Vol.23 No.4

Original Article

A phase 3 randomized, double-blind, multicenter comparative study evaluating the effect of etanercept versus methotrexate on radiographic outcomes, disease activity, and safety in Japanese subjects with active rheumatoid arthritis


Tsutomu Takeuchi1 , Nobuyuki Miyasaka2 , Chuanbo Zang3 , Daniel Alvarez3 , Tracey Fletcher3 , Joseph Wajdula3 , Hirotoshi Yuasa4 , Bonnie Vlahos3

  • Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
  • Tokyo Medical and Dental Hospital, Tokyo, Japan
  • Pfizer Inc., Collegeville, PA, USA
  • Pfizer Japan, Tokyo, Japan

4 July 2012


6 August 2012

Published online:

26 September 2012

Full Text

PDF (Free Access)


Objectives The aim of this phase 3, double-blind study was to compare the radiographic and clinical effects of etanercept (ETN) versus methotrexate (MTX) over 52 weeks in Japanese subjects with active rheumatoid arthritis.
Methods The study population comprised 550 subjects with inadequate response to C1 disease-modifying antirheumatic drugs who were randomized to treatment groups of ETN 25 mg twice weekly (BIW; n = 182), ETN 10 mg BIW (n = 192), or MTX (B8.0 mg/week; n = 176).
Results Of the 550 subjects initially enrolled in the three treatment groups, 21.6 % discontinued the study; a significantly higher proportion of those who withdrew from the study due to lack of efficacy were in the MTX (21.6 %) group compared with the ETN 25 mg (3.3 %) and ETN 10 mg (6.8 %) groups (P%ABST%.001). Mean change from baseline in the modified total Sharp score at week 52 (primary endpoint) was significantly lower in the ETN 25 mg [3.33; standard error (SE), 0.73] and ETN 10 mg (5.19; SE 0.93) groups than in the MTX group (9.82; SE 1.16; P%ABST%.0001 vs. either ETN group). Compared with subjects receiving MTX, significantly higher percentages of subjects treated with ETN 25 and 10 mg achieved American College of Rheumatology (ACR) ACR20 and ACR50 response rates at all time points (P%ABST%.01). ETN was well-tolerated, with no unexpected safety findings. Conclusions ETN 25 mg BIW and ETN 10 mg BIW slowed radiographic progression and improved clinical outcomes more effectively than MTX in this Japanese population.

Key words

Etanercept, Methotrexate, Randomized controlled trial, Rheumatoid arthritis