TNF and rheumatoid arthritis: Second-line biologics, including abatacept (CTLA-4-Ig), rituximab (anti-CD20), and tocilizumab (anti-IL-6R), which target B and T cell responses, have shown increased efficacy in RA patients failing response to a first anti-TNF therapeutic [47–51], further suggesting the involvement of the adaptive compartment in the lack of response to anti-TNF.