tocilizumab + leflunomide

The combination of **tocilizumab** and **leflunomide** is used off-label for the treatment of moderate to severe rheumatoid arthritis, particularly in patients who are intolerant or contraindicated to methotrexate. Tocilizumab is a humanized monoclonal antibody that inhibits the interleukin-6 (IL-6) receptor, thereby reducing inflammation associated with autoimmune conditions. Leflunomide is a small molecule immunomodulator that acts primarily by inhibiting dihydroorotate dehydrogenase, blocking de novo pyrimidine synthesis, and suppressing T-cell proliferation. Studies suggest that this combination can serve as a safe and effective alternative to tocilizumab plus methotrexate, with comparable efficacy and tolerability in improving disease activity and functional disability in rheumatoid arthritis[1][3].