Cytokine Signalling Forum

Publications





May 15

Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme

Curtis JR, Lee EB, Kaplan IV, Kwok K, Geier J, Benda B, Soma K, Wang L, Riese R.
Ann Rheum Dis. 2015 Apr 22. pii: annrheumdis-2014-205847. doi: 10.1136/annrheumdis-2014-205847. [Epub ahead of print]

The developments of certain malignancies associated with chronic inflammatory diseases such as RA is known to occur to a greater extent than that of the general population. It is also know that certain RA treatments can affect malignancy rates. As such, newer immunomodulatory agents, such as the JAK inhibitor tofacitinib, are closely monitored for safety events of special interest, including malignancies. This paper analyses pooled malignancy data from the tofacitinib RA clinical development...

Keywords: JAK, Tofacitinib, Malignancy

January 15

Potential Mechanisms Leading to the Abnormal Lipid Profile in Patients With Rheumatoid Arthritis Versus Healthy Volunteers and Reversal by Tofacitinib

Charles-Schoeman C, Fleischmann R, Davignon J, Schwartz H, Turner S, Beysen C, Milad M, Hellerstein M, Luo Z, Kaplan I, Riese R, Zuckerman A, McInnes IB.
Arthritis Rheumatol. 2015;67(3):616-25.

Active RA is associated with changes in both high- and low-density lipoprotein cholesterol as well as changes in the level and function of several HDL-associated proteins, yet the pathways and mechanisms involved with systemic inflammation altered lipid metabolism have not been determined. In addition, treatments for active RA are known to modify lipid metabolism, such as increasing circulating cholesterol levels. In the clinical development programme, a proportion of tofacitinib-treated patien...

Keywords: Cytokine Signalling, Preclinical, MOA

December 14

The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis

Boyle DL, Soma K, Hodge J, Kavanaugh A, Mandel D, Mease P, Shurmur R, Singhal AK, Wei N, Rosengren S, Kaplan I, Krishnaswami S, Luo Z, Bradley J, Firestein GS.
Ann Rheum Dis. 2014 Nov 14. pii: annrheumdis-2014-206028. doi: 10.1136/annrheumdis-2014-206028. [Epub ahead of print]

Targeting intracellular pathways such as JAK/STAT represents a novel approach to the treatment of RA. Tofacitinib is an oral JAK inhibitor, proven to be effective in the treatment of RA, yet the pathways affected by tofacitinib and the effects on gene expression in situ are unknown. In this study, Boyle et al. tested the hypothesis that tofacitinib targets cytokine signalling critical to the pathogenesis of rheumatoid synovitis by investigating tofacitinib effects on synovial pathobiology. A...

Keywords: JAK, Tofacitinib, Preclinical, MOA