Objectives To quantify connective tissue turnover from type III collagen in response to 4 different types of intervention in rheumatoid arthritis (RA); methotrexate (MTX) combined with or without either tocilizumab (TCZ), tofacitinib (TOFA) or adalimumab (ADA) in RA.
Methods 149 RA patients were treated with 1) MTX; 23, 2) ADA+MTX; 49, 3) TOFA+MTX; 27 or 4) TCZ+MTX; 50. Four specific neo-epitopes biomarkers were measured in the serum samples; C3M and PRO-C3 markers of type III collagen degradation and formation respectively.
Results Tissue destruction measured by C3M increased in RA patients and was significantly correlated with total sharp score (SHS) as well as disease activity (DAS28) at baseline even after adjustment for covariates (rho=0.20, 0.33, p=0.018, <0.0001, respectively). PRO-C3 was also increased and the levels correlated with both SHS, and DAS28 (rho=0.22, 0.43, p=0.0067, <0.0001, respectively). Tissue destruction measured by C3M was reversed to healthy levels in all treatment after the treatment with MTX, ADA+MTX, TOFA+MTX or TCZ+MTX. However, JAK inhibition resulted in a decrease of PRO-C3, a sign of fibrogenesis, whereas MTX increased PRO-C3 in RA. (Figure)
Conclusions Interstitial tissue remodeling was increased in RA as compared to healthy controls. All four different intervention inhibited inflammation-driven tissue destruction to the same level, whereas only TOFA blocked fibrogenesis in RA patients, indicating that JAK inhibition could attenuate tissue fibrosis.
Disclosure of Interest S. Hirata Speakers bureau: AbbVie, Eisai, Bristol Meyers Squibb, N. Gudmann Employee of: Nordic Bioscience A/S, S. Kubo: None declared, M. Karsdal Shareholder of: Nordic Bioscience A/S, Employee of: Nordic Bioscience A/S, A. Bay-Jensen Employee of: Nordic Bioscience A/S, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Chugai, MSD, Astellas, Novartis, Speakers bureau: Abbvie, Chugai, Astellas, Takeda, Santen, Mitsubishi-Tanabe, Pfizer, Janssen, Eisai, Daiichi-Sankyo, UCB, GlaxoSmithKline, Bristol-Myers