Advances in kinase inhibition: treating rheumatic diseases and beyond

Kinases inhibitors are now used for the treatment of autoimmune diseases. Here, the most recent findings related to their mechanism of action and some of the newest molecules and targets which are being investigated for autoimmune and inflammatory disorders are reviewed.

Similarly to p38 inhibitors, current spleen tyrosine kinase inhibitors have not fulfilled the expectations of researchers and clinicians, and will likely not be used therapeutically in autoimmunity. Bruton's tyrosine kinase inhibitors remain in the preclinical phase. Studies on the mechanism of action of successful Janus kinase (Jak) inhibitors have revealed that, apart from T and B cells, bone cells such as osteoclasts and innate immunity cells such as dendritic cells are positively affected. More specific, novel Jak inhibitors are now in clinical trials and newer Jak inhibitors are being developed. Other kinases are emerging from basic studies as potentially druggable and will surely be investigated.

First-generation pan-Jak inhibitors can be useful for a wide variety of diseases. They act on adaptive as well as innate immune cells and can promote tolerance. More specific inhibitors will soon be available and these may be used in a disease-specific manner.