Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study

van der Heijde, Désirée, Tanaka, Yoshiya, Fleischmann, Roy, Keystone, Edward, Kremer, Joel, Zerbini, Cristiano, Cardiel, Mario H., Cohen, Stanley, Nash, Peter, Song, Yeong-Wook, Tegzova, Dana, Wyman, Bradley T., Gruben, David, Benda, Birgitta, Wallenstein, Gene, Krishnaswami, Sriram, Zwillich, Samuel H., Bradley, John D., Connell, Carol A. and 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 and Rheumatism, 65 3: 559-570. doi:10.1002/art.37816


Author van der Heijde, Désirée
Tanaka, Yoshiya
Fleischmann, Roy
Keystone, Edward
Kremer, Joel
Zerbini, Cristiano
Cardiel, Mario H.
Cohen, Stanley
Nash, Peter
Song, Yeong-Wook
Tegzova, Dana
Wyman, Bradley T.
Gruben, David
Benda, Birgitta
Wallenstein, Gene
Krishnaswami, Sriram
Zwillich, Samuel H.
Bradley, John D.
Connell, Carol A.
ORAL Scan Investigators
Title Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study
Formatted title
Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four–month phase III randomized radiographic study
Journal name Arthritis and Rheumatism   Check publisher's open access policy
ISSN 0004-3591
1529-0131
Publication date 2013-03-01
Sub-type Article (original research)
DOI 10.1002/art.37816
Open Access Status DOI
Volume 65
Issue 3
Start page 559
End page 570
Total pages 12
Place of publication United States
Publisher John Wiley & Sons
Language eng
Formatted abstract
Objective 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.

Methods 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.

Results 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.

Conclusion 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.
Keyword Modifying antirheumatic drugs
Inadequate response
Clinical-trials
Disease
Placebo
Inhibitor
Combination
Adalimumab
Recommendations
Monotherapy
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Presented in part at the 75th Annual Scientific Meeting of the American College of Rheumatology, Chicago, IL, November 2011.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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