Systemic corticosteroids + methotrexate (SCS + MTX)

Systemic corticosteroids + methotrexate is a therapeutic drug combination rather than a single biological target [1, 2]. This regimen is frequently employed in the management of chronic inflammatory and autoimmune disorders, such as rheumatoid arthritis and various forms of vasculitis, to achieve rapid symptom control and long-term disease remission [1, 4]. Systemic corticosteroids provide immediate anti-inflammatory effects by modulating gene expression through the glucocorticoid receptor, while methotrexate serves as a disease-modifying antirheumatic drug (DMARD) that inhibits dihydrofolate reductase and increases adenosine signaling [2, 5]. The combination is often used as a "steroid-sparing" strategy, allowing for a reduction in corticosteroid dosage once methotrexate reaches therapeutic efficacy, thereby minimizing long-term steroid-related side effects [4]. Clinical monitoring is essential due to the potential for cumulative immunosuppression and organ toxicity, particularly affecting the liver and bone marrow [1, 2]. This combination remains a cornerstone of rheumatological practice due to its synergistic effects on the immune system [3].

Other names

Methotrexate and corticosteroid combination therapyMTX plus steroidsCorticosteroid-methotrexate regimenSteroid-sparing methotrexate therapy

Systemic corticosteroids bind to the cytosolic glucocorticoid receptor (NR3C1), leading to the inhibition of pro-inflammatory transcription factors like NF-kappaB and the induction of anti-inflammatory genes [2]. Methotrexate (MTX) inhibits dihydrofolate reductase (DHFR), disrupting the synthesis of thymidylate and purines required for DNA replication in rapidly dividing immune cells [1]. Furthermore, MTX promotes the release of adenosine, which binds to A2A receptors to suppress inflammatory cytokine production [3, 5].