Orally bioavailable inhibitors of the tyrosine kinases (TYKs), also referred to 
as Janus kinases (JAKs), are being evaluated for the treatment of patients with 
Crohn's disease (CD), ulcerative colitis (UC), and other chronic inflammatory 
disorders. To date, three JAK inhibitors have been tested in patients with 
moderate-to-severe CD: tofacitinib (pan-JAK inhibitor), filgotinib (JAK1 
inhibitor) and upadacitinib (JAK1 inhibitor). Clinical development of 
tofacitinib was discontinued in CD because the primary endpoint of clinical 
remission in the phase II induction and maintenance trials was not met, although 
outcomes may have been influenced by trial design flaws and a high placebo rate 
was noted. In contrast, filgotinib did meet its primary endpoint of clinical 
remission at week 10 in the phase II FITZROY trial, in addition to several other 
clinically important secondary outcomes, spurring a subsequent larger phase III 
trial. Following promising results for upadacitinib in its phase II trial, 
larger phase III trials were also initiated to corroborate the efficacy results. 
Although JAK inhibitors appear to have an acceptable safety profile, higher 
rates of infections compared to placebo were noted. Overall, JAK inhibitors 
constitute a new promising class of drugs, given the efficacy signals observed 
in pivotal clinical trials in several chronic inflammatory diseases. Here we 
review the existing evidence on the pharmacology, safety and efficacy of 
JAK-STAT inhibitors that are currently under investigation for the treatment of 
patients with CD.