Review Article

J Rheum Dis 2012; 19(3): 118-124

Published online June 30, 2012

© Korean College of Rheumatology

류마티스관절염의 새로운 치료제인 소분자억제제

이은봉

서울대학교 의과대학 내과학교실

Small Molecule Inhibitors in Rheumatoid Arthritis

Eun Bong Lee

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Correspondence to : Eun Bong Lee

Abstract

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease predominantly affecting diarthroidal joints. Following the successful application of biologic agents, several small molecule inhibitors are currently under clinical trials. Small molecule inhibitors have several strengths compared with biologics. First, they can target several inflammatory cytokines together by blocking common signal transduction pathways. Second, they can be taken orally. Third, the price can be made flexible. Among the several small molecule inhibitors in the development process, fostamatinib and tofacitinib are the closest to the clinics at the moment. Fostamatinib, which is a Syk inhibitor, showed superior efficacy over placebo with tolerable safety signals. Diarrhea, hypertension and infection are representative adverse events. Tofacitinib, which is JAK inhibitor, is now finishing phase 3 clinical trials. It showed clinical efficacy comparable to Adalimumab and similar adverse effect profiles to the biologics, which include opportunistic infections. For laboratory abnormalities, leukopenia, anemia, increase of LDL and serum Cr were reported, which, however, were stabilized with prolonged use. Other classes of small molecule inhibitors did not show impressive efficacy as these small molecule inhibitors. In conclusion, small molecule inhibitors are promising novel therapeutic agents for the treatment of RA. They will be able to change the treatment paradigm of RA if they can show long-term safety.

Keywords Rheumatoid arthritis, Small molecule inhibitor

Article

Review Article

J Rheum Dis 2012; 19(3): 118-124

Published online June 30, 2012

Copyright © Korean College of Rheumatology.

류마티스관절염의 새로운 치료제인 소분자억제제

이은봉

서울대학교 의과대학 내과학교실

Small Molecule Inhibitors in Rheumatoid Arthritis

Eun Bong Lee

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Correspondence to:Eun Bong Lee

Abstract

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease predominantly affecting diarthroidal joints. Following the successful application of biologic agents, several small molecule inhibitors are currently under clinical trials. Small molecule inhibitors have several strengths compared with biologics. First, they can target several inflammatory cytokines together by blocking common signal transduction pathways. Second, they can be taken orally. Third, the price can be made flexible. Among the several small molecule inhibitors in the development process, fostamatinib and tofacitinib are the closest to the clinics at the moment. Fostamatinib, which is a Syk inhibitor, showed superior efficacy over placebo with tolerable safety signals. Diarrhea, hypertension and infection are representative adverse events. Tofacitinib, which is JAK inhibitor, is now finishing phase 3 clinical trials. It showed clinical efficacy comparable to Adalimumab and similar adverse effect profiles to the biologics, which include opportunistic infections. For laboratory abnormalities, leukopenia, anemia, increase of LDL and serum Cr were reported, which, however, were stabilized with prolonged use. Other classes of small molecule inhibitors did not show impressive efficacy as these small molecule inhibitors. In conclusion, small molecule inhibitors are promising novel therapeutic agents for the treatment of RA. They will be able to change the treatment paradigm of RA if they can show long-term safety.

Keywords: Rheumatoid arthritis, Small molecule inhibitor

JRD
Jan 01, 2025 Vol.32 No.1, pp. 1~7
COVER PICTURE
Cumulative growth of rheumatology members and specialists (1980~2024). Cumulative distribution of the number of the (A) Korean College of Rheumatology members and (B) rheumatology specialists. (J Rheum Dis 2025;32:63-65)

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