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

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63 Scopus citations


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.

Original languageEnglish
Pages (from-to)878-891
Number of pages14
JournalArthritis and Rheumatology
Issue number6
StatePublished - Jun 2019

Bibliographical note

Funding Information:
1Désirée van der Heijde, MD, PhD: Leiden University Medical Center, Leiden, The Netherlands; 2Vibeke Strand, MD: Biopharmaceutical Consultant, Portola Valley, California; 3Yoshiya Tanaka, MD, PhD: University of Occupational and Environmental Health, Kitakyushu, Japan; 4Edward Keystone, MD: Mount Sinai Hospital, Toronto, Ontario, Canada; 5Joel Kremer, MD: Albany Medical College, Albany, New York; 6Cristiano A. F. Zerbini, MD: Centro Paulista de 阀nvestigação Clinica, Sao Paulo, Brazi7lM; ario H. Cardiel, MD: Centro de 阀nvestigacion Clinica de Morelia, Morelia, Mexico8;S tanley Cohen, MD, Roy Fleischmann, MD: Metroplex Clinical Research Center, Dallas, Texas; 9Peter Nash, PhD: Nambour General Hospital, Nambour, Queensland, Australia, and University of Queensland, Brisbane, Queensland, Australia; 10Yeong-Wook Song, MD, PhD: Seoul National University Hospital, Seoul, Republic of Korea; 11Dana Tegzová, MD: 阀nstitute of Rheumatology, Prague, Czech Republic; 12David Gruben, PhD, Gene Wallenstein, PhD, Carol A. Connell, PhD: Pfizer, 阀nc., Groton, Connecticut.

Funding Information:
Pfizer, Inc. personnel developed the study protocol, supervised the conduct of the study, and were involved in data analysis and interpretation. Medical writing support under the guidance of the authors was provided by Rebecca J. Douglas, PhD (CMC Connect, a division of McCann Health Medical Communications Ltd, Macclesfield, UK) and was funded by Pfizer, Inc. in accordance with Good Publication Practice (GPP3) guidelines (Battisti WP, Wager E, Baltzer L, Bridges D, Cairns A, Carswell CI, et al. Good publication practice for communicating company-sponsored medical research: GPP3 Ann Intern Med 2015;163:461–4). The authors had the final decision to submit the manuscript for publication.

Publisher Copyright:
© 2019 Pfizer Inc. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology


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