SEOUL NATIONAL UNIVERSITY HOSPITAL

In June issue of the New England Journal of Medicine (NEJM), Professor Eun Bong Lee (Department of Internal Medicine) at the SNU College of Medicine, in collaboration with 157 institutions worldwide, published the result of a study evaluating the efficacy and safety of tofactinib, a new therapeutic agent developed by Pfizer for rheumatoid arthritis. In this study, the efficacy and safety of tofacitinib was compared with methotrexate (MTX), a conventional disease modifying anti-rheumatic drug (DMARD) which is the current standard therapeutic agent, in 956 patients with rheumatoid arthritis all over the world. The patients took 5mg or 10mg of tofacitinib twice daily (373 and 397 patients respectively) or methotrexate once a week (186 patients) for 24 months.

The result showed that tofacitinib was significantly superior to MTX in improving the number of inflamed joints, bone destruction in joint X-radiograph and quality of life of the enrolled patients In particular, the proportion of patients who achieved more than 70% of clinical improvement (ACR70), which is considered a tough target for treatment, was 25-38%in tofacitinib group, while it was only 12% in methotrexate group.

Rheumatoid arthritis, which is affected by 1% of population world widely, is a chronic disease that disables patients by causing inflammation in multiple joints throughout the body. It develops when the immune system, which is an essential defense mechanism against microorganisms, attacks the human body itself and causes inflammation in the joints. In this process, various immune and inflammatory cells which are activated play a critical role. Currently, several classes of therapeutic agents are being used for the treatment of rheumatoid arthritis, and these are represented by conventional DMARDs and parenteral biological DMARDs. However, complete remission of the disease is still difficult to achieve. Consequently, the search for novel anti-inflammatory drugs still continues. Inflammation processes are activated by various inflammatory cytokines through several classes of signaling molecules. Since several signaling molecules are commonly present in the different kinds of immune or inflammatory cells, blocking these signaling molecules is a novel strategy to effectively and concurrently control the inflammatory cells. Tofacitinib, which is a leader in this class of signaling blockers, targets a signaling molecule called Janus kinase (JAK).

Professor Lee stated, “The value of this study lies in showing that a new class of anti-rheumatic drug can be considered as a better option than the currently used drugs and it also can be a signal to a fundamental change in the future paradigm of rheumatoid arthritis treatment. In other words, tofacitinib has added signal transduction inhibitors as a new treatment option besides traditional anti-rheumatic drugs and biological agents. It will stimulate new discussions on what the primary therapeutic agent for rheumatoid arthritis should be.”

In particular, tofacitinib is an oral agent and so has the advantage of being taken easily by patients. Current existing biological agents are all injection agents, thus leading to drug administration discomforts for both patients and clinicians and injection-related adverse events. Despite the better efficacy in the treatment of rheumatoid arthritis, tofacitinib can be related to similar safety issues of biologic DMARDs, which are inevitable side effects resulting from the process of controlling various immune and inflammatory cells, requiring careful monitoring by the specialists.

The NEJM (impact factor (IF) = 51.658) is one of the foremost journals around the globe, and also the most frequently cited journal in medicine. Professor Lee has continued to report noteworthy research results in the field of rheumatic diseases and has contributed to elevating the level of South Korean rheumatic research to world-class by publishing the outcome of his study in the NEJM.