title: A randomised, double-blind, phase III study comparing SB2, an infliximab biosimilar, to the infliximab reference product Remicade in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy.
abstract: OBJECTIVE
  To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy.
  
  
  METHODS
  This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30. Inclusion of the 95% CI of the ACR20 response difference within a ±15% margin was required for equivalence.
  
  
  RESULTS
  584 subjects were randomised into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate difference was -1.88% (95% CI -10.26% to 6.51%), which was within the predefined equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity score measured by 28 joints and European League against Rheumatism response were similar between SB2 and INF. The incidence of treatment-emergent adverse events was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by ADA subgroup were comparable between SB2 and INF.
  
  
  CONCLUSIONS
  SB2 was equivalent to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a comparable safety profile, immunogenicity and PK to INF.
  
  
  BACKGROUND
  NCT01936181.
authors: Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea.
authors: Jung-Yoon
authors: JY
authors: Choe
authors: Clinical Center Banja Luka, Banja Luka, Bosnia and Herzegovina.
authors: Nenad
authors: N
authors: Prodanovic
authors: Medica Pro Familia, Gdynia, Poland.
authors: Jaroslaw
authors: J
authors: Niebrzydowski
authors: MHAT "Dr. Ivan Seliminski", AD, Sliven, Bulgaria.
authors: Ivan
authors: I
authors: Staykov
authors: MEDICAL PLUS s.r.o, Uherske Hradiste, Czech Republic.
authors: Eva
authors: E
authors: Dokoupilova
authors: Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors: Asta
authors: A
authors: Baranauskaite
authors: Internal Medicine #1 Department, Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine.
authors: Roman
authors: R
authors: Yatsyshyn
authors: University Clinic Centre Sarajevo, Sarajevo, Bosnia and Herzegovina.
authors: Mevludin
authors: M
authors: Mekic
authors: Poznanski Osrodek Medyczny NOVAMED, Poznan, Poland.
authors: Wieskawa
authors: W
authors: Porawska
authors: Institute of Rheumatology and First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors: Hana
authors: H
authors: Ciferska
authors: MCBK S.C., Grodzisk Mazowiecki, Poland.
authors: Krystyna
authors: K
authors: Jedrychowicz-Rosiak
authors: Medica Pro Familia Sp. z o.o. Spolka Komandytowo-Akcyjna, Warszawa, Poland.
authors: Agnieszka
authors: A
authors: Zielinska
authors: Samsung Bioepis Co., Ltd., Incheon, Republic of Korea.
authors: Jasmine
authors: J
authors: Choi
authors: Samsung Bioepis Co., Ltd., Incheon, Republic of Korea.
authors: Young Hee
authors: YH
authors: Rho
authors: Medical University of Vienna, Vienna, Austria.
authors: Josef S
authors: JS
authors: Smolen
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012720:Severity of Illness Index; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D018501:Antirheumatic Agents; D059451:Biosimilar Pharmaceuticals; D000069285:Infliximab; D008727:Methotrexate
keywords: Anti-TNF; DMARDs (biologic); Disease Activity; Rheumatoid Arthritis