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, ORAL Scan Investigators, Prabha Adhikari, Kouichi Amano, Sang-Cheol Bae, Srikantiah Chandrashekara, Arvind K Chopra, Ping-Ning Hsu, Mitsuhiro Iwahashi, Jugal Kishore Kadel, Yojiro Kawabe, Eun-Mi Koh, Joung-liang Lan, Soo-Kon Lee, Hsiao-Yi Lin, Lieh-bang Liou, Ming-Fei Liu, Kiyoshi Migita, Toshiaki Miyamoto, Nobuyuki Miyasaka, Shunsuke Mori, Yasuhiko Munakata, Shuji Ohta, Sung-Hwan Park, Won Park, Uppuluri Ramakrishna Rao, Seung Cheol Shim, Vineeta Shobha, Yeong-Wook Song, Yoshinari Takasaki, Tsutomu Takeuchi, Yoshiya Tanaka, Shigeto Tohma, Wen-Chan Tsai, Yukitaka Ueki, Sarath Chandra Mouli Veeravalli, Shrikant Wagh, Hisashi Yamanaka, Bin Yoo, Stephen Hall, David Nicholls, Maureen Rischmueller, Milton F Baker, Louis Bessette, Alfred A Cividin, Boulos Haraoui, Henry Niall Jones, Edward C Keystone, Majed Khraishi, J Thorne, Anastas Batalov, Daniela Bichovska, Zdenek Dvorak, Ivan Goranov, Halyna M Hrytsenko, Jana Kopackova, Zdenka Mosterova, Boycho Oparanov, Andriy Petrov, Ines Pokrzywnicka-Gajek, Vladyslav V Povoroznyuk, Jan Rosa, Zofia Ruzga, Loukas Settas, Mykola A Stanislavchuk, Dana Tegzova, Vira Iosypivna Tseluyko, Petr Vitek, Joao Carlos Tavares Brenol, Mario H Cardiel-Rios, William Jose Otero Escalante, Javier Dario Marquez Hernandez, Edwin Antonio Jauregui, Mauro W Keiserman, Ana Claudia Cauceglia Melazzi, Virginia Pascual- Ramos, Luciana Teixeira Pinto, Juan Jose Jaller Raad, Sebastiao C Radominski, Antonio Carlos Ximenes, Cristiano Augusto de Freitas Zerbini, Herbert Stuart Block Baraf, Joan Marie Bathon, Charles Allen Birbara, Alan Lawrence Brodsky, John Joseph Cush, Ara Hagop Dikranian, Erdal Diri, Paul Andrew Dura, Roy Mitchell Fleischmann, Robert Michael Griffin Jr, Dale George Halter, Jody Kay Hargrove, Geneva Louise Hill, Raymond Edward Jackson, Shelly Pearl Kafka, Jeffrey Louis Kaine, Paul L Katzenstein, Kevin James Kempf, Karen Sue Kolba, Joel Marc Kremer, Selden Longley 3rd, Steven D Mathews, Ami Charise Milton, Richard James Misischia, Haydon Anthony Moorman, Larry W Moreland, Mark William Niemer, William Rodney Palmer, Michael Eugene Sayers, Patrick Thomas Schuette, Talha Shamim, William Julius Shergy, David Hilton Sikes, Joel Charles Silverfield, Chokkalingam Siva, James D Taborn, Bridget Tyrell Walsh, Alvin Francis Wells, Sanford Mayer Wolfe, 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, ORAL Scan Investigators, Prabha Adhikari, Kouichi Amano, Sang-Cheol Bae, Srikantiah Chandrashekara, Arvind K Chopra, Ping-Ning Hsu, Mitsuhiro Iwahashi, Jugal Kishore Kadel, Yojiro Kawabe, Eun-Mi Koh, Joung-liang Lan, Soo-Kon Lee, Hsiao-Yi Lin, Lieh-bang Liou, Ming-Fei Liu, Kiyoshi Migita, Toshiaki Miyamoto, Nobuyuki Miyasaka, Shunsuke Mori, Yasuhiko Munakata, Shuji Ohta, Sung-Hwan Park, Won Park, Uppuluri Ramakrishna Rao, Seung Cheol Shim, Vineeta Shobha, Yeong-Wook Song, Yoshinari Takasaki, Tsutomu Takeuchi, Yoshiya Tanaka, Shigeto Tohma, Wen-Chan Tsai, Yukitaka Ueki, Sarath Chandra Mouli Veeravalli, Shrikant Wagh, Hisashi Yamanaka, Bin Yoo, Stephen Hall, David Nicholls, Maureen Rischmueller, Milton F Baker, Louis Bessette, Alfred A Cividin, Boulos Haraoui, Henry Niall Jones, Edward C Keystone, Majed Khraishi, J Thorne, Anastas Batalov, Daniela Bichovska, Zdenek Dvorak, Ivan Goranov, Halyna M Hrytsenko, Jana Kopackova, Zdenka Mosterova, Boycho Oparanov, Andriy Petrov, Ines Pokrzywnicka-Gajek, Vladyslav V Povoroznyuk, Jan Rosa, Zofia Ruzga, Loukas Settas, Mykola A Stanislavchuk, Dana Tegzova, Vira Iosypivna Tseluyko, Petr Vitek, Joao Carlos Tavares Brenol, Mario H Cardiel-Rios, William Jose Otero Escalante, Javier Dario Marquez Hernandez, Edwin Antonio Jauregui, Mauro W Keiserman, Ana Claudia Cauceglia Melazzi, Virginia Pascual- Ramos, Luciana Teixeira Pinto, Juan Jose Jaller Raad, Sebastiao C Radominski, Antonio Carlos Ximenes, Cristiano Augusto de Freitas Zerbini, Herbert Stuart Block Baraf, Joan Marie Bathon, Charles Allen Birbara, Alan Lawrence Brodsky, John Joseph Cush, Ara Hagop Dikranian, Erdal Diri, Paul Andrew Dura, Roy Mitchell Fleischmann, Robert Michael Griffin Jr, Dale George Halter, Jody Kay Hargrove, Geneva Louise Hill, Raymond Edward Jackson, Shelly Pearl Kafka, Jeffrey Louis Kaine, Paul L Katzenstein, Kevin James Kempf, Karen Sue Kolba, Joel Marc Kremer, Selden Longley 3rd, Steven D Mathews, Ami Charise Milton, Richard James Misischia, Haydon Anthony Moorman, Larry W Moreland, Mark William Niemer, William Rodney Palmer, Michael Eugene Sayers, Patrick Thomas Schuette, Talha Shamim, William Julius Shergy, David Hilton Sikes, Joel Charles Silverfield, Chokkalingam Siva, James D Taborn, Bridget Tyrell Walsh, Alvin Francis Wells, Sanford Mayer Wolfe
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.
Trial registration: ClinicalTrials.gov NCT00847613.
Copyright © 2013 by the American College of Rheumatology.
Source: PubMed