Phase III Study of the Efficacy and Safety of Subcutaneous Versus Intravenous Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis

Authors

  • Atsushi Ogata,

    Corresponding author
    1. Osaka University, Osaka, Japan
    • Department of Respiratory Medicine, Allergy and Rheumatic Disease, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: ogata@imed3.med.osaka-u.ac.jp

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    • Dr. Ogata has received speaking fees (less than $10,000 each) from Abbott, BMS, Mitsubishi-Tanabe, and Pfizer, and has received consulting fees (more than $10,000) from Chugai.

  • Kazuhide Tanimura,

    1. Hokkaido Medical Center for Rheumatic Diseases, Hokkaido, Japan
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    • Dr. Tanimura has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Abbott, BMS, Chugai, Eisai, and Mitsubishi-Tanabe.

  • Toyohiko Sugimoto,

    1. National Hospital Organization, Shimoshizu Hospital, Chiba, Japan
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  • Hiroshi Inoue,

    1. Inoue Hospital, Gunma, Japan
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    • Dr. Inoue has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from BMS, Chugai, Eisai, Mitsubishi-Tanabe, and Takeda.

  • Yukitomo Urata,

    1. Seihoku Central Hospital, United Municipalities of Tsugaru, Aomori, Japan
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    • Dr. Urata has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from BMS, Chugai, Janssen, and Pfizer.

  • Tsukasa Matsubara,

    1. Matsubara Mayflower Hospital, Hyogo, Japan
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  • Masakazu Kondo,

    1. Kondo Clinic of Rheumatology and Orthopedic Surgery, Fukuoka, Japan
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    • Dr. Kondo has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Abbott, Chugai, Eisai, Mitsubishi-Tanabe, and UCB and (more than $10,000) from Pfizer.

  • Yukitaka Ueki,

    1. Sasebo Chuo Hospital, Nagasaki, Japan
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    • Dr. Ueki has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Abbott, BMS, Chugai, Eisai, Mitsubishi-Tanabe, and Pfizer.

  • Mitsuhiro Iwahashi,

    1. Higashihiroshima Memorial Hospital, Hiroshima, Japan
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    • Dr. Iwahashi has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Abbott, Asahi Kasei, Janssen, Mitsubishi-Tanabe, Pfizer, and Santen and (more than $10,000 each) from BMS and Chugai.

  • Shigeto Tohma,

    1. National Hospital Organization, Sagamihara Hospital, Kanagawa, Japan
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    • Dr. Tohma has received consulting fees, speaking fees, and/or honoraria (more than $10,000) from Chugai.

  • Shuji Ohta,

    1. Taga General Hospital, Ibaraki, Japan
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    • Dr. Ohta has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Abbott, Astellas, BMS, Chugai, Eisai, Shionogi, and Takeda and (more than $10,000) from Mitsubishi-Tanabe.

  • Yukihiko Saeki,

    1. National Hospital Organization, Osaka Minami Medical Center, Osaka, Japan
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    • Dr. Saeki has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Abbott Japan, BMS, Chugai, Mitsubishi-Tanabe, Pfizer Japan, and Takeda.

  • Toshio Tanaka,

    1. Osaka University, Osaka, Japan
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    • Dr. Tanaka has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Chugai and Mitsubishi-Tanabe.

  • the Musashi Study Investigators


  • ClinicalTrials.jp identifier: JapicCTI-101117.

Abstract

Objective

To evaluate the efficacious noninferiority of subcutaneous tocilizumab injection (TCZ-SC) monotherapy to intravenous TCZ infusion (TCZ-IV) monotherapy in Japanese patients with rheumatoid arthritis (RA) with an inadequate response to synthetic and/or biologic disease-modifying antirheumatic drugs (DMARDs).

Methods

This study had a double-blind, parallel-group, double-dummy, comparative phase III design. Patients were randomized to receive TCZ-SC 162 mg every 2 weeks or TCZ-IV 8 mg/kg every 4 weeks; no DMARDs were allowed during the study. The primary end point was to evaluate the noninferiority of TCZ-SC to TCZ-IV regarding the American College of Rheumatology criteria for 20% improvement in disease activity (ACR20) response rates at week 24 using an 18% noninferiority margin. Additional efficacy, safety, pharmacokinetic, and immunogenicity parameters were assessed.

Results

At week 24, ACR20 response was achieved in 79.2% (95% confidence interval [95% CI] 72.9, 85.5) of the TCZ-SC group and in 88.5% (95% CI 83.4, 93.5) of the TCZ-IV group; the weighted difference was −9.4% (95% CI −17.6, −1.2), confirming the noninferiority of TCZ-SC to TCZ-IV. Remission rates of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate and the Clinical Disease Activity Index at week 24 were 49.7% and 16.4% in the TCZ-SC group and 62.2% and 23.1% in the TCZ-IV group, respectively. Serum trough TCZ concentrations were similar between the groups over time. Incidences of all adverse events and serious adverse events were 89.0% and 7.5% in the TCZ-SC group and 90.8% and 5.8% in the TCZ-IV group, respectively. Anti-TCZ antibodies were detected in 3.5% of the TCZ-SC group; no serious hypersensitivity was reported in these patients.

Conclusion

TCZ-SC monotherapy demonstrated comparable efficacy and safety to TCZ-IV monotherapy. TCZ-SC could provide additional treatment options for patients with RA.

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