Dr. van der Heijde has received consulting fees, speaking fees, and/or honoraria from Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Chugai, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Otsuka, Pfizer Inc., Roche, Sanofi-Aventis, Schering-Plough, UCB, and Wyeth (less than $10,000 each).
Article first published online: 25 FEB 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 3, pages 559–570, March 2013
How to Cite
van der Heijde, D., Tanaka, Y., Fleischmann, R., Keystone, E., Kremer, J., Zerbini, C., Cardiel, M. H., Cohen, S., Nash, P., Song, Y.-W., Tegzová, D., Wyman, B. T., Gruben, D., Benda, B., Wallenstein, G., Krishnaswami, S., Zwillich, S. H., Bradley, J. D., Connell, C. A. and and the ORAL Scan Investigators (2013), Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: Twelve-month data from a twenty-four–month phase III randomized radiographic study. Arthritis & Rheumatism, 65: 559–570. doi: 10.1002/art.37816
ClinicalTrials.gov identifier: NCT00847613.
Presented in part at the 75th Annual Scientific Meeting of the American College of Rheumatology, Chicago, IL, November 2011.
- Issue published online: 25 FEB 2013
- Article first published online: 25 FEB 2013
- Accepted manuscript online: 24 JAN 2013 09:46AM EST
- Manuscript Accepted: 27 NOV 2012
- Manuscript Received: 9 MAR 2012
- Pfizer Inc.
The purpose of this 24-month phase III study was to examine structural preservation with tofacitinib in patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). Data from a planned 12-month interim analysis are reported.
In this double-blind, parallel-group, placebo-controlled study, patients receiving background MTX were randomized 4:4:1:1 to tofacitinib at 5 mg twice daily, tofacitinib at 10 mg twice daily, placebo to tofacitinib at 5 mg twice daily, and placebo to tofacitinib at 10 mg twice daily. At month 3, nonresponder placebo-treated patients were advanced in a blinded manner to receive tofacitinib as indicated above; remaining placebo-treated patients were advanced at 6 months. Four primary efficacy end points were all analyzed in a step-down procedure.
At month 6, response rates according to the American College of Rheumatology 20% improvement criteria for tofacitinib at 5 mg and 10 mg twice daily were higher than those for placebo (51.5% and 61.8%, respectively, versus 25.3%; both P < 0.0001). At month 6, least squares mean (LSM) changes in total modified Sharp/van der Heijde score for tofacitinib at 5 mg and 10 mg twice daily were 0.12 and 0.06, respectively, versus 0.47 for placebo (P = 0.0792 and P ≤ 0.05, respectively). At month 3, LSM changes in the Health Assessment Questionnaire disability index score for tofacitinib at 5 mg and 10 mg twice daily were –0.40 (significance not declared due to step-down procedure) and –0.54 (P < 0.0001), respectively, versus –0.15 for placebo. At month 6, rates of remission (defined as a value <2.6 for the 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate) for tofacitinib at 5 mg and 10 mg twice daily were 7.2% (significance not declared due to step-down procedure) and 16.0% (P < 0.0001), respectively, versus 1.6% for placebo. The safety profile was consistent with findings in previous studies.
Data from this 12-month interim analysis demonstrate that tofacitinib inhibits progression of structural damage and improves disease activity in patients with RA who are receiving MTX.