Op0034 Differential Joint-Level Responses to TNF Inhibitors in Psoriatic Arthritis: A Collaborative European Observational Cohort Study

Background: In psoriatic arthritis (PsA), the assessment of TNFi treatment outcomes primarily focuses on the improvement in the number of affected joints, disregarding their specific locations. Transcriptomic variances identified in synovial fibroblasts (SF) from various joint sites in rheumatoid arthritis translated into joint-specific SF phenotypes with distinct characteristics and responsiveness to cytokines. These findings suggest that various joints may potentially respond differently to specific immunosuppressive treatments. Objectives: To investigate whether joints at different anatomical locations might respond differently to TNFi treatment in patients with PsA. Methods: PsA patients starting a first TNFi between 2000 and 2022 in eight European registries met the following additional inclusion criteria: age ≥18 years, TNFi initiation as monotherapy or added to methotrexate, and at least one swollen joint out of 28 at treatment start (baseline). The primary outcome was time to the first resolution of joint swelling on the individual joint level, assessed at baseline and at 6, 12, 18, and 24 months. Hazard ratios (HR) for resolution comparing different joint locations were estimated using interval-censored mixed-effects Cox proportional hazards models. The nested data structure was accounted for by including a random effect for the country and the patient. Analyses were adjusted for age and sex. Results: A total of 1729 patients with 8397 swollen joints at baseline met the inclusion criteria. The proportion of women was 54%. The proportion of patients on concomitant methotrexate was 77%. The mean (SD) age was 49.4 (12.1) years, and the symptom duration 9.0 (8.6) years. The mean number of swollen and tender joints at baseline was 4.8 (4.1) and 7.4 (6.0), respectively, with a mean disease activity score using the C-reactive protein (DAS28-CRP) of 4.7 (1.0). The proportion of patients with joint swelling at specified locations at baseline is depicted in Figure 1. Concerning the upper limb and using the response of the proximal interphalangeal joint of the third digit (PIP3) as a reference, a significantly higher rate of resolution of joint swelling was observed for the elbow and the shoulder (HR 1.80, 95% CI 1.29-2.51 and HR 1.56, 95% CI 1.08-2.26, respectively) (Figure 2). In contrast, a lower rate of resolution of joint swelling was found for the wrist in relation to the PIP3 joint (HR 0.68, 95% CI 0.56-0.82, Figure 2). No evidence for a difference in resolution of joint swelling was found for the knee in comparison to the elbow (HR 0.78, 95% CI 0.51-1.20). Conclusion: The clinical response of articular inflammation to a TNFi in PsA, in terms of time to the first resolution of joint swelling, appears to depend on joint location. This suggests that local factors, such as differences in mechanical factors or synovial fibroblast phenotypes, might impact treatment effectiveness at specific joints. Future analyses exploring whether joint specific responses in PsA are associated with distinct therapeutic modes of action are warranted. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Adrian Ciurea: None declared, Seraphina Kissling: None declared, Andrea Goetschi: None declared, Lykke Midtbøll Ørnbjerg Research grant from Novartis, Simon Horskjær Rasmussen Research grant from Novartis, Bálint Tamási: None declared, Burkhard Moeller Speakers bureau: Eli-Lilly, Janssen, Novartis, Pfizer, Grant/research support: Amgen, Michael J. Nissen Speaker fees from AbbVie, Amgen, Eli Lilly, Janssens, Novartis, Pfizer, Consulting fees from AbbVie, Eli Lilly, Janssens, Novartis, Pfizer, Research grants from Novartis and Pfizer, Bente Glintborg Research grants from Pfizer, AbbVie, BMS, Sandoz, Anne Gitte Loft Speaking and/or consulting fees from AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Speaking and/or consulting fees from AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Research grant from Novartis, João Madruga Dias: None declared, Paula Valente: None declared, Almut Scherer Employed by Bristol-Myers-Squib in 2007-2008, René Braem: None declared, Karel Pavelka Consultant: AbbVie, UCB, Pfizer, Eli Lilly, Celltrion, MSD, and Novartis, Jakub Zavada Speakers bureau: AbbVie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Sanofi, Astra Zeneca, Sobi, Bjorn Gudbjornsson Speaking fees from Novartis and Nordic-Pharma, Consulting fees from Novartis, Olafur Palsson: None declared, Gareth T. Jones Speaker fee from Janssen, Research grants (paid to employer) from AbbVie, Pfizer, UCB, Amgen, GSK, Gary J. Macfarlane Research grant from GSK, Catalin Codreanu Speaker fees from AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Consultancy fees from AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Corina Mogosan Speaker fees from AbbVie, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Vappu Rantalaiho Speakers bureau: Novartis, Viatris, Consultant: Pfizer, Ritva Peltomaa Consultant: AbbVie, Boehringer, Celltrion, Fresenius, Lilly, UCB, Isabel Castrejon Speaker and/or consultancy fees from BMS, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, MSD, Pfizer, GSK, Speaker and/or consultancy fees from BMS, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, MSD, Pfizer, GSK, Ziga Rotar Speakers bureau: Abbvie, Amgen, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek, Janssen, Consultant: Abbvie, Novartis, Eli Lilly, Pfizer, Janssen, SOBI, Swixx BioPharma, AstraZeneca, Brigitte Michelsen Consulting fees from Novartis, Research grant from Novartis (paid to employer). Centre for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY) is funded as a Centre for Clinical Treatment Research by The Research Council of Norway (project 328657), Florenzo Iannone Consulting and/or speaking from Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Consulting and/or speaking from Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Research grant from BMS, Galapagos, Pfizer, Francesca Cozzini Speaker fees from Eli Lilly, Janssen, BMS, Pfizer, Galapagos, Boehringer-Ingheleim, Consultation fees from Eli Lilly, Janssen, BMS, Pfizer, Galapagos, Boehringer-Ingheleim, Research grant from BMS, Johan K Wallman Speaker fees from AbbVie, Amgen, Research support from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Irene van der Horst-Bruinsma Speaker and/or consultancy fees from UCB. Fees received for Lectures from BMS, AbbVie, Pfizer, MSD, UCB, Consultant for Abbvie, UCB, MSD, Novartis, Lilly, Unrestricted Grants received for investigator initiated studies from MSD, Pfizer, AbbVie, UCB., Oliver Distler: None declared, Mikkel Østergaard Speaker and/or consultancy fees from Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, Speaker and/or consultancy fees from Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, Research grants from Abbvie, BMS, Merck, Novartis and UCB, Merete Lund Hetland Speaker for Pfizer, Medac, Sandoz (no personal income, institution), Advisory Board Abbvie (No personal income, paid to institution). Prev. chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies., Research grants (institution) from Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Nordforsk, Raphael Micheroli Honoraria for lectures or presentations from AbbVie, Eli Lilly, Janssen, Gilead, and Pfizer, Caroline Ospelt: None declared.