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

Désirée Van Der Heijde, Yoshiya Tanaka, Roy Fleischmann, Edward Keystone, Joel Kremer, Cristiano Zerbini, Mario H. Cardiel, Stanley Cohen, Peter Nash, Yeong-Wook Song, Dana Tegzová, Bradley T. Wyman, David Gruben, Birgitta Benda, Gene Wallenstein, Sriram Krishnaswami, Samuel H. Zwillich, John D. Bradley, Carol A. Connell

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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.

Original languageEnglish
Pages (from-to)559-570
Number of pages12
JournalArthritis and Rheumatism
Volume65
Issue number3
DOIs
StatePublished - 1 Mar 2013

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Methotrexate
Rheumatoid Arthritis
Placebos
Least-Squares Analysis
tofacitinib
Blood Sedimentation
Double-Blind Method
Joints
Safety
Health

Cite this

Van Der Heijde, Désirée ; Tanaka, Yoshiya ; Fleischmann, Roy ; Keystone, Edward ; Kremer, Joel ; Zerbini, Cristiano ; Cardiel, Mario H. ; Cohen, Stanley ; Nash, Peter ; Song, Yeong-Wook ; Tegzová, Dana ; Wyman, Bradley T. ; Gruben, David ; Benda, Birgitta ; Wallenstein, Gene ; Krishnaswami, Sriram ; Zwillich, Samuel H. ; Bradley, John D. ; Connell, Carol A. / Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate : Twelve-month data from a twenty-four-month phase III randomized radiographic study. In: Arthritis and Rheumatism. 2013 ; Vol. 65, No. 3. pp. 559-570.
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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",
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.",
author = "{Van Der Heijde}, D{\'e}sir{\'e}e and Yoshiya Tanaka and Roy Fleischmann and Edward Keystone and Joel Kremer and Cristiano Zerbini and Cardiel, {Mario H.} and Stanley Cohen and Peter Nash and Yeong-Wook Song and Dana Tegzov{\'a} and Wyman, {Bradley T.} and David Gruben and Birgitta Benda and Gene Wallenstein and Sriram Krishnaswami and Zwillich, {Samuel H.} and Bradley, {John D.} and Connell, {Carol A.}",
year = "2013",
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doi = "10.1002/art.37816",
language = "English",
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Van Der Heijde, D, Tanaka, Y, Fleischmann, R, Keystone, E, Kremer, J, Zerbini, C, Cardiel, MH, Cohen, S, Nash, P, Song, Y-W, Tegzová, D, Wyman, BT, Gruben, D, Benda, B, Wallenstein, G, Krishnaswami, S, Zwillich, SH, Bradley, JD & Connell, CA 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, vol. 65, no. 3, pp. 559-570. https://doi.org/10.1002/art.37816

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; Tegzová, Dana; Wyman, Bradley T.; Gruben, David; Benda, Birgitta; Wallenstein, Gene; Krishnaswami, Sriram; Zwillich, Samuel H.; Bradley, John D.; Connell, Carol A.

In: Arthritis and Rheumatism, Vol. 65, No. 3, 01.03.2013, p. 559-570.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate

T2 - Twelve-month data from a twenty-four-month phase III randomized radiographic study

AU - Van Der Heijde, Désirée

AU - Tanaka, Yoshiya

AU - Fleischmann, Roy

AU - Keystone, Edward

AU - Kremer, Joel

AU - Zerbini, Cristiano

AU - Cardiel, Mario H.

AU - Cohen, Stanley

AU - Nash, Peter

AU - Song, Yeong-Wook

AU - Tegzová, Dana

AU - Wyman, Bradley T.

AU - Gruben, David

AU - Benda, Birgitta

AU - Wallenstein, Gene

AU - Krishnaswami, Sriram

AU - Zwillich, Samuel H.

AU - Bradley, John D.

AU - Connell, Carol A.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - 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.

AB - 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.

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