BACKGROUND: Baricitinib is an oral, reversible inhibitor of the Janus kinases 
JAK1 and JAK2 that may have therapeutic value in patients with rheumatoid 
arthritis.
METHODS: We conducted a 52-week, phase 3, double-blind, placebo- and 
active-controlled trial in which 1307 patients with active rheumatoid arthritis 
who were receiving background therapy with methotrexate were randomly assigned 
to one of three regimens in a 3:3:2 ratio: placebo (switched to baricitinib 
after 24 weeks), 4 mg of baricitinib once daily, or 40 mg of adalimumab (an 
anti-tumor necrosis factor α monoclonal antibody) every other week. End-point 
measures evaluated after adjustment for multiplicity included 20% improvement 
according to the criteria of the American College of Rheumatology (ACR20 
response) (the primary end point), the Disease Activity Score for 28 joints 
(DAS28), the Health Assessment Questionnaire-Disability Index, and the 
Simplified Disease Activity Index at week 12, as well as radiographic 
progression of joint damage as measured by the van der Heijde modification of 
the total Sharp score (mTSS) (range, 0 to 448, with higher scores indicating 
greater structural joint damage) at week 24.
RESULTS: More patients had an ACR20 response at week 12 with baricitinib than 
with placebo (primary end point, 70% vs. 40%, P<0.001). All major secondary 
objectives were met, including inhibition of radiographic progression of joint 
damage, according to the mTSS at week 24 with baricitinib versus placebo (mean 
change from baseline, 0.41 vs. 0.90; P<0.001) and an increased ACR20 response 
rate at week 12 with baricitinib versus adalimumab (70% vs. 61%, P=0.014). 
Adverse events, including infections, were more frequent through week 24 with 
baricitinib and adalimumab than with placebo. Cancers were reported in five 
patients (two who received baricitinib and three who received placebo). 
Baricitinib was associated with reductions in neutrophil counts and increases in 
levels of creatinine and low-density lipoprotein cholesterol.
CONCLUSIONS: In patients with rheumatoid arthritis who had had an inadequate 
response to methotrexate, baricitinib was associated with significant clinical 
improvements as compared with placebo and adalimumab. (Funded by Eli Lilly and 
Incyte; ClinicalTrials.gov number, NCT01710358 .).