYUMI Pharmaceutical Corp., Bristol-Myers Squibb, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan, Gilead Sciences, Inc., Mitsubishi-Tanabe Pharma Corp., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd, Beatrix Bartok Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Shangbang Rao Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., I-Heng Lee Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, 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, Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme

Background:Filgotinib (FIL), an oral, potent, selective JAK-1 inhibitor, provided statistically significant and clinically meaningful improvement in rheumatoid arthritis (RA) signs and symptoms, physical function, radiographic progression, and quality of life in a comprehensive clinical program of 4 phase 3 (FINCH 1–4;NCT02889796,NCT02873936,NCT02886728,NCT03025308) and 3 phase 2 (DARWIN 1–3;NCT01668641,NCT01894516,NCT02065700) trials in patients (pts) with early and biologic-refractory RA.1–3Objectives:To assess long-term safety of FIL.Methods:Treatment-emergent adverse events (TEAEs) from the FIL clinical program were integrated and presented for pts receiving FIL 200 mg or FIL 100 mg QD (including pts who transitioned to FIL from placebo [PBO], methotrexate [MTX], adalimumab [ADA], or another dose of FIL) as well as pts receiving PBO, MTX, and ADA across all 7 studies. Exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY) were calculated for adverse events (AEs) of interest per treatment. Incidence was total number of pts with events, and PY exposure was time between first and last doses. Major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) were centrally adjudicated by an independent committee.Results:Across the 7 trials, 4057 pts with RA (2227 pts FIL 200 mg; 1600 pts FIL 100 mg) received >1 dose of treatment for 5493 total PY of exposure (3079.2 PY FIL 200 mg; 1465.3 PY FIL 100 mg) (Table). EAIRs of serious AEs and TEAEs leading to death in pts receiving FIL were comparable to those for PBO, ADA, or MTX, with no dose-dependent effect (Figure 1). EAIR for herpes zoster (HZ), serious, and opportunistic infections are shown in Figure 2. EAIR for HZ were low overall, but numerically slightly higher for FIL relative to PBO, ADA, and similar to MTX. Serious infection EAIRs were comparable between pts receiving FIL 100 mg and ADA, and numerically slightly lower for FIL 200 mg and MTX. Rates of opportunistic infections (including active tuberculosis) were low overall; EAIR for FIL doses were comparable to placebo and numerically lower than ADA or MTX. Rates of MACE and VTE were numerically lower for FIL relative to PBO (Figure 1). Malignancies, including nonmelanoma skin cancer, were rare overall, and rates were low in pts receiving FIL (Figure 1).Table.Total exposure to study treatments pooled from 7 studiesNumber of patientsPatient-years of exposureFIL 200 mg22273079.2FIL 100 mg16001465.3ADA325290.1MTX416356.2PBO781302.4Patients could contribute to >1 treatment group.ADA, adalimumab; FIL, filgotinib; MTX, methotrexate; PBO, placebo.Conclusion:In this integrated analysis, FIL was well-tolerated, and no new safety concerns were identified. No clinically meaningful dose-dependent safety effects were observed. MACE and VTE were uncommon. Serious infections rates were low; HZ reactivation was infrequent. Safety results were consistent with selective JAK-1 inhibition and highlight the favourable safety and tolerability of FIL in patients with RA.References:[1]Genovese, et al.JAMA2019;322(4):315–25.[2]Westhovens, et al.Ann Rheum Dis2017;76:998–1008.[3]Kavanaugh, et al.Ann Rheum Dis2017;76:1009–19.Disclosure of Interests:Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme, Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd., Alan Kivitz Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim,,Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, Franziska Matzkies Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Lei Ye Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Deyuan Jiang Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Ying Guo Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Beatrix Bartok Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, 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

Background The effectiveness of vedolizumab (VDZ), a monoclonal antibody targeting the α4β7 integrin, and ustekinumab (UST), an anti-interleukin-12/anti-interleukin-23 antibody, for the treatment of patients with inflammatory bowel disease (IBD) has been demonstrated. Nearly 50% of patients with IBD have extraintestinal manifestation(s) (EIM). The most frequent are rheumatologic. In contrast to the data available for infliximab (IFX), only retrospective or small studies with contradictory results have been published regarding the effect of VDZ or UST on IBD-associated articular manifestations. The aim of our study was to evaluate the effect of VDZ and UST used in the treatment of Crohn’s disease or ulcerative colitis on associated articular manifestations, compared with patients receiving IFX. Methods We conducted a single-centre observational prospective study. All consecutive patients diagnosed with IBD and treated with IFX, VDZ or UST were included and classified into two groups: group 1, not presenting articular manifestations at the baseline, and group 2, having articular manifestations at the inclusion. We evaluated the occurrence of articular manifestations assessed by the BASDAI score in group 1 and the evolution of articular manifestations according to the BASDAI score in group 2. EIM activity was assessed at months 0, 3, 6, 9 and 12. Improvement or worsening of joint manifestations was considered significant if the BASDAI decreased or increased by 10 mm or 20 % in relative value between its initial value and its last available value (M12 or earlier for patients with shorter follow-up times). Results From September 2017 to April 2019, 54 patients were included. Twenty-nine patients were analysed in group 1: 9 treated with IFX, 8 with VDZ and 12 with UST. During the follow-up period, 12 (41.4 %) patients in group 1 without EIM at baseline developed articular manifestations: 44.4 %, 50 % and 33.3 % respectively under IFX, VDZ and UST. The mean time from treatment initiation to the development of articular symptoms was 3.3, 3.8 and 2.6 months, respectively on IFX, VDZ and UST. Twenty-five patients were analysed in group 2, 6 treated with IFX, 7 with VDZ and 12 with UST. A significant improvement of the BASDAI score was observed in 50 % of patients treated with IFX, 71.4 % with VDZ and 41.7 % with UST. BASDAI scores were 31.2, 51.8 and 27.9 at M0 and 31.0, 44.7 and 27.5 on average over the entire follow-up for the following treatments respectively: IFX, VDZ and UST. Conclusion This prospective study suggests a potential beneficial effect of VDZ and UST on articular manifestations associated with IBD compared with IFX. However, these results need to be confirmed by larger prospective trials.

Introduction L’IL-6 joue un role important dans la physiopathologie du syndrome de Sjogren primaire (SJp), notamment via l’activation des lymphocytes B et la polarisation des lymphocytes T. Nous avons realise un essai randomise en double aveugle Tocilizumab versus placebo (ETAP, Efficacite et Tolerance du RoActemra au cours du syndrome de Sjogren Primitif) chez des patients ayant un SJp. Patients et methodes Les criteres d’inclusion etaient un SJp selon les criteres diagnostiques de l’AECG et un ESSDAI (score de complications systemiques) ≥ 5. Les patients ont recu 6 perfusions mensuelles de tocilizumab (8 mg/kg) ou de placebo. Le critere de jugement principal etait la reponse au traitement, evaluee a la semaine 24 (S24), sur un critere composite associant : – la diminution d’au moins 3 points de l’ESSDAI ; – l’absence d’apparition d’un nouveau domaine d’activite moderee ou severe de l’ESSDAI ; – l’absence d’aggravation ≥ 1/10 en evaluation globale du medecin. Le suivi etait poursuivi jusqu’a S44. Les donnees ont ete analysees par methode bayesienne en intention de traiter. Resultats Au total 110 patients ont ete inclus et randomises : 55 dans le groupe tocilizumab (98 % femmes, âge moyen 50,9 ans [26 ; 76], anti-SSA+ 84,7 %), et 55 dans le groupe placebo (90 % femmes, 54,9 ans [30 ; 80], anti-SSA+ 87,6 %). A l’inclusion, dans le groupe tocilizumab et dans le groupe placebo respectivement, l’ESSDAI moyen etait de 11,5 [5 ; 25] et 12,4 [5 ; 39] et l’ESSPRI moyen de 6,4 [2 ; 9] et 6,4 [1 ; 9]. Les proportions de patients repondeurs selon le critere d’evaluation principal a S24 etaient semblables : 54,2 % [41,3 ; 66,7] groupe tocilizumab versus 62,1 % [49,0 ; 74,1] groupe placebo, OR = 1,6 [0,3 ; 3,3]. L’ESSDAI moyen a S24 etait de 6,6 [4,7 ; 9,0] et de 5,4 [3,7 ; 7,6] dans le groupe tocilizumab et le groupe placebo, respectivement. La difference des variations d’ESSDAI par rapport a l’inclusion etait similaire dans les 2 groupes (interaction, 0,9 [−1,3 ; 3,2]). L’ESSPRI moyen a S24 etait de 6,0 [5,0 ; 7,0] et de 6,2 [5,2 ; 7,1] dans le groupe tocilizumab et le groupe placebo. La difference des variations d’ESSPRI par rapport a l’inclusion etait similaire dans les 2 groupes (0,1 [−0,4 ; 0,7]). Les variations du test de Schirmer a S24 versus j0 etaient similaires dans les deux groupes. La diminution du nombre d’articulations douloureuses et gonflees etait plus importante dans le groupe tocilizumab (de 7,4 [6,7 ; 8,1] a 3,6 [3,3 ; 3,9] et de 2,2 [1,8 ; 2,6] a 0,6 [0,5 ; 0,7], respectivement) que dans le groupe placebo (de 7,8 [7,1 ; 8,6] a 4,9 [4,6 ; 5,3] et de 2,4 [2,0 ; 2,8] a 1,3 [1,1 ; 1,5]) (interaction 1,2 [0,2 ; 2,7] et 0,8 [0,3 ; 1,4]). La proportion d’effets indesirables graves etait semblable dans les deux groupes. Conclusion Dans cette etude randomisee controlee versus placebo, le tocilizumab n’est pas superieur au placebo sur les principaux symptomes du SJp. Une certaine efficacite a ete observee sur les signes articulaires. L’importance de l’effet placebo, egalement observee avec d’autres biotherapies, souligne les limites des criteres actuels d’evaluation utilises dans le SJp.

Background:At a time when vaccines are being prioritized for individuals most at risk, there is currently no clear evidence that risk of SARS-CoV-2 infection is higher for patients with than without inflammatory arthritides (IA). Biologic use was not associated with worse COVID-19 outcomes for yet but the case of rituximab (RTX) remains an issue, given its immunological long term effect, the role of humoral response against SARS-CoV-2 and its indirect effect on T-cell response. A potential association between rituximab and worse COVID-19 outcomes was raised by case reports and retrospective, declarative studies (with few data on the total number of patients exposed).Objectives:To address differently the issue of the risk of COVID-19 related to RTX and limit biases, we examined the occurrence of severe COVID-19 in all patients receiving intravenous biologic agents at day-hospitals during the pandemic in France.Methods:From 1st September 2019 to 1st January 2021, we analyzed patients with IA prospectively treated with intravenous biologic agents (RTX, abatacept, infliximab or tocilizumab) in 7 clinical centers in France. We obtained the list of patients receiving intravenous biologic agents in each center from the pharmacist of the hospitals. Therefore, all consecutive patients receiving 1 of the 4 drugs at the time of the study were included in each center. Patients with no follow-up after September 2020 were systematically contacted by phone. The occurrence of a severe COVID -19 (i.e. resulting in death, hospitalization or increase in length of hospitalization related to COVID-19) was the primary outcome criteria.Results:In total, 1116 patients receiving intravenous biologic agents were included: 449 with infliximab, 392 RTX, 170 tocilizumab and 105 abatacept. From 1st September 2019, the median follow-up time was 15 months (interquartile range 14-16). In total, 10 cases of severe COVID-19 occurred, 9 treated with RTX and 1 with infliximab (supplementary Table 1). Four deaths occurred in our cohort during follow-up but none was related to COVID-19 (1 patient treated by tocilizumab, 1 by RTX and 2 by infliximab). In univariate analysis, the proportion of severe COVID-19 was significantly higher for patients receiving RTX than other biologic agents (9/392 vs 1/724, p=0.0003, OR [95%CI] 17.0 [2.1-134.6]). To take into account potential confounders, we performed multivariate analysis accounting for baseline parameters that differed between RTX and other biologic groups. RTX remained significantly associated with risk of severe COVID-19 (p=0.019) (Table 1).Patient characteristicsRituximab (n= 392)Other bDMARDs (n= 724)Univariate analysis, p-valueMultivariate analysis, p-valueMedian age (years), — [IQR]64 [56-71]57.3 [47.0-67.0]< 0.00010.51Female — n (%)285 (72.7)426 (58.8)< 0.00010.58IA diagnosis< 0.00010.12Median follow-up from 1st September to last news14 [13-15]15 [14-16]< 0.00010.86Confirmed severe COVID-19 cases —n (%)9 (2.3)1 (0.1)0.00030.019Comorbidities** (history of) — n (%) Cardiovascular disease60 (15.4)167 (23.1)0.00250.77 Chronic lung disease,92 (23.5)84 (11.6)0.00010.88Median BMI (kg/m2) — [IQR]25.8 [23.2-29.4]27.3 [23.4-31.2]0.0150.80Treatments — n (%) Methotrexate179 (45.8)322 (44.5)0.71 Leflunomide41 (10.5)39 (5.4)0.00230.43 Hydroxychloroquine35 (8.9)24 (3.3)0.00010.15 Glucocorticoids127 (41.8)100 (19.4)< 0.00010.36 Median dose (mg/day) — [IQR]1 [0-5]0 [0-0]< 0.0001No significant difference in terms of baseline gammaglobulins (p=0.46) or number of previous RTX infusions (p=0.57) was observed among patients receiving RTX with or without a severe COVID-19.Conclusion:The present results highly indicate increased risk of severe COVID-19 with RTX. Among patients with inflammatory arthritides, those receiving RTX should be prioritized for vaccination against SARS-CoV-2, sufficiently long before infusion/reinfusion and the immunization checked, or an alternative targeted therapy proposed.Acknowledgements:We thank Dr. Karine Demesmay and all the pharmacists who helped us for this study.Disclosure of Interests:Renaud FELTEN Speakers bureau: Abbvie, Biogen, BMS, Lilly, Novartis, Pfizer, Pierre-Marie Duret: None declared, Elodie BAUER: None declared, Marc Ardizzone: None declared, H Julien Djossou: None declared, Jean-Hugues Salmon: None declared, Cassandre Fabre: None declared, Julia Walther: None declared, Isabelle CHARY VALCKENAERE: None declared, marion geoffroy: None declared, Laurent Messer: None declared, Francis Berenbaum: None declared, Martin SOUBRIER: None declared, Jérémie SELLAM Speakers bureau: MSD, Pfizer, Abbvie, Roche, BMS, Lilly, Janssen, Novartis, Galapagos, Sandoz, Fresenius Kabi, Grant/research support from: Roche, MSD, Pfizer, Jacques-Eric Gottenberg: None declared

Background:Several large randomised controlled trials (RCTs) in primary Sjögren’s syndrome (pSS) failed to demonstrate drug efficacy.1-4 Many of these trials used ESSDAI as primary endpoint, showing large but similar response rates in active treatment and placebo groups.1,3,4 Given the heterogeneous nature of pSS, there is need for a composite endpoint including multiple clinically relevant parameters.Objectives:To develop and validate the Composite of Relevant Endpoints in Sjögren’s Syndrome (CRESS).Methods:A multidisciplinary team of pSS experts selected clinically relevant items and measurements to include in the CRESS. Definition of response of CRESS items was based on clinical relevance, previously defined minimal clinically important improvement (MCII) and data of the single-centre ASAP-III (abatacept) trial.1 CRESS was validated in three independent RCTs: TRACTISS (rituximab) trial2, multi-centre abatacept trial3 and ETAP (tocilizumab) trial4. CRESS response rates were assessed at the primary endpoint visit of all four trials.Results:Five complementary items were selected to form CRESS: systemic disease activity, patient-reported symptoms, tear gland, salivary gland and serological item. Definition of response per item is presented in Table 1. Total CRESS response was defined as response on ≥3 of 5 items. Since not all trials have ocular staining score or salivary gland ultrasonography (SGUS) available, the concise CRESS (cCRESS) was developed simultaneously, leaving Schirmer’s test and unstimulated whole saliva flow for the tear and salivary gland items, respectively. In the ASAP-III trial, CRESS response rates were 24/40 (60%) for abatacept vs. 7/39 (18%) for placebo at week 24 (pTable 1.CRESS items and definition of responseItemsMeasurementsDefinition of responseSystemic disease activityClinESSDAIScorePatient-reported symptomsESSPRIDecrease of ≥1 point or ≥15%Tear gland*Schirmer/OSS**-If abnormal Schirmer (≤5 mm) at baseline: increase of ≥5 mm in Schirmer-Or if abnormal OSS (≥3 points) at baseline: decrease ≥2 points in OSS-Or if both Schirmer/OSS normal scores at baseline: no change to abnormal in bothSalivary gland*UWS/SGUSIncrease of ≥25% in UWS (or if score is 0 at baseline, any increase)Or decrease of ≥25% in total Hocevar score (SGUS)SerologicalRF/IgGDecrease of ≥25% in RFOr decrease of ≥10% in IgGCRESS responderResponder on ≥3 of 5 itemsOcular Staining Score (OSS), Unstimulated whole salivary flow (UWS), Salivary gland ultrasonography (SGUS), Rheumatoid factor (RF), Immunoglobuline G (IgG)*Concise CRESS (cCRESS): CRESS without OSS and SGUS, leaving Schirmer and UWS for tear and salivary gland items, respectively**Mean of both eyesIn the external validation trials, cCRESS response rates for TRACTISS were: 33/67 (49%) rituximab vs. 20/66 (30%) placebo at week 48 (p=0.026). CRESS response rates (without SGUS) for the multi-centre abatacept trial were: 41/92 (45%) abatacept vs. 30/95 (32%) placebo at week 24 (p=0.067). cCRESS response rates (without rheumatoid factor) for ETAP were: 10/55 (18%) tocilizumab vs. 13/55 (24%) placebo at week 24 (p=0.482) (Figure 1A-D). Compared to ESSDAI MCII of ≥3 points decrease, CRESS was able to approximately halve placebo response rates in RCTs with high baseline ESSDAI scores (>5) (Figures 1E-H).Conclusion:CRESS shows lower placebo response rates compared to ESSDAI MCII, which is crucial for demonstrating treatment efficacy. With the CRESS, higher response rates in abatacept and rituximab treated patients compared to placebo were found in RCTs which previously showed negative primary endpoint results. CRESS confirmed that no differences were found for almost all outcome measures between tocilizumab and placebo,4 with low response rates. The CRESS is a well-balanced, feasible, composite endpoint for use in clinical trials in pSS patients.References:[1]Van Nimwegen 2020;9913(19):1–11[2]Bowman 2017;69(7):1440–50[3]Baer (doi:218599)[4]Felten (doi:21846)Acknowledgements:The authors would like to acknowledge all contributors of the included trials.Disclosure of Interests:Suzanne Arends: None declared, Liseth de Wolff: None declared, Jolien F. van Nimwegen Speakers bureau: Bristol Myers Squibb, Consultant of: Bristol Myers Squibb, Gwenny M. Verstappen: None declared, Jelle Vehof: None declared, Michele Bombardieri Consultant of: MedImmune, GlaxoSmithKline, Grant/research support from: MedImmune, Simon J. Bowman Consultant of: AstraZenecea/MedImmune, Bristol Myers Squibb, Celgene, Eli Lilly, Glenmark, GlaxoSmithKline, MTPharma, Novartis, Ono, Pfizer, Takeda, UCB, XTLBio, Elena Pontarini: None declared, Alan Baer Consultant of: Bristol Myers Squibb, Sanofi, VielaBio, Novartis, Marleen Nys Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Jacques-Eric Gottenberg Grant/research support from: Bristol Myers Squibb, Pfizer, Renaud FELTEN: None declared, Neelanjana Ray Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Arjan Vissink: None declared, Frans G.M. Kroese Speakers bureau: Bristol Myers Squibb, Roche and Janssen-Cilag, Consultant of: Bristol Myers Squibb, Grant/research support from: Unrestricted grants from Bristol Myers Squibb, Hendrika Bootsma Speakers bureau: Bristol Myers Squibb and Novartis, Consultant of: Bristol Myers Squibb, Roche, Novartis, Medimmune, Union Chimique Belge, Grant/research support from: Unrestricted grants from Bristol Myers Squibb and Roche

Background:Gout and psoriatic arthritis (PsA) can co-exist in the same patient. These 2 diseases seem strongly linked, but the pathophysiological mechanisms of this link have not yet been defined. Hyperuricemia could be an important determinant of PsA1.Objectives:To study the impact of hyperuricemia on clinical presentation, severity and associated comorbidities of PsA.Methods:We conducted a retrospective bicenter case–control study in Strasbourg and Colmar, France. Patients with PsA (according to “L40.5 arthropathic psoriasis” ICD-10 coding) and at least one available serum urate level measurement, were included from 2009 to 2019. Demographic, comorbidities, clinical and radiographic data were collected. Hyperuricemia was defined as serum urate level ≥ 360 µmol/L. We defined “good responders to ongoing PsA treatment” as patients with no outbreak of PsA, biological inflammatory syndrome and therapeutic modification at the last follow-up. Patients with “destructive” disease had one or more erosion(s) seen on standard X-ray, ultrasonography, MRI or TDM.Results:We included 242 patients. 73 (30.2%) had hyperuricemia and 15 (6.2%) met criteria for gout. On univariate analysis, as compared with normo-uricemic patients, hyperuricemic patients were more often male (72.6% vs. 39.1%, p = 1.6x10-06), had higher BMI (30.9 vs. 28.7 kg/m2, p = 0.015) and had more comorbidities (Charlson Comorbidity Index: 2.6 vs. 1.8, p = 0.005). In hyperuricemic versus normo-uricemic patients, PsA started at an older age (47.5 vs 43 years, p = 0.016); PsA was more polyarticular (56.2% vs 41.9%, p = 0.049) than axial (9.6% vs 22.8%, p = 0.019) and more destructive (52.8% vs. 37.4%, p = 0.032). Median uricemia was higher in patients with destructive than non-destructive PsA (321 vs 288.8 μmol/l, p = 0.0038), and hyperuricemia was more frequent with than without joint destruction (37.6% vs 25.8%, p = 0.047). The multivariate analysis confirmed hyperuricemia associated with peripheral joint involvement (OR 2.98, p = 0.025) and less good response to PsA treatment (OR 0.35, p = 0.024).Figure 1.Description of normo- and hyperuricemic psoriatic arthritisCRF: moderate to severe chronic renal failure. MACEs: major adverse cardiovascular events. HBP: high blood pressure. MetS: metabolic syndrome. PsA: psoriatic arthritisConclusion:Patients with hyperuricemic PsA have less good response to PsA treatment than those with normo-uricemia and more peripheral and destructive joint damage. Recognition of PsA in which hyperuricemia would play an aggravating role could modify the management. This would justify a diagnostic reassessment in case of doubt, the possible introduction of hypouricemic treatment and the careful use of NSAIDs in the context of multiple morbidities.References:[1]Felten R, Duret P-M, Gottenberg J-E, Spielmann L, Messer L. At the crossroads of gout and psoriatic arthritis: « psout ». Clin Rheumatol. Febr 2020.Acknowledgements:We thank all participating patients. We also thank the medical secretaries for their help with the ICD-10 extraction, and Dr Thomas Lavaux for helping with serum urate tests at Strasbourg University Hospital.Disclosure of Interests:None declared

Background:Vaccination is an important and effective tool to prevent infections in the general population as well as in patients with systemic autoimmune or inflammatory rheumatic diseases (AIIRDs) who may be at increased risk of serious infection. While the global race for vaccines against COVID-19 has already lead to first authorizations and vaccinations in some countries, multiple questions arise for access and provisions as well as for the acceptance of vaccine policies by immunocompromised patients.Objectives:We conducted an international survey about expectations and potential concerns regarding SARS-CoV-2 vaccine in patients with AIIRDs and healthcare professionals.Methods:The online study consisted of 57 questions which addressed determinants associated with SARS-2-CoV-2 vaccine willingness. Dissemination was ensured through social media and patient associations between December 12 and December 21, 2020.Results:The study included 1266 patients with AIIRDs and 265 healthcare professionals from 56 countries. SARS-CoV-2 vaccine willingness was reported by 54.2% of AIIRD patients (uncertainty in 32.2% and unwillingness in 13.6%) and 74.0% of healthcare professionals. In patients, the willingness to get vaccinated increased significantly with age (pSubject groupsPatientsHealthcare professionalsN1266265Age (years), median [IQR25-75]50 [40-61]40 [32.5-53]Female, n (%)1141 (90.1%)150 (56.6%)Male, n (%)115 (9.9%)115 (43.4%)Country, n (%) France320 (25.3%)159 (60%) UK345(27.3%)4 (1.5%) Chile123 (9.7%)4 (1.5%) USA114 (9.0%)7 (2.6%) Venezuela43 (3.4%)26 (9.8%) Spain57 (4.5%)3 (1.1%) Mexico53 (4.2%)3 (1.1%) Argentina45 (3.6%)8 (3.0%) Other*166 (13.1%)51 (19.2%)Rheumatic diagnosis, n (%)1266- Systemic lupus erythematosus492 (38.9%)- Spondyloarthritis176 (13.9%)- Rheumatoid arthritis160 (12.6%)- Giant cell arteritis / Polymyalgia rheumatica144 (11.4%)- Primary anti-phospholipid syndrome64 (5.1%)- Inflammatory myositis62 (4.9%)- Relapsing polychondritis45 (3.6%)- Other**123 (9.7%)--Health professionals, n (%)-265 Doctor-203 (76.6%) Nurse (or equivalent)-23 (8.7%) Nursing assistant-11 (4.2%) Other***-28 (10.6%)Associated comorbidities, n (%) Diabetes69 (5.5%)6 (2.3%) Hypertension267 (21.1%)24 (9.1%) Myocardial infarction, stroke, transient stroke60 (4.7%)1 (0.4%) Respiratory disease (asthma, chronic bronchitis, emphysema, etc.)169 (13.3%)13 (4.9%)Renal failure47 (3.7%)1 (0.4%)Obesity (BMI > 30)228 (18.0%)18 (6.8%)At least one associated comorbidity, n (%)588 (46.4%)50 (18.9%)Smoker, n (%)128 (10.2%)22 (8.3%) Current411 (32.7%)51 (19.2%) Past719 (57.1%)192 (72.5%) NeverUse of oral glucocorticoids, n (%)551 (56.1%)3 (1.1%)Immunocompromised$, n (%)770 (60.8%)0On a 0 to 10 scale, median8 (6-10)5 (3-8)[IQR25-75]9 (7-10)5 (1-8)−Afraid to get infected by SARS-CoV-2−Afraid to get a severe COVID-19Willing to get vaccinated (Yes / uncertain / No), %54.2 / 32.2 / 13.674.0 / 18.1 / 7.9Vaccine hesitancy, n (%)357 (28.2%)59 (22.3%)Conclusion:Data from this study are crucial to understand the main expectations and concerns regarding SARS-CoV-2 vaccination in patients with AIIRDs and healthcare workers and allow the identification of valuable strategies to increase vaccine coverage in those populations.Acknowledgements:We wish to acknowledge the crucial role of the following patient associations: LupusEurope (tweeter: @LupusEurope), Agrupacion Lupus Chile (@Lupus_Chile), RarasNoInvisibles (@Noinvisibles), Lupus UK, Lupus France, SPONDYL’ASSO, Spondyl(O)action, AFL+, in the dissemination of the survey. We are indebted to Gonzalo Tobar Carrizo (@pinkycito) for the Spanish translation of the survey, all patients, families, and health professionals for their kind participation in our study. We wish to thank Ms. Sylvie Thuong for her invaluable assistance.Disclosure of Interests:Renaud FELTEN Speakers bureau: Pfizer, Maxime Dubois: None declared, Manuel F. Ugarte-Gil Speakers bureau: Janssen and Pfizer, Jérémy Fort: None declared, Luc PIJNENBURG: None declared, Aurore Chaudier: None declared, Lou Kawka: None declared, Charlotte Costecalde: None declared, Hugo Bergier: None declared, Emmanuel Chatelus: None declared, Rose-Marie Javier: None declared, Christelle Sordet: None declared, Jacques-Eric Gottenberg Speakers bureau: Pfizer and Astra-Zeneca, Jean Sibilia Speakers bureau: Pfizer, Yurilis Fuentes-Silva: None declared, Laurent Arnaud Speakers bureau: Pfizer and Astra-Zeneca.

Background Response to disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is often heterogeneous. We aimed to identify types of disease activity trajectories following the initiation of a new biologic DMARD (bDMARD). Methods Pooled analysis of nine national registries of patients with diagnosis of RA, who initiated Abatacept and had at least two measures of disease activity (DAS28). We used growth mixture models to identify groups of patients with similar courses of treatment response, and examined these patients' characteristics and effectiveness outcomes. Findings We identified three types of treatment response trajectories: ‘gradual responders’ (GR; 3576 patients, 91·7%) had a baseline mean DAS28 of 4·1 and progressive improvement over time; ‘rapid responders’ (RR; 219 patients, 5·6%) had higher baseline DAS28 and rapid improvement in disease activity; ‘inadequate responders’ (IR; 103 patients, 2·6%) had high DAS28 at baseline (5·1) and progressive worsening in disease activity. They were similar in baseline characteristics. Drug discontinuation for ineffectiveness was shorter among inadequate responders (p = 0.03), and EULAR good or moderate responses at 1 year was much higher among ‘rapid responders’ (p, Highlights • This study examined disease activity trajectories in a multinational cohort of 3898 rheumatoid arthritis patients. • Growth mixture models identified three groups: gradual, rapid, and inadequate responders (GR: 91·7%, RR: 5·6%, IR: 2·6%). • At baseline, groups were similar in demographic and clinical characteristics, and moderately different in function and disease activity. • The groups had large difference in drug retention and in good or moderate response rate. Using nine national registries, this study of 3898 established RA patients initiating a new bDMARD identified distinct types of responders: gradual, rapid and inadequate responders. Neither socio-demographic nor clinical characteristics at baseline allowed the prediction of the type of response trajectory after treatment initiation, but effectiveness outcomes strongly differed, suggesting that these empirically derived subgroups have clinical relevance. As a major aim of precision medicine is to make anti-rheumatic therapy more personalized, the detection of responder types following initiation of a specific bDMARD underscores the need to find reliable predictors of trajectories to identify patients needing a distinct treatment strategy.

To investigate the role of rheumatoid factor (RF) positivity and antibodies against citrullinated peptides (ACPA) as predictors of abatacept (ABA) effectiveness in a large observational cohort of patients with rheumatoid arthritis (RA).

Introduction Dans la PR, l’EULAR recommande une approche « treat-to-target » avec pour objectif d’atteindre une faible activite ou une remission [1] . Pour les patients, la reduction de la douleur, de la fatigue, la preservation des fonctions physiques et l’amelioration de la qualite de vie (HRQoL) sont egalement des objectifs importants [2] . L’etude FINCH 2 ( NCT02873936 ) a montre que FIL, inhibiteur selectif per os de JAK1, associe a un medicament antirhumatismal synthetique conventionnel (csDMARD) a ameliore de maniere significative (vs PBO) les signes et symptomes de la PR chez des patients presentant une reponse insuffisante a ≥ 1 bDMARD [3] . De plus, une amelioration significative (vs PBO) du HAQ-DI a ete observe a S12 et S24 avec FIL 100 ou 200 mg [3] . Le but de cette analyse est d’evaluer par des questionnaires patients (PRO), l’amelioration de la douleur, de la fatigue et de la qualite de vie sous FIL dans l’etude FINCH 2. Patients et methodes Les patients inclus dans cette etude randomisee en double aveugle ont recu FIL 200 mg (n = 147), FIL 100 mg (n = 153) ou PBO (n = 148) en plus de leur traitement par csDMARD. Les PRO ont ete recueillis de maniere prospective a j1, S2, S4, S8, S12, S14, S16, S20 et S24 pour evaluer la douleur (EVA) ; a j1, S4, S12 et S24 pour evaluer la fatigue (FACIT–Fatigue) et la qualite de vie (SF-36). Resultats Au total, 448 patients ont ete randomises et traites, 381 (85,0 %) ont fini l’etude ( Fig. 1 ). Les valeurs moyennes (ET) des PRO a l’inclusion etaient : 67 (21,0) pour l’EVA douleur, 31 (7,89) pour la composante physique (PCS) du SF-36 et 44,3 (11,6) pour sa composante psychologique (MCS) et 24,4 (11,6) pour le FACIT. Une amelioration significative de l’EVA douleur a debute a S2 et s’est maintenue jusqu’a S24 pour les bras FIL vs PBO. Le score FACIT s’est significativement ameliore a S4, S12, S24 dans le bras FIL 200 mg et a S4 et S12 dans le bras 100 mg. Le sous-score PCS du SF-36 s’est significativement ameliore a S4, S12 et S24 dans les bras FIL vs PBO et le sous-score SF-36 MCS s’est significativement ameliore a S4 et S12 dans le bras FIL 200 vs PBO. Conclusion Associe a un csDMARD, le FIL a permis, chez des patients presentant une reponse insuffisante sous bDMARD, d’ameliorer rapidement et durablement la douleur, la qualite de vie et la fatigue evaluees a l’aide de scores patients valides.

Introduction Nous avons recemment observe une prevalence elevee de myosite a inclusion dans une cohorte de patients atteints de syndrome de Sjogren (SS) primaire. La signification du SS chez les patients ayant une myosite est inconnue. L’anticorps anti 5′-nucleotidase 1A cytosolique (cN1A) a recemment ete propose comme biomarqueur de myosite a inclusion mais cet anticorps est aussi frequent chez les patients ayant un SS. Son utilite pour le diagnostic de myosite a inclusion chez les patients atteints de SS et de myosite est inconnue. Ce travail a pour objectif de decrire la signification du SS chez les patients atteints de myosites. Patients et methodes Dans cette etude monocentrique, les donnees des patients repondant aux criteres EULAR/ACR 2017 de myosite, et evalues pour le SS (criteres ACR/EULAR 2016) ont ete analysees. Quatre-vingt-dix-neuf patients ont ete inclus, couvrant l’ensemble des sous-groupes de myosite EULAR/ACR 2017, avec un suivi median de 6 ans [extremes 1,0 a 37,5]. Les 34 patients ayant une myosite avec SS (myosite/SS + ) ont ete compares aux 65 patients ayant une myosite sans SS (myosite/SS-). Resultats Une myosite a inclusion etait presente chez 24 % des patients myosite/SS+ contre 6 % du groupe myosite/SS- (p = 0,02). Aucun des patients presentant une myosite a inclusion n’a repondu au traitement immunomodulateur, qu’il soit atteint de SS ou non. L’anti-cN1A etait plus frequent chez les patients myosites/SS+ (38 % contre 6 %, p = 0,0005), independamment de la prevalence plus elevee de myosite a inclusion dans ce groupe (valeur p multivariee : 0,02). La specificite des anticorps anti-cN1A pour le diagnostic de myosite a inclusion etait de 0,96 [IC 95 %, 0,87–0,99] dans le groupe myosite SS- mais de seulement 0,70 [IC 95 %, 0,48–0,85] dans le groupe myosite/SS+. Conclusion Chez les patients atteints de myosite, la presence d’un SS est associee a une plus forte prevalence de myosite a inclusion et de l’anticorps anti-cN1A de facon independante au diagnostic de myosite a inclusion. En consequence, l’anti-cN1A a une specificite basse pour le diagnostic de myosite a inclusion chez les patients atteints de myosite avec SS associe.

Introduction Des recommandations pour les patients atteints de maladies auto-immunes (MAI) ont ete emises face a la pandemie a COVID-19. Toutefois, l’impact d’une infection a SARS-CoV2 sur une MAI et sa prise en charge est mal connu. L’objectif de notre etude etait d’evaluer la prevalence et les facteurs predictifs d’infection a SARS-CoV2 ainsi que le risque de poussee inflammatoire chez les patients atteints de MAI et systemique rares (MAISR). Patients et methodes Les patients presentant une MAISR (lupus, Sjogren, myosites inflammatoires, sclerodermie systemique, vascularites et autres connectivites) et suivis dans notre Centre national de reference ont ete contactes par telephone (3 appels en l’absence de reponse) et invites a repondre a un questionnaire standardise evaluant : les facteurs de risque d’exposition et de severite au SARS-CoV2, la prevalence des symptomes evocateurs, la documentation de l’infection ainsi que les informations concernant la MAISR, son traitement et une eventuelle poussee de celle-ci. Chaque participant recevait une ordonnance pour realiser une serologie SARS-CoV2. L’enquete telephonique a eu lieu entre le 9 avril et le 2 juillet 2020. Celle de seroprevalence entre le 18 mai et le 2 juillet 2020. Resultats Au total, 1232 patients ont ete contactes. Parmi eux, 7 n’ont pas pu etre joints (5 deces anterieurs au COVID et 2 demenagements a l’etranger) et 171 ont ete exclus (58 absences de consentement, 110 presentant une autre maladie, 3 non suivis dans notre centre). Un total de 1054 patients a ete analyse avec des donnees serologiques pour 469 (44,5 %). Il s’agissait de 840 femmes (79,6 %) d’âge median 53 ans ([IQR25–75] 38–65) et suivis pour lupus (n = 205, 19,5 %), syndrome de Sjogren (n = 189, 17,9 %), sclerodermie systemique (n = 159, 15,1 %), myopathies inflammatoires (n = 113, 10,7 %), arthrite juvenile idiopathique (n = 110, 10,4 %), vascularites (n = 94, 8,9 %) et d’autres MAISR (n = 184, 17,5 %). Au total 201 patients (19,1 %) ont rapporte des symptomes evocateurs de SARS-CoV2 mais seuls 40 sur les 495 disposant de donnees de RT-PCR, scanographiques ou serologiques avaient une infection prouvee (8,1 %) : par RT-PCR (n = 14), TDM pulmonaire (n = 6) ou serologie (n = 31). Parmi eux, seulement 3 patients avaient consulte aux urgences et 3 avaient ete hospitalises dont 1 en reanimation. Parmi les 146 patients rapportant des symptomes evoquant un COVID-19 et dont les resultats de PCR, TDM et/ou serologie etaient disponibles, seuls 34 (23,3 %) avaient une infection confirmee. L’arret de travail preventif (ATP) n’etait pas statistiquement protecteur de l’infection a SARS-CoV2 (5,8 % si ATP vs 8,1 %, p = 0,78). L’infection a SARS-CoV2 etait statistiquement associee a la modification du traitement de fond de la MAISR (27,5 % de modifications en cas de COVID confirme vs 6,8 % p Conclusion Cette enquete systematique chez plus de 1000 patients atteints de maladie auto-immune systemique rare rapporte une faible prevalence d’infection prouvee a SARS-CoV2 (8,1 %), probablement en rapport avec une bonne observance des mesures prophylactiques chez ces patients. L’interruption des traitements immunosuppresseurs s’accompagne d’un sur-risque important de poussee justifiant les recommandations actuelles.

Introduction Le traitement par l’inhibiteur du TNF etanercept (enbrel) (ETA) des patients atteints de polyarthrite rhumatoide (PR) est efficace mais une proportion (30–40 %) de ces patients ne repond pas ou de facon insuffisante a ce traitement. L’ETA, un TNF-R2, fixe le TNF ainsi que la lymphotoxine–a (LTa). Le dosage du TNF, de la LTa et du medicament peuvent etre des elements permettant de predire la reponse therapeutique ou de l’expliquer sur un plan physiopathologique. Patients et methodes Nous avons utilise les donnees du registre ROC (Rotation or Change of Biotherapy After First Anti-TNF Treatment Failure for Rheumatoid Arthritis) afin d’evaluer les concentrations seriques d’ETA, de TNF et de LTa en fonction de la reponse therapeutique. Resultats Nous avons observe que les concentrations en TNF et en LTa etaient significativement plus elevees dans le serum des patients repondeurs (R) que ceux des non-repondeurs (NR) au traitement par ETA. De plus, les concentrations d’ETA etaient plus elevees chez les R que les NR apres 6 mois de traitement, en accord avec les resultats de Daien et al. [1] . Faisant l’hypothese d’une biodistribution de l’ETA differente chez les patients en fonction de leur indice de masse corporelle (IMC), nous avons evalue celui-ci mais n’avons pas trouve de correlation avec la reponse therapeutique, contrairement a ce qui ete rapporte dans la litterature. L’explication d’une concentration plus elevee d’ETA reste donc a evaluer. Nos experiences montrent une stabilisation du TNF en presence d’ETA in vitro. Ceci pourrait expliquer l’augmentation serique du TNF en presence de concentrations plus elevees d’ETA chez les repondeurs. Conclusion Nos futures etudes auront pour but de comprendre les mecanismes pouvant expliquer l’augmentation serique d’ETA et, par consequent, l’augmentation de TNF et LTa chez les patients repondeurs au traitement.

Introduction Dans le cadre d’un programme clinique compose de 4 essais de Phase 3 (FINCH 1-4 : NCT02889796 , NCT02873936 , NCT02886728 , NCT03025308 ) et 3 essais de Phase 2 (DARWIN 1–3 : NCT01668641 , NCT01894516 , NCT02065700 ), FIL, inhibiteur selectif de JAK1 per os, a entraine une amelioration statistiquement et cliniquement significative des signes et symptomes, de la fonction physique, de la progression radiographique et de la qualite de vie de patients [pts] atteints de PR active 1–3. Patients et methodes Les evenements indesirables apparus sous traitement [EIAST] ont ete integres et presentes pour les pts ayant recu FIL 200 mg 1 fois/j ou FIL 100 mg 1 fois/j (y compris les pts qui ont switche du placebo [PBO], du methotrexate [MTX] ou de l’adalimumab [ADA] ou d’une autre dose de FIL au FIL 100 ou 200 mg/j) ainsi que les pts ayant recu PBO, MTX et ADA dans les 7 etudes. Les taux d’incidence ajustes a l’exposition [TIAE] pour 100 patients-annee [p-a] ont ete calcules pour les evenements indesirables [EI] d’interet de chaque traitement. Resultats Dans les 7 essais, 4057 pts atteints de PR (2227 pts FIL 200 mg, 1600 pts FIL 100 mg, 325 pts ADA, 416 pts MTX et 781 pts PBO) ont recu > 1 dose de traitement pour une exposition totale de 5493 p-a. Les TIAE des EI graves et des EIAST entrainant le deces chez les patients ayant recu FIL ont ete comparables a ceux des patients ayant recu PBO, ADA ou MTX, sans effet dose-dependant. Le TIAE du zona a ete globalement faible, numeriquement superieur sous FIL a ADA et PBO, similaire au MTX : TIAE FIL 200 mg : 1,7 ; intervalle de confiance [IC] a 95 % : 1,3-2,3, FIL 100 mg : 1,1 ; IC : 0,7-1,8, ADA : 0,7 ; IC : 0,2-2,8, MTX : 1,1 ; IC : 0,4-3,0, PBO : 1,0 ; IC : 0,3-3,1. Les TIAE des infections graves ont ete comparables entre FIL 100 mg (3,3 ; IC : 2,2-4,9) et ADA (3,4 ; IC : 1,9-6,4), et numeriquement inferieurs pour FIL 200 mg (1,7 ; IC : 1,3-2,3) et MTX (2,2 ; IC : 1,1-4,5). Les taux d’infections opportunistes (y compris la tuberculose active) ont ete globalement faibles ; les TIAE pour FIL 100 mg (0,3 ; IC : 0,1-0,7) et FIL 200 mg (0,1 ; IC : 0,0-0,3) ont ete comparables au PBO et numeriquement inferieurs a ADA (0,7 ; IC : 0,2-2,8) ou MTX (0,6 ; IC : 0,1-2,2). Les taux d’evenements cardiovasculaires indesirables graves et de thromboembolie veineuse ont ete numeriquement inferieurs sous FIL vs PBO. Les tumeurs malignes, y compris les cancers de la peau hors melanomes, ont ete globalement rares, et les taux ont ete faibles chez les patients ayant recu FIL. Conclusion FIL a ete bien tolere et aucune nouvelle toxicite n’a ete identifiee. Les resultats de tolerance sont concordants avec l’inhibition selective de JAK1 et mettent en avant le profil de tolerance favorable du FIL chez les patients atteints de PR.

Background:Little is known about autoimmune myelofibrosis (AIMF), a rare entity that can occur alone or in association with another autoimmune disease (AID) and is responsible for bone marrow (BM) failure and life-threatening complications.Objectives:We conducted a nationwide retrospective observational study of AIMF cases to better characterize the epidemiology, clinical presentation and evolution of this rare entity.Methods:The aim of the study was to analyze the characteristics of AIMF and the nature and indication of treatments currently used. Response to treatment was evaluated by the revised Tefferi et al. response criteria.Results:Among 30 cases of AIMF, the sex ratio (F/M) was 4:1 and the median age at diagnosis was 37 years (interquartile range 30–49). AIMF was diagnosed after the onset of an associated AID in 12 cases and concomitant to an AID in the remaining 18 cases. The most frequently associated AID was systemic lupus erythematous, followed by Sjögren syndrome. All cases consisted of reticulin fibers, and no collagen fibrosis was described. More than 50% of cases showed complete response after first-line therapy, with glucocorticoids (GC) in 28 cases. Half of the cases had treatment complications mainly related to GC therapy.Conclusion:Diagnosis of AIMF remains challenging in the absence of a validated set of diagnosis criteria, and must always be searched in the presence of hematological abnormalities at onset or during follow-up of AID. Clinical context, search for mutations and pathology findings can help differentiating this rare disease from a clonal pathology. GC is currently an effective first-choice therapy for AIMF, but a high rate of GC dependency and long-term complications indicate the need to find new sparing drugs.Disclosure of Interests:PHILIPPE MERTZ: None declared, Emilie Chalayer: 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, Anne-Sophie Korganow: None declared, Laurent Arnaud: None declared, Thierry Martin: None declared

Background:There are discordant results regarding a potential increased risk of gastro-intestinal perforation (GIP) in rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ) compared to conventional synthetic disease modifying anti rheumatic drugs (csDMARDs) or TNF inhibitors (TNFis) (1–3).Objectives:The aim of our study was to compare the risk of diverticulitis and GIP in RA patients treated with TCZ compared to rituximab (RTX) and abatacept (ABA).Methods:We conducted a multicentric study of patients with RA, prospectively followed in 3 observational French registries evaluating the effectiveness and safety of RTX (Autoimmunity and Rituximab (AIR)), ABA (Orencia and Rheumatoid Arthritis (ORA)), and TCZ (REGistry–RoAcTEmra (REGATE)). Using a propensity score approach, we compared the risk of diverticulitis or GIP during treatment with TCZ vs RTX and ABA. The following covariates were included in the propensity score: age, sex, history of diabetes and neoplasia, Charlson Comorbidity Index, number of previous csDMARDs and TNFi, history of TNFi, daily dose of glucocorticoids (GCs) at baseline, co-treatment with a csDMARDs, average DAS28 during follow-up, duration of RA, and exposure time to the considered bDMARDs.Results:4501 patients (1496 treated by TCZ, 1986 by RTX and 1019 by ABA) were included. 21 and 9 GIP occurred in the TCZ treated patients, compared to 10 and 8 in the RTX treated patients and 10 and 2 in the ABA treated patients (corresponding incidence rate (IR) are shown in table 1). Two deaths occurred in patients experiencing GIP: 1 (12.5%) due to undetermined rectal perforation among a RTX treated patient, and 1 (11.1%) due to a perforated ulcer among a TCZ treated patient. Based on inverse probability weighting (IPW), there was an increased risk of diverticulitis and GIP in the TCZ treated patients compared with RTX or ABA (table 1). In a subgroup analysis, we confirmed an increased risk of GIP due to diverticulitis but not to any other etiology. Older age (p=0.05), GCs at baseline (p=0.10) and average daily dose of GCs during follow-up (p=0.08) seemed associated with GIP only in univariate analysis. Compared to RTX and ABA, diverticulitis and GIP among TCZ patients occurred earlier after the last perfusion (p=0.01), with atypical clinical presentation (slow transit in 30%, p=0.04) and lower acute phase reactants when the event occurred (C-reactive protein: 31.2±58.4 vs 88.2±89.6 mg/L, p=0.005). Perforated diverticulitis seemed to have higher dose of GCs at the time of the event compared to diverticulitis without perforation in univariate analysis (p=0.06).Table 1.Incidence (/1000 PY) and risk of diverticulitis or GIPAE (n)IRAE (n)IRAE (n)IRIPW analysisOR[95 CI]pOR[95 CI]pExposition (PY)TCZ (ref)3 990RTX6 322ABA2 389TCZ vs RTXTCZ vs ABADiverticulitis215.3101.6104.24.5[2.6-7.6]3.4[1.7-6.5]GIP92.381.320.82.8[1.5-5.1]0.0015.4[1.4-19.9]0.01*Diverticular GIP61.530.520.83.8[1.7-8.5]0,0016.9[1.9-25.4]0.004*Due to another etiology30.750.8001.4[0.5-3.9]0.5--AE=adverse events; PY=person-yearsConclusion:TCZ was associated with an increased risk of diverticulitis, and GIP due to diverticulitis, compared to RTX and ABA. Our study confirms an increased risk of GIP in RA patients treated with TCZ, which might be explained by an increased risk of diverticulitis with misleading clinical presentation.References:[1]Strangfeld A et al. Ann Rheum Dis. 2016 Jul 12[2]Xie F, Yun H et al. Arthritis Rheumatol. 2016 May 1[3]Barbulescu A et al. OP0231, Ann Rheum Dis. 2018 Jun 1;77(Suppl 2):164–5.Disclosure of Interests:Claire Rempenault: None declared, Cédric Lukas: 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, Thierry Schaeverbeke: None declared, Daniel Wendling: None declared, Thao Pham Speakers bureau: Novartis, Janssen, Lilly, Xavier Mariette Consultant of: BMS, Gilead, Medimmune, Novartis, Pfizer, Servier, UCB, 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, Jacques Morel: None declared

Background:Sarilumab, an anti-IL-6R antibody, is approved for the treatment of moderate to severe RA and shown efficacy on disease activity and patient-reported outcomes (PROs). Detailed analyses of drug efficacy from the patient point of view is important. SariPRO is a pragmatic interventional study close to the daily practice.Objectives:To assess the effectiveness of sarilumab on several PROs using the RAID (Rheumatoid Arthritis Impact of Disease) score.Methods:The SariPRO study (NCT 03449758) was a French multicenter interventional study assessing the effects of sarilumab 200 mg on PROs in patients with moderately to severely active RA with an inadequate response or intolerance to conventional synthetic or biologic DMARDs. The primary endpoint was change in total RAID score from baseline to week 24 (RAID ranges 0-10 where 10 is maximal impact). Changes from baseline for RAID, DAS28-ESR and CDAI according to baseline disease activity were analyzed as secondary outcomes. Safety was assessed by monitoring adverse events (AE). All statistical analyses were descriptive, 95% CI was given when appropriate.Results:84 patients were included in 31 centers and 62 were evaluable and analyzed for effectiveness. They had similar characteristics to the 84 patients at baseline and were as expected for an RA population initiating a biologic: mean (SD) age: 59.9 (12.4) years, 71.0% female, disease duration 9.7 (10.3) years, rheumatoid factor positivity 82.5%, ACPA positivity 86.4%, and DAS28=4.9 (11). Total RAID score decreased significantly from 5.7 (2.0) at baseline to 3.3 (2.5) at W24; mean change was -2.4 [95% CI: -3.0; -1.8]. Furthermore, this improvement was noted both for highly and less active patients at baseline: for patients with DAS28-ESR < 5.1 (n=31), mean change was -1.56 [-2.28; -0.83] and for patients with DAS28-ESR≥5.1 (n=27), mean change was -1.98 [-2.91; -1.05]. Changes in DAS28-ESR and CDAI were significant (-2.8 [-3.2; -2.4] and -15.2 [-18.5; -11.8], respectively). AEs were consistent with the safety profile of anti-IL-6R antibodies and with results from RCTs (data not shown).Conclusion:In this real world study, treatment with sarilumab during 24 weeks in RA patients led to an improvement in the total RAID score irrespective of baseline levels of disease activity. This is the first time RAID score is used as the primary endpoint in a study.References:[1]Study was sponsored by Sanofi GenzymeDisclosure of Interests:Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, René-Marc Flipo Consultant of: Johnson and Johnson, MSD France, Novartis, Sanofi, Speakers bureau: Johnson and Johnson, MSD France, Novartis, Sanofi, Thierry Schaeverbeke: None declared, Christine Albert: None declared, Athan Baillet Consultant of: Athan BAILLET has received honorarium fees from Abbvie for his participation as the coordinator of the systematic literature review, marie-Christophe Boissier: None declared, Cyrille Confavreux: None declared, Gregoire CORMIER: None declared, Emmanuelle Dernis Speakers bureau: Lilly, Novartis, Elisabeth Gervais Solau: None declared, Sophie Godot: 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, 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, Slim Lassoued: None declared, Thierry Lequerre: None declared, Frederic Lioté Consultant of: CME: Nordic Pharma, Christian Marcelli: None declared, Yves Maugars: None declared, Minh Nguyen: None declared, Aleth Perdriger: None declared, Yves-Marie Pers: None declared, Edouard Pertuiset: None declared, Lucile Poiroux: None declared, Carole Rosenberg: None declared, Christian Roux: None declared, Adeline Ruyssen-Witrand Grant/research support from: Abbvie, Pfizer, Consultant of: Abbvie, BMS, Lilly, Mylan, Novartis, Pfizer, Sandoz, Sanofi-Genzyme, Martin SOUBRIER: None declared, Pascale Vergne-Salle: None declared, Charles Zarnitsky: None declared, Eric Fakra Consultant of: Janssen, Lundbeck, Otsuka, Sanofi, Hubert MAROTTE Grant/research support from: Bristol Myers Sqibb, Lilly France, MSD, Novartis, Nordic Pharma, Pfizer, SanofiAventis, Consultant of: AbbVie, Amgen, Bristol Myers Sqibb, Lilly France, MSD, Novartis, Nordic Pharma, Pfizer, SanofiAventis, Paid instructor for: Sanofi-Aventis, Speakers bureau: Sanofi-Aventis, Florence E Lévy-Weil Employee of: Sanofi Genzyme employee

Objectives:To assess long term efficacy of tocilizumab in treatment-naive patients with Takayasu arteritis (TAK).Methods:In this multicenter, prospective, open-labelled trial, we aim to evaluate the benefit of adding tocilizumab to steroids in treatment-naïve patients with TAK, on discontinuation of steroids after 6 months of tocilizumab treatment, and to assess relapse-free survival following tocilizumab discontinuation.Results:Thirteen patients with TAK were included, with a median age of 32 years [19-45] and 12 (92%) females. Six (54%) patients met the primary end-point. Among 11 (85%) patients which achieved remission at 6 months, 6 (54%) have reached primary endpoint.. Among the 5 remaining patients which continued steroids, 3 had a prednisone-equivalent dosage < 5mg/day. A significant decrease of disease activity was observed after 6 months of tocilizumab therapy: decrease of median NIH scale (3 [3-4] at baseline, versus 1 [0-2] after 6 months; p No severe AEs were considered related to study treatment and none required tocilizumab interruption or dose reduction. No deaths have occurred during the study period.Conclusion:Tocilizumab seems an effective steroid sparing therapy in TAK but its effect appears to be suspensive.Disclosure of Interests:Arsene Mekinian: None declared, david Saadoun: None declared, jerome.connault@chu-nantes.fr jerome.connault@chu-nantes.fr: None declared, i-quere@chu-montpellier.fr i-quere@chu-montpellier.fr: None declared, Patrick Jégo: None declared, nicolas.limal@aphp.fr nicolas.limal@aphp.fr: None declared, wxv wxv: 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, Mathieu Vautier: None declared, lea.savey@aphp.fr>; lea.savey@aphp.fr>;: None declared, Patrice cacoub: None declared, olivier fain: None declared

Background:Cutaneous involvement is common during primary Sjogren’s Syndrome (pSS) but prevalence and characteristics are difficult to establish precisely because of the limited number of patients studied in most cohorts, the variability of the disorders evaluated in each cohort, the rarity of some of them, and the heterogeneity of evaluations from previous studies (1).Objectives:To determine the prevalence and significance of dermatological disorders in primary Sjogren Syndrome.Methods:We use 2 French cohorts (ASSESS, in which prevalence of skin disorders in 395 pSS patients was evaluated, and diapSS in which 91 consecutive 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 out of 100).Results:Skin manifestations included in the ESSDAI were rare in the ASSESS cohort (n=16/395, 4.1%, mainly purpuras; only 3 had high activity) but associated with activity in the other ESSDAI domains (peripheral neurological (p50; 48.2%) and that these dry skin patients had higher pain VAS (61.5+/-28.2 vs 46.8+/-27.0; p=0.003) and drought (79.4+/-15.2 vs 62.5+/-21.7; pCutaneous involvementNo Cutaneous involvementTotalp values*Muscular3/16 (18.8)10/373 (2.7)13/389 (3.3)0.001Peripheral nervous system PNS4/16 (25)34/373 (9.1)38/389 (9.8)0.00001Biological8/16 (50)138/371 (37.2)146/387 (37.7)0.017Hematologic7/16 (43.8)55/373 (14.7)62/389 (15.9)0.017History of arthritis12/16 (75)154/374 (41.2)166/390 (42.6)0.008History of splenomegaly2/16 (12.5)10/3762.7)12/392 (3.1)0.024History of lymphoma0/16 (0)18/379 (4.7)18/395 (4.6)0.372Mean (SD) ESSDAI score14.5 (6.8)4.4 (5.1)0.00001Mean (SD) ESSDAI score after excluding the points awarded by skin manifestations8.1 (6.2)4.4 (5.1)0.014Gammaglobulin levels (mean +/- SD)23.1 +/-7.318.5 +/-8.1-0.006Conclusion:The most common skin disorder is dryness, which is associated with a higher level of pain and overall subjective dryness. ESSDAI skin activity is rare, associated with hypergammaglobulinemia and ESSDAI activity. Systematic dermatological examination is informative for non-specific pSS lesionsReferences:[1]Orgeolet L, Foulquier N, Misery L, Redou P, Pers J-O, Devauchelle-Pensec V, et al. Can artificial intelligence replace manual search for systematic literature? Review on cutaneous manifestations in primary Sjögren’s syndrome. Rheumatol Oxf Engl. 2019 Aug 31;Disclosure of Interests:Camille Villon: None declared, Laure Orgeolet: None declared, Anne-Marie Roguedas-Contios: None declared, Laurent Misery: 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, Divi Cornec: None declared, Sandrine Jousse-Joulin: None declared, Raphaèle Seror Consultant of: BMS UCB Pfizer Roche, Jean-Marie Berthelot: None declared, Philippe Dieudé: None declared, Jean-Jacques Dubost: None declared, anne-laure Fauchais: None declared, Vincent Goeb: None declared, Eric Hachlla: None declared, Pierre-Yves Hatron: None declared, Claire Larroche: None declared, Gilles Hayem: None declared, Véronique LE GUERN Grant/research support from: UCB for GR2 study (to our institution), Aleth Perdriger: None declared, Jacques Morel: None declared, Olivier VITTECOQ: None declared, Xavier Mariette Consultant of: BMS, Gilead, Medimmune, Novartis, Pfizer, Servier, UCB, Valerie Devauchelle-Pensec: None declared, alain saraux: None declared

Background:Objectives:To describe current management and outcome of septic arthritis on native joint in French rheumatology departments.Methods:Retrospective, nation-wide multicentric study. 127 French rheumatology departments were contacted to report 10 successive cases of septic arthritis on native joint that occurred between the 01/01/16 to 31/12/17 (excluding mycobacteria). Characteristics, diagnosis procedure, therapeutic management and outcome were recorded.Results:52 centers included 363 patients (mean age 64± 18.7 years, mean Charlson comorbidity index 4±3). 28.3% patients had a preexisting arthropathy on affected joint. Monoarthritis was observed in 89.6% patients, knee was the most frequent site (38.9%). The most frequent pathogens wereStaphylococcus sp(50.7%) andStreptococcus sp.(23.3%). Bacteremia was found in 156 (45.1%) patients and endocarditis in only 12 (3.0%). Management was heterogeneous. All patients received antibiotics for a mean duration of 46.7±22 days (including intravenous route: 17.3±15.4 d). An initial monotherapy was administered in 42.3% of patients. Surgical procedure (mostly lavage 70.6%) was performed in 171 (48.3%), joint immobilization in 128 (35.3%) (median duration of 21.7±14.1 days). 94 (29.2%) patients have had serious complications including 29 (9.5%) death. Factors associated with death are reported in the table.Conclusion:This study shows that management of septic arthritis is very heterogenous with a still high rate of morbidity and mortality. We identified age, comorbidities, bacteremia and recent antibiotherapy were associated with mortality. Of note, duration of antibiotics was not. Thus, new guidelines are needed in order to facilitate septic arthritis management.Table:FactorsSurvivor(N=276)Dead(N=29)Univariate analysispAdjusted Odds ratio (95%IC)Multivariate analysispAge65 (16-97)82 (32-98)1,07 (1,03-1,12)< 0.001Charlson’s index1 (0-12)2 (0-9)0,00011,3 (1,05-1,63)0,018Delay before antibiotic initiation8,5 (0-310)5 (0-75)0,04840,99 (0,96-1,02)0,562Corticosteroid in the previous 3 months13,9%33,3%0,01842,56 (0,75-8,74)0,133Bacteriemia42,4%71,4%0,00615,07 (1,4-18,370,013Antibiotics in the previous 3 months26,6%56,6%0,00566,7 (2,04-22,01)0,002Disclosure of Interests:Pauline Richebé: None declared, Sophie Godot: None declared, Guillaume Coiffier: None declared, Pascal GUGGENBUHL: None declared, Denis Mulleman: None declared, Marion Couderc: None declared, Emmanuelle Dernis Speakers bureau: Lilly, Novartis, Valentine Deprez: None declared, Carine Salliot: None declared, Saik Urien: None declared, Rachel Brault: None declared, Adeline Ruyssen-Witrand Grant/research support from: Abbvie, Pfizer, Consultant of: Abbvie, BMS, Lilly, Mylan, Novartis, Pfizer, Sandoz, Sanofi-Genzyme, Emmanuel Hoppe: 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, Christian Roux: None declared, Sebastien Ottaviani: None declared, Maxime Breban: None declared, Marie Beaufrere: None declared, Alexia Michaut: None declared, Loic Pauvele: None declared, Christelle Darrieutort: None declared, Daniel Wendling: None declared, Pascal COQUERELLE: None declared, Géraldine Bart: None declared, Elisabeth Gervais: None declared, Vincent Goeb: None declared, Marc Ardizzone: None declared, Edouard Pertuiset: None declared, Sophie Derolez: None declared, Jean Marc Ziza: None declared, René-Marc Flipo Consultant of: Johnson and Johnson, MSD France, Novartis, Sanofi, Speakers bureau: Johnson and Johnson, MSD France, Novartis, Sanofi, Raphaèle Seror Consultant of: BMS UCB Pfizer Roche