THU0097 Phosphodiesterases 4 (PDE4) inhibitor ameliorates experimental arthritis

Background Rheumatoid arthritis (RA) is a chronic inflammatory bone-destructive disorder with autoimmune features. Apremilast is a novel phosphodiesterases 4 (PDE4) inhibitor suppressing immune and inflammatory responses. Objectives We assessed the anti-inflammatory and bone protection effects of apremilast in collagen CII induced arthritis (CIA)models. Methods Apremilast was given starting from day 14 after immunisation, we investigated whether apremilast (5 mg/kg or 25 mg/kg) can ameliorate arthritis onset. Bone erosion was measured by histological and micro-computed tomographic analysis. Anti–mouse type II collagen (CII) antibody levels were measured by enzyme-linked immunosorbent assay. Human cartilage and rheumatoid arthritis (RA) synovial fibroblasts (RASFs) implantation in the severe combined immunodeficiency (SCID) mouse model of RA were used to study the role of apremilast in suppression of RASFs destroying cartilage in vivo. Results We found that apremilast therapy delayed arthritis onset and reduced arthritis scores in CIA model at a different dose, compared to CIA model and blank vector (figure 1A). Total serum IgG, IgG1, IgG2a, and IgG2b were all decreased in apremilast groups. Furthermore, apremilast can prevent CIA mice from bone erosion by CT analysis. High dose of apremilast (25 mg/kg) was superior to low dose (5 mg/kg) in treating CIA (figure 1B, C). Apremilast treatment can inhibit destroy and migratory ability of RASFs to cartilages. Compared to the model group, Apremilast treatment significantly reduced the invasion scores in both primary implant and contralateral implant. Conclusions Our data suggest that apremilast was effective in preventing arthritis and bone erosion in CIA model, implicating a potential promise of therapy on rheumatoid arthritis. Acknowledgements This work is supported in part by the grants from the Celgene Foundation, NIH R01 059103, National Natural Science Foundation of China (81671611, 81701600). Disclosure of Interest None declared