Effects of Janus kinase inhibitor tofacitinib on circulating serum amyloid A and interleukin-6 during treatment for rheumatoid arthritis

Abstract

SummaryThe Janus kinase inhibitor tofacitinib is currently being investigated as a disease-modifying agent in rheumatoid arthritis (RA). We investigated the in-vivo effects of tofacitinib treatment for 4 weeks on elevated circulating acute-phase serum amyloid (SAA) levels in 14 Japanese patients with RA. SAA levels fell from 110·5 ± 118·5 μg/ml (mean ± standard deviation) at treatment initiation to 15·3 ± 13·3 μg/ml after 4 weeks treatment with tofacitinib. The reduction in SAA levels was greater in patients receiving tofacitinib plus methotrexate compared with those receiving tofacitinib monotherapy. Tofacitinib was also associated with reduced serum interleukin (IL)-6, but had no effect on serum levels of soluble IL-6 receptor. Patients were divided into groups with adequate (normalization) and inadequate SAA responses (without normalization). Serum IL-6 levels were reduced more in the group with adequate SAA response compared with those with inadequate SAA response. These results suggest that tofacitinib downregulates the proinflammatory cytokine, IL-6, accompanied by reduced serum SAA levels in patients with active RA. The ability to regulate elevated serum IL-6 and SAA levels may explain the anti-inflammatory activity of tofacitinib.

The acute‐phase mediator serum amyloid A is associated with symptoms of depression and fatigue

“…One of them could be the Janus kinase (JAK) inhibitor, tofacitinib, which has been used successfully to treat patients suffering from rheumatoid arthritis. One of the possible mechanisms could be the observed decrease in circulating SAA levels . Cell culture study using rheumatoid synoviocytes have found that tofacitinib is able to abrogate SAA mRNA expression by preventing JAK‐2/STAT‐3 activation .…”

Tofacitinib enhances delivery of antibody-based therapeutics to tumor cells through modulation of inflammatory cells

“…To determine if transcript changes correlated with protein levels, CXCL2 and CCL4 serum levels were analyzed by ELISA. Furthermore, circulating IL-6 and CCL2 levels were analyzed because these cytokines are routinely lowered in RA patients treated with tofacitinib (42,51). Non-tumor-bearing mice displayed low levels of circulating CXCL2 (15.4 pg/ml) and essentially undetectable levels of circulating CCL4 (2.3 pg/ml).…”

Expression and Significance of IL-6 and bFGF in Human Tongue Squamous Cell Carcinoma

“…It is a pleiotropic cytokine that can regulate a variety of cell functions including cell proliferation, cell differentiation, immune defense mechanism, hematopoiesis, etc. [11]. IL-6 correlates with genesis and progress of several kinds of tumors; it can influence tumor progress through intervening cells adhesion and activity, thrombosis, expression of tumor specific antigen, and tumor cells proliferation [12].…”