Evaluation of the pharmacokinetic equivalence and 54-week efficacy and safety of CT-P13 and innovator infliximab in Japanese patients with rheumatoid arthritis

Abstract

Objectives. 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.

Conclusion. 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.

Keywords:

• Biosimilar
• CT-P13
• Infliximab
• PK equivalence
• Rheumatoid arthritis

Acknowledgments

The studies described herein were funded by Celltrion, Inc. and Nippon Kayaku Co., Ltd. The authors acknowledge all investigators at the following hospitals for their contribution to the study: Sapporo City General Hospital; Hokkaido Medical Center for Rheumatic Diseases; Inoue Hospital; Saitama Medical Centre, Saitama Medical University; School of Medicine, Keio University; Tokyo Medical and Dental University; Institute of Rheumatology, Tokyo Women's Medical University; Niigata Rheumatic Center; Shizuoka Kousei Hospital; Aichi Medical University School of Medicine; Kyoto University Graduate School of Medicine; National Hospital Organization Osaka-Minami Medical Center; Matsubara Mayflower Hospital; Higashihiroshima Memorial Hospital; University of Occupational and Environmental Health; Kyushu University Graduate School of Medical Sciences; Nagasaki University Graduate School of Biomedical Sciences; Sasebo Chuo Hospital; Shimin- No-Mori Hospital; and Kagoshima Red Cross Hospital. All costs associated with development of this manuscript were funded by Nippon Kayaku Co., Ltd.

Conflict of interest

T. Takeuchi has received grants from Astellas Pharma Inc., Bristol–Myers K.K., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma Corp., Pfizer Japan Inc., Santen Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co. Ltd., and SymBio Pharmaceuticals Ltd., speaking fees from AbbVie GK, Bristol–Myers K.K., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corp., Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Astellas Pharma Inc., Daiichi Sankyo Co. Ltd., Celltrion, and Nippon Kayaku Co. Ltd., and consultant fees from AstraZeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Corp., Asahi Kasei Medical Co. Ltd., AbbVie GK, Daiichi Sankyo Co. Ltd., Bristol–Myers K.K., and Nippon Kayaku Co. Ltd.

H. Yamanaka has received honorarium for a lecture or consultancy from Teijin Pharma Ltd., Chugai Pharmaceutical Co. Ltd., Astellas Pharma Inc., Bristol-Myers K.K., AbbVie GK, Daiichi Sankyo Co. Ltd., Nippon Kayaku Co. Ltd., Mitsubishi-Tanabe Pharma Corp., Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., and UCB Japan Co. Ltd., and has received research grant from AbbVie GK, Asahi Kasei Pharma Corp., Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Eisai Co. Ltd., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corp., MSD K.K., Nippon Kayaku Co. Ltd., Pfizer Japan Inc., Santen Pharmaceutical Co. Ltd., Taisho Toyama Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Teijin Pharma Ltd.

T. Sakurai has declared no conflicts of interest.

Y. Tanaka has received consulting fees, speaking fees, and/or honoraria from AbbVie GK, Chugai Pharmaceutical Co. Ltd., Astellas Pharma Inc., Takeda Pharmaceutical Co. Ltd., Santen Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp., Pfizer Japan Inc., Janssen Pharmaceutical K.K., Eisai Co. Ltd., Daiichi Sankyo Co. Ltd., UCB Japan Co. Ltd., GlaxoSmithKline K.K., Bristol-Myers K.K., Celltrion, and Nippon Kayaku Co. Ltd. and has received research grants from Mitsubishi-Tanabe Pharma Corp., Chugai Pharmaceutical Co. Ltd., MSD K.K., Astellas Pharma Inc., Novartis Pharma K.K., and Nippon Kayaku Co. Ltd.

K. Saito has received speaking fees from Mitsubishi Tanabe Pharma Corp., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., AbbVie GK, Pfizer Japan Inc., Santen Pharmaceutical Co. Ltd., Janssen Pharmaceutical K.K., Takeda Pharmaceutical Co. Ltd., Bristol-Myers K.K., Astellas Pharma Inc., Celltrion, and Nippon Kayaku Co. Ltd.

H. Ohtsubo has received consulting fees, speaking fees, and/or honoraria from Eli Lilly Japan K.K., Bristol-Myers K.K., Asahi Kasei Pharma Corp., AbbVie GK., Janssen Pharmaceutical K.K., Astellas Pharma Inc., Daiichi Sankyo Co. Ltd., Chugai Pharmaceutical Co. Ltd., and Nippon Kayaku Co. Ltd. and has received research grants from Bristol-Myers K.K. and Nippon Kayaku Co. Ltd.

S.J. Lee is an employee of Celltrion, Inc.

Y. Nambu is an employee of Nippon Kayaku Co. Ltd.

Supplementary material available online

Supplementary Tables 1, 2, and 3.