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

Mod Rheumatol. 2014 Nov;24(6):885-91. doi: 10.3109/14397595.2014.881954. Epub 2014 Apr 7.

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.

Keywords: Abatacept; Intravenous infusion; Japan; Rheumatoid arthritis; Subcutaneous injection.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Adult
  • Aged
  • Antibodies / blood
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / pharmacokinetics
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunoconjugates / adverse effects
  • Immunoconjugates / immunology
  • Immunoconjugates / pharmacokinetics
  • Immunoconjugates / therapeutic use*
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Japan
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Retreatment
  • Treatment Outcome

Substances

  • Antibodies
  • Antirheumatic Agents
  • Immunoconjugates
  • Abatacept
  • Methotrexate