Pos0981 precision medicine in rheumatoid arthritis. evaluation of two novel tests to predict clinical response to methotrexate in patients with early rheumatoid arthritis

Background The main goal of treatment in patients with early Rheumatoid Arthritis (RA) is to achieve a clinical remission. Methotrexate (MTX) should be the first treatment strategy in naïve patients, but about one third will not respond to this therapy. There is a lack of tools to predict the individual response to MTX. Pre-treatment number of circulating monocytes may predict clinical response to MTX (1) and ROS production may be related to the pharmacological action of MTX (2, 3). Objectives To evaluate the feasibility of 2 novel tests (ROS and Monocytes Tests) to measure in vitro the sensitivity to MTX in patients with new-onset RA and the association of MTX response with clinical remission at 6 months. Methods This is an observational, longitudinal Proof-of-Concept with a follow-up of 6 months. 33 adult patients with early RA according EULAR criteria and with a DAS28 ≥2.6 were included before treatment with a disease-modifying antirheumatic drugs disease (DMARD). 26 patients had a valid sample for tests performance. At baseline a patient blood sample was collected, where PBMCs were isolated and frozen. After 3 weeks, PBMCS were defrost, placed in a plate p96, activated with phytohemagglutinin, and exposed to MTX. In the ROS test, Reactive Oxygen Species were measured by means of a specific vital probe with fluorimetry. In the Monocytes test, monocytes metabolic activity was determined with resazurin and measured with fluorimetry. Clinical and analytical variables were registered along patients´ follow-up and DAS28<2.6 was used as criteria for clinical remission. Results of both tests were compared in patients with and without clinical remission at 6 months. Results ROS levels as determined with the ROS test showed to be increased in patients with clinical remission when compared with patients without remission (p<0.001) (Figure 1). Monocytes number determined with the Monocytes test was decreased in the patients with clinical remission vs patients without remission (p<0.05) (Figure 1). The predictive capacity of these models was analyzed with the area under the operating characteristics curve (ROC), showing for ROS Test an AUC of 0.919 (CI95% 0.813- 1.025) (p<0.0001) and for Monocytes test 0.826 (CI95% 0.664-0.989) (p<0.0001). Figure 1. Conclusion In naïve patients with new-onset RA, the pharmacological response to MTX can be measured in vitro by the quantification of total monocytes and ROS production from PBMCs. Low monocyte percentages and high levels of ROS production are associated with patients´ clinical remission at 6 months. References [1]Chara et al. Journal of Translational Medicine. 2015; 13:2. DOI: 10.1186/s12967-014-0375. [2]Benjamin Friedman and Bruce Cronstein. Joint Bone Spine. 2019; 86(3):301–307. DOI: 10.1016/j.jbspin.2018.07.004. [3]Bedoui et al. International Journal of Molecular Sciences. 2019; 20(20):5023. DOI: 10.3390/ijms20205023. Acknowledgements: NIL. Disclosure of Interests Alejandro Escudero Contreras: None declared, Francisco J. Blanco: None declared, Mercedes Alperi-López: None declared, Ana Isabel Turrión: None declared, Chary Lopez-Pedrera: None declared, Tatiana Yebra Employee of: Biohope Scientific Solutions for Human Health, Gema Cordero Employee of: Biohope Scientific Solutions for Human Health, Teresa Diez Employee of: Biohope Scientific Solutions for Human Health, Isabel Portero Shareholder of: Biohope Scientific Solutions for Human Health, Employee of: Biohope Scientific Solutions for Human Health.