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

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.

October 2013

Current JAK inhibitors CP-690,550 and INCB020850 have inhibitory effects on multiple JAK pathways, therefore Migita et al. tested whether selective inhibition of JAK3, using PF-956980, would be enough to ameliorate the rheumatoid inflammatory process. The results indicated that the inhibition of JAK3 alone is does not achieve control of STAT3-dependent signalling, and while it is suggested that the targeting of singular JAK pathways should lead to fewer adverse events, it appears that this appro...

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September 2013

Inhibition of spleen tyrosine kinase in the treatment of rheumatoid arthritis

Rheumatology 2013;52:1556–1562 doi:10.1093/rheumatology/ket225

Both the innate and adaptive immune responses are targeted by current RA treatments, but these treatments do not achieve consistent sustained disease remission. Protein kinase inhibitors represent a promising new therapeutic target, owing to their influence on downstream signalling and oral bioavailability. Fostamatinib (R788) has shown ACR20 responses of 67–72% in MTX inadequate responder patients at doses of 100mg bd and 150mg bd. However, the results in biologic non-responder patients were no...

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