Targeting kinases: a new approach to treating inflammatory rheumatic diseases


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Abstract

Highlights▸ First oral kinase inhibitor drug approved by FDA for rheumatoid disease. ▸ Intense activity to expand the utility of JAK inhibitors in other auto-immune indications. ▸ Focus is on discovering inhibitors of the JAK family with different and more selective profiles. ▸ Progress is also being made with orally active Syk inhibitors. ▸ Last two to three years have been transformative for kinase inhibitors in auto-immune diseases.After two decades of research and development activity focussed on orally active kinase inhibitors, the first such drug (the JAK inhibitor Xeljanz, tofacitinib) was approved by the FDA in November 2012 for the treatment of rheumatoid arthritis (RA). There is an intense activity in many companies both on expanding the utility of JAK inhibitors in other auto-immune indications and in discovering inhibitors of the JAK family with different and more selective profiles. Progress is also being made with orally active Syk inhibitors. One such inhibitor (fostamatinib) is currently in large-scale phase 3 trials, and there are others in clinical development. The last two to three years have been transformative for kinase inhibitors in auto-immune diseases, as several inhibitors have finally progressed beyond phase 2 trials after so many failures on other targets. Thus, there are new treatment options for RA patients beyond existing oral DMARDs and parenteral biologics.

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