Abstract

Modern research in rheumatic diseases has led to the development of anti-cytokine therapies and some treatment specific biomarkers have been discovered. Our aim in this report is to observe the changes in a set of cytokine/chemokine pre- and post Actemra anti-cytokine therapy in naive rheumatoid arthritis (RA) patients. Thirty-four naive RA patients were selected and treated with 8 mg/kg of Actemra once every 4 weeks. Before, and 16 weeks after therapy, we used Bio-plex beads based array method to measure and analyze patients’ serum cytokine/chemokine levels: IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, 101 IL-10, IL-12 (p70), IL-13, IL-15, IL-17, basic FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, VEGF. Clinical response according to disease activity score (DAS-28) criteria was determined at week 16 of therapy and clinical efficacy was judged as remission or non-remission (further divided into high, moderate, low) depending on patients’ DAS-28 value. Fifty percent of patients (n = 17) experienced complete remission and the remaining 17 patients were classified as non-remission even though many of them displayed some improvements. A comparison of cytokine/chemokine changes before and after therapy revealed that patients with extremely high levels of inflammatory cytokines (such as IL-1b, IL-8, IL-12p40, IFN-γ) before therapy did not go into remission even though these cytokine levels decreased after treatment. Contrary to this, these cytokines significantly decreased in patients who went into complete remission. These results demonstrate that anti-IL-6 therapy affects many kinds of cytokine/chemokine systems, and suppression of the IL-6 network may lead to clinical efficacy. Further analysis is required to reveal more detailed mechanism of anti-IL-6 therapy.

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