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As of February 2018, 5 originator TNF inhibitors(infliximab, etanercept, adalimumab, golimumab and certolizumab pegol)and biosimilar agents of infliximab and etanercept are available for rheumatoid arthritis(RA)in Japan. The effectiveness of TNF inhibitors considerably improves with concomitant methotrexate regardless of their immunogenicity. The Japan College of Rheumatology guideline for TNF inhibitor use in RA has been updated in March 2017 according to recent evidences. During the remission induction phase, maintenance of drug trough level above effective blood concentration is paramount, while the tapering and withdrawal of TNF inhibitors may be considered after achieving sustained remission.

Objective: To evaluate the safety and effectiveness of certolizumab pegol (CZP) in a real-world setting among Japanese patients with rheumatoid arthritis., Methods: Post-marketing surveillance data from 2,579 patients treated with CZP were analyzed. Adverse events (AEs) observed during the 24-week CZP treatment period were recorded. Disease activity was evaluated using DAS28-ESR and DAS28-CRP at baseline, Week 12, Week 24, or at withdrawal., Results: The total period of exposure to CZP was 1313.8 patient-years (PY). AEs were reported in 658 (25.5%) patients, at an event rate (ER) of 73.68/100 PY. The most frequent serious AEs were pneumonia, herpes zoster, and interstitial lung disease, at ER per 100 PY of 2.06, 1.29, and 1.22, respectively. Mean disease activity scores at baseline, as measured by DAS28-ESR and DAS28-CRP, were 4.77 ± 1.34 and 4.21 ± 1.27, respectively. Mean changes from baseline at the last observation were -1.29 ± 1.46 and -1.30 ± 1.42, respectively. EULAR good or moderate responses were achieved in 65% of patients. Longer disease duration, prior biologics use, and treatment without MTX co-therapy were associated with EULAR no response., Conclusion: In this interim analysis, no new safety signals were observed. Clinical response to CZP was observed in approximately two thirds of patients.

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.