Phase III, multicentre, double-blind, randomised, parallel-group study to evaluate the similarities between LBEC0101 and etanercept reference product in terms of efficacy and safety in patients with active rheumatoid arthritis inadequately responding to methotrexate

Ann Rheum Dis. 2018 Apr;77(4):488-494. doi: 10.1136/annrheumdis-2017-212172. Epub 2017 Dec 19.

Abstract

Objective: To evaluate the similarities between LBEC0101 (etanercept biosimilar) and the etanercept reference product (ETN-RP) in terms of efficacy and safety, including immunogenicity, in patients with active rheumatoid arthritis despite methotrexate treatment.

Methods: This phase III, multicentre, randomised, double-blind, parallel-group, 54-week study was conducted in Japan and Korea. The primary efficacy endpoint was the change from baseline in the disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) at week 24. American College of Rheumatology 20% (ACR20) response rate, adverse events (AEs), pharmacokinetics and development of antidrug antibodies (ADAs) were also evaluated.

Results: In total, 374 patients were randomised to LBEC0101 (n=187) or ETN-RP (n=187). The least squares mean changes from baseline in DAS28-ESR at week 24 in the per-protocol set were -3.01 (95% CI -3.198 to -2.820) in the LBEC0101 group and -2.86 (95% CI -3.051 to -2.667) in the ETN-RP group. The estimated between-group difference was -0.15 and its 95% CI was -0.377 to 0.078, which was within the prespecified equivalence margin of -0.6 to 0.6. ACR20 response rates at week 24 were similar between the groups (LBEC0101 93.3% vs ETN-RP 86.7%). The incidence of AEs up to week 54 was comparable between the groups (LBEC0101 92.0% vs ETN-RP 92.5%), although fewer patients in the LBEC0101 group (1.6%) than the ETN-RP group (9.6%) developed ADAs.

Conclusion: The clinical efficacy of LBEC0101 was equivalent to that of ETN-RP. LBEC0101 was well tolerated and had a comparable safety profile to ETN-RP.

Trial registration number: NCT02357069.

Keywords: Das28; Methotrexate; Rheumatoid Arthritis.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / pharmacokinetics
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Biosimilar Pharmaceuticals / therapeutic use*
  • Blood Sedimentation
  • Double-Blind Method
  • Etanercept / pharmacokinetics
  • Etanercept / therapeutic use*
  • Female
  • Humans
  • Immunoglobulin G / metabolism
  • Immunoglobulin G / therapeutic use*
  • Least-Squares Analysis
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Severity of Illness Index
  • Therapeutic Equivalency
  • Treatment Outcome
  • Young Adult

Substances

  • Antirheumatic Agents
  • Biosimilar Pharmaceuticals
  • Immunoglobulin G
  • LBEC0101
  • Receptors, Tumor Necrosis Factor
  • Etanercept
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT02357069