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Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial

  • Original Article
  • Published:
Modern Rheumatology

Abstract

The superiority of the combination therapy of methotrexate (MTX) and anti-tumor necrosis factor (TNF) biological agents over anti-TNF monotherapy in MTX-naïve patients with rheumatoid arthritis (RA) has been demonstrated. We investigated the efficacy and safety of continuation versus discontinuation of MTX at the commencement of etanercept (ETN) in patients with active RA despite MTX therapy. In total, 151 patients with active RA despite treatment with MTX were randomized to either ETN 25 mg twice a week and MTX 6–8 mg/week (the E + M group) or ETN alone (the E group). Co-primary endpoints included the European League Against Rheumatism (EULAR) good response rate and the American College of Rheumatology (ACR) 50 response rate at week 24. Demographic and clinical features between groups at baseline were similar. The EULAR good response rates were significantly higher in the E + M group (52%) than in the E group (33%) at week 24 (p = 0.0001). Although the ACR50 response rate, one of the co-primary endpoints, and the ACR70 response rate at week 24 were not significantly greater in the E + M group (64 and 38%, respectively) than in the E group (48 and 26%, respectively), the ACR20 response rate was significantly greater in the E + M group (90%) than in the E group (64%; p = 0.0002). Safety profiles were similar for the groups. Thus, MTX should be continued at the commencement of ETN therapy, even in RA patients who show an inappropriate response to MTX.

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Acknowledgments

We would like to acknowledge the following investigators, their staff and sites: Shiozawa K. (Konan Hospital Foundation, Kakogawa Hospital), Kobayashi S. (Juntendo University School of Medicine, Koshigaya Hospital), Tamura N. (Juntendo University School of Medicine, Juntendo Hospital), Sawada T. (The University of Tokyo Hospital), Yamana S. (Higashihiroshima Memorial Hospital), Honda Y. (Kurume University Hospital), Kojima T. (Nagoya University Hospital), Takahashi H. (Sapporo Medical University Hospital), Sugiyama T. (Shimoshizu National Hospital), Taniguchi A. (Tokyo Women’s Medical University, Institute of Rheumatology), Nannki T. (Tokyo Medical & Dental University, Hospital Faculty of Medicine), Yamamura M. (Aich Medical University Hospital), Kurasawa K. (Dokkyo Medical University Hospital), Chiba K. (Fukushima Daiich Hospital), Kato K. (Fujita Health University Hospital), Ezawa K. (Kurashiki Kousai Hospital), Fujii T. (Kyoto University Hospital), Nakata S. (Matsuyama Red Cross Hospital), Tamachi S. (Mie Chuou Medical Center), Kawabe Y. (National Hospital Organization, Ureshino Medical Center), Yano R. (Okayama University Hospital), Kuroiwa T. (The Hospital of Hyogo College of Medicine), Kubota A. (Toho University Omori Medical Center), Kanbe K. (Tokyo Women’s Medical University Medical Center East); Hyogo Prefectural General Rehabilitation Center; Konan Hospital Foundation, Rokko Island Hospital; Kurume University Medical Center; Nagasaki University Hospital of Medicine and Dentistry; Nihon University Itabashi Hospital; Niigata University Medical and Dental Hospital; Osaki Citizen Hospital; Saiseikai Takaoka Hospital; St. Marianna University School of Medicine Hospital; Taihakusakura Hospital; Tohoku Kosei Nenkin Hospital; Tohoku University Hospital; Tsukuba University Hospital. This study was supported by the Advanced Clinical Research Organization (ACRO, Japan) and by research grants from the Japanese Ministry of Health, Labour and Welfare.

Conflict of interest statement

HK, TH, TA and YT received honoraria from Wyeth. SS received an unrestricted research grant from Wyeth. SN, MT, TK and TT received unrestricted research grants and honoraria from Wyeth.

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Authors and Affiliations

  1. Department of Rheumatology/Clinical Immunology, Saitama Medical Center, Kawagoe, Japan

    Hideto Kameda & Tsutomu Takeuchi

  2. Division of Rheumatology/Clinical Immunology, Department of Internal Medicine, Faculty of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Hideto Kameda & Tsutomu Takeuchi

  3. Rheumatic and Collagen Disease Center, Sasebo Chuo Hospital, Sasebo, Japan

    Yukitaka Ueki

  4. First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

    Kazuyoshi Saito & Yoshiya Tanaka

  5. Department of Rheumatology, Yokohama Minami Kyosai Hospital, Yokohama, Japan

    Shouhei Nagaoka

  6. Institute of Rheumatology, Zenjinkai Shimin-No-Mori-Hospital, Miyazaki, Japan

    Toshihiko Hidaka

  7. Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Tatsuya Atsumi

  8. Kumamoto Orthopaedic Hospital, Kumamoto, Japan

    Michishi Tsukano

  9. Division of Rheumatology and Clinical Immunology, Showa University School of Medicine, Tokyo, Japan

    Tsuyoshi Kasama

  10. Division of Rheumatology, Kobe University Graduate School of Medicine, Kobe, Japan

    Shunichi Shiozawa

Authors
  1. Hideto Kameda
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  2. Yukitaka Ueki
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  3. Kazuyoshi Saito
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  4. Shouhei Nagaoka
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  5. Toshihiko Hidaka
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  6. Tatsuya Atsumi
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  7. Michishi Tsukano
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  8. Tsuyoshi Kasama
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  9. Shunichi Shiozawa
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  10. Yoshiya Tanaka
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  11. Tsutomu Takeuchi
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Japan Biological Agent Study Integrated Consortium (JBASIC)

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Correspondence to Hideto Kameda.

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Kameda, H., Ueki, Y., Saito, K. et al. Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial. Mod Rheumatol 20, 531–538 (2010). https://doi.org/10.1007/s10165-010-0324-4

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  • DOI: https://doi.org/10.1007/s10165-010-0324-4

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