Evaluation of the pharmacokinetic equivalence and 54-week efficacy and safety of CT-P13 and innovator infliximab in Japanese patients with rheumatoid arthritis.
OBJECTIVE
To demonstrate the pharmacokinetic equivalence of CT-P13 and its innovator infliximab (IFX) in Japanese patients with rheumatoid arthritis (RA), and to compare the efficacy and safety of these drugs, administered for 54 weeks.


METHODS
In a randomized, double-blind, parallel-group, multicenter study, 3 mg/kg of CT-P13 or IFX, in combination with methotrexate (MTX) (6-16 mg/week), was administered for 54 weeks to Japanese active RA patients with an inadequate response to MTX, to demonstrate the pharmacokinetic equivalence, based on the area under the curve (AUC(τ)) (weeks 6-14) and C(max) (week 6) of these drugs, and to compare their efficacy and safety.


RESULTS
The CT-P13-to-IFX ratios (90% confidence intervals) of the geometric mean AUC(τ) and C(max) values in patients negative for antibodies to infliximab at week 14 were 111.62% (100.24-124.29%) and 104.09% (92.12-117.61%), respectively, demonstrating the pharmacokinetic equivalence of these drugs. In the full analysis set, CT-P13 and IFX showed comparable therapeutic effectiveness, as measured by the American College of Rheumatology, Disease Activity Score in 28 joints, the European League Against Rheumatism, and other efficacy criteria, at weeks 14 and 30. The incidence of adverse events was similar for these drugs.


CONCLUSIONS
CT-P13 and IFX, administered at a dose of 3 mg/kg in combination with MTX to active RA patients, were pharmacokinetically equivalent and comparable in efficacy and safety.
a Division of Rheumatology, Department of Internal Medicine , School of Medicine, Keio University , Tokyo , Japan.
Tsutomu
T
Takeuchi
b Institute of Rheumatology, Tokyo Women's Medical University , Tokyo , Japan.
Hisashi
H
Yamanaka
c First Department of Internal Medicine , University of Occupational and Environmental Health , Fukuoka , Japan.
Yoshiya
Y
Tanaka
d Inoue Hospital , Gunma , Japan.
Takeo
T
Sakurai
c First Department of Internal Medicine , University of Occupational and Environmental Health , Fukuoka , Japan.
Kazuyoshi
K
Saito
e Kagoshima Red Cross Hospital , Kagoshima , Japan.
Hideo
H
Ohtsubo
f Data center, Product development, Celltrion, Inc. , Incheon , Republic of Korea.
Sang Joon
SJ
Lee
g Pharmaceutical Development Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd. , Tokyo , Japan.
Yoshihiro
Y
Nambu
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; C000591237:CT-P13; D000069285:Infliximab; D008727:Methotrexate
Biosimilar; CT-P13; Infliximab; PK equivalence; Rheumatoid arthritis