Abatacept in combination with methotrexate in Japanese biologic-naive patients with active rheumatoid arthritis: A randomised placebocontrolled phase IV study

Tsukasa Matsubara, Hiroshi Inoue, Toshihiro Nakajima, Kazuhide Tanimura, Akira Sagawa, Yukio Sato, Kei Osano, Shuji Nagano, Yukitaka Ueki, Tadamasa Hanyu, Koichi Hashizume, Norihito Amano, Yoshiya Tanaka, Tsutomu Takeuchi

Research output: Contribution to journalArticle

Abstract

Objectives: To evaluate efficacy and safety of abatacept+methotrexate (MTX) in biologic-naive, anticitrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) and early erosion versus placebo+MTX. Methods: In this phase IV, multicentre, double-blind study (NCT01758198), patients were randomised (1:1) to receive intravenous abatacept (~10 mg/kg) or placebo, plus MTX (≥6 mg/week). Primary efficacy objectives were to compare American College of Rheumatology 20 (ACR20) response rates at week 16 and mean change from baseline in van der Heijde-modified total Sharp score (vdH-mTSS) at week 24 between abatacept+MTX and placebo+MTX groups. Results: Overall, 203 and 202 patients received abatacept+MTX and placebo+MTX, respectively. At week 16, ACR20 response rates were higher in the abatacept (75.4%) versus placebo group (27.7%; p<0.001). Mean change from baseline in vdH-mTSS at week 24 was 0.84 in the abatacept and 1.26 in the placebo group (p=0.017). Radiographic nonprogression rates (change in vdH-mTSS≤smallest detectable change (2.4)) were 88.1% and 75.4% in abatacept and placebo groups, respectively. Adjusted mean change from baseline in Disease Activity Score 28 (C-reactive protein) (DAS28 (CRP)) at week 16 demonstrated a numerically greater reduction in the abatacept versus placebo group. Proportions of patients with DAS28 (CRP), Simplified Disease Activity Index and Clinical Disease Activity Index remission up to week 52 were higher in the abatacept versus placebo group. The abatacept safety profile was consistent with previous observations. Conclusions: C ompared with MTX alone, abatacept+MTX improved clinical symptoms and inhibited structural damage progression in ACPA-positive, Japanese patients with RA, early erosion and inadequate response to MTX.

Original languageEnglish
Article numbere000813
JournalRMD Open
Volume4
Issue number2
DOIs
Publication statusPublished - 2018 Dec 1

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Biological Products
Methotrexate
Rheumatoid Arthritis
Placebos
C-Reactive Protein
Abatacept
Safety
Antibodies
Rheumatology
Double-Blind Method
Proteins

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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Abatacept in combination with methotrexate in Japanese biologic-naive patients with active rheumatoid arthritis : A randomised placebocontrolled phase IV study. / Matsubara, Tsukasa; Inoue, Hiroshi; Nakajima, Toshihiro; Tanimura, Kazuhide; Sagawa, Akira; Sato, Yukio; Osano, Kei; Nagano, Shuji; Ueki, Yukitaka; Hanyu, Tadamasa; Hashizume, Koichi; Amano, Norihito; Tanaka, Yoshiya; Takeuchi, Tsutomu.

In: RMD Open, Vol. 4, No. 2, e000813, 01.12.2018.

Research output: Contribution to journalArticle

Matsubara, T, Inoue, H, Nakajima, T, Tanimura, K, Sagawa, A, Sato, Y, Osano, K, Nagano, S, Ueki, Y, Hanyu, T, Hashizume, K, Amano, N, Tanaka, Y & Takeuchi, T 2018, 'Abatacept in combination with methotrexate in Japanese biologic-naive patients with active rheumatoid arthritis: A randomised placebocontrolled phase IV study', RMD Open, vol. 4, no. 2, e000813. https://doi.org/10.1136/rmdopen-2018-000813
Matsubara, Tsukasa ; Inoue, Hiroshi ; Nakajima, Toshihiro ; Tanimura, Kazuhide ; Sagawa, Akira ; Sato, Yukio ; Osano, Kei ; Nagano, Shuji ; Ueki, Yukitaka ; Hanyu, Tadamasa ; Hashizume, Koichi ; Amano, Norihito ; Tanaka, Yoshiya ; Takeuchi, Tsutomu. / Abatacept in combination with methotrexate in Japanese biologic-naive patients with active rheumatoid arthritis : A randomised placebocontrolled phase IV study. In: RMD Open. 2018 ; Vol. 4, No. 2.
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abstract = "Objectives: To evaluate efficacy and safety of abatacept+methotrexate (MTX) in biologic-naive, anticitrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) and early erosion versus placebo+MTX. Methods: In this phase IV, multicentre, double-blind study (NCT01758198), patients were randomised (1:1) to receive intravenous abatacept (~10 mg/kg) or placebo, plus MTX (≥6 mg/week). Primary efficacy objectives were to compare American College of Rheumatology 20 (ACR20) response rates at week 16 and mean change from baseline in van der Heijde-modified total Sharp score (vdH-mTSS) at week 24 between abatacept+MTX and placebo+MTX groups. Results: Overall, 203 and 202 patients received abatacept+MTX and placebo+MTX, respectively. At week 16, ACR20 response rates were higher in the abatacept (75.4{\%}) versus placebo group (27.7{\%}; p<0.001). Mean change from baseline in vdH-mTSS at week 24 was 0.84 in the abatacept and 1.26 in the placebo group (p=0.017). Radiographic nonprogression rates (change in vdH-mTSS≤smallest detectable change (2.4)) were 88.1{\%} and 75.4{\%} in abatacept and placebo groups, respectively. Adjusted mean change from baseline in Disease Activity Score 28 (C-reactive protein) (DAS28 (CRP)) at week 16 demonstrated a numerically greater reduction in the abatacept versus placebo group. Proportions of patients with DAS28 (CRP), Simplified Disease Activity Index and Clinical Disease Activity Index remission up to week 52 were higher in the abatacept versus placebo group. The abatacept safety profile was consistent with previous observations. Conclusions: C ompared with MTX alone, abatacept+MTX improved clinical symptoms and inhibited structural damage progression in ACPA-positive, Japanese patients with RA, early erosion and inadequate response to MTX.",
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T1 - Abatacept in combination with methotrexate in Japanese biologic-naive patients with active rheumatoid arthritis

T2 - A randomised placebocontrolled phase IV study

AU - Matsubara, Tsukasa

AU - Inoue, Hiroshi

AU - Nakajima, Toshihiro

AU - Tanimura, Kazuhide

AU - Sagawa, Akira

AU - Sato, Yukio

AU - Osano, Kei

AU - Nagano, Shuji

AU - Ueki, Yukitaka

AU - Hanyu, Tadamasa

AU - Hashizume, Koichi

AU - Amano, Norihito

AU - Tanaka, Yoshiya

AU - Takeuchi, Tsutomu

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Objectives: To evaluate efficacy and safety of abatacept+methotrexate (MTX) in biologic-naive, anticitrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) and early erosion versus placebo+MTX. Methods: In this phase IV, multicentre, double-blind study (NCT01758198), patients were randomised (1:1) to receive intravenous abatacept (~10 mg/kg) or placebo, plus MTX (≥6 mg/week). Primary efficacy objectives were to compare American College of Rheumatology 20 (ACR20) response rates at week 16 and mean change from baseline in van der Heijde-modified total Sharp score (vdH-mTSS) at week 24 between abatacept+MTX and placebo+MTX groups. Results: Overall, 203 and 202 patients received abatacept+MTX and placebo+MTX, respectively. At week 16, ACR20 response rates were higher in the abatacept (75.4%) versus placebo group (27.7%; p<0.001). Mean change from baseline in vdH-mTSS at week 24 was 0.84 in the abatacept and 1.26 in the placebo group (p=0.017). Radiographic nonprogression rates (change in vdH-mTSS≤smallest detectable change (2.4)) were 88.1% and 75.4% in abatacept and placebo groups, respectively. Adjusted mean change from baseline in Disease Activity Score 28 (C-reactive protein) (DAS28 (CRP)) at week 16 demonstrated a numerically greater reduction in the abatacept versus placebo group. Proportions of patients with DAS28 (CRP), Simplified Disease Activity Index and Clinical Disease Activity Index remission up to week 52 were higher in the abatacept versus placebo group. The abatacept safety profile was consistent with previous observations. Conclusions: C ompared with MTX alone, abatacept+MTX improved clinical symptoms and inhibited structural damage progression in ACPA-positive, Japanese patients with RA, early erosion and inadequate response to MTX.

AB - Objectives: To evaluate efficacy and safety of abatacept+methotrexate (MTX) in biologic-naive, anticitrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) and early erosion versus placebo+MTX. Methods: In this phase IV, multicentre, double-blind study (NCT01758198), patients were randomised (1:1) to receive intravenous abatacept (~10 mg/kg) or placebo, plus MTX (≥6 mg/week). Primary efficacy objectives were to compare American College of Rheumatology 20 (ACR20) response rates at week 16 and mean change from baseline in van der Heijde-modified total Sharp score (vdH-mTSS) at week 24 between abatacept+MTX and placebo+MTX groups. Results: Overall, 203 and 202 patients received abatacept+MTX and placebo+MTX, respectively. At week 16, ACR20 response rates were higher in the abatacept (75.4%) versus placebo group (27.7%; p<0.001). Mean change from baseline in vdH-mTSS at week 24 was 0.84 in the abatacept and 1.26 in the placebo group (p=0.017). Radiographic nonprogression rates (change in vdH-mTSS≤smallest detectable change (2.4)) were 88.1% and 75.4% in abatacept and placebo groups, respectively. Adjusted mean change from baseline in Disease Activity Score 28 (C-reactive protein) (DAS28 (CRP)) at week 16 demonstrated a numerically greater reduction in the abatacept versus placebo group. Proportions of patients with DAS28 (CRP), Simplified Disease Activity Index and Clinical Disease Activity Index remission up to week 52 were higher in the abatacept versus placebo group. The abatacept safety profile was consistent with previous observations. Conclusions: C ompared with MTX alone, abatacept+MTX improved clinical symptoms and inhibited structural damage progression in ACPA-positive, Japanese patients with RA, early erosion and inadequate response to MTX.

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