Tofacitinib or adalimumab versus placebo in rheumatoid arthritis
Ronald F van Vollenhoven, Roy Fleischmann, Stanley Cohen, Eun Bong Lee, Juan A García Meijide, Sylke Wagner, Sarka Forejtova, Samuel H Zwillich, David Gruben, Tamas Koncz, Gene V Wallenstein, Sriram Krishnaswami, John D Bradley, Bethanie Wilkinson, ORAL Standard Investigators, David H Bossingham, Stephen Hall, Peter T Nash, Leslie Schrieber, Sekib Sokolovic, Boycho Oparanov, Kiril Yablanski, Anastas Batalov, Daniela Bichovska, Ivan Goranov, Nikolay G Nikolov, Andrew Chow, Alice V Klinkhoff, Andre Damien Beaulieu, Janet Pope, Jean-Luc Tremblay, Bindu Nair, Diane B Wilson, Marta Aliste, Francisco Ballesteros, Gloria Holuigue, Ana Maria Flores, Raul Alpizar, Francisco Brenes-Silesky, Daniel Alfaro-Vargas, Dusanka Martinovic Kaliterna, Nada Cikes, Visnja Prus, Jan Rosa, Petr Nemec, Petr Vitek, Sarka Forejtova, Zdenek Dvorak, Libor Novosad, Zuzana Urbanova, Zdenka Mosterova, Bente Danneskiold-Samsoe, Peter Mosborg Petersen, Patricia Alvarez-Felix, Pentti Jarvinen, Rieke Alten, Juergen Braun, Anke Liebhaber, Hans-Peter Tony, Siegfried Wassenberg, Reiner Kurthen, Harald Burkhardt, Sylke Wagner, Eun Bong Lee, Dae-Hyun Yoo, Shin-Seok Lee, Jung-Yoon Choe, Carlos Abud-Mendoza, Diego Cesar-Ricardo Ramos-Remus, Rafael Horacio, Cornejo-Ballesteros, Maria de Lourdes, Sanchez-Gonzalez, Allan E Lanzon, Harold Michael P Gomez, Josephine Abao Lim, Joanna Badowska, Jerzy Klimczak, Elzbieta Langer-Bieda, Jaroslaw Marcinkiewicz, Artur Racewicz, Pawel Hrycaj, Maria Rell-Bakalarska, Slawomir Jeka, Pavol Polak, Peter Belica, Agnesa Szolnokiova, Maria Kolkusova, Danica Telepkova, Zuzana Bubanova, Juan Garcia Meijide, Francisco J Blanco Garcia, Desamparados Ybañez Garcia, Federico Navarro Sarabia, Isabel Mateo Bernardo, Worawit Louthreno, Paijit Asavatanabodee, Emmanuel George, T Sheeran, Karen May Jane Douglas, Guillermo Jose Valenzuela, Beata Joanna Filip-Majewski, Douglas Menzies Haselwood, Joel Charles Silverfield, Edward Joel Fudman, Jeffrey Stewart Neal, Stephen Michael Lindsey, Stuart Michael Weisman, Mohammed Yaseen Abubaker, Shelly Pearl Kafka, Geneva Louise Hill, Philip Judson Mease, Charles Allen Birbara, Michael Edmund Luggen, Ara Hagop Dikranian, Roy Mitchell Fleischmann, Arnaldo Torres, Michael James Fairfax, Jeffrey Alan Alper, James Michael Calmes, William Martin Schnitz, Larry Grant Willis, Philip A Waller, Richard Roy Olson, Ralph Edward Bennett, Atul Kumar Singhal, Ronald F van Vollenhoven, Roy Fleischmann, Stanley Cohen, Eun Bong Lee, Juan A García Meijide, Sylke Wagner, Sarka Forejtova, Samuel H Zwillich, David Gruben, Tamas Koncz, Gene V Wallenstein, Sriram Krishnaswami, John D Bradley, Bethanie Wilkinson, ORAL Standard Investigators, David H Bossingham, Stephen Hall, Peter T Nash, Leslie Schrieber, Sekib Sokolovic, Boycho Oparanov, Kiril Yablanski, Anastas Batalov, Daniela Bichovska, Ivan Goranov, Nikolay G Nikolov, Andrew Chow, Alice V Klinkhoff, Andre Damien Beaulieu, Janet Pope, Jean-Luc Tremblay, Bindu Nair, Diane B Wilson, Marta Aliste, Francisco Ballesteros, Gloria Holuigue, Ana Maria Flores, Raul Alpizar, Francisco Brenes-Silesky, Daniel Alfaro-Vargas, Dusanka Martinovic Kaliterna, Nada Cikes, Visnja Prus, Jan Rosa, Petr Nemec, Petr Vitek, Sarka Forejtova, Zdenek Dvorak, Libor Novosad, Zuzana Urbanova, Zdenka Mosterova, Bente Danneskiold-Samsoe, Peter Mosborg Petersen, Patricia Alvarez-Felix, Pentti Jarvinen, Rieke Alten, Juergen Braun, Anke Liebhaber, Hans-Peter Tony, Siegfried Wassenberg, Reiner Kurthen, Harald Burkhardt, Sylke Wagner, Eun Bong Lee, Dae-Hyun Yoo, Shin-Seok Lee, Jung-Yoon Choe, Carlos Abud-Mendoza, Diego Cesar-Ricardo Ramos-Remus, Rafael Horacio, Cornejo-Ballesteros, Maria de Lourdes, Sanchez-Gonzalez, Allan E Lanzon, Harold Michael P Gomez, Josephine Abao Lim, Joanna Badowska, Jerzy Klimczak, Elzbieta Langer-Bieda, Jaroslaw Marcinkiewicz, Artur Racewicz, Pawel Hrycaj, Maria Rell-Bakalarska, Slawomir Jeka, Pavol Polak, Peter Belica, Agnesa Szolnokiova, Maria Kolkusova, Danica Telepkova, Zuzana Bubanova, Juan Garcia Meijide, Francisco J Blanco Garcia, Desamparados Ybañez Garcia, Federico Navarro Sarabia, Isabel Mateo Bernardo, Worawit Louthreno, Paijit Asavatanabodee, Emmanuel George, T Sheeran, Karen May Jane Douglas, Guillermo Jose Valenzuela, Beata Joanna Filip-Majewski, Douglas Menzies Haselwood, Joel Charles Silverfield, Edward Joel Fudman, Jeffrey Stewart Neal, Stephen Michael Lindsey, Stuart Michael Weisman, Mohammed Yaseen Abubaker, Shelly Pearl Kafka, Geneva Louise Hill, Philip Judson Mease, Charles Allen Birbara, Michael Edmund Luggen, Ara Hagop Dikranian, Roy Mitchell Fleischmann, Arnaldo Torres, Michael James Fairfax, Jeffrey Alan Alper, James Michael Calmes, William Martin Schnitz, Larry Grant Willis, Philip A Waller, Richard Roy Olson, Ralph Edward Bennett, Atul Kumar Singhal
Abstract
Background: Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated for the treatment of rheumatoid arthritis.
Methods: In this 12-month, phase 3 trial, 717 patients who were receiving stable doses of methotrexate were randomly assigned to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, 40 mg of adalimumab once every 2 weeks, or placebo. At month 3, patients in the placebo group who did not have a 20% reduction from baseline in the number of swollen and tender joints were switched in a blinded fashion to either 5 mg or 10 mg of tofacitinib twice daily; at month 6, all patients still receiving placebo were switched to tofacitinib in a blinded fashion. The three primary outcome measures were a 20% improvement at month 6 in the American College of Rheumatology scale (ACR 20); the change from baseline to month 3 in the score on the Health Assessment Questionnaire-Disability Index (HAQ-DI) (which ranges from 0 to 3, with higher scores indicating greater disability); and the percentage of patients at month 6 who had a Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating greater disease activity).
Results: At month 6, ACR 20 response rates were higher among patients receiving 5 mg or 10 mg of tofacitinib (51.5% and 52.6%, respectively) and among those receiving adalimumab (47.2%) than among those receiving placebo (28.3%) (P<0.001 for all comparisons). There were also greater reductions in the HAQ-DI score at month 3 and higher percentages of patients with a DAS28-4(ESR) below 2.6 at month 6 in the active-treatment groups than in the placebo group. Adverse events occurred more frequently with tofacitinib than with placebo, and pulmonary tuberculosis developed in two patients in the 10-mg tofacitinib group. Tofacitinib was associated with an increase in both low-density and high-density lipoprotein cholesterol levels and with reductions in neutrophil counts.
Conclusions: In patients with rheumatoid arthritis receiving background methotrexate, tofacitinib was significantly superior to placebo and was numerically similar to adalimumab in efficacy. (Funded by Pfizer; ORAL Standard ClinicalTrials.gov number, NCT00853385.).
Source: PubMed