BACKGROUND: Ulcerative colitis is a chronic inflammatory disease of the colon 
for which current treatments are not universally effective. One additional 
treatment may be tofacitinib (CP-690,550), an oral inhibitor of Janus kinases 1, 
2, and 3 with in vitro functional specificity for kinases 1 and 3 over kinase 2, 
which is expected to block signaling involving gamma chain-containing cytokines 
including interleukins 2, 4, 7, 9, 15, and 21. These cytokines are integral to 
lymphocyte activation, function, and proliferation.
METHODS: In a double-blind, placebo-controlled, phase 2 trial, we evaluated the 
efficacy of tofacitinib in 194 adults with moderately to severely active 
ulcerative colitis. Patients were randomly assigned to receive tofacitinib at a 
dose of 0.5 mg, 3 mg, 10 mg, or 15 mg or placebo twice daily for 8 weeks. The 
primary outcome was a clinical response at 8 weeks, defined as an absolute 
decrease from baseline in the score on the Mayo scoring system for assessment of 
ulcerative colitis activity (possible score, 0 to 12, with higher scores 
indicating more severe disease) of 3 or more and a relative decrease from 
baseline of 30% or more with an accompanying decrease in the rectal bleeding 
subscore of 1 point or more or an absolute rectal bleeding subscore of 0 or 1.
RESULTS: The primary outcome, clinical response at 8 weeks, occurred in 32%, 
48%, 61%, and 78% of patients receiving tofacitinib at a dose of 0.5 mg 
(P=0.39), 3 mg (P=0.55), 10 mg (P=0.10), and 15 mg (P<0.001), respectively, as 
compared with 42% of patients receiving placebo. Clinical remission (defined as 
a Mayo score ≤2, with no subscore >1) at 8 weeks occurred in 13%, 33%, 48%, and 
41% of patients receiving tofacitinib at a dose of 0.5 mg (P=0.76), 3 mg 
(P=0.01), 10 mg (P<0.001), and 15 mg (P<0.001), respectively, as compared with 
10% of patients receiving placebo. There was a dose-dependent increase in both 
low-density and high-density lipoprotein cholesterol. Three patients treated 
with tofacitinib had an absolute neutrophil count of less than 1500.
CONCLUSIONS: Patients with moderately to severely active ulcerative colitis 
treated with tofacitinib were more likely to have clinical response and 
remission than those receiving placebo. (Funded by Pfizer; ClinicalTrials.gov 
number, NCT00787202.).