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


BACKGROUND
NCT01534884.
Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.
Dae Hyun
DH
Yoo
Ajou University Hospital, Suwon, Korea.
Chang-Hee
CH
Suh
Chungnam National University Hospital, Daejeon, Korea.
Seung Cheol
SC
Shim
University Hospital No. 2, Collegium Medicum in Bydgoszcz, UMK in Toruń, Poland.
Slawomir
S
Jeka
Centro de Investigacion en Artritis y Osteoporosis, Mexicali, Mexico.
Francisco Fidencio
FF
Cons-Molina
Poznań University of Medical Sciences, Poznań, Poland.
Pawel
P
Hrycaj
Medical University of Wrocław, Wrocław, Poland.
Piotr
P
Wiland
Seoul National University College of Medicine, Seoul, Korea.
Eun Young
EY
Lee
LaSalle University, Philadelphia, Pennsylvania, USA.
Francisco G
FG
Medina-Rodriguez
Krasnoyarsk State Medical University, Krasnoyarsk, Russia.
Pavel
P
Shesternya
Universidade Federal do Parana, Curitiba, Brazil.
Sebastiao
S
Radominski
Research Rheumatology Institute n. a. V.A. Nassonova, Moscow, Russia.
Marina
M
Stanislav
National Scientific Center, Kiev, Ukraine.
Volodymyr
V
Kovalenko
Eulji University Hospital, Daejeon, Korea.
Dong Hyuk
DH
Sheen
Research Medical Complex Vashe Zdorovie, Kazan, Russia.
Leysan
L
Myasoutova
IN-HA University, School of Medicine, Incheon, Korea.
Mie Jin
MJ
Lim
Catholic University of Daegu, School of Medicine, Daegu, Korea.
Jung-Yoon
JY
Choe
CELLTRION, Incheon, Korea.
Sang Joon
SJ
Lee
CELLTRION, Incheon, Korea.
Sung Young
SY
Lee
CELLTRION, Incheon, Korea.
Taek Sang
TS
Kwon
IN-HA University, School of Medicine, Incheon, Korea.
Won
W
Park
D000328:Adult; D000906:Antibodies / Q000097:blood; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D000069283:Rituximab / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013810:Therapeutic Equivalency
D000906:Antibodies; D018501:Antirheumatic Agents; D000069283:Rituximab; D008727:Methotrexate
B cells; DMARDs (biologic); Pharmacokinetics; Rheumatoid Arthritis; Treatment