The goal of this research is to assess the relationship among RFC1 G80A (rs1051266), TYMS-2R/3R (rs34743033), and ATIC C347G (rs2372536) variants found in the MTX metabolic cascade and the outcome (response to/or toxicity of) methotrexate therapy in Egyptian patients with RA. This evidence concerns the gene RFC1 and rheumatoid arthritis.