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

Ann Rheum Dis. 2017 Jan;76(1):65-71. doi: 10.1136/annrheumdis-2015-207613. Epub 2016 Feb 23.

Abstract

Objectives: 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.

Conclusion: 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.

Trial registration number: NCT01270997; Results.

Keywords: Anti-TNF; DMARDs (biologic); Rheumatoid Arthritis.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies / blood
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / immunology
  • Antirheumatic Agents / pharmacokinetics*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Biosimilar Pharmaceuticals / pharmacokinetics*
  • Biosimilar Pharmaceuticals / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Etanercept / adverse effects
  • Etanercept / immunology
  • Etanercept / pharmacokinetics*
  • Etanercept / therapeutic use*
  • Female
  • Humans
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Therapeutic Equivalency
  • Treatment Outcome

Substances

  • Antibodies
  • Antirheumatic Agents
  • Biosimilar Pharmaceuticals
  • Etanercept
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT01270997