Tofacitinib in Combination With Methotrexate in Patients With Rheumatoid Arthritis: Clinical Efficacy, Radiographic, and Safety Outcomes From a Twenty‐Four–Month, Phase III Study Academic Article uri icon

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abstract

  • OBJECTIVE: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). The phase III, 24-month, placebo-controlled Oral Rheumatoid Arthritis (ORAL) Scan trial was undertaken to evaluate the efficacy, including inhibition of structural progression, and safety of tofacitinib in patients with active RA and an inadequate response to methotrexate (MTX). Month 24 data from the completed study are reported here. METHODS: Patients were randomized 4:4:1:1 to receive tofacitinib 5 mg or 10 mg twice daily, or placebo, switched to tofacitinib 5 mg or 10 mg twice daily, with stable background MTX. Patients receiving placebo switched to tofacitinib at month 3 (nonresponders) or month 6 (remaining patients). Clinical efficacy, structural progression, and treatment-emergent adverse events were evaluated. Analyses were performed on the full analysis set with observed data or nonresponder imputation with no advancement penalty for clinical efficacy, and imputation by linear extrapolation for structural progression. RESULTS: Overall, 797 patients were treated; 539 (67.6%) completed 24 months of treatment. Responses according to the American College of Rheumatology criteria for 20% improvement (ACR20), ACR50, and ACR70; the proportion of patients in whom remission or low disease activity was achieved according to the 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate, Clinical Disease Activity Index, or Simplified Disease Activity Index; Boolean remission; and Health Assessment Questionnaire disability index scores were maintained from month 12 to 24 and were similar between tofacitinib dosages. Limited structural damage was observed at months 12 and 24. Safety events were similar in type and frequency for both tofacitinib dosages, and were consistent with those previously reported. CONCLUSION: Our findings indicate that clinical and radiographic treatment effects are sustained in months 12-24 in patients with RA receiving tofacitinib 5 mg or 10 mg twice daily plus MTX. The safety profile is consistent with that of other tofacitinib studies.

authors

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

publication date

  • June 2019