Polymorphisms within the adenosine receptor 2a gene are associated with adverse events in RA patients treated with MTX

Objective. To examine the role of adenosine receptor 2a gene (ADORA2a) polymorphisms on outcome of MTX treatment in RA. Methods. Subjects included 309 RA patients with a defined response to MTX. Patients were included if they were (i) good responders (n=147) (ESR < 20 for > 6/12 on stable dose of MTX) (ii) inefficacy failures (n=101) (physician statement and failure to reduce ESR/CRP by 20%) or (iii) adverse event (AE) failures (n=61) (verified by medical record review). AEs were sub-divided into gastrointestinal (GI) (n=24), abnormal LFTs (n=20) or other (n=17). 8 single nucleotide polymorphisms (SNPs) within ADORA2a were genotyped using the Sequenom MALDI-TOF platform. Results. Five SNPs within ADORA2a were associated with stopping MTX for AEs (OR 2.1-3.07, P < 0.05 for all). Analysis by AE type showed that the association was specific for GI toxicity. No association was observed between ADORA2a and inefficacy outcomes. Conclusion. Genetic variation within ADORA2a is significantly associated with AEs on MTX, specifically GI AEs. Knowledge of the ADORA2a genotype may help to improve identification of patients at high risk of GI toxicity with MTX.