In patients with RA, treatment with MTX reduced area of knee synovitis at the suprapatellar pouch by 35% [33]; inhibited inflammatory response in synovial tissue, including reducing numbers of macrophage, and suppressing expressions of intercellular adhesion molecule 1, IL-1, TNF-α, and CRP [48]; and decreased BMLs and synovitis even at very early stage [49]. This evidence concerns the gene TNF and rheumatoid arthritis.