BACKGROUND & AIMS: We evaluated the efficacy and safety of upadacitinib, an oral 
selective Janus kinase 1 inhibitor, in a randomized trial of patients with 
Crohn's disease (CD).
METHODS: We performed a double-blind, phase 2 trial in adults with moderate to 
severe CD and inadequate response or intolerance to immunosuppressants or tumor 
necrosis factor antagonists. Patients were randomly assigned (1:1:1:1:1:1) to 
groups given placebo; or 3 mg, 6 mg, 12 mg, or 24 mg upadacitinib twice daily; 
or 24 mg upadacitinib once daily and were evaluated by ileocolonoscopy at weeks 
12 or 16 of the induction period. Patients who completed week 16 were 
re-randomized to a 36-week period of maintenance therapy with upadacitinib. The 
primary endpoints were clinical remission at week 16 and endoscopic remission at 
week 12 or 16 using the multiple comparison procedure and modeling and the 
Cochran-Mantel-Haenszel test, with a 2-sided level of 10%.
RESULTS: Among the 220 patients in the study, clinical remission was achieved by 
13% of patients receiving 3 mg upadacitinib, 27% of patients receiving 6 mg 
upadacitinib (P < .1 vs placebo), 11% of patients receiving 12 mg upadacitinib, 
and 22% of patients receiving 24 mg upadacitinib twice daily, and by 14% of 
patients receiving 24 mg upadacitinib once daily, vs 11% of patients receiving 
placebo. Endoscopic remission was achieved by 10% (P < .1 vs placebo), 8%, 8% 
(P < .1 vs placebo), 22% (P < .01 vs placebo), and 14% (P < .05 vs placebo) of 
patients receiving upadacitinib, respectively, vs none of the patients receiving 
placebo. Endoscopic but not clinical remission increased with dose during the 
induction period. Efficacy was maintained for most endpoints through week 52. 
During the induction period, patients in the upadacitinib groups had higher 
incidences of infections and serious infections vs placebo. Patients in the 
twice-daily 12 mg and 24 mg upadacitinib groups had significant increases in 
total, high-density lipoprotein, and low-density lipoprotein cholesterol levels 
compared with patients in the placebo group.
CONCLUSIONS: In a phase 2 trial of patients with CD, upadacitinib induced 
endoscopic remission in a significant proportion of patients compared with 
placebo. Upadacitinib's benefit/risk profile supports further development for 
treatment of CD. (Clinicaltrials.gov, Number: NCT02365649).