OBJECTIVES: To investigate baricitinib (LY3009104, formerly INCB028050), a 
novel, oral inhibitor of JAK1/JAK2 in patients with moderate to severe 
rheumatoid arthritis (RA) despite treatment with methotrexate.
METHODS: In this phase IIb study, 301 patients were randomised 2:1:1:1:1 to 
receive once daily doses of placebo or 1, 2, 4 or 8 mg baricitinib for 12 weeks. 
Patients assigned to 2, 4 and 8 mg baricitinib continued blinded treatment for 
an additional 12 weeks. Patients assigned to placebo or 1 mg baricitinib were 
reassigned to 2 mg twice daily or 4 mg once daily baricitinib between weeks 
12-24. The primary endpoint was the proportion of patients in the combined 4 and 
8 mg groups achieving an American College of Rheumatology 20% (ACR20) response 
versus placebo at week 12.
RESULTS: Significantly more patients in the combined baricitinib 4 and 8 mg 
groups compared with placebo achieved an ACR20 response at week 12 (76% vs 41%, 
p<0.001). At week 12, significant differences versus placebo were also observed 
in patients achieving ACR50, ACR70 and remission as measured by Disease Activity 
Score for 28-joint counts, Clinical Disease Activity Index and Simplified 
Disease Activity Index. Patients receiving 2, 4, or 8 mg baricitinib maintained 
or improved in all measures through 24 weeks. Similar proportions of patients 
experienced at least one adverse event in the placebo and baricitinib groups. 
Serious infections developed in three patients receiving baricitinib. No cases 
of tuberculosis, herpes zoster, opportunistic infections or deaths were 
reported. Dose-dependent decreases in haemoglobin were observed with 
baricitinib.
CONCLUSIONS: Baricitinib improved the signs and symptoms of RA in methotrexate 
inadequate responders with active disease. Baricitinib was well tolerated with 
no unexpected safety findings through week 24.
TRIAL REGISTRATION NUMBER: NCT01185353.