SIMULTANEOUS ANALYSIS OF ANTI-CCP, RHEUMATOID FACTOR, ANTI-PAD4 AND ANTI-CARBAMYLATED PROTEIN ANTIBODIES REVEALS INTERACTION EFFECTS WITH RESPONSE TO ANTI-TNF THERAPY IN RHEUMATOID ARTHRITIS

Background: Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 2 out of 3 Rheumatoid Arthritis patients. Identifying the patients that will not respond to this therapeutic approach is a major translational goal in RA. Association of seropositivity to rheumatoid factor (RF) or anti-cyclic-citrullinated antibodies (anti-CCP) with anti-TNF response has proven inconclusive, suggesting that other yet unexplored biomarkers could be more informative for this goal. Objectives: We tested the association of two recently introduced biomarkers in RA: anti-carbamylated protein antibodies (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4). Methods: A prospective cohort of n=80 RA patients starting anti-TNF therapy was recruited and levels for all four autoantibodies -RF, anti-CCP, anti-CarP and anti-PAD4- were measured at baseline. The change in DAS28 score between baseline and week 12 of therapy was used as the clinical endpoint. Results: Single marker-analysis showed no significant association with drug response. However, when testing for interactions between autoantibodies, we found highly significant associations with drug response. Anti-CCP and RF showed a positive interaction with the response to anti-TNF therapy (P=0.00068), and anti-PAD4 and antiCarP titers showed a negative interaction with the clinical response at week 12 (P=0.0062). Using an independent retrospective sample (n=199 patients), we validated the interaction between anti-CCP and RF with the clinical response to anti-TNF agents. (P=0.044). Conclusion: The results of this study show that interactions between antibodies are important in the response to anti-TNF therapy and suggest potential pathogenic relationships. Acknowledgments : We would like to thank the clinical researchers and patients participating in the IMID Consortium for their collaboration Disclosure of Interests: Antonio Julia: None declared, Maria Lopez Lasanta: None declared, Francisco Blanco: None declared, Antonio Gomez: None declared, Isabel Haro: None declared, Antonio Juan Mas: None declared, Alba Erra: None declared, Ma Luz Garcia Vivar: None declared, Jordi Monfort: None declared, Simon Sanchez Fernandez: None declared, Isidoro Gonzalez-Alvaro Grant/research support from: Roche Laboratories, Consultant of: Lilly, Sanofi, Paid instructor for: Lilly, Speakers bureau: Abbvie, MSD, Roche, Lilly, Mercedes Alperi-Lopez: None declared, Raul Castellanos: None declared, Antonio Fernandez-Nebro: None declared, Cesar Diaz Torne: None declared, Nuria Palau: None declared, Raquel M Lastra: None declared, Jordi Llados: None declared, Raimon Sanmarti: None declared, Sara Marsal: None declared