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
Total Author Count Override 20
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
Collection year 2014
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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