AB0139 ASSOCIATION OF RS17004921 ADORA2A GENE POLYMORPHISM WITH EFFICACY OF METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Vera Milic, Milka Grk, Nemanja Damjanov, Biljana Jekic
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Adenosine A2A receptors (ADORA2A) are part of the adenosine-mediated antiinflammatory pathway. These receptors are over-expressed in peripheral blood leukocytes of patients with rheumatoid artritis (RA). Methotrexate (MTX), the gold standard for therapy, exerts its antiinflamatory effects via increased release of adenosine into the extracellular space. Adenosine binds to ADOR A2A and A3 and initiates an antiinflammatory response. Therefore, ADOR gene polymorphisms could have an impact on MTX therapy outcome. <h3>Objectives:</h3> To examine the role of adenosine receptor 2A gene (<i>ADORA2A, rs 17004921</i>) polymorhism on outcome of MTX treatment in RA. <h3>Methods:</h3> A total of 123 patients with RA (mean age 56.5±10.73, 91 (74% female), treated with MTX for 6 months (mean dose 12.22±3.20/weekly) were enrolled in a prospective study. Genotypisation within <i>ADORA2A</i> gene was performed using the KASP genotyping assays. MTX efficacy assessment was based on the changes in the Disease activity score (DAS28) after 6 months of treatment according to the EULAR response criteria. Patients with good and moderate response were classified as "responders", whereas patients with poor response were considered "nonresponders". Data of adverse effects were collected during this period. MTX efficacy and toxicity were compared among patients with different genotypes. All statiscal analyses were performed by SPSS version 16.0. <h3>Results:</h3> Median DAS 28 at the beginning of MTX treatment was 7.43±0.89. According to EULAR response criteria, 111 (90.2%) patients with RA were classified as responders. Among all RA patients, 97 (78.9%) had CC, 20 (16.3%) CT and 6 (4.9%) TT genotype. The distribution of <i>ADORA2</i> genotypes in responders (CC 77.5%, CT 17% and TT 5.4%) was not significantly different from nonresponders (CC 91.7%, CT 8.3%), p&gt;0.05. After 6 months, 26 carriers of T allele (CT+TT) had higher reduction DAS 28 (7.16 vs. 3.88) in comparison to other 97 patients (7.50 vs.4.64, p=0.013). Adverse effects were reported in 24 (19.5%) patients. Most of patients had hepatotoxicity and nausea, 14 (58%) and 9 (37%) respectively. No statistically significant association between <i>ADORA2</i>A genotype and side events has been observed (p&gt;0.05). <h3>Conclusion:</h3> According to our results, T allele of <i>ADORA2A rs17004921</i> polymorphism may have favourable influence on efficacy in RA patients treated with methotexatate. <h3>References</h3> [1] Cronstein B, Sitkovsky M. Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseasess. www.nature.com/nrrheum [2] Hider SL, Thomson W, Mack LF, et al. Polymorhisms within the adenosine receptor 2a gene are associated with adverse events in RA patients treated with MTX. Rheumatology2008;47:1156-1159. <h3>Disclosure of Interests:</h3> Vera Milic: None declared, Milka Grk: None declared, Nemanja Damjanov Grant/research support from: AbbVie, Pfizer and Roche, Consultant for: Abbvie, Gedeon Richter, Merck, Novartis, Pfizer and Roche., Speakers bureau: Abbvie, Gedeon Richter, Merck, Novartis, Pfizer and Roche., Biljana Jekic: None declared