title: Phase III study of the efficacy and safety of subcutaneous versus intravenous tocilizumab monotherapy in patients with rheumatoid arthritis.
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.
  
  
  CONCLUSIONS
  TCZ-SC monotherapy demonstrated comparable efficacy and safety to TCZ-IV monotherapy. TCZ-SC could provide additional treatment options for patients with RA.
authors: Osaka University, Osaka, Japan.
authors: Atsushi
authors: A
authors: Ogata
authors: Kazuhide
authors: K
authors: Tanimura
authors: Toyohiko
authors: T
authors: Sugimoto
authors: Hiroshi
authors: H
authors: Inoue
authors: Yukitomo
authors: Y
authors: Urata
authors: Tsukasa
authors: T
authors: Matsubara
authors: Masakazu
authors: M
authors: Kondo
authors: Yukitaka
authors: Y
authors: Ueki
authors: Mitsuhiro
authors: M
authors: Iwahashi
authors: Shigeto
authors: S
authors: Tohma
authors: Shuji
authors: S
authors: Ohta
authors: Yukihiko
authors: Y
authors: Saeki
authors: Toshio
authors: T
authors: Tanaka
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab
references: Ann Rheum Dis. 2013 Jan;72(1):43-50
references: 22562983
references: Arthritis Rheum. 1995 Jun;38(6):727-35
references: 7779114
references: BMJ. 1997 Dec 20-27;315(7123):1704-8
references: 9448547
references: Rheumatology (Oxford). 2006 Dec;45(12):1575-6
references: 17085468
references: Ann Rheum Dis. 2010 Jan;69(1):88-96
references: 19297346
references: Patient Prefer Adherence. 2009 Nov 29;3:335-44
references: 20016797
references: Ann Rheum Dis. 2012 Jun;71(6):817-24
references: 22121129
references: Arthritis Care Res (Hoboken). 2012 May;64(5):625-39
references: 22473917
references: Stat Med. 1999 Aug 15;18(15):1905-42
references: 10532877
references: Lancet. 2008 Mar 22;371(9617):987-97
references: 18358926
references: Ann Rheum Dis. 2014 Jan;73(1):69-74
references: 23904473
references: Arthritis Rheum. 2003 Dec 15;49(6):784-8
references: 14673964
references: Ann Rheum Dis. 2012 Jan;71(1):38-44
references: 21917824
references: Ann Rheum Dis. 2008 Nov;67(11):1516-23
references: 18625622
references: Clin Ther. 2010 Aug;32(9):1597-609
references: 20974317
references: Mod Rheumatol. 2008;18(3):252-62
references: 18330677
references: Clin Exp Rheumatol. 2007 Jan-Feb;25(1):40-6
references: 17417989
references: Arthritis Rheum. 2008 Oct;58(10):2968-80
references: 18821691
references: Arthritis Rheum. 1988 Mar;31(3):315-24
references: 3358796
references: Ann Rheum Dis. 2010 May;69(5):817-21
references: 19581278
references: Blood. 2008 Nov 15;112(10):3959-64
references: 18784373
references: Mod Rheumatol. 2013 Mar;23(2):284-96
references: 22588312
references: Ann Rheum Dis. 2007 Jul;66(7):921-6
references: 17301106
references: Ann Rheum Dis. 2007 Sep;66(9):1162-7
references: 17485422
references: Musculoskeletal Care. 2008 Mar;6(1):1-14
references: 17726671
references: Mod Rheumatol. 2009;19(1):12-9
references: 18979150
references: Arthritis Rheum. 2011 Mar;63(3):609-21
references: 21360490
references: Mod Rheumatol. 2013 Mar;23(2):297-303
references: 22572888
references: Ann Rheum Dis. 2010 Jun;69(6):964-75
references: 20444750