Targeting GM-CSF in rheumatoid arthritis

Clin Exp Rheumatol. Jul-Aug 2016;34(4 Suppl 98):39-44. Epub 2016 Jul 21.

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is well-known as a haemopoietic growth factor. However, it is also essential in regulating functions of mature myeloid cells such as macrophages. Preclinical studies and observations of flares of arthritis in patients following GM-CSF treatment supported its important contribution to the pathogenesis of rheumatoid arthritis (RA). As the most advanced compound, mavrilimumab, a monoclonal antibody against GM-CSF receptor, has already completed phase II trials with a long term of follow-up period of 74 weeks. During this exposure period, an acceptable sustained safety and tolerability profile has been observed addressing the concerns of development of cytopenias or pulmonary alveolar proteinosis. Of note, a rapid and sustained efficacy and normalisation of acute phase reactants were consistently shown in studies both targeting GM-CSF and its receptor. Its tumour necrosis factor (TNF) independent mode of action with concurrent blockade of GM-CSF as well as IL-17 signalling reported from preclinical studies supports the assumption that it can be a useful biologic and an alternative agent in TNF inhibitor resistant patients with RA. Therefore, subsequent studies are warranted to investigate the safety and efficacy of GM-CSF blocking agents in different subgroups of RA.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Molecular Targeted Therapy*
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Signal Transduction / drug effects
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • mavrilimumab
  • Granulocyte-Macrophage Colony-Stimulating Factor