AIMS: To investigate the effects of methotrexate (MTX) on the pharmacokinetics 
(PK) of CP-690,550, a novel Janus kinase (JAK) inhibitor in development as a 
therapy for rheumatoid arthritis (RA), to determine the effects of multiple 
doses of CP-690,550 on the PK of MTX, and to evaluate the short-term safety and 
tolerability of co-administration of CP-690,550 and MTX.
METHODS: This was a fixed-dose drug-drug interaction study. Twelve patients 
diagnosed with RA for at least 6 months were enrolled in a Phase I, open-label 
study of the PK of multiple doses of CP-690,550 (30 mg b.i.d.) and single doses 
of MTX (15-25 mg per week).
RESULTS: All patients completed the study and were evaluated for PK and safety. 
CP-690,550 exposure was not affected by co-administration with MTX; AUC(12) 
ratio (CP-690,550 + MTX/CP-690,550) was 103.06% [90% confidence interval (CI) 
99.00, 107.29]. MTX exposure decreased by 10%; AUC(12) ratio (CP-690,550 + 
MTX/MTX) was 89.53% (90% CI 77.38, 103.57), which was not considered clinically 
significant. Co-administration of CP-690,550 and MTX was safe and well 
tolerated. There were no serious adverse events or withdrawals from the study 
and there was no trend in the incidence or severity of adverse events across 
treatments.
CONCLUSIONS: Co-administration of CP-690,550 and MTX was safe and well 
tolerated. There was no clinically significant effect on the PK profile of 
either drug. Therefore, dose adjustments should not be required when 
co-administering CP-690,550 and MTX.