tregalizumab + methotrexate

Tregalizumab + methotrexate is a combination therapy investigated for the treatment of moderate-to-severe active rheumatoid arthritis in patients with inadequate response to methotrexate alone. **Tregalizumab** is a humanized monoclonal antibody that binds a unique epitope on CD4 (D2 domain), selectively activating regulatory T cells (Tregs) without depleting them, leading to increased immunosuppressive function and downmodulation of CD4 surface expression[3][5]. **Methotrexate** is a small molecule antimetabolite and antifolate that acts primarily through inhibition of enzymes required for purine and pyrimidine synthesis, notably dihydrofolate reductase and AICART, leading to increased extracellular adenosine and anti-inflammatory effects in rheumatoid arthritis[2][4]. This specific combination was studied in a randomized, placebo-controlled, Phase IIb clinical trial (TREAT 2b), but did not demonstrate significantly improved efficacy over methotrexate monotherapy in the target population[1][3][5].