Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial

Roy Fleischmann, Eduardo Mysler, Stephen Hall, Alan J. Kivitz, Robert J. Moots, Zhen Luo, Ryan DeMasi, Koshika Soma, Richard Zhang, Liza Takiya, Svitlana Tatulych, Christopher Mojcik, Sriram Krishnaswami, Sujatha Menon, Josef S. Smolen, Luthando Adams, Mahmood M. Ally, Maria C. du Plooy, Ingrid C. Louw, Savithree NayiagerChristoffel B. Nel, Debra Nel, Helmuth Reuter, Ahmed S. Soloman, Catherine E. Spargo, Stephen Hall, Maureen Rischmueller, Shunil D. Sharma, Robert K. Will, Peter P. Youssef, Caroline Arroyo, Rosario P. Baes, Roger B. Dulos, Llewellyn T. Hao, Allan E. Lanzon, Juan Javier T. Lichauco, Jill H. Mangubat, Edgar B. Ramiterre, Bernadette Heizel M. Reyes, Perry P. Tan, Jung Yoon Choe, Young Mo Kang, Seong Ryul Kwon, Sang Heon Lee, Shin Seok Lee, Dae Hyun Yoo, Hsiao Yi Lin, Shue Fen Luo, Shih Tzu Tsai, Wen Chan Tsai, Jui Cheng Tseng, Cheng Chung C. Wei, Paijit Asavatanabodee, Kanokrat Nantiruj, Surasak Nilganuwong, Parichat Uea-Areewongsa, Ljubinka Bozic Majstorovic, Suada Mulic Bacic, Anastas Z. Batalov, Gabriela Georgieva-Slavcheva, Mariyana Mihailova, Nikolay G. Nikolov, Dimitar P. Penev, Yuliy A. Spasov, Krasimira Stanimirova, Stoyan Todorov, Antoaneta R. Toncheva, Nadezhda Yordanova, Zdenka Mosterova, Libor Novosad, Leona Prochazkova, Helena Stehlikova, Zuzana Stejfova, Natalia Kiseleva, Lea Pank, Triin Savi, Balbir Gurman Alexandra, Howard Amital, Dror Mevorach, Itzhak A. Rosner, Anna Mihailova, Evija Stumbra-Stumberga, Vida Basijokiene, Virginija Lietuvininkiene, Dalia Unikiene, Jan Brzezicki, Anna M. Dudek, Maria B. Glowacka-Kulesz, Barbara Grabowicz-Wasko, Sabina Hajduk-Kubacka, Joanna Hilt, Pawel Hrycaj, Slawomir Jeka, Renata Kolasa, Marek Krogulec, Hanna Mastalerz, Anna Olak-Popko, Elzbieta Owczarek, Zofia Ruzga, Alina Walczak, Codrina I. Ancuta, Ioan Ancuta, Andra R. Balanescu, Florian Berghea, Silvia Bojin, Mihaela A.Ianuli Arvunescu, Ruxandra M. Ionescu, Eugenia Mociran, Mariana Pavel, Simona Rednic, Adriana Voie, Carmen M. Zainea, Olga V. Bugrova, Alexander Demin, Olga B. Ershova, Inna A. Gavrisheva, Diana G. Krechikova, Gennady V. Kuropatkin, Irina M. Marusenko, Irina V. Menshikova, Sergey M. Noskov, Andrey P. Rebrov, Svetlana A. Smakotina, Sergey S. Yakushin, Evgeny Zhilyaev, Juan Jose Amarelo Ramos, Francisco Javier Blanco Garcia, Antonio Fernandez Nebro, Silvia Perez Esteban, Juan Miguel Sanchez Burson, Raimon Sanmarti Sala, Sebnem Ataman, Sami Hizmetli, Omer Kuru, Karen M. Douglas, Paul Emery, Robert J. Moots, Voon H. Ong, Thomas P. Sheeran, Rafat Y. Faraawi, Clode Lessard, Carlos Abud Mendoza, Hilario Ernesto Avila-Armengol, Francisco I.Avila Zapata, Fedra Consuelo Irazoque-Palazuelos, Marco Antonio Maradiaga Cecena, Cesar F. Pacheco-Tena, Juan C. Rizo-Rodriguez, Isaura M. Rodriguez-Torres, Jacob A. Aelion, Barbara A. Caciolo, James M. Calmes, Prem Chatpar, Nimesh Dayal, Alex De Jesus, Ara H. Dikranian, Erdal Diri, Michael J. Fairfax, Ira F. Fenton, Roy M. Fleischmann, Norman B. Gaylis, Ronald L. George, Dale G. Halter, Paul Hernandez, Susan A. Hole, Antony C. Hou, John P. Huff, Suzanne Kafaja, Alastair C. Kennedy, Howard Kenney, Steven C. Kimmel, Brian S. Kirby, Alan J. Kivitz, Clarence W. Legerton, Stephen M. Lindsey, Jyothi R. Mallepalli, Steven D. Mathews, Samy K. Metyas, Wesley T. Mizutani, Sabeen Najam, Joao M. Nascimento, Shirley W. Pang, Rakesh C. Patel, Jeffrey E. Poiley, Carlos E. Ramirez, Riteesha Reddy, Qaiser Rehman, William M. Schnitz, Craig D. Scoville, William J. Shergy, Joel C. Silverfield, Atul K. Singhal, Yvonne R. Smallwood-Sherrer, Suthin N. Songcharoen, Michael T. Stack, William Stohl, Tien I.K. Su, James Udell, Saleem Waraich, Charles E. Weidmann, Nathan Wei, Craig W. Wiesenhutter, Anne E. Winkler, Karen E. Zagar, Alberto Berman, Eduardo F. Mysler, Rodolfo A.Pardo Hidalgo, Horacio O. Venarotti, Irmgadt Annelise Goecke Sariego, Renato E.Jimenez Calabresse, Juan Ignacio Vargas Ruiz-Tagle, Luis Fernando M.Bellatin Vargas, Alfredo E. Berrocal, Manuel Gustavo Leon Portocarrero, Felix Jesus, Romero Pena

Research output: Contribution to journalArticlepeer-review

Abstract

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. The Oral Rheumatoid Arthritis triaL (ORAL) Strategy aimed to assess the comparative efficacy of tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate for the treatment of rheumatoid arthritis in patients with a previous inadequate response to methotrexate. Methods ORAL Strategy was a 1 year, double-blind, phase 3b/4, head-to-head, non-inferiority, randomised controlled trial in patients aged 18 years or older with active rheumatoid arthritis despite methotrexate therapy. Patients were randomly assigned (1:1:1) to receive oral tofacitinib (5 mg twice daily) monotherapy, oral tofacitinib (5 mg twice daily) plus methotrexate, or subcutaneous adalimumab (40 mg every other week) plus methotrexate at 194 centres in 25 countries. Eligible patients received live zoster vaccine at investigators' discretion. The primary endpoint was the proportion of patients who attained an American College of Rheumatology response of at least 50% (ACR50) at month 6 in the full analysis set (patients who were randomly assigned to a group and received at least one dose of the study treatment). Non-inferiority between groups was shown if the lower bound of the 98·34% CI of the difference between comparators was larger than −13·0%. This trial is registered with ClinicalTrials.gov, number NCT02187055. Findings 1146 patients received treatment (384 had tofacitinib monotherapy; 376 had tofacitinib and methotrexate; and 386 had adalimumab and methotrexate). At 6 months, ACR50 response was attained in 147 (38%) of 384 patients with tofacitinib monotherapy, 173 (46%) of 376 patients with tofacitinib and methotrexate, and 169 (44%) of 386 patients with adalimumab and methotrexate. Non-inferiority was declared for tofacitinib and methotrexate versus adalimumab and methotrexate (difference 2% [98·34% CI −6 to 11]) but not for tofacitinib monotherapy versus either adalimumab and methotrexate (−6 [−14 to 3]) or tofacitinib and methotrexate (−8 [−16 to 1]). In total, 23 (6%) of 384 patients receiving tofacitinib monotherapy, 26 (7%) of 376 patients receiving tofacitinib plus methotrexate, and 36 (9%) of 386 patients receiving adalimumab plus methotrexate discontinued due to adverse events. Two (1%) of the 384 patients receiving tofacitinib monotherapy died. No new or unexpected safety issues were reported for either treatment in this study for up to 1 year. Interpretation Tofacitinib and methotrexate combination therapy was non-inferior to adalimumab and methotrexate combination therapy in the treatment of rheumatoid arthritis in patients with an inadequate response to methotrexate in this trial. Tofacitinib monotherapy was not shown to be non-inferior to either combination. Funding Pfizer Inc.

Original languageEnglish
Pages (from-to)457-468
Number of pages12
JournalThe Lancet
Volume390
Issue number10093
DOIs
StatePublished - 29 Jul 2017

Fingerprint

Dive into the research topics of 'Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial'. Together they form a unique fingerprint.

Cite this