3. Biologic Drugs Targeting Cellular Surface Antigens

Abstract

Rheumatoid arthritis (RA) is a chronic polyarthritis driven by autoimmune inflammatory processes involving various factors and molecules. Not only humoral factors but cellular surface antigens can be promising targets for regulation of the disease. Rituximab (RTX) and abatacept (ABT) are drugs targeting cellular surface antigens that are now available for the treatment of RA. RTX is partially humanized chimeric anti-CD20 antibody, which was developed for the treatment of B cell lymphoma. The efficacy of RTX when added on methotrexate (MTX) for the treatment of RA was confirmed by the DANCER trial. RTX is now established as a second-line biologic drug in RA treatment guidelines in EU and US because of the effectiveness proven by the REFLEX trial. Unfortunately, RTX is not approved in Japan, and clinical trials of ocrelizumab and ofatumumab, newly developed anti-CD20 antibodies, had failed because of safety issues. ABT is a chimeric protein that combines the extracellular domain of CTLA-4 and the Fc portion of IgG1. CTLA-4 is a surface molecule expressed on T cell and is a negative regulator of the interaction between T cells and antigen presenting cells. CTLA-4 or ABT competitively inhibits CD28-CD80/86 interaction, which is an essential co-stimulatory pathway of T cell activation, and induces an anergic state in T cells. The effectiveness of ABT for biologics-naïve RA and tumor necrosis factor (TNF) antagonist-refractory RA were confirmed by the AIM trial and the ATTAIN trial, respectively. ABT is now available globally and is established as a therapeutic option for RA treatment also in Japan. (Jpn J Clin Pharmacol Ther 2013; 44(1): 15-21)