title: Small-molecule inhibitors for autoimmune arthritis: success, failure and the future.
abstract: Treatment of patients with aggressive autoimmune arthritis, such as rheumatoid arthritis (RA), is a considerable challenge for physicians, particularly rheumatologists. Because of the nature of autoimmune arthritis, effective and complete suppression of disease activity has been the primary therapeutic goal. Although currently available disease-modifying antirheumatic drugs (DMARDs) can successfully control the disease progression in a large proportion of patients, the benefit/risk ratio is not very much satisfied. The introduction of biologic agents such as anti-tumor necrosis factor-α, anti-interleukin-6, and anti-CD20 brings significant help to those patients with an inadequate response to treatment with DMARDs. In considering the limitation of currently available DMARDs and biologics, the development of new DMARDs, small-molecule inhibitors (SMIs), has recently emerged. In the past few years, a great volume of knowledge has been revealed from the experience of examining the usefulness of several SMIs for therapeutics of autoimmune arthritis. This paper addresses the up-to-date knowledge regarding autoimmune arthritis, therapeutics, findings from recently developed SMIs and the benefits and drawbacks of the development of SMIs. In addition, perspectives on the future development of SMIs for autoimmune arthritis will be described and discussed.
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institute, Zhunan, Taiwan, ROC.
authors.forename: Ling-Jun
authors.initials: LJ
authors.lastname: Ho
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan, ROC; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Tao-Yuan, Taiwan, ROC. Electronic address: laiandho@gmail.com.
authors.forename: Jenn-Haung
authors.initials: JH
authors.lastname: Lai
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D054852:Small Molecule Libraries / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018501:Antirheumatic Agents; D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries
keywords: Autoimmune arthritis; Janus kinases; P38; Phosphodiesterase 4; Small-molecule inhibitors; Spleen tyrosine kinase