Small-molecule inhibitors for autoimmune arthritis: success, failure and the future

Eur J Pharmacol. 2015 Jan 15:747:200-5. doi: 10.1016/j.ejphar.2014.08.031. Epub 2014 Sep 16.

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.

Keywords: Autoimmune arthritis; Janus kinases; P38; Phosphodiesterase 4; Small-molecule inhibitors; Spleen tyrosine kinase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antirheumatic Agents / pharmacology*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / enzymology
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Small Molecule Libraries / pharmacology*
  • Small Molecule Libraries / therapeutic use

Substances

  • Antirheumatic Agents
  • Enzyme Inhibitors
  • Small Molecule Libraries