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

Dae Hyun Yoo, Chang Hee Suh, Seung Cheol Shim, Slawomir Jeka, Francisco Fidencio Cons-Molina, Pawel Hrycaj, Piotr Wiland, Eun Young Lee, Francisco G. Medina-Rodriguez, Pavel Shesternya, Sebastiao Radominski, Marina Stanislav, Volodymyr Kovalenko, Dong Hyuk Sheen, Leysan Myasoutova, Mie Jin Lim, Jung Yoon Choe, Sang Joon Lee, Sung Young Lee, Taek Sang KwonWon Park

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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.

Original languageEnglish
Pages (from-to)566-570
Number of pages5
JournalAnnals of the Rheumatic Diseases
Volume76
Issue number3
DOIs
StatePublished - 1 Mar 2017

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Pharmacokinetics
Rheumatoid Arthritis
Randomized Controlled Trials
Pharmacodynamics
Safety
Therapeutic Equivalency
Serum
Methotrexate
Rituximab
Necrosis
Antibodies

Keywords

  • B cells
  • DMARDs (biologic)
  • Pharmacokinetics
  • Rheumatoid Arthritis
  • Treatment

Cite this

Yoo, Dae Hyun ; Suh, Chang Hee ; Shim, Seung Cheol ; Jeka, Slawomir ; Cons-Molina, Francisco Fidencio ; Hrycaj, Pawel ; Wiland, Piotr ; Lee, Eun Young ; Medina-Rodriguez, Francisco G. ; Shesternya, Pavel ; Radominski, Sebastiao ; Stanislav, Marina ; Kovalenko, Volodymyr ; Sheen, Dong Hyuk ; Myasoutova, Leysan ; Lim, Mie Jin ; Choe, Jung Yoon ; Lee, Sang Joon ; Lee, Sung Young ; Kwon, Taek Sang ; Park, Won. / A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis. In: Annals of the Rheumatic Diseases. 2017 ; Vol. 76, No. 3. pp. 566-570.
@article{5b55a478499c48d0ba33c784f7cc99ed,
title = "A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis",
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.",
keywords = "B cells, DMARDs (biologic), Pharmacokinetics, Rheumatoid Arthritis, Treatment",
author = "Yoo, {Dae Hyun} and Suh, {Chang Hee} and Shim, {Seung Cheol} and Slawomir Jeka and Cons-Molina, {Francisco Fidencio} and Pawel Hrycaj and Piotr Wiland and Lee, {Eun Young} and Medina-Rodriguez, {Francisco G.} and Pavel Shesternya and Sebastiao Radominski and Marina Stanislav and Volodymyr Kovalenko and Sheen, {Dong Hyuk} and Leysan Myasoutova and Lim, {Mie Jin} and Choe, {Jung Yoon} and Lee, {Sang Joon} and Lee, {Sung Young} and Kwon, {Taek Sang} and Won Park",
year = "2017",
month = "3",
day = "1",
doi = "10.1136/annrheumdis-2016-209540",
language = "English",
volume = "76",
pages = "566--570",
journal = "Annals of the rheumatic diseases",
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Yoo, DH, Suh, CH, Shim, SC, Jeka, S, Cons-Molina, FF, Hrycaj, P, Wiland, P, Lee, EY, Medina-Rodriguez, FG, Shesternya, P, Radominski, S, Stanislav, M, Kovalenko, V, Sheen, DH, Myasoutova, L, Lim, MJ, Choe, JY, Lee, SJ, Lee, SY, Kwon, TS & Park, W 2017, 'A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis', Annals of the Rheumatic Diseases, vol. 76, no. 3, pp. 566-570. https://doi.org/10.1136/annrheumdis-2016-209540

A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis. / Yoo, Dae Hyun; Suh, Chang Hee; Shim, Seung Cheol; Jeka, Slawomir; Cons-Molina, Francisco Fidencio; Hrycaj, Pawel; Wiland, Piotr; Lee, Eun Young; Medina-Rodriguez, Francisco G.; Shesternya, Pavel; Radominski, Sebastiao; Stanislav, Marina; Kovalenko, Volodymyr; Sheen, Dong Hyuk; Myasoutova, Leysan; Lim, Mie Jin; Choe, Jung Yoon; Lee, Sang Joon; Lee, Sung Young; Kwon, Taek Sang; Park, Won.

In: Annals of the Rheumatic Diseases, Vol. 76, No. 3, 01.03.2017, p. 566-570.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis

AU - Yoo, Dae Hyun

AU - Suh, Chang Hee

AU - Shim, Seung Cheol

AU - Jeka, Slawomir

AU - Cons-Molina, Francisco Fidencio

AU - Hrycaj, Pawel

AU - Wiland, Piotr

AU - Lee, Eun Young

AU - Medina-Rodriguez, Francisco G.

AU - Shesternya, Pavel

AU - Radominski, Sebastiao

AU - Stanislav, Marina

AU - Kovalenko, Volodymyr

AU - Sheen, Dong Hyuk

AU - Myasoutova, Leysan

AU - Lim, Mie Jin

AU - Choe, Jung Yoon

AU - Lee, Sang Joon

AU - Lee, Sung Young

AU - Kwon, Taek Sang

AU - Park, Won

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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.

AB - 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.

KW - B cells

KW - DMARDs (biologic)

KW - Pharmacokinetics

KW - Rheumatoid Arthritis

KW - Treatment

UR - http://www.scopus.com/inward/record.url?scp=84987818368&partnerID=8YFLogxK

U2 - 10.1136/annrheumdis-2016-209540

DO - 10.1136/annrheumdis-2016-209540

M3 - Article

C2 - 27624791

AN - SCOPUS:84987818368

VL - 76

SP - 566

EP - 570

JO - Annals of the rheumatic diseases

JF - Annals of the rheumatic diseases

SN - 0003-4967

IS - 3

ER -