title: Phase III, multicenter, open-label, long-term study of the safety of abatacept in Japanese patients with rheumatoid arthritis and an inadequate response to conventional or biologic disease-modifying antirheumatic drugs.
abstract: OBJECTIVE
  To examine the long-term safety of intravenous (IV) abatacept treatment in Japanese patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) or other conventional or biologic disease-modifying antirheumatic drugs.
  
  
  METHODS
  This Phase III, open-label, long-term study (NCT00484289) comprised Japanese patients with RA who had completed abatacept Phase I or Phase II studies, and new patients intolerant to MTX. Patients from Phase I and Phase II studies received a weight-tiered dosing equivalent of 10 mg/kg abatacept, with MTX at doses up to 8 mg/week; newly enrolled patients received weight-tiered 10 mg/kg abatacept monotherapy. Safety and efficacy were assessed.
  
  
  RESULTS
  A total of 217 patients (Phase I, n = 13; Phase II, n = 178; newly enrolled, n = 26) were treated with IV abatacept for a mean of 3 years. Serious adverse events occurred in 67/217 (30.9%) patients. Most adverse events were mild or moderate. For all cohorts combined, American College of Rheumatology 20% response rates ranged from 61.3 to 81.8% for as-observed and last observation carried forward analyses over 192 weeks. Following initial response, clinical and functional outcomes were maintained for up to 3 years.
  
  
  CONCLUSIONS
  In Japanese patients with RA, IV abatacept with and without background MTX showed tolerable safety and sustained efficacy over 3 years.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University , Tokyo , Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Matsubara
authors.forename: Yukitomo
authors.initials: Y
authors.lastname: Urata
authors.forename: Eiichi
authors.initials: E
authors.lastname: Suematsu
authors.forename: Shuji
authors.initials: S
authors.lastname: Ohta
authors.forename: Shigeru
authors.initials: S
authors.lastname: Honjo
authors.forename: Tohru
authors.initials: T
authors.lastname: Abe
authors.forename: Ami
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
mesh_terms: D000069594:Abatacept; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D019233:Retreatment; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D018796:Immunoconjugates; D000069594:Abatacept
keywords: Japanese; abatacept; long-term study; rheumatoid arthritis
references.citation: Ann Rheum Dis. 2010 Mar;69(3):510-6
references.pmid: 19933744
references.citation: Mod Rheumatol. 2013 Jul;23(4):634-45
references.pmid: 22833376
references.citation: J Rheumatol. 2012 Aug;39(8):1546-54
references.pmid: 22798265
references.citation: Ann Rheum Dis. 2009 Jul;68(7):1220-7
references.pmid: 18772191
references.citation: J Rheumatol. 2011 Nov;38(11):2362-8
references.pmid: 21885491
references.citation: Arthritis Rheum. 1992 May;35(5):498-502
references.pmid: 1575785
references.citation: Curr Rheumatol Rep. 1999 Dec;1(2):157-63
references.pmid: 11123030
references.citation: Expert Rev Clin Immunol. 2012 Jul;8(5):455-65
references.pmid: 22882220
references.citation: Ann Rheum Dis. 2009 Jul;68(7):1100-4
references.pmid: 19060002
references.citation: Arthritis Rheum. 1995 Jun;38(6):727-35
references.pmid: 7779114
references.citation: Ann Rheum Dis. 2008 Aug;67(8):1096-103
references.pmid: 18055472
references.citation: J Rheumatol. 2009 Apr;36(4):736-42
references.pmid: 19273451
references.citation: Arthritis Rheum. 1980 Feb;23(2):137-45
references.pmid: 7362664
references.citation: Ann Rheum Dis. 2008 Apr;67(4):547-54
references.pmid: 17921185
references.citation: Ann Rheum Dis. 2011 Jun;70(6):886-90
references.pmid: 21378403
references.citation: Ann Rheum Dis. 2011 Oct;70(10):1826-30
references.pmid: 21893583
references.citation: J Rheumatol. 2006 Nov;33(11):2162-6
references.pmid: 17014006
references.citation: Acta Pharmacol Sin. 2009 Mar;30(3):364-71
references.pmid: 19262560
references.citation: Mod Rheumatol. 2013 Mar;23(2):226-35
references.pmid: 22684431
references.citation: Arthritis Rheum. 1988 Mar;31(3):315-24
references.pmid: 3358796
references.citation: Ann Rheum Dis. 2011 Nov;70(11):1949-56
references.pmid: 21821865
references.citation: Curr Med Res Opin. 2006 Jan;22(1):185-98
references.pmid: 16393444
references.citation: Arthritis Rheum. 2002 Jun;46(6):1470-9
references.pmid: 12115176
references.citation: Ann Rheum Dis. 2009 Jul;68(7):1094-9
references.pmid: 19033290