title: Targeting GM-CSF in rheumatoid arthritis.
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.
authors: Department of Internal Medicine, Rheumatology, Akdeniz University, Faculty of Medicine, Antalya, Turkey. avcialiberkant@yahoo.com.
authors: Ali Berkant
authors: AB
authors: Avci
authors: Department of Rheumatology and Clinical Immunology, Charite-University Medicine Berlin, Germany.
authors: Eugen
authors: E
authors: Feist
authors: Department of Rheumatology and Clinical Immunology, Charite-University Medicine Berlin, Germany.
authors: Gerd-Rüdiger
authors: GR
authors: Burmester
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; C561644:mavrilimumab; D016178:Granulocyte-Macrophage Colony-Stimulating Factor