Cytokine Signalling Forum

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Combined inhibition of TNFα and IL-17 as therapeutic opportunity for treatment in rheumatoid arthritis: Development and characterization of a novel bispecific antibody

Fischer JA, Hueber AJ, Wilson S, Galm M, Baum W, Kitson C, Auer J, Lorenz S, Moelleken J, Bader M, Tissot AC, Tan SL, Seeber S, Schett G. - Arthritis Rheumatol. 2015;67(1):51–62

Single cytokine inhibition, e.g. TNFα or IL-6, has fundamentally improved the therapeutic armamentarium for the treatment of RA; yet clinically meaningful responses are achieved in only about half of RA patients treated. In addition, it is now well established that the pathogenesis of RA involves multiple mechanisms of cell activation and cell recruitment. These two factors have led to the emergence of the concept of dual specificity, sparking interest in the biologic arena, with a focus on what multiple receptor targeting entails with smaller molecules. A previous study by Kirkham et al. 2006 has already highlighted the synergistic effect of IL-17 with TNFα in prediction of joint damage.

To this end, Fischer et al. investigated whether combined inhibition of TNFα and IL-17 has an additive/synergistic effect in the suppression of mesenchymal cell activation in vitro and inflammation and tissue destruction in arthritis in vivo, using mouse models. Their research into the single and combined effects of TNFα and IL-17, in cultures of human fibroblast-like synoviocytes, demonstrated a more effective response in vitro with combined blockade (bi-specific anti-TNFα/IL-17 antibodies), and a positive impact in vivo on rebalance of bone homeostasis. Combined inhibition of these two cytokines may represent a powerful strategy to treat inflammatory arthritis.