Efficacy and safety of CT-P47 versus reference tocilizumab: 32-week results of a randomised, active-controlled, double-blind, phase III study in patients with rheumatoid arthritis, including 8 weeks of switching data from reference tocilizumab to CT-P47

RMD Open. 2024 Oct 18;10(4):e004514. doi: 10.1136/rmdopen-2024-004514.

Abstract

Objectives: To demonstrate efficacy equivalence of CT-P47 and EU-approved reference tocilizumab (r-TCZ) in patients with rheumatoid arthritis (RA).

Methods: This double-blind, phase III study randomised (1:1) patients to receive CT-P47 or r-TCZ (8 mg/kg) every 4 weeks until week 20 during treatment period (TP) 1. Prior to week 24 dosing, patients receiving r-TCZ were randomised (1:1) to continue r-TCZ or switch to CT-P47; patients receiving CT-P47 continued CT-P47 (TP2, 8 mg/kg every 4 weeks until week 48). The dual primary endpoints (for different regulatory requirements) were mean changes from baseline in Disease Activity Score in 28 joints (DAS28; erythrocyte sedimentation rate (ESR)) at week 12 and week 24. Efficacy equivalence was determined if CIs for the treatment difference were within predefined equivalence margins: (95% CI -0.6, 0.6 (analysis of covariance (ANCOVA)) at week 12 or 90% CI -0.6, 0.5 (ANCOVA with multiple imputation) at week 24). Additional efficacy, pharmacokinetic (PK) and safety endpoints, including immunogenicity, were investigated. Findings up to week 32 are presented.

Results: In TP1, 471 patients were randomised (234 CT-P47; 237 r-TCZ). The 95% and 90% CIs for the estimated treatment differences were contained within the predefined equivalence margins; the estimated difference in DAS28-ESR at week 12 was -0.01 (95% CI -0.26, 0.24) and at week 24 was -0.10 (90% CI -0.30, 0.10). Secondary efficacy endpoints, PKs and overall safety were comparable between groups up to week 32.

Conclusions: Efficacy equivalence, alongside comparable PK, safety and immunogenicity profiles, was determined between CT-P47 and r-TCZ in adults with RA, including after switching from r-TCZ to CT-P47.

Keywords: arthritis, rheumatoid; autoimmune diseases; biosimilar pharmaceuticals.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antirheumatic Agents* / administration & dosage
  • Antirheumatic Agents* / adverse effects
  • Antirheumatic Agents* / therapeutic use
  • Arthritis, Rheumatoid* / drug therapy
  • Biosimilar Pharmaceuticals / administration & dosage
  • Biosimilar Pharmaceuticals / adverse effects
  • Biosimilar Pharmaceuticals / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Therapeutic Equivalency
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • tocilizumab
  • Antirheumatic Agents
  • Biosimilar Pharmaceuticals