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| Meetings/Links : Meeting Reports : Psoriasis and Biologic Therapy |
Differences in the Clinical Profiles of the Biologic Agents May Be Due to Differences in Mechanism of Action
We are just beginning to understand the true mechanisms of action of the biologic agents, and we will learn much more in the next few years. Two posters highlighted the differences in the mechanism of action of the TNF inhibitors adalimumab, infliximab, and etanercept.16,17 While all three agents have the Fc portion of complement-activating human IgG1 (which activates the complement system to mediate complement-dependent cytotoxicity [CDC] or antibody-dependent cellular cytotoxicity [ADCC]), a poster by Kohno et al described the differences in their immunologic mechanisms.16 The monoclonal antibodies infliximab and adalimumab form large precipitable protein complexes with TNF. This was not the case with etanercept, a soluble TNF receptor. Similarly, while both adalimumab and infliximab bind to the Fc receptors and C1q in the presence of TNF, this was again not the case for etanercept, which might explain why etanercept lacks efficacy in Crohn's disease and also why etanercept appears to be associated with lower rates of opportunistic infections.
Lizzui et al reported on a study designed to further elucidate the mechanism of action of etanercept.17 Using immunohistochemical analysis of psoriatic plaques from patients treated with etanercept 25 mg twice a week for 6 months, it was found that etanercept treatment resulted in a down-regulation of the cell cycle factor NFkB. This correlated with a histologic response in both epidermal thickness and keratin 16, and with clinical response. These data indicate that down-regulation of NFkB may be one potential mechanism of action of etanercept and may in turn result in modulation of the inflammatory infiltrate in the dermis and epidermis, a decrease in cell proliferation, and/or an increase in cell death.
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