Efficacy, safety, pharmacokinetics and immunogenicity of abatacept administered subcutaneously or intravenously in Japanese patients with rheumatoid arthritis and inadequate response to methotrexate: a Phase II/III, randomized study

Mitsuhiro Iwahashi, Hiroshi Inoue, Tsukasa Matsubara, Takaaki Tanaka, Koichi Amano, Toshihisa Kanamono, Teruaki Nakano, Shoichi Uchimura, Tomomaro Izumihara, Akira Yamazaki, Chetan S. Karyekar, Tsutomu Takeuchi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

OBJECTIVE: To evaluate efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept and background methotrexate (MTX) in Japanese patients with rheumatoid arthritis (RA) and inadequate response to MTX (MTX-IR).

METHODS: Double-dummy, double-blind study (NCT01001832); 118 adults with ≥ 10 swollen joints, ≥ 12 tender joints and C-reactive protein (CRP) ≥ 0.8 mg/dL randomized 1:1 to SC abatacept (125 mg weekly) with IV loading (∼10 mg/kg on Day 1), or IV abatacept (∼10 mg/kg monthly) for 169 days, both also receiving MTX (6-8 mg/week). Primary endpoint was Day 169 American College of Rheumatology (ACR)20 response; other efficacy endpoints, safety and immunogenicity were assessed.

RESULTS: Similar proportions of patients achieved ACR20 responses at Day 169 with SC (91.5% [95% CI 81.3, 97.2]) and IV abatacept (83.1% [71.0, 91.6]). ACR50/70 responses, adjusted mean changes from baseline in Health Assessment Questionnaire-Disability Index scores and remission rates (28-joint Disease Activity Score [CRP] <2.6) were also comparable between groups. Serious adverse event frequencies (5.1% vs. 3.4%) were similar with both formulations. One patient per group tested seropositive for immunogenicity. Weekly SC abatacept dosing achieved mean serum concentrations > 10 μg/mL (minimum therapeutic target).

CONCLUSIONS: SC abatacept demonstrated comparable efficacy and safety to IV abatacept, with low immunogenicity rates, in MTX-IR Japanese patients with RA.

Original languageEnglish
Pages (from-to)885-891
Number of pages7
JournalModern rheumatology / the Japan Rheumatism Association
Volume24
Issue number6
DOIs
Publication statusPublished - 2014 Nov 1

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Methotrexate
Rheumatoid Arthritis
Pharmacokinetics
Safety
C-Reactive Protein
Joints
Joint Diseases
Double-Blind Method
Abatacept
Health

Keywords

  • Abatacept
  • Intravenous infusion
  • Japan
  • Rheumatoid arthritis
  • Subcutaneous injection

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Efficacy, safety, pharmacokinetics and immunogenicity of abatacept administered subcutaneously or intravenously in Japanese patients with rheumatoid arthritis and inadequate response to methotrexate : a Phase II/III, randomized study. / Iwahashi, Mitsuhiro; Inoue, Hiroshi; Matsubara, Tsukasa; Tanaka, Takaaki; Amano, Koichi; Kanamono, Toshihisa; Nakano, Teruaki; Uchimura, Shoichi; Izumihara, Tomomaro; Yamazaki, Akira; Karyekar, Chetan S.; Takeuchi, Tsutomu.

In: Modern rheumatology / the Japan Rheumatism Association, Vol. 24, No. 6, 01.11.2014, p. 885-891.

Research output: Contribution to journalArticle

Iwahashi, Mitsuhiro ; Inoue, Hiroshi ; Matsubara, Tsukasa ; Tanaka, Takaaki ; Amano, Koichi ; Kanamono, Toshihisa ; Nakano, Teruaki ; Uchimura, Shoichi ; Izumihara, Tomomaro ; Yamazaki, Akira ; Karyekar, Chetan S. ; Takeuchi, Tsutomu. / Efficacy, safety, pharmacokinetics and immunogenicity of abatacept administered subcutaneously or intravenously in Japanese patients with rheumatoid arthritis and inadequate response to methotrexate : a Phase II/III, randomized study. In: Modern rheumatology / the Japan Rheumatism Association. 2014 ; Vol. 24, No. 6. pp. 885-891.
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abstract = "OBJECTIVE: To evaluate efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept and background methotrexate (MTX) in Japanese patients with rheumatoid arthritis (RA) and inadequate response to MTX (MTX-IR).METHODS: Double-dummy, double-blind study (NCT01001832); 118 adults with ≥ 10 swollen joints, ≥ 12 tender joints and C-reactive protein (CRP) ≥ 0.8 mg/dL randomized 1:1 to SC abatacept (125 mg weekly) with IV loading (∼10 mg/kg on Day 1), or IV abatacept (∼10 mg/kg monthly) for 169 days, both also receiving MTX (6-8 mg/week). Primary endpoint was Day 169 American College of Rheumatology (ACR)20 response; other efficacy endpoints, safety and immunogenicity were assessed.RESULTS: Similar proportions of patients achieved ACR20 responses at Day 169 with SC (91.5{\%} [95{\%} CI 81.3, 97.2]) and IV abatacept (83.1{\%} [71.0, 91.6]). ACR50/70 responses, adjusted mean changes from baseline in Health Assessment Questionnaire-Disability Index scores and remission rates (28-joint Disease Activity Score [CRP] <2.6) were also comparable between groups. Serious adverse event frequencies (5.1{\%} vs. 3.4{\%}) were similar with both formulations. One patient per group tested seropositive for immunogenicity. Weekly SC abatacept dosing achieved mean serum concentrations > 10 μg/mL (minimum therapeutic target).CONCLUSIONS: SC abatacept demonstrated comparable efficacy and safety to IV abatacept, with low immunogenicity rates, in MTX-IR Japanese patients with RA.",
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T1 - Efficacy, safety, pharmacokinetics and immunogenicity of abatacept administered subcutaneously or intravenously in Japanese patients with rheumatoid arthritis and inadequate response to methotrexate

T2 - a Phase II/III, randomized study

AU - Iwahashi, Mitsuhiro

AU - Inoue, Hiroshi

AU - Matsubara, Tsukasa

AU - Tanaka, Takaaki

AU - Amano, Koichi

AU - Kanamono, Toshihisa

AU - Nakano, Teruaki

AU - Uchimura, Shoichi

AU - Izumihara, Tomomaro

AU - Yamazaki, Akira

AU - Karyekar, Chetan S.

AU - Takeuchi, Tsutomu

PY - 2014/11/1

Y1 - 2014/11/1

N2 - OBJECTIVE: To evaluate efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept and background methotrexate (MTX) in Japanese patients with rheumatoid arthritis (RA) and inadequate response to MTX (MTX-IR).METHODS: Double-dummy, double-blind study (NCT01001832); 118 adults with ≥ 10 swollen joints, ≥ 12 tender joints and C-reactive protein (CRP) ≥ 0.8 mg/dL randomized 1:1 to SC abatacept (125 mg weekly) with IV loading (∼10 mg/kg on Day 1), or IV abatacept (∼10 mg/kg monthly) for 169 days, both also receiving MTX (6-8 mg/week). Primary endpoint was Day 169 American College of Rheumatology (ACR)20 response; other efficacy endpoints, safety and immunogenicity were assessed.RESULTS: Similar proportions of patients achieved ACR20 responses at Day 169 with SC (91.5% [95% CI 81.3, 97.2]) and IV abatacept (83.1% [71.0, 91.6]). ACR50/70 responses, adjusted mean changes from baseline in Health Assessment Questionnaire-Disability Index scores and remission rates (28-joint Disease Activity Score [CRP] <2.6) were also comparable between groups. Serious adverse event frequencies (5.1% vs. 3.4%) were similar with both formulations. One patient per group tested seropositive for immunogenicity. Weekly SC abatacept dosing achieved mean serum concentrations > 10 μg/mL (minimum therapeutic target).CONCLUSIONS: SC abatacept demonstrated comparable efficacy and safety to IV abatacept, with low immunogenicity rates, in MTX-IR Japanese patients with RA.

AB - OBJECTIVE: To evaluate efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept and background methotrexate (MTX) in Japanese patients with rheumatoid arthritis (RA) and inadequate response to MTX (MTX-IR).METHODS: Double-dummy, double-blind study (NCT01001832); 118 adults with ≥ 10 swollen joints, ≥ 12 tender joints and C-reactive protein (CRP) ≥ 0.8 mg/dL randomized 1:1 to SC abatacept (125 mg weekly) with IV loading (∼10 mg/kg on Day 1), or IV abatacept (∼10 mg/kg monthly) for 169 days, both also receiving MTX (6-8 mg/week). Primary endpoint was Day 169 American College of Rheumatology (ACR)20 response; other efficacy endpoints, safety and immunogenicity were assessed.RESULTS: Similar proportions of patients achieved ACR20 responses at Day 169 with SC (91.5% [95% CI 81.3, 97.2]) and IV abatacept (83.1% [71.0, 91.6]). ACR50/70 responses, adjusted mean changes from baseline in Health Assessment Questionnaire-Disability Index scores and remission rates (28-joint Disease Activity Score [CRP] <2.6) were also comparable between groups. Serious adverse event frequencies (5.1% vs. 3.4%) were similar with both formulations. One patient per group tested seropositive for immunogenicity. Weekly SC abatacept dosing achieved mean serum concentrations > 10 μg/mL (minimum therapeutic target).CONCLUSIONS: SC abatacept demonstrated comparable efficacy and safety to IV abatacept, with low immunogenicity rates, in MTX-IR Japanese patients with RA.

KW - Abatacept

KW - Intravenous infusion

KW - Japan

KW - Rheumatoid arthritis

KW - Subcutaneous injection

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