methotrexate + glucocorticoids

**Methotrexate + glucocorticoids** is a combination therapy commonly used in the treatment of autoimmune inflammatory diseases, especially **rheumatoid arthritis**. Methotrexate is a small molecule antimetabolite and disease-modifying antirheumatic drug (DMARD), acting primarily through inhibition of enzymes required for nucleotide synthesis (notably **dihydrofolate reductase**, **thymidylate synthase**, and **amido phosphoribosyltransferase**) which suppresses inflammation and prevents immune cell proliferation[2]. Glucocorticoids are steroidal anti-inflammatory drugs that bind and activate the **glucocorticoid receptor** to regulate gene transcription, broadly suppressing inflammatory responses and immune activity[5]. This combination is recommended in early rheumatoid arthritis to rapidly control inflammation and prevent joint damage, with methotrexate also functioning as a steroid-sparing agent to reduce the required glucocorticoid dose[1][5][6]. Methotrexate appears to increase sensitivity to glucocorticoids in immune cells by upregulating the active glucocorticoid receptor alpha isoform and downregulating the inhibitory beta isoform in lymphocytes[4]. Recent research shows methotrexate may also protect against glucocorticoid-induced osteoporosis by inhibiting osteoclast formation through activation of the IFN-γ receptor/STAT1 pathway[6].

Other names

systemic corticosteroids/methotrexatecorticosteroids + methotrexate