However, an increase in serious infections was observed when the IL-1-receptor antagonist anakinra was added to the anti-TNF agent etanercept in RA (Genovese et al., 2004), and also when other biologics were added to the CTLA-4 co-stimulatory blocking agent abatacept (Weinblatt et al., 2006). This evidence concerns the gene TNF and rheumatoid arthritis.