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Rheumatoid Arthritis
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Brent A. Luedders, Ted R. Mikuls, James R. O’Dell, Bryant R. England
Further insights into the pathogenesis of RA will lead to novel discoveries, including perhaps more precise targets for RA therapies. Targeting the pathways most directly involved in causing RA can produce better efficacy, lower toxicities, and promote the pursuit of cures over treatments. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine involved in the production and maturation of bone marrow myeloid cells and regulates mature myeloid cell functions, both implicated in the pathogenesis of RA.50 Several biologic agents targeting the GM-CSF pathway are currently under investigation for RA. Both mavrilimumab and otilimab have shown efficacy in phase 1 and 2 clinical trials.137–139
Emerging injectable therapies for osteoarthritis
Published in Expert Opinion on Emerging Drugs, 2022
Otilimab is a monoclonal antibody which inhibits GM-CSF. GM-CSF can act as a pro-inflammatory cytokine affecting the JAK/STAT pathway [55], and its inhibition has some evidence in reducing synovitis in rheumatoid arthritis [56,57]. A single-phase IIa study has been performed in patients with inflammatory hand OA which demonstrated no significant difference in pain and function between those who received subcutaneous otilimab compared to placebo. There was also no significant difference in MRI synovitis scores. There was, however, a nonsignificant trend toward a reduction in pain and functional impairment with otilimab [58]. It should be noted that two of the 22 patients in the otilimab group had a herpes zoster infection, which is not surpsing given its mechanism of action [58].
Axial spondyloarthritis: emerging drug targets
Published in Expert Opinion on Therapeutic Targets, 2021
Bilade Cherqaoui, Luiza M. Araujo, Simon Glatigny, Maxime Breban
Phase II clinical trials using neutralizing monoclonal antibodies to target GM-CSF (otilimab, namilumab) or its receptor (mavrilimumab) have been undertaken in rheumatoid arthritis, showing preliminary evidence of rapid and sustained efficacy with a satisfactory safety profile [82,83]. A phase II study is ongoing in AxSpA. However, the role of GM-CSF in systemic immune response, especially regarding its immunoregulatory effects, is not well defined and should raise caution [84,85].