Future therapeutic targets in rheumatoid arthritis?

Semin Immunopathol. 2017 Jun;39(4):487-500. doi: 10.1007/s00281-017-0623-3. Epub 2017 Apr 27.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches.

Keywords: BTK; GM-CSF; JAK; PI3K; Rheumatoid arthritis; Tolerogenic dendritic cells.

Publication types

  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / therapy*
  • Biomarkers
  • Combined Modality Therapy
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Immunotherapy
  • Janus Kinases / metabolism
  • Molecular Targeted Therapy*
  • Neuroimmunomodulation / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Signal Transduction / drug effects

Substances

  • Antirheumatic Agents
  • Biomarkers
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Phosphatidylinositol 3-Kinases
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Janus Kinases