A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis

Ann Rheum Dis. 2017 Mar;76(3):566-570. doi: 10.1136/annrheumdis-2016-209540. Epub 2016 Sep 13.

Abstract

Objective: To demonstrate pharmacokinetic equivalence of CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate responses or intolerances to antitumour necrosis factor agents.

Methods: In this randomised phase I trial, patients with active RA were randomly assigned (2:1) to receive 1000 mg CT-P10 or RTX at weeks 0 and 2 (alongside continued methotrexate therapy). Primary endpoints were area under the serum concentration-time curve from time zero to last quantifiable concentration (AUC0-last) and maximum serum concentration after second infusion (Cmax). Additional pharmacokinetic parameters, efficacy, pharmacodynamics, immunogenicity and safety were also assessed. Data are reported up to week 24.

Results: 103 patients were assigned to CT-P10 and 51 to RTX. The 90% CIs for the ratio of geometric means (CT-P10/RTX) for both primary endpoints were within the bioequivalence range of 80%-125% (AUC0-last: 97.7% (90% CI 89.2% to 107.0%); Cmax: 97.6% (90% CI 92.0% to 103.5%)). Pharmacodynamics and efficacy were comparable between groups. Antidrug antibodies were detected in 17.6% of patients in each group at week 24. CT-P10 and RTX displayed similar safety profiles.

Conclusions: CT-P10 and RTX demonstrated equivalent pharmacokinetics and comparable efficacy, pharmacodynamics, immunogenicity and safety.

Trial registration number: NCT01534884.

Keywords: B cells; DMARDs (biologic); Pharmacokinetics; Rheumatoid Arthritis; Treatment.

Publication types

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

MeSH terms

  • Adult
  • Antibodies / blood
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / pharmacokinetics*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Rituximab / adverse effects
  • Rituximab / immunology
  • Rituximab / pharmacokinetics*
  • Rituximab / therapeutic use*
  • Severity of Illness Index
  • Therapeutic Equivalency

Substances

  • Antibodies
  • Antirheumatic Agents
  • Rituximab
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT01534884