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Background:Methotrexate (MTX) is the first line standard of care for the management of rheumatoid arthritis (RA). In the event of an inadequate response to MTX and the presence of a poor RA prognosis factor, recommendations include initiation of biological (bDMARD) or synthetic (tsDMARD) targeted therapy in combination with MTX.Objectives:STRATEGE2 aims to establish the maintenance of MTX within two years after initiating a first targeted therapy.Methods:STRATEGE2 is a non-interventional study including RA patients treated with MTX for at least 3 months (M) and requiring initiation of a first b/tsDMARD due to disease activity. MTX maintenance was evaluated 12M (primary endpoint) and 24M after initiation of targeted therapy. Non-maintenance is defined as: permanent discontinuation of MTX and/or dose reduction and/or transition from the subcutaneous (SC) to oral (PO) route. To identify potential predictors of MTX maintenance, univariate and multivariate analysis were applied.Results:Between Feb. 2019 and Dec. 2020, 53 French sites enrolled 180 RA patients, with 173 patients being followed up at 12M and 157 at 24M. At baseline: 75.1% women, mean age 56.1±13.7 years, average duration of diagnosis 5.6±7.3 years, MTX treatment for an average duration of 4.3±5.4 years. The majority (72.3%) received MTX via SC with an average dose of 18.8±4.2 mg/week. And 50.0% of patients received associated corticosteroid therapy (CS) at a mean dose of 9.6±6.0 mg/day.MTX treatment characteristics (dose in mg/week±SD and SC administration in %) changed from 17.8±4.5 - SC: 66.3% at baseline to 15.9±4.5 - SC: 54.9% at 12M, then 15.8±4.6 - SC: 55.9% at 24M. Based on the composite endpoint, MTX maintenance remained unchanged for 39.9% of patients at 12M and 34.4% at 24M. MTX was discontinued at 12M and 24M in 16.8% and 24.8% of patients respectively (cumulative). MTX modifications at 12M and 24M were: dose reduction 2.9% and 2.5%, change of route (SC to PO) 26.0% and 23.6% or both strategies 14.4% and 14.6%.Therapeutic adaptations were noted for b/tsDMARDs from inclusion to 12M and 24M: For anti-TNF, the changes were 57.6%, 46.5%, and 40.9%. For anti-IL6 or IL17, the changes were 12.8%, 17.0%, and 20.5%. Other b/DMARDs exhibited changes of 19.2%, 19.5%, and 21.2%. For tsDMARDs, changes were observed at 10.5%, 17.0%, and 17.4%.Use of CS (% and dose in mg/day±SD) remains high with 47.1%; 9.3±7.5 at inclusion, 39.0%; 8.9±9.0 at 12M, then 37.8%; 9.3±9.3 at 24M.Finally, since inclusion, RA activity measured by DAS28 and HAQ (mean±SD) improved at 12M and stabilized at 24M. Specifically, DAS28 improved from 4.3±1.2 at baseline to 2.6±1.1 at 12M and further to 2.4±1.1 at 24M. HAQ improved from 1.0±0.7 at baseline to 0.8±1.0 at 12M and remained stable with 0.8±1.0 at 24M.Uni- and multivariate analysis indicated that age (OR=1.04, 95% CI [1.01; 1.07], p <0.020) and disease activity’s patients assessment (VAS) (OR=1.02 95% CI [1.00; 1.04], p <0.047) are parameters associated with MTX maintenance.Conclusion:Many therapeutic adaptations were observed in the two years following the initiation of b/tsDMARD. Twenty-four months after the introduction of b/tsDMARD, MTX was adjusted (reduction in dosage and/or return to the PO route) for almost 41% of patients. More than 3 out of 4 patients continued to use MTX as a combination therapy and more than 1 out of 3 did not require any adaptation. These practices are in line with the latest EULAR guidelines [1] which recommend the combination of b/tsDMARDs with MTX.REFERENCES:[1] Smolen JS, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis 2023;82:3–18.Acknowledgements:NIL.The authors wish to acknowledge RCTs for their contribution to the statistical analysis, the investigators, centres and patients.Disclosure of Interests:Cécile Gaujoux-Viala AbbVie; Amgen; Boehringer Ingelheim, Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; UCB Pharma and Viatrix., AbbVie; Amgen; Boehringer Ingelheim, Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; UCB Pharma and Viatrix., Emmanuelle Dernis AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Roche-Chugaï, Sandoz, Sanofi and UCB Pharma., AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Roche-Chugaï, Sandoz, Sanofi and UCB Pharma., Eric Senbel Abbvie, Amgen, Biogen, Celltrion, Fresenius Kabi, Janssen, Lilly, MSD, Nordic Pharma, Pfizer, Roche-Chugai Sandoz and Sanofi, Abbvie, Amgen, Biogen, Celltrion, Fresenius Kabi, Janssen, Lilly, MSD, Nordic Pharma, Pfizer, Roche-Chugai Sandoz and Sanofi, Hélène Herman-Demars Nordic Pharma France, Jennifer Becker Nordic Pharma France, Agnès Courbeyrette Nordic Pharma France, René-Marc Flipo Abbvie, Amgen, Bristol-Myers Squibb, Galapagos, Janssen-Cilag, Lilly, Medac, MSD, Nordic-Pharma, Novartis, Pfizer, Roche-Chugaï, Sandoz and Sanofi-Genzyme, Abbvie, Amgen, Bristol-Myers Squibb, Galapagos, Janssen-Cilag, Lilly, Medac, MSD, Nordic-Pharma, Novartis, Pfizer, Roche-Chugaï, Sandoz and Sanofi-Genzyme.

Background:Treatment adherence is a major challenge in chronic inflammatory rheumatic diseases. Mainly studied in rheumatoid arthritis (RA), adherence rates range from 30 to 80% [1]. Given the impact of non-adherence to disease-modifying therapy among RA patients, guidelines aiming to facilitate adherence’s management were published in 2019 [2]. These guidelines highlight the multifactorial characteristics and importance of clarifying the factors contributing to non-adherence. Additionally, an EULAR task force highlighted the importance of addressing treatment adherence in the management of difficult-to-treat RA [3].Objectives:Based on STRATEGE2 results, we investigated real-life treatment adherence in RA patients treated with methotrexate (MTX) at time of initiation of a first b/tsDMARD and during a two-year follow-up.Methods:The STRATEGE2 cohort included RA patients who have been treated with MTX for at least 3 months (M) and were eligible for the initiation of their first targeted biological (bDMARD) or synthetic (tsDMARD) therapy due to RA activity. At 3 steps (baseline, M12 and M24) patients completed the Compliance Questionnaire for Rheumatology (CQR) [4], a 19-item self-administered questionnaire specifically designed for rheumatology to assess treatment adherence. A CQR19≤80 indicates a non-adherent patient (N-Ad). The profile of N-Ad at all 3 steps were compared with the profile of patients considered adherent (Ad) at least once during these steps. In addition, participation in shared decision-making (SDM) was evaluated using a 5-point Likert scale, adapted for both patient and physician use.Results:Between Feb. 2019 and Dec. 2020, 180 RA patients were enrolled, with 100 patients having an analyzable CQR19 at all 3 steps. Patient were divided in 2 groups: 32 patients were N-Ad throughout the study and 68 were Ad at least once. At baseline, no significant difference in patient profiles (except in MTX route): 75.0% females, mean age 57.2±12.8 years, diagnosed 6.1±7.8 years previously, treatment with MTX for 4.8±5.5 years and a mean MTX dose 18.9±4.2 mg/week. B/tsDMARD management was identical for both groups with 92.0% bDMARD and 8.0% tsDMARD initiation. The evolution of the therapeutic strategy over 24 months showed no difference between the 2 groups. 55.0% of patients had at least one adaptation to their b/tsDMARD treatment and 16.0% discontinued this treatment. The mean dose of MTX decreased overall to 14.9±4.7 mg/week and only 21.0% of patients discontinued it. The main difference between the 2 groups was the significant (p<0.05) lowest use of MTX SC route in N-Ad vs. Ad at the 3 steps (Baseline: 62.5% vs. 86.8%, M12: 38.5% vs. 68.3%, and M24: 38.5% vs. 64.2%). Between inclusion and 24M, RA activity decreased in both patients’ group (NS).Evolution of Patients and Physicians perception of their SDM participation during 24M:N-Ad(N=32)Ad(N=68)P valuePatient: Participation in SDM “completely” vs. others - n/N (%)Baseline6/29 (20.7)44/68 (66.7)p < 0.0001M1210/31 (32.3)40/68 (59.7)p < 0.05M249/30 (30.0)40/68 (58.8)p < 0.05Physician: Patient participation in SDM “completely” vs. others - n/N (%)Baseline19/32 (59.4)47/68 (69.1)M1217/31 (54.8)48/68 (70.6)M2414/32 (43.8)37/68 (54.4)Conclusion:This analysis comparing the profiles of N-Ad patients to treatment throughout the study vs Ad patients at least once, identifies 2 particularities of N-Ad patients. During the 24 months follow-up period, N-Ad used MTX SC route less than Ad patients, and feel less involved in SDM, although this perception is not shared by the physician.REFERENCES:[1] Beauvais C, et al. Joint Bone Spine 2020;87(6):668-669.[2] Gossec C, et al. Joint Bone Spine 2019;86(1):13-19.[3] Nagy G, et al. Ann Rheum Dis 2021;0:1–14.[4] De Klerk E, et al. J Rheumatol 2003;30(11):2469-2475Acknowledgements:The authors wish to acknowledge RCTs for their contribution to the statistical analysis, the investigators, centres and patients.Disclosure of Interests:Cécile Gaujoux-Viala AbbVie; Amgen; Boehringer Ingelheim, Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; UCB Pharma and Viatrix., AbbVie; Amgen; Boehringer Ingelheim, Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; UCB Pharma and Viatrix., Emmanuelle Dernis AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Roche-Chugaï, Sandoz, Sanofi and UCB Pharma., AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Roche-Chugaï, Sandoz, Sanofi and UCB Pharma., Eric Senbel Abbvie, Amgen, Biogen, Celltrion, Fresenius Kabi, Janssen, Lilly, MSD, Nordic Pharma, Pfizer, Roche-Chugai Sandoz and Sanofi, Abbvie, Amgen, Biogen, Celltrion, Fresenius Kabi, Janssen, Lilly, MSD, Nordic Pharma, Pfizer, Roche-Chugai Sandoz and Sanofi, Hélène Herman-Demars Nordic Pharma France, Jennifer Becker Nordic Pharma France, Agnès Courbeyrette Nordic Pharma France, René-Marc Flipo Abbvie, Amgen, Bristol-Myers Squibb, Galapagos, Janssen-Cilag, Lilly, Medac, MSD, Nordic-Pharma, Novartis, Pfizer, Roche-Chugaï, Sandoz and Sanofi-Genzyme, Abbvie, Amgen, Bristol-Myers Squibb, Galapagos, Janssen-Cilag, Lilly, Medac, MSD, Nordic-Pharma, Novartis, Pfizer, Roche-Chugaï, Sandoz and Sanofi-Genzyme.

BackgroundThe EULAR 2022 guidelines for the management of rheumatoid arthritis (RA) recommends methotrexate (MTX) combined with short-term corticoids (CS) as a 1st line standard of care [1]. In the event of an inadequate response to MTX and the presence of a poor RA prognosis factor, recommendations include initiation of biological (bDMARD) or synthetic (tsDMARD) targeted therapy in combination with MTX. Corticoids should be tapered as clinically feasible.ObjectivesBased on inclusion results of STRATEGE 2, we explore the evolution of therapeutic strategies after the initiation of a 1st b/tsDMARD, focusing on CS. Then patients’ profiles with or without CS were investigated.MethodsSTRATEGE2 is a non-interventional, prospective study including RA patients treated with MTX for at least 3 months and requiring initiation of a first b/tsDMARD due to disease activity. Evolution of main treatments was followed during 12 months. Data regarding therapeutic strategies were collected at inclusion (baseline treatment and end-of-visit prescription) and at 12 months (treatment at the 12 months visit entry and the end-of-visit prescription).ResultsBetween Feb. 2019 and Dec. 2020, 186 RA patients were included, among them 173 being reviewed at the 12 months visit. Cohort baseline conditions: 75.1% female, mean age 56.1 ±13.7 years, mean diagnostic oldness of 5.6 ±7.3 years, MTX treatment since 4.3 ±5.4 years.At the end of the inclusion visit, rheumatologists initiated a first targeted therapy. Then, patients were reviewed 12 months after inclusion (377.8 ±41.5 days). Patients’ clinical conditions and treatments prescriptions are presented in the Table 1 here after.Table 1.Inclusion consultation N = 17312 months after inclusion N= 171Baseline conditionAfter b/tsDMARD PrescriptionEntryAfter prescriptionMean DAS284.3 ±1.22.6 ±1.1Radiographic features, n (%)82 (47.7)NARadiographic progression, n (%)NA5 (3.3)Extra-articular manifestations, n (%)27 (16.2)11 (6.7)Mean HAQ1.0 ±0.70.7 ±0.7MTX (N + Discontinued)→ Mean dosage (mg/week)→ SC (%)17318.8 ±4.271.7169 + 417.9 ±4.466.9143 + 2816.4 ±4.559.4141 + 3016.0 ±4.559.4b/tsDMARD (N*+ Discontinued)NA173149*+18148*+19Corticosteroids therapy (N*)→ Yes, n (%)→ Mean dosage (mg/day)→ Median (Q1-Q3)→ Min-Max17286 (50.0)9.6 ±6.07.5 (5.0-10.0)2.5-30.017280 (46.5)8.6 ±4.97.5 (5.0-10.0)2.5-20.0170*66 (38.8)9.1 ±9.05.0 (5.0-10.0)2.0-60.0170*68 (40.0)9.7 ±10.95.0 (5.0-10.0)2.5-60.0N* excludes missing dataDifferences between patients’ profiles with or without CS were investigated. At baseline, profiles tend to show some differences between patients treated by CS vs others compared to the full population: Age (57.4 ±14.1 vs 54.9 ±13.2; full population mean: 56.1 ±13.7), unemployed (50.0% vs 34.9%; full: 43.9%), normal body mass index (38.4% vs 51.2%; full: 44.6%), at least one comorbidity (48.8% vs 54.7%; full: 51.4%) and DAS28 score (4.5 ±1.1 vs 4.1 ±1.2; full: 4.3 ±1.2). At 12 months, the number of patients treated by CS decrease (from 50 to 40%). Patients’ profiles still treated by CS are similar to inclusion except for “at least one comorbidity” (54.4% vs 50.0%; full: 51.4%).ConclusionOne year after the initiation of a b/tsDMARD the proportion of patients treated by CS is still important with high doses. These patients are older, present comorbidities and active disease. This long-term maintenance of CS is not in line with the Eular guidelines which recommend discontinuing CS as rapidly as clinically feasible. Further analyses on patients’ profiles are ongoing and supplementary data on 24 months follow-up may help to better understand the use of long-term CS in those patients.Reference[1]Smolen JS, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis 2023;82:3–18.AcknowledgementsThe authors wish to acknowledge RCTs for their contribution to the statistical analysis, the investigators, centres and patients.Disclosure of InterestsCécile Gaujoux-Viala Consultant of: AbbVie; Amgen; Boehringer Ingelheim, Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB Pharma., Grant/research support from: AbbVie; Amgen; Boehringer Ingelheim, Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB Pharma., Emmanuelle Dernis Consultant of:Emmanuelle Dernis (MAJ 06/2022): AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Roche-Chugaï, Sandoz, Sanofi and UCB Pharma., Grant/research support from:Emmanuelle Dernis (MAJ 06/2022): AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Roche-Chugaï, Sandoz, Sanofi and UCB Pharma., Eric Senbel Consultant of: Abbvie, Amgen, Biogen, Celltrion, Fresenius Kabi, Janssen, Lilly, MSD, Nordic Pharma, Pfizer, Roche-Chugai and Sandoz, Sanofi., Grant/research support from: Abbvie, Amgen, Biogen, Celltrion, Fresenius Kabi, Janssen, Lilly, MSD, Nordic Pharma, Pfizer, Roche-Chugai and Sandoz, Sanofi., Hélène Herman-Demars Employee of: Nordic Pharma France, Jennifer Becker Employee of: Nordic Pharma France, Agnès Courbeyrette Employee of: Nordic Pharma France, René-Marc Flipo Consultant of: Abbvie, Bristol-Myers Squibb, Eli-Lilly, Janssen, MSD, Nordic-Pharma, Novartis, Pfizer, Roche-Chugaï, Sandoz and Sanofi., Grant/research support from: Abbvie, Bristol-Myers Squibb, Eli-Lilly, Janssen, MSD, Nordic-Pharma, Novartis, Pfizer, Roche-Chugaï, Sandoz and Sanofi.

BackgroundMethotrexate (MTX) is the first line standard of care for the management of rheumatoid arthritis (RA). In the event of an inadequate response to MTX and the presence of a poor RA prognosis factor, recommendations include initiation of biological (bDMARD) or synthetic (tsDMARD) targeted therapy in combination with MTX.ObjectivesSTRATEGE 2 aims to establish the maintenance of MTX within two years of initiating a first targeted therapy.MethodsSTRATEGE 2 is a non-interventional study including RA patients treated with MTX for at least 3 months and requiring initiation of a first b/tsDMARD due to disease activity. The primary endpoint is maintenance of MTX unchanged within 12 months of initiation of targeted therapy. Non-maintenance is defined as: permanent discontinuation of MTX and/or dose reduction and/or transition from the subcutaneous route (SC) to oral (PO). Then, univariate and multivariate analysis was applied to identify potential predictors of MTX maintenance.ResultsBetween Feb. 2019 and Dec. 2020, 53 French sites included 186 RA patients. Among them, data from 180 patients were analysable: 73.4% female, mean age 56.4 ±13.6 years, mean diagnostic oldness of 5.6 ±7.2 years, MTX treatment since 4.3 ±5.3 years, 71.7% via SC and the average dose was 19.9 ±3.9 mg/wk. The mean DAS28 score was 4.3 ±1.2 and the mean HAQ score was 1.0 ±0.7.At the end of the inclusion consultation, rheumatologists initiated a first targeted therapy: 8.6% by bDMARDs (anti-TNF: 58.4%, anti-IL6: 12.7%, Abatacept/Rituximab: 18.5%) and 10.4% by tsDMARDs. MTX was maintained unchanged in 76.1%, changed in 21.7% and stopped in 2.2% of the cases. The changes consisted of a dose reduction to 13.8 ±3.8 mg/wk for 19.4% of patients and a pathway change for 31.4% (from SC to PO).Approximately 12 months (377.8 ± 41.5 days) after initiation of targeted therapy, 95% of patients completed a follow-up visit (N=171). Of these patients, 6.4% had discontinued targeted therapy, 85.9% were on bDMARD (anti-TNF: 50.3%, anti-IL6: 12.8%, Abatacept/Rituximab: 22.8%) and 14.1% on tsDMARD.The average MTX dose was 18.0 ±4.2 mg/wk and MTX was administered SC for 59.4% of patients. According to the composite endpoint definition, MTX was maintained for 40.9% of patients. Non-maintenance was represented by 30% discontinuation, 44% of patients with a dose decrease only, 3% of patients with only a change in route of administration (from SC to PO) and 23% of patients with the two strategies.Using univariate analysis, three factors were selected for the multivariate: age (p=0.009), physicians’ mode of practice (p=0.096) and patients who estimate having completely participated in the decision-making for the targeted therapy (p= 0.197). Only age was significative (OR=1.06, 95%CI [1.03,1.10], p<0.001), decision-making shows a strong trend (p=0.052) and both characteristics were adjusted on the mode of practice (p=0.256).ConclusionThere are many therapeutic adaptations in the year following the initiation of b/tsDMARD. Twelve months after the introduction of b/tsDMARD, more than 8 out of 10 patients retained MTX as a combination therapy. Nearly 46% of patients had an adaptation of this treatment (dose reduction and/or return to the PO route). These practices are in line with the latest EULAR guidelines [1] which recommend the association of b/tsDMARDs with MTX.Reference[1]Smolen JS, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis 2023;82:3–18.AcknowledgementsThe authors wish to acknowledge RCTs for their contribution to the statistical analysis, the investigators, centres and patients.Disclosure of InterestsCécile Gaujoux-Viala Consultant of: AbbVie; Amgen; Boehringer Ingelheim, Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB Pharma., Grant/research support from: AbbVie; Amgen; Boehringer Ingelheim, Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB Pharma., Emmanuelle Dernis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Roche-Chugaï, Sandoz, Sanofi and UCB Pharma., Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Roche-Chugaï, Sandoz, Sanofi and UCB Pharma., Eric Senbel Consultant of: Abbvie, Amgen, Biogen, Celltrion, Fresenius Kabi, Janssen, Lilly, MSD, Nordic Pharma, Pfizer, Roche-Chugai and Sandoz, Sanofi., Hélène Herman-Demars Employee of: Nordic Pharma France, Jennifer Becker Employee of: Nordic Pharma France, Agnès Courbeyrette Employee of: Nordic Pharma France, René-Marc Flipo Consultant of: Abbvie, Bristol-Myers Squibb, Eli-Lilly, Janssen, MSD, Nordic-Pharma, Novartis, Pfizer, Roche-Chugaï, Sandoz and Sanofi., Grant/research support from: Abbvie, Bristol-Myers Squibb, Eli-Lilly, Janssen, MSD, Nordic-Pharma, Novartis, Pfizer, Roche-Chugaï, Sandoz and Sanofi.

Background:Delayed diagnosis of axial spondyloarthritis (axSpA) remains a challenge for multiple reasons, including lack of awareness in primary care and difficulty in distinguishing chronic inflammatory back pain from other, more prevalent back pain types. Longer diagnostic delays are associated with worse clinical, psychological, social and economic outcomes [1]. Investigating the time to diagnosis and associated comorbidity burden will help inform targets for improvement and raise awareness.Objectives:To describe the patient characteristics and comorbidity burden at the time of earliest recorded back pain in general practice and at the time of axSpA diagnosis, and to estimate the time to diagnosis of axSpA from earliest recorded back pain in general practice.Methods:This retrospective descriptive study utilized data from the French electronic health records THIN® database from a representative sample of 2,000 general practitioners (GPs) between January 2010 and August 2023. Adult patients with axSpA and at least 3 years of continuous enrollment with their GP prior to axSpA diagnosis with documented back pain in their medical history prior to axSpA diagnosis were included. Patients diagnosed with rheumatoid arthritis and psoriatic arthritis within one year preceding axSpA diagnosis were excluded. Musculoskeletal, non-musculoskeletal manifestations and comorbidities were assessed at 1) the time of earliest recorded back pain by the GP and 2) the time of axSpA diagnosis. Time to diagnosis was defined as time between these two time points. Results were reported descriptively using summary statistics.Results:A total of 4,402 patients with axSpA were included, with a mean (standard deviation, SD) number of years with available data before axSpA diagnosis of 10.4 (4.9) years. In this cohort, 43% were male and the mean (SD) age was 40 (14) at earliest back pain diagnosis and 47 (14) years at axSpA diagnosis. The burden of musculoskeletal, non-musculoskeletal manifestations and comorbidities increased between the time of earliest recorded back pain and the time of axSpA diagnosis, with the number of patients with multiple comorbidities increasing from 32% to 60%. The largest increases were seen for enthesitis, fatigue, depression and anxiety (Figure 1). The mean (SD) time in years between the earliest back pain diagnosis recorded by the GP and the first axSpA diagnosis was 6.3 (4.5) years, with 38% of patients experiencing a time to diagnosis longer than 7 years. No differences in time to diagnosis between males and females were observed. Patients had a median (Q1, Q3) of 3 (2, 7) documented back pain episodes recorded in their GP records prior to their axSpA diagnosis, with 26,857 total back pain consultations recorded for the entire cohort over the study period. The distribution of specific locations and types of back pain diagnoses are shown in Figure 2.Conclusion:Diagnostic delay remains a key challenge for patients with axSpA in France, with several consultations for back pain in primary care prior to diagnosis and an average time to diagnosis of over 6 years after the earliest back pain consultation. An increased number of musculoskeletal, non-musculoskeletal manifestations and comorbidities were observed at the time of axSpA diagnosis compared to when back pain was first consulted for, highlighting worsening disease burden over time. Importantly, patients may have experienced pain long before consulting their GP, further contributing to diagnostic delays. Interventions are needed to support GPs in recognising chronic back pain patients who could benefit from a timely referral to rheumatology. Earlier diagnosis of axSpA may ultimately lower the burden on patients, healthcare systems and society.REFERENCES:[1] Yi E et al. Rheumatol Ther. 2020 Mar;7(1):65-87.Acknowledgements:Funded by UCB Pharma.Disclosure of Interests:Clément Prati Speakers bureau for AbbVie, Janssen, Novartis, Sandoz and UCB Pharma, Consultant for Celltrion, Janssen, Lilly, Novartis and Sandoz, Grant/research support from Fresenius and Pfizer, Arnaud Constantin Speakers bureau for AbbVie, Amgen, Biogen, BMS, Boehringer Ingelheim, Celltrion, Fresenius Kabi, Galapagos, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche, Sanofi, Sandoz, UCB Pharma and Viatris, Consultant for AbbVie, Amgen, Boehringer Ingelheim, Celltrion, Fresenius Kabi, Galapagos, Janssen, Lilly, Novartis, Pfizer, Sanofi and UCB Pharma, Grant/research support from AbbVie, Biogen, BMS, Galapagos, Lilly, Hoffman-La Roche, MSD, Janssen, Novartis, Pfizer, Sanofi and UCB Pharma, Emmanuelle Dernis Speakers bureau for Abbvie, BMS, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche and UCB Pharma, Consultant for Janssen, Lilly, Novartis, Pfizer and UCB Pharma, Grant/research support from Lilly and Novartis, Stéphane Le Mouel Paid instructor for Amgen and Sanofi, Consultant for Boiron, Kappa Santé and LEO Pharma, Marc Rozenblat: None declared, Jacques-Eric Gottenberg Speakers bureau for Abbvie, BMS, Galapagos, Gilead, Lilly, MSD, Novartis, Pfizer, Sanofi and UCB Pharma, Cheikh Tamberou As a consultant in a research firm, we are called upon to collaborate with the entire pharmaceutical industry, Elise Arnee Previous employee of Biocodex and Novartis, As a consultant in a research firm, we are called upon to collaborate with the entire pharmaceutical industry, Anneleen Vyncke Employee of UCB Pharma, Marie Ducros As a consultant in a research firm, we are called upon to collaborate with the entire pharmaceutical industry, Julie Gandrup Horan Shareholder of UCB Pharma, Employee of UCB Pharma.

Background:Therapeutic strategies for rheumatoid arthritis (RA) are based on national and international recommendations, having as main aim achieving remission or a low level of activity using a ‘treat-to-target’ strategy. In this context, targeted therapies are used more frequently and at an earlier stage.Objectives:-To describe the characteristics of RA patients initiating TNFi in real life and included in the ART-SFR registry, and to assess if they have been treated according to current recommendations.-To compare RA patients included in ART-SFR to other RA populations treated by TNFi, either in contemporary randomized controlled trials, and in previous national or international registries.Methods:The recent multicenter French registry ART-SFR (NCT03062865) included RA patients initiating a TNFi between 2016 and 2022, with a 5-year prospective follow-up. We described here patient characteristics at inclusion in the registry. The adherence to recent guidelines on TNFi initiation (EULAR, ACR and French society for rheumatology (SFR)) was assessed by the percentage of patients treated according these guidelines. Then, a systematic review was performed to compare characteristics of patients of the ART-SFR registry to other RA patients treated by TNFi in previous registries or cohort studies (including > 1000 patients treated with anti TNF). Finally, another systematic review on trial registration platforms (clinicaltrial.gov...) was carried out to identify all randomized controlled trials (RCT) with a TNFi arm including RA patients over the same period as inclusion in the ART-SFR registry. The main eligibility criteria for these trials were collected, and eligibility of patients from the ART-SFR registry to inclusion in these trials was assessed.Results:1483 RA patients were included (1078 (73%) female, mean age = 55.6 yrs ± 14.1, mean disease duration = 7.6 yrs). 47% of patients had erosive status, 80% had positive ACPA and/or RF, and 86% had moderate to high disease activity (mean DAS-28 CRP: 4.1 ± 1.1). Patients were mostly biologic-naïve at enrollment (n = 1182, 80%). TNFi were Etanercept in 782 (53%), Adalimumab (23%). TNFi was associated with csDMARD in 83% and glucocorticoids in 49% (9.1 mg/day ± 7.3).In biologic-naïve patients, TNFi was initiated in accordance to EULAR 2016, ACR 2015 and SFR 2014 recommendations in 98 % for each, and in patients with previous biologic use in 100, 74 and 100 % respectively.Systematic review identified 20 observational studies conducted from 1999 to 2020. Compared to these studies, patients in ART-SFR registry had similar age (43 to 56 yrs), and gender (women 73-100%). They tended to have a shorter disease duration (lower than 17/20 registries), similar proportion of RF/ACPA positivity (69 to 85%), but lower disease activity (DAS28 4.4, vs DAS 28 > 5.1, in all except 3 registries).When compared to RCT recruiting during the same period as ART-SFR registry, according to trial 4 to 72% of patients of ART-SFR registry (< 50% for 21/27 trials) met the main eligibility criteria (including RA activity criteria, ESR/CPR, erosive status, DMARD use). In trial requiring increased acute phase reactants (ESR and/or CRP), this rate ranged from 4.4 to 25%, while it was between 60.1 and 71.8% for other trials.Conclusion:Data from the ART-SFR national registry show that TNFi, the oldest class of biologics in RA, are still used predominantly as first-line biologic. Given the design of the registry, their characteristics can be considered representative of those of patients initiating TNFi for RA in France. Most patients in the registry were treated in accordance with recommendations. Conversely, the eligibility of patients for trial inclusion criteria was highly heterogeneous, and particularly low when acute phase reactants were part of eligibility criteria. These results suggest that trial and real-life populations are not similar, and specifically, that generalizability of results of trials requiring elevated acute phase reactant for inclusion should be interpreted with caution. Their characteristics are also quite different from previous observational studies, it will provide new data on the real-life efficacy and safety of TNFi.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

BackgroundTo prevent infections, EULAR recommends to vaccinate RA patients against streptococcal pneumoniae. It is recommended to vaccine with the conjugate vaccine (PCV13) followed by a dose of PPSV23 at least 8 weeks later. PCV13 is a T- cell dependent vaccine whereas PPSV23 induces a T-independent humoral response. Abatacept is a biological DMARD that inhibits T cell activation.ObjectivesWe hypothesized that the humoral response may be more affected under abatacept after PCV13 vaccination than after PPSV23. To adress this question, we compared the humoral response four weeks after vaccination with PCV13 or PPSV23 in RA patients treated with abatacept.MethodsWe conducted a prospective, multicenter, randomized, open-label study in patients with RA according to ACR/EULAR 2010 criteria, and starting abatacept because of inadequate response to MTX or leflunomide (DAS28>3,2). Patients were randomized in 2 groups: the first group (G1) was vaccinated with the PPSV23 and the second group (G2) with PCV13 and PPSV23 8 weeks later. Abatacept was to be started on the same day as the first vaccine (PCV13 or PPSV23). Patients having been treated previously with rituximab within the last year were excluded. A patient was considered as responder if there was a two-fold increase in the antibodies titer measured by ELISA for at least 3 of 5 serotypes of interest (1, 3, 14, 7F, 19A) which are the most frequently involved in pneumococcal infections. For the primary endpoint, we compared the rate of responders at one month in G1 and G2 using a Chi-Square test. Sample size calculation based on alpha risk 5% and 80% power requirements resulted in 80 patients. Tolerance of the vaccines were collected within the first week and later in a patient booklet. Adverse events were also collected at 1, 2, 6 and 12 months.ResultsEighty patients were included and randomized in the two groups: 40 in G1 and 40 in G2 (1 patient withdrew his consent before any treatment in G2). Characteristics of patients are described in Table 1. Female were more represented in G1 (82.5%) compared to G2 (64.1%). Lymphocyte count were significantly higher in G1 compared to G2: 1841/uL (+/-887) vs 1603/uL (+/-580). In the mITT, the rate of responders was 47.5% in in G1 and 38.46% in G2 (p=0.42) with a RR of 1.23 (IC95%: 0.73-2,06; when comparing responders in PPSV23 vs PCV13 groups. This absence of difference was confirmed with a per protocol analysis (p=1) and after adjusting for gender and lymphocytes count with a logistic regression test (RR=1.6 IC95% 0.6-4.2). 17 infections were reported in G1 and 28 in G2 with 3 severe infections but no pneumococcal infection.ConclusionIn RA patients treated with abatacept combined with sDMARDs (MTX or LEF), the rate of responders is similar 28 days following vaccination with PCV13 or PPSV23. Although PCV13 is a T cell dependent vaccine, immunogenicity to PCV13 under abatacept is similar to PPSV23. There were no unexpected side effects after pneumococcal vaccines.Table 1.Characteristics of patients at inclusionVariableModalityAll population N=79Group1 PPSV23 N=40Group 2 PCV 13 N=39Age (years)Mean (±SD)59.61 (± 12.59)58.08 (± 13.74)61.18 (± 11.24)GenderWomen58 (73.42)33 (82.50)25 (64.10)BMI (kg/m²)Mean (±SD)26.03 (± 5.09)26.76 (± 6.17)25.29 (± 3.62)Previous pneumocccal vaccineYes/ (%)17 (21.52)10 (25.00)7 (17.95)DAS28 CRPMean (±SD)4.33 (± 0.90)4.20 (± 0.79)4.46 (± 1.00)RF positiveYes/ (%)55 (70.51)30 (75.00)25 (64.10)ACPA positiveYes/ (%)55 (70.51)31 (77.50)24 (61.54)Erosive RAYes/ (%)47 (61.04)24 (60.00)23 (58.97)Lymphocytes count n/uLMean (±SD)1822.31 (± 778.25)2029.73 (± 886.68)1603.97 (± 579.90)MTXYes/ (%)63 (79.75)32 (80.00)31 (79.49)MTX dose (mg/w)Mean (±SD)15.67 (± 4.52)15.63 (± 5.12)15.73 (± 3.88)LeflunomideYes/ (%)8 (10.13)4 (10.00)4 (10.26)SteroidsYes/ (%)33 (41.77)16 (40.00)17 (43.59)Steroid dose (mg/d)Mean (±SD)7.77 (± 2.42)7.50 (± 2.58)8.03 (± 2.30)AcknowledgementsWe thank the Bristol Myers Squibb and the French Society of Rheumatology for an unrestricted grant.Disclosure of InterestsJacques Morel Speakers bureau: Amgen, Biogen, Bristol Myers Squibb, Fresenius Kabi, Janssen, Lilly, Merck Sharp and Dohme, Medac, Mylan, Nordic Pharma, Novartis, Pfizer, Roche Sanofi, Sandoz, Union Chimique Belge, Consultant of: Abbvie, Boerhinger Ingelheim, Galapagos, Glaxo Smith Kline, Pfizer, Grant/research support from: Pfizer, Novartis, Bristol Myers Squibb, Lilly, Olilvier Brocq: None declared, Cécile Gaujoux-Viala: None declared, Arnaud Constantin: None declared, Slim Lassoued: None declared, Emmanuelle Dernis: None declared, Christophe Richez: None declared, Cédric Lukas: None declared, Claire Daien: None declared, Claire Duflos: None declared.

Background:The SEMAPHORE trial[1] was a randomized controlled prospective study to assess the safety and efficacy (success defined by PMR-AS≤10 and GC≤5mg or GC decrease ≥10mg/day) of intra venous (i.v.) tocilizumab (TCZ) in glucocorticoids (GC)-dependent polymyalgia rheumatica (PMR). Tocilizumab was shown to reduce GC while improving clinical and biological inflammatory parameters at 24 weeks. After the 24-week study, patients entered a double-blind extension.Objectives:In this study, we aimed to assess after the 24th week the relapse rate and markers of patients who received a 6-month TCZ treatment and achieved remission.Methods:Among 101 patients randomly 1:1 allocated to receive i.v. 8mg/kg TCZ or placebo for 24 weeks in the SEMAPHORE trial, 49 received TCZ and 33 of them succeed (Figure 1). All 33 patients but one stopped TCZ at week 24 and they visited at week 32, with optional follow-up visits every 8 weeks until week 48. The relapse was defined by the failure of the primary composite outcome during follow-up or the need for ≥1 TCZ infusion. Results are presented by proportion of patients achieving success at each visit and the outcome over time using a Kaplan Meier curve.Results:Among the 33 TCZ group patients in remission at week 24, 7 stopped follow-up before the 48th week, 5 of the other 26 subjects (19.2%) sustained remission in the 6 following months, 21 (80.8%) relapsed. Median time to relapse was 15 weeks (interquartile range: 8-25). 15 patients were considered in relapse because of PMR-AS≥10, 4 for isolated CRP elevation, 2 after the clinician’s decision. Among the 16 patients treated with TCZ but not in remission at 24th week, 4 of them (25%) achieved the primary outcome after continuing TCZ for 24 other weeks.Conclusion:Among patients with GC-dependent PMR, in remission after a 6-month TCZ treatment, only a quarter remained relapse-free after treatment discontinuation. This study suggests that a 6-month treatment is not enough to withdraw TCZ. Further studies assessing the required duration of anti-IL6-receptor treatment to limit PMR relapses are needed.REFERENCES:[1] Devauchelle-Pensec, V. et al. Effect of tocilizumab on Disease Activity in patients with active polymyalgia rheumatica receiving glucocorticoid therapy: A Randomized Clinical Trial. JAMA 328, 1053–1062 (2022).Figure 1.Flow chart of the patients included in the SEMAPHORE trial, orientation of patients after the 24th weekFigure 2.Relapse-free survival among GC-dependant PMR patients in remission after a 6-month treatment of TocilizumabFootnotes: Remission was defined by PMR-AS<10, and GC≤5mg/j or daily GC dose decreased by ≥10mg. Day 0 was the visit at 24th week in the SEMAPHORE trialAbbreviations: PMR: Polymyalgia rheumatica; PMR-AS: Polymyalgia rheumatica activity scoreAcknowledgements:We thank the French rheumatologists, particularly those from the French University Hospital VICTOR HUGO (InnoVation en reCherche OsTeo-aRticulaire des Hôpitaux Universitaires du Grand Ouest) network (srouest.fr), and the general practitioners who referred their patients to this trial. We are grateful to the Clinical Investigations Center (CIC) 1412, Institut National de la Santé et de la Recherche Médicale (INSERM), Brest, France, for centralizing the trial data and to Audrey le Goff, MS; Adrien Clarysse, MS; and Valentine Guiton, MS, of the Brest University Hospital research board (DRCI) at the Brest University Hospital, who received no compensation for their role in the study.Disclosure of Interests:Baptiste Chevet Galapagos, I wrote congress review for a journal they own, I received support outside of this work from Amgen, Abbviie, Novartis, Santi, Sandoz, Souki Aghiles: None declared, Nowak Emmanuel Dr Nowak reported receiving nonfinancial support from Roche-Chugai Pharmaceutical, which donated the infusion form of tocilizumab during the conduct of the study., Dr Nowak reported receiving grants from the French National Program for Clinical Research, Guillermo Carvajal Alegria Dr Carvajal Alegria reported receiving personal fees from Chugai Pharmaceutical outside the submitted work., Emmanuelle Dernis Dr Dernis reported receiving personal fees from Novartis, Bristol Myers Squibb, UCB, AbbVie, Nordic Pharma, Amgen, and Janssen outside the submitted work., Christophe Richez Dr Richez reported receiving personal fees from Sanofi, personal fees from Lilly, and personal fees from Novartis outside the submitted work., Marie-Elise Truchetet: None declared, Daniel Wendling Dr Wendling reported personal fees from AbbVie, Bristol Myers Squibb, MSD, Pfizer, Chugai Pharmaceutical, Amgen, Nordic Pharma, UCB, Novartis, Janssen, Eli Lilly, Grunenthal, and Galapagos outside the submitted work, Eric Toussirot: None declared, Aleth Perdriger: None declared, Jacques-Eric Gottenberg Dr Gottenberg reported receiving personal fees from Roche-Chugai Pharmaceutical, Sanofi, Pfizer, Eli Lilly, Gilead, and Abbvie and grants from Bristol Myers Squibb outside the submitted work., Renaud Felten: None declared, Bruno Fautrel Dr Fautrel reported receiving personal fees from Roche Chugai Pharmaceutical during the conduct of the study., Anne Lohse: None declared, Laurent Chiche: None declared, Pascal Hilliquin: None declared, Catherine Le Henaff Bourhis: None declared, Dervieux Benjamin: None declared, Guillaume Direz Dr Direz reported receiving personal fees from Novartis and personal fees from Roche-Chugai Pharmaceutical outside the submitted work., Isabelle Chary-Valckenaere: None declared, Divi Cornec: None declared, Dewi Guellec: None declared, Thierry Marhadour: None declared, Alain Saraux Dr Saraux reported receiving grants from Roche-Chugai Pharmaceutical and grants from the French National Program for Clinical Research during the conduct of the study and personal fees from Nordic Galapagos, AbbVie, Eli Lilly, Nordic, and Roche-Chugai and grants from Eli Lilly outside the submitted work., Valerie Devauchelle-Pensec Dr Devauchelle reported receiving personal fees from Chugai Pharmaceutical and AbbVie a, Dr Devauchelle-Pensec reported grants and personal fees from Novartis during the conduct of the study and personal fees from Galapagos, Pfizer, Bristol Myers Squibb, Janssen, and AbbVie outside the submitted work.

Background:Rheumatoid arthritis (RA) regularly affects women of childbearing age1. A higher obstetric morbidity in women with RA is suggested in the literature in several countries, but no comparison between patients with RA and women in the general population is available for France.Objectives:The aim of the study was to compare adverse fetal, maternal and pregnancy outcomes in women with RA with matched controls from the French general population.Methods:We conducted a matched comparative study of RA patients included in the GR2 (Groupe de Recherche sur la Grossesse et les Maladies Rares) national multicentre cohort from 2014 to June 2021 and controls from the French general population included in the French national perinatal surveys (Enquête Nationale Périnatale)2. The latter is a national survey carried out for one week every 5 years and recording around 13 000 births. As births before 22 gestational week (GW) and birth weights < 500 grams were excluded from the French national perinatal survey, the same exclusion criteria were applied to women with RA from the GR2 cohort. Each pregnancy in patients with RA was matched to 4 pregnancies in controls on age group (≤ 29, 30-34, 35-39, or ≥ 40 years), parity, area of residence, and gemellity. These matching variables were chosen according to their association with adverse pregnancy outcomes (potential confounders). Births in the GR2 cohort between 2015 and 2018 were matched to births in the 2016 survey and those between 2019 and 2021 were matched to births in the 2021 survey. RStudio’s MatchIt package was used to match RA patients to controls. The frequency of each adverse pregnancy outcome was compared between the two groups using Fisher’s exact test or Chi-2. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated for each variable.Results:Of the 92 patients with RA included in the GR2 cohort, 83 (including one twin pregnancy) were retained after excluding births before 22 GW and/or birth weight < 500 grams. They were matched with 332 control pregnancies from the French national perinatal survey (180 pregnancies from the 2016 survey and 152 from the 2021 survey). The mean age of RA patients was 33.7 (± 5.06) years and 53% were nulliparous. Preterm birth was significantly higher in newborns of RA patients than in newborns of controls (16.9% versus 6.3%, p < 0.01). Among the cases of preterm birth, only one case of extreme prematurity (at 30 GW) and no case of very extreme prematurity were found in the GR2 cohort. However, there was no significant difference for gestational diabetes nor macrosomia (despite the use of corticosteroids at least once during pregnancy in 42.1% of RA patients), gestational hypertension, low birth weight, severe postpartum hemorrhage, maternal or neonatal transfer to intensive care unit or congenital malformation between the two populations (Table 1).Conclusion:This study found an increased risk of preterm delivery in RA patients compared with control women in the French general population, which is consistent with an increased risk observed in other countries. These results raise the need for particular attention to obstetrical follow-up in these patients and providing useful insights for physician-patient dialogue.Table 1. Matched comparative analysis of adverse fetal, maternal and pregnancy outcomes in RA patients (GR2 cohort) and control women of the French general population (2016 and 2021 French national perinatal surveys).REFERENCES:[1] Van den Brandt S. Arthritis Res Ther. 2017;19(1):64.[2] https://enp.inserm.fr/Acknowledgements:The GR2 Cohort is supported by the French Society of Rheumatology, the French Internal Medicine Society, and unrestricted grants from UCB.Disclosure of Interests:None declared.

Background:Sjögren’s disease (SjD) is a heterogenous autoimmune disease, with a wide range of symptoms, from dryness, fatigue, pain, to systemic manifestations, and an increased risk of lymphoma. Recently, three clusters of patients with SjD have been described based on unsupervised clustering analysis according to symptoms, clinical signs and biologic parameters: 1/ BA-LS (B-cell active with low symptoms); 2/ HSA (High systemic activity); 3/ LSA-HS (Low systemic activity with high symptoms). These findings suggest potential heterogeneity in pathophysiological mechanisms.Objectives:To investigate this hypothesis, we examined whether these three clusters were associated with distinct biomarkers.Methods:This study involved SjD patients meeting AECG criteria from the ASSESS cohort. The following biomarkers were measured in sera at the time of inclusion: for IFN pathways—IFN-alpha 2, IFN gamma, CXCL-10; for B cell activation—CXCL-13, BAFF, B2-microglobulin, FLT-3; for T cell activation—IL-7, CCL-19, TNF-RII. Additionally, the IFN signature was assessed using transcriptomic analysis. Kruskal-Wallis rank sum test was used to compare different clusters for continuous variables. Additionally, the risk of lymphoma and of new immunosuppressive drugs prescriptions were compared according to the IFN signature.Results:This analysis included 395 (94% female, median age 53 [43-63] years) patients from the ASSESS cohorts. The three clusters displayed differences in the IFN pathways (IFN signature), primarily driven by type I IFN (IFN-a2 level) elevated only in BA-LS and HSA clusters and not in the LSA-HS cluster (p=0.001). IFN gamma and CXCL-10 were not different between the 3 clusters.The same clusters that exhibit high level of type 1 IFN also had higher CXCL-13 levels (p=0.0032) reflecting B-cell activation, higher IL-7 (p=0.0042) and TNFRII (p<0.001) levels reflecting T-cell activation. Higher levels of FLT-3 were found in the HSA cluster. BAFF level was not different between the 3 clusters.Lastly, there were a trend indicating an increased risk of lymphoma in patients with positive IFN signature (HR 2.53; 95%CI 0.67–9.55), and an increased risk of immunosuppressant prescription during follow-up (HR 2.81; 95%CI 1.26-6.29).Conclusion:The two clusters BA-LS and HSA have a very distinct cytokine signature than the patients with LSA-HS. These two active clusters share a high type 1 IFN level, and elevated markers of both B-cell and T-cell activation. Patients from the BA-LS cluster being younger, it is likely that this cluster represent an earlier disease stage than HSA cluster. In order to go towards personalized medicine, work is in progress for deciphering patients in these two active clusters exhibiting one predominant pathways among type 1 IFN, B-cell and T-cell activation.REFERENCES:[1] Nguyen Y, Nocturne G, Henry J. Identification of distinct phenotypes of Sjögren disease by cluster analysis based on clinical and biological manifestations: data from the cross-sectional Paris-Saclay and the prospective ASSESS cohorts. Lancet Rheumatology 2024.Acknowledgements:The authors are indebted to all patients for their participation, and to all physicians who included patients in the Paris-Saclay and ASSESS cohorts. The Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome (ASSESS) national multicenter prospective cohort was formed in 2006 with a French Ministry of Health grant (Programme Hospitalier de Recherche Clinique 2005 P060228). The ASSESS cohort is promoted by the French Society of Rheumatology and receives research grants from the French Society of Rheumatology.Disclosure of Interests:Yann Nguyen: None declared, Xavier Mariette Xavier Mariette received consulting fees from Astra Zeneca, Bristol Myer Squib, Galapagos, GSK, Novartis and Pfizer, Maxime Beydon: None declared, Divi Cornec: None declared, Jacques-Olivier Pers: None declared, Jacques MorelJacques Morel received honoraria from Abbvie, Boehringer Ingelheim, Biogen, Lilly, Mylan, Pfizer, Sanofi, Bristol Myers Squib, Fresenius Kabi, Galapagos, Medac, Novartis, Roche Chugai;,Jacques Morel received grants from Bristol Myers Squib, Fresenius Kabi, Lilly, Novartis, Pfizer, and Roche-Chugaï;, Aleth PERDRIGER: None declared, Emmanuelle Dernis Emmanuelle Dernis received consulting fees from BMS, Celgène, Lilly, MSD, Novartis, UCB; honoria for lectures from Abbvie, BMS, Janssen, Lilly, Medac, MSD, Novartis, Roche-Chugaï, Sanofi, UCB, Celgène, Amgen, Galapagos;, Valerie Devauchelle-Pensec: None declared, Damien Sene: None declared, Philippe Dieudé Philippe Dieudé received consulting fees from Pfizer, Roche Chugai, Bristol Myers Squibb, Abbvie, MSD., Philippe Dieudé received grants from Novartis, Marion Couderc: None declared, Anne-Laure Fauchais: None declared, Claire Larroche: None declared, Olivier Vittecoq: None declared, Carine Salliot Carine Salliot received Honoria from Novartis, Roche Chugaï, Eric Hachulla: None declared, Véronique Le Guern: None declared, Jacques-Eric Gottenberg Jacques-Eric Gottenberg consulting fees from Abbvie, Astra Zeneca, Sanofi, Lilly, Galapagos, Gilead, Roche Chugai, Pfizer, Bristol Myer Squib, MSD., Jacques-Eric Gottenberg received grants from Pfizer, Abbvie, Lilly, Raphaèle Seror Raphaèle Seror received consulting fees from GSK, Bristol Myer Squib, Boerhinger and Janssen; honoraria from GSK, Bristol Myer Squib, Boehringer, Amgen, Pfizer and Roche; travel fees from Amgen and GSK;, Gaetane Nocturne: None declared.