Rheumatoid Factors (RFs) Do Not Bind Fc‑Free Certolizumab Pegol, but Do Bind to Fc‑Containing Biological DMARDs, Leading to Immune Complex Formation Which Induces Cytokine Release from Human Peripheral Blood Mononuclear Cells (PBMC) In Vitro (ACR Convergence 2026) - Sep 8, 2026 - Abstract #101; Pres time: Nov 8, 2026; 10:30 AM - 12:30 PM; Location: WB1&2; In Person; "In contrast, Fc-free certolizumab pegol (CZP) maintains stable drug levels and efficacy regardless of RF levels.1-4 Monoclonal recombinant RF IgMs and RF in RA patient sera bind Fc-containing bDMARDs, forming complexes cleared by macrophages, whereas CZP avoids this clearance.5-8 This study assessed the ability of RF, tumor necrosis factor alpha (TNF-α) and Fc-containing bDMARD, adalimumab (ADA) complexes to stimulate pro-inflammatory cytokine release from human peripheral blood mononuclear cells (PBMC), compared to Fc-free CZP. This study provides a mechanistic basis for the reduced efficacy of Fc‑containing anti‑TNF-α bDMARDs in high‑RF patients.1-8 RF+TNF-α+ADA complexes stimulate cytokine production, whereas Fc‑free CZP does not bind RF, does not form complexes, and does not induce cytokine release. These findings further explain why CZP is consistently efficacious in patients irrespective of their RF status.1-8"
Preclinical • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • CXCL8 • IFNG • IL10 • IL13 • IL1B • IL2 • IL4 • IL6
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Susanna Bidgood1; Sophie Hopkin1; Jacqueline O'Neill1; Joana Sousa1; Kathryn R. Malpas1; David M. Kallenberg1; Geofrey Odede1; Kerry Tyson1; Sue Cross1; Tatiana Sokolova2; Bernard Lauwerys3; Lena D'Hooghe1; Baran Ufuktepe3; Patrick Durez2; David P. Humphreys1
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