P091 Effects of biologics on IL-17A and TNF induced cytokine secretion on synovial fibroblasts from rheumatoid and psoriatic arthritis patients

Career situation of first and presenting author Post-doctoral fellow. Introduction Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are both rheumatic autoimmune diseases, which share a number of similarities but also display differences. For example, the anti-IL17A biologic secukinumab turned out to be more effective in PsA than in RA. The anti-TNF biologic adalimumab on the other hand is equally indicated for both diseases. Synovial fibroblasts (SF) are one of the key effector cell types in the pathophysiology of RA and PsA. Objectives We therefore investigated whether the effect of the two cytokines IL-17A and TNF-α as well as the effect of their corresponding biologics differs between RASF and PsASF, thus contributing to the difference seen in the therapeutic response. The effect of the IL-17A homolog IL-17F was also analyzed. Methods SF were isolated from patients with PsA or RA, each undergoing surgery. SF from RA and PsA patients were stimulated with recombinant IL-17A, IL-17F and TNF-α alone or with respective combinations. Dose-response curve analysis was performed with IL-17A. The biologics secukinumab and adalimumab were used to block the effects on the SF. As a measure of the proinflammatory response, secretion of the cytokine IL–6 was quantified using an immunoassay. Results RASF as well as PsASF responded to IL-17A (IL-17A: 13.7-fold vs 6.9–fold; n=3), while IL-17F alone caused no induction of IL-6 secretion in either SF type. However, when used in combination with TNF-α, both IL-17 isoforms, IL–17A and IL-17F, increased IL-6 secretion due to a strong synergistic effect with TNF-α. Surprisingly, these effects were notably stronger for RASF than for PsASF (IL-17A: 544-fold vs 127-fold, IL-17F: 54-fold vs 27-fold; n=3). However, adalimumab and secukinumab were similarly effective in abolishing the synergistic effect of IL-17A and TNF-α in RASF as well as PsASF. Conclusions SF appear not to contribute to the differences in the therapeutic effectiveness of the anti-IL17A biologic secukinumab as the response to IL-17A alone and IL-17A together with TNF–α is not stronger for PsASF than for RASF. Furthermore, secukinumab was similarly effective for both SF types. The data also suggest that in a proinflammatory milieu with increased TNF levels IL-17A as well as IL-17F play a role in the SF-mediated pathophysiology of PsA and, therefore, approaches targeting TNF are effective in both diseases. Acknowledgements Supported by an unrestricted educational grant from Celgene GmbH. Disclosure of Interest K. Frommer Grant/research support from: unrestricted educational grant from Celgene GmbH, S. Rehart: None declared, U. Muller-Ladner: None declared, E. Neumann: None declared.