V.C. was an employee of Pfizer at the time of the study.
Co-administration of the JAK inhibitor CP-690,550 and methotrexate is well tolerated in patients with rheumatoid arthritis without need for dose adjustment
Article first published online: 23 OCT 2009
© 2010 Pfizer Inc. Journal compilation © 2010 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 69, Issue 2, pages 143–151, February 2010
How to Cite
Cohen, S., Zwillich, S. H., Chow, V., LaBadie, R. R. and Wilkinson, B. (2010), Co-administration of the JAK inhibitor CP-690,550 and methotrexate is well tolerated in patients with rheumatoid arthritis without need for dose adjustment. British Journal of Clinical Pharmacology, 69: 143–151. doi: 10.1111/j.1365-2125.2009.03570.x
- Issue published online: 21 JAN 2010
- Article first published online: 23 OCT 2009
- Received 8 December 2008Accepted21 September 2009
- rheumatoid arthritis
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• CP-690,550 is a novel JAK inhibitor in development as a therapy for rheumatoid arthritis.
• Methotrexate is the cornerstone of combination treatment for rheumatoid arthritis.
• The safety and tolerability of co-administration of CP-690,550 with methotrexate have not been addressed to date.
WHAT THIS STUDY ADDS
• This study in patients with rheumatoid arthritis shows that there are no clinically relevant effects on the pharmacokinetics of either drug following short-term co-administration.
• Co-administration of CP-690,550 and methotrexate was safe and well tolerated.
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.
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).
All patients completed the study and were evaluated for PK and safety. CP-690,550 exposure was not affected by co-administration with MTX; AUC12 ratio (CP-690,550 + MTX/CP-690,550) was 103.06% [90% confidence interval (CI) 99.00, 107.29]. MTX exposure decreased by 10%; AUC12 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.
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.