INTRODUCTION: The JAK kinases are a family of four tyrosine receptor kinases 
that play a pivotal role in cytokine receptor signalling pathways via their 
interaction with signal transducers and activators of transcription proteins. 
Selective inhibitors of JAK kinases are viewed as of considerable potential as 
disease-modifying anti-inflammatory drugs for the treatment of rheumatoid 
arthritis.
AREAS COVERED: This article provides a review of the clinical development and 
available clinical results for those JAK inhibitors currently under 
investigation. Phase II data for four JAK inhibitors (baricitinib, decernotinib, 
filgotinib and INCB-039110) are contrasted with that reported for the recently 
approved JAK inhibitor tofacitinib. The preclinical data on these, in addition 
to peficitinib, ABT-494, INCB-047986 and AC-410 are also discussed, as are some 
of the inhibitors in preclinical development.
EXPERT OPINION: JAK inhibitors are effective in the treatment of rheumatoid 
arthritis as evidenced by several inhibitors enabling the majority of treated 
patients to achieve ACR20 responses, with baricitinib and INCB-039110 both 
effective when administered once daily. JAK inhibitors differ in isoform 
specificity profiles, with good efficacy achievable by selective inhibition of 
either JAK1 (filgotinib or INCB-039110) or JAK3 (decernotinib). It remains to be 
seen what selectivity provides the optimal side-effect profile and to what 
extent inhibition of JAK2 should be avoided.