TY - JOUR
T1 - Safety and tolerability of anifrolumab, a monoclonal antibody targeting type I interferon receptor, in Japanese patients with systemic lupus erythematosus
T2 - A multicenter, phase 2, open-label study
AU - Tanaka, Yoshiya
AU - Takeuchi, Tsutomu
AU - Okada, Masato
AU - Ishii, Tomonori
AU - Nakajima, Hiroshi
AU - Kawai, Shinichi
AU - Nagashima, Takao
AU - Hayashi, Nobuya
AU - Wang, Liangwei
AU - Tummala, Raj
N1 - Funding Information:
Y. Tanaka has received speaking fees and/or honoraria from Daiichi-Sankyo, Astellas, Eli Lilly, Chugai, Sanofi, Abbvie, YL Biologics, Bristol-Myers, Glaxo-Smithkline, UCB, Mitsubishi-Tanabe, Novartis, Eisai, Takeda, Janssen, and Asahi-kasei, and has received research grants from Mitsubishi-Tanabe, Bristol-Myers, Eisai, Chugai, Takeda, Abbvie, Astellas, Daiichi-Sankyo, Ono, MSD, and Taisho-Toyama. T. Takeuchi has received grants from Astellas Pharma Inc, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Asahikasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Eisai Co., Ltd., AYUMI Pharmaceutical Corporation, Nipponkayaku Co.Ltd., Novartis Pharma K.K., has received speaking fees from AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Astellas Pharma Inc, Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Sanofi K.K., Teijin Pharma Ltd., Takeda Pharmaceutical Co., Ltd., Novartis Pharma K.K. and has received consultant fees from AstraZeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Abbvie GK, Nipponkayaku Co.Ltd, Janssen Pharmaceutical K.K., Astellas Pharma Inc,. Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co, Ltd., Taisho Toyama Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., and UCB Japan Co. Ltd. M. Okada has received speaking fees and/or honoraria from Ayumi Pharmaceutical, Mitsubishi Tanabe Pharma, Ono Pharmaceutical, Pfizer, and Abbott Japan. T. Ishii has received speaking fees and/or honoraria from Daiichi-Sankyo, Astellas, Chugai, Sanofi, Abbvie, Bristol-Myers, Mitsubishi-Tanabe, Eisai, Janssen, Asahi-kasei, Ayumi Pharmaceutical, Ono Pharmaceutical and Pfizer. H. Nakajima has received research scholarship grants from Chugai, Astellas and Bristol-Myers Squibb. S. Kawai and T. Nagashima have no conflicts of interest to declare. N. Hayashi is an employee of AstraZeneca K.K. L. Wang and R. Tummala are employees of AstraZeneca Pharmaceuticals.
Funding Information:
We would like to thank Mimi Chan, PhD, of inScience Communications, Springer Healthcare, who wrote the outline and first draft of the manuscript. This medical writing assistance was funded by AstraZeneca.
Publisher Copyright:
© 2019, © 2019 Japan College of Rheumatology. Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020/1/2
Y1 - 2020/1/2
N2 - Objectives: This study evaluated the safety and tolerability of anifrolumab, a monoclonal antibody targeting the type I interferon (IFN) receptor, in Japanese patients with moderate-to-severe systemic lupus erythematosus (SLE). Methods: In this open-label, phase 2, dose-escalation study, patients received intravenous (IV) anifrolumab 100, 300, or 1000 mg every 4 weeks from days 29 to 337 (Stage 1). Patients who completed Stage 1 continued anifrolumab 300 mg every 4 weeks for 156 weeks (Stage 2). The primary objective was to evaluate the safety of anifrolumab for 48 weeks (Stage 1) and 156 weeks (Stage 2). The pharmacokinetics and pharmacodynamics of anifrolumab were also assessed. Results: Of 20 patients enrolled in Stage 1, 17 received IV anifrolumab 100 mg (n = 6), 300 mg (n = 5), or 1000 mg (n = 6). Adverse events (AE) and serious AE (SAE) incidences were similar between dose cohorts. SAEs occurred in 41% (Stage 1) and 33% (Stage 2) of patients; AEs leading to discontinuation occurred in 24% (Stage 1) and 22% (Stage 2) of patients. Anifrolumab had non-linear pharmacokinetics after the first and last dose and dose-dependently suppressed the IFN gene signature. Conclusion: Anifrolumab was well tolerated among Japanese patients with moderate-to-severe SLE.
AB - Objectives: This study evaluated the safety and tolerability of anifrolumab, a monoclonal antibody targeting the type I interferon (IFN) receptor, in Japanese patients with moderate-to-severe systemic lupus erythematosus (SLE). Methods: In this open-label, phase 2, dose-escalation study, patients received intravenous (IV) anifrolumab 100, 300, or 1000 mg every 4 weeks from days 29 to 337 (Stage 1). Patients who completed Stage 1 continued anifrolumab 300 mg every 4 weeks for 156 weeks (Stage 2). The primary objective was to evaluate the safety of anifrolumab for 48 weeks (Stage 1) and 156 weeks (Stage 2). The pharmacokinetics and pharmacodynamics of anifrolumab were also assessed. Results: Of 20 patients enrolled in Stage 1, 17 received IV anifrolumab 100 mg (n = 6), 300 mg (n = 5), or 1000 mg (n = 6). Adverse events (AE) and serious AE (SAE) incidences were similar between dose cohorts. SAEs occurred in 41% (Stage 1) and 33% (Stage 2) of patients; AEs leading to discontinuation occurred in 24% (Stage 1) and 22% (Stage 2) of patients. Anifrolumab had non-linear pharmacokinetics after the first and last dose and dose-dependently suppressed the IFN gene signature. Conclusion: Anifrolumab was well tolerated among Japanese patients with moderate-to-severe SLE.
KW - Anifrolumab
KW - dose escalation
KW - intravenous
KW - safety
KW - systemic lupus erythematosus
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U2 - 10.1080/14397595.2019.1583833
DO - 10.1080/14397595.2019.1583833
M3 - Article
C2 - 30793642
AN - SCOPUS:85063133915
VL - 30
SP - 101
EP - 108
JO - Japanese Journal of Rheumatology
JF - Japanese Journal of Rheumatology
SN - 1439-7595
IS - 1
ER -