title: A phase III, multicentre, randomised, double-blind, active-controlled, parallel-group trial comparing safety and efficacy of HD203, with innovator etanercept, in combination with methotrexate, in patients with rheumatoid arthritis: the HERA study.
abstract: OBJECTIVE
  To evaluate equivalence in efficacy for rheumatoid arthritis (RA) and compare the safety of the biosimilar HD203 with innovator etanercept (ETN) plus methotrexate (MTX) (ClinicalTrials.gov NCT01270997).
  
  
  METHODS
  Patients with active RA received 25 mg HD203 or ETN subcutaneously twice-weekly with MTX for 48 weeks in a phase III, multicentre, randomised, double-blind, parallel-group design. The primary end point was the proportion of patients achieving the American College of Rheumatology 20% response (ACR20) at week 24 for per-protocol study completer set (PPS). Secondary end points included ACR response criteria, ACRn, European League against Rheumatism (EULAR) response, change in Disease Activity Score 28 (DAS28), patient-reported outcomes, safety and immunogenicity.
  
  
  RESULTS
  Of the 294 randomised patients (HD203, n=147; ETN, n=147), 233 comprised the 24-week PPS (n=115 and 118, respectively). ACR20 at week 24 was achieved by 83.48% and 81.36% of PPS patients, respectively, demonstrating equivalent efficacy within predefined margins of ±20% (treatment difference 2.12%, 95% CI -7.65% to 11.89%). Outcomes for secondary end points were consistent with the primary efficacy findings. Groups were comparable for overall incidences of treatment-emergent (all-causality) adverse events (AEs) (HD203 113 (76.9%) vs ETN 114 (78.1%) (p=0.804)), adverse drug reactions, serious AEs and discontinuations due to AEs. Few patients (HD203, n=8; ETN, n=3) tested positive for anti-drug antibodies.
  
  
  CONCLUSIONS
  The study met the primary objective of demonstrating equivalent efficacy of HD203 and ETN. HD203 was well tolerated, with safety comparable with ETN in this population of patients with RA.
  
  
  BACKGROUND
  NCT01270997; Results.
authors.affiliation: Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Bae
authors.affiliation: Jeju National University Hospital, Jeju, Republic of Korea.
authors.forename: Jinseok
authors.initials: J
authors.lastname: Kim
authors.affiliation: Catholic University of Daegu School of Medicine, Daegu, Republic of Korea.
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Choe
authors.affiliation: Inha University Hospital, Incheon, Republic of Korea.
authors.forename: Won
authors.initials: W
authors.lastname: Park
authors.affiliation: Konkuk University School of Medicine, Seoul, Republic of Korea.
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yong-Beom
authors.initials: YB
authors.lastname: Park
authors.affiliation: Chungnam National University Hospital, Daejeon, Republic of Korea.
authors.forename: Seung-Cheol
authors.initials: SC
authors.lastname: Shim
authors.affiliation: Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Shin-Seok
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Yoon-Kyoung
authors.initials: YK
authors.lastname: Sung
authors.affiliation: Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Chan-Bum
authors.initials: CB
authors.lastname: Choi
authors.affiliation: Hanwha Chemical Biologics, Seoul, Republic of Korea.
authors.forename: So-Ra
authors.initials: SR
authors.lastname: Lee
authors.affiliation: Hanwha Chemical Biologics, Seoul, Republic of Korea.
authors.forename: HanYu
authors.initials: H
authors.lastname: Park
authors.affiliation: Hanwha Chemical Biologics, Daejeon, Republic of Korea.
authors.forename: Yongho
authors.initials: Y
authors.lastname: Ahn
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 / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; 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