Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial

Rheumatology (Oxford). 2021 May 14;60(5):2277-2287. doi: 10.1093/rheumatology/keaa580.

Abstract

Objective: To assess non-inferiority of s.c. to i.v. CT-P13 in RA.

Methods: Patients with active RA and inadequate response to MTX participated in this phase I/III double-blind study at 76 sites. Patients received CT-P13 i.v. 3 mg/kg [week (W) 0 and W2] before randomization (1:1) at W6 to CT-P13 s.c. via pre-filled syringe (PFS) 120 mg biweekly until W28, or CT-P13 i.v. 3 mg/kg every 8 weeks until W22. Randomization was stratified by country, W2 serum CRP and W6 body weight. From W30, all patients received CT-P13 s.c. In a usability sub-study, patients received CT-P13 s.c. via auto-injector (W46-54) then PFS (W56-64). The primary endpoint was change (decrease) from baseline in disease activity score in 28 joints (DAS28)-CRP at W22 (non-inferiority margin: -0.6).

Results: Of 357 patients enrolled, 343 were randomized to CT-P13 s.c. (n = 167) or CT-P13 i.v. (n = 176) at W6. The least-squares mean change (decrease) from baseline (standard error) in DAS28-CRP at W22 was 2.21 (0.22) for CT-P13 s.c. (n = 162) and 1.94 (0.21) for CT-P13 i.v. [n = 168; difference 0.27 (95% CI: 0.02, 0.52)], establishing non-inferiority. Efficacy findings were similar between arms at W54. Safety was similar between arms throughout: 92 (54.8%; CT-P13 s.c.) and 117 (66.9%; CT-P13 i.v.) patients experienced treatment-emergent adverse events (from W6). There were no treatment-related deaths or new safety findings. Usability was similar for CT-P13 s.c. via auto-injector or PFS.

Conclusion: CT-P13 s.c. was non-inferior to CT-P13 i.v. in active RA. The convenience of s.c. administration could benefit patients.

Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT03147248.

Keywords: CT-P13; biosimilar; immunogenicity; infliximab; non-inferiority; pharmacokinetics; rheumatoid arthritis; subcutaneous; switching.

Publication types

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

MeSH terms

  • Adult
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / pharmacokinetics
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Biosimilar Pharmaceuticals / administration & dosage
  • Biosimilar Pharmaceuticals / adverse effects
  • Biosimilar Pharmaceuticals / therapeutic use*
  • Double-Blind Method
  • Humans
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Biosimilar Pharmaceuticals
  • CT-P13

Associated data

  • ClinicalTrials.gov/NCT03147248