Abstract
TNF inhibitors, infliximab, etanercept and adalimumab, and tocilizumab are available in Japan and have been successful at improving the signs and symptoms of RA and, thereby, have set a new standard for disease control of RA and have the potential to protect joints from structural damage or to improve quality of life and mortality. However, the rate of successful induction of remission was about 30% and the treatment strategies for the patients who do not respond to these biologics should be established. Randomized clinical trials targeting T or B lymphocytes have been conducted in addition to the new anti-TNF blockers like golimumab or certolizumab pegol. Anti-CD20 antibodies such as rituximab (chimeric), ocrelizumab (humanized), ofatuzumab (full human) demonstrated effectiveness to the patients who do not respond to TNF blockers. CTLA-4 Ig, which can transduce negative signal into T lymphocytes in the co-stimulatory pathway, has also showed a good response to refractory RA. Furthermore, low molecular agents such as Jak (Janus kinase) 3 or syk (spleen tyrosine kinase) inhibitors demonstrated rapid and strong suppression of synovitis and are thought to be new candidates for the drugs to overcome refractory RA.
