OBJECTIVE: To determine the efficacy, safety, and tolerability of 3 different 
dosages of CP-690,550, a potent, orally active JAK inhibitor, in patients with 
active rheumatoid arthritis (RA) in whom methotrexate, etanercept, infliximab, 
or adalimumab caused an inadequate or toxic response.
METHODS: Patients (n = 264) were randomized equally to receive placebo, 5 mg of 
CP-690,550, 15 mg of CP-690,550, or 30 mg of CP-690,550 twice daily for 6 weeks, 
and were followed up for an additional 6 weeks after treatment. The primary 
efficacy end point was the American College of Rheumatology 20% improvement 
criteria (ACR20) response rate at 6 weeks.
RESULTS: By week 6, the ACR20 response rates were 70.5%, 81.2%, and 76.8% in the 
5 mg, 15 mg, and 30 mg twice daily groups, respectively, compared with 29.2% in 
the placebo group (P < 0.001). Improvements in disease activity in 
CP-690,550-treated patients compared with placebo were seen in all treatment 
groups as early as week 1. ACR50 and ACR70 response rates significantly improved 
in all treatment groups by week 4. The most common adverse events reported were 
headache and nausea. The infection rate in both the 15 mg twice daily group and 
the 30 mg twice daily group was 30.4% (versus 26.2% in the placebo group). No 
opportunistic infections or deaths occurred. Increases in mean low-density 
lipoprotein cholesterol and high-density lipoprotein cholesterol levels, and 
increases in mean serum creatinine level (0.04-0.06 mg/dl) were seen in all 
CP-690,550 treatment arms.
CONCLUSION: Our findings indicate that CP-690,550 is efficacious in the 
treatment of RA, resulting in rapid, statistically significant, and clinically 
meaningful reductions in the signs and symptoms of RA. Further studies of 
CP-690,550 in RA are warranted.