Patients with severe disease who do not respond effectively to this therapy are subsequently given biological disease modifying anti-rheumatic drugs (bDMARDs), which now cover a range of effector molecules in RA such as IL-1, IL-6, IL-17, TNF-α, T cell co-stimulatory molecules, B cell activation and JAK/STAT signaling (106). This evidence concerns the gene TNF and rheumatoid arthritis.