title: A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy.
abstract: OBJECTIVE
  To compare the efficacy and safety of SB4 (an etanercept biosimilar) with reference product etanercept (ETN) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy.
  
  
  METHODS
  This is a phase III, randomised, double-blind, parallel-group, multicentre study with a 24-week primary endpoint. Patients with moderate to severe RA despite MTX treatment were randomised to receive weekly dose of 50 mg of subcutaneous SB4 or ETN. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 24. Other efficacy endpoints as well as safety, immunogenicity and pharmacokinetic parameters were also measured.
  
  
  RESULTS
  596 patients were randomised to either SB4 (N=299) or ETN (N=297). The ACR20 response rate at week 24 in the per-protocol set was 78.1% for SB4 and 80.3% for ETN. The 95% CI of the adjusted treatment difference was -9.41% to 4.98%, which is completely contained within the predefined equivalence margin of -15% to 15%, indicating therapeutic equivalence between SB4 and ETN. Other efficacy endpoints and pharmacokinetic endpoints were comparable. The incidence of treatment-emergent adverse events was comparable (55.2% vs 58.2%), and the incidence of antidrug antibody development up to week 24 was lower in SB4 compared with ETN (0.7% vs 13.1%).
  
  
  CONCLUSIONS
  SB4 was shown to be equivalent with ETN in terms of efficacy at week 24. SB4 was well tolerated with a lower immunogenicity profile. The safety profile of SB4 was comparable with that of ETN.
  
  
  BACKGROUND
  NCT01895309, EudraCT 2012-005026-30.
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK.|NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.affiliation: Institute of Rheumatology, Prague, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Vencovský
authors.affiliation: NZOZ Medica Pro Familia Sp. z o.o., Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Sylwestrzak
authors.affiliation: Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Leszczyński
authors.affiliation: Poznanski Osrodek Medyczny NOVAMED, Pultusk, Poland.
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Porawska
authors.affiliation: Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Asta
authors.initials: A
authors.lastname: Baranauskaite
authors.affiliation: Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine.
authors.forename: Vira
authors.initials: V
authors.lastname: Tseluyko
authors.affiliation: M.V.Sklifosovskyi Poltava Regional Clinical Hospital, Poltava, Ukraine.
authors.forename: Vyacheslav M
authors.initials: VM
authors.lastname: Zhdan
authors.affiliation: Medicome Sp. z o.o., Oswiecim, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Stasiuk
authors.affiliation: Klaipeda University Hospital, Klaipeda, Lithuania.
authors.forename: Roma
authors.initials: R
authors.lastname: Milasiene
authors.affiliation: Unidad de Atención Medica e Investigación en Salud (UNAMIS), Yucatán, México.
authors.forename: Aaron Alejandro
authors.initials: AA
authors.lastname: Barrera Rodriguez
authors.affiliation: Samsung Bioepis Co., Ltd., Incheon, Republic of Korea.
authors.forename: Soo Yeon
authors.initials: SY
authors.lastname: Cheong
authors.affiliation: Samsung Bioepis Co., Ltd., Incheon, Republic of Korea.
authors.forename: Jeehoon
authors.initials: J
authors.lastname: Ghil
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000276:immunology / 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; D000068800:Etanercept / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D018501:Antirheumatic Agents; D059451:Biosimilar Pharmaceuticals; D000068800:Etanercept; D008727:Methotrexate
keywords: Anti-TNF; DMARDs (biologic); Rheumatoid Arthritis