Safety and tolerability of sifalimumab, an anti-interferon-α monoclonal antibody, in Japanese patients with systemic lupus erythematosus: A multicenter, phase 2, open-label study

Abstract

Objectives: To evaluate the safety of sifalimumab in Japanese patients with systemic lupus erythematosus (SLE).

Methods: This phase 2, open-label study consisted of a 52-week initial stage (Stage I) and a long-term extension (Stage II). In Stage I, sequential cohorts of patients received ascending doses of sifalimumab (intravenous [IV] 1.0, 3.0, and 10.0 mg/kg or subcutaneous 100 mg every 2 weeks; IV 600 and 1200 mg every 6 weeks). In Stage II, patients enrolled before June 2012 received the same dose of sifalimumab as during Stage I for up to 157 weeks or sifalimumab 600 mg IV every 4 weeks if they enrolled later. The safety of sifalimumab was assessed by adverse events (AEs).

Results: Thirty patients enrolled in Stage I and 21 patients entered Stage II. The majority of patients experienced AEs (96.7% in Stage I and 100% in Stage II); most were mild or moderate in severity. Serious AEs occurred in 30.0% and 57.1% of patients in Stage I and II, respectively; most were instances of SLE flares. The proportion of patients in Stage I and II who had AEs leading to discontinuation was 10.0% and 28.6%, respectively.

Conclusion: Sifalimumab was well tolerated in Japanese patients with SLE.

Trial registration: ClinicalTrials.gov identifier: NCT01031836.

Keywords:

• Dose escalation
• intravenous
• safety
• sifalimumab
• subcutaneous
• systemic lupus erythematosus

Acknowledgments

We would like to thank Simone Tait and Georgii Filatov of inScience Communications, Springer Healthcare, who wrote the outline and the first draft of the manuscript, respectively. This medical writing assistance was funded by AstraZeneca.

Conflicts of interest

T. Takeuchi has received grants from Astellas Pharma Inc, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Eisai Co., Ltd., AYUMI Pharmaceutical Corporation, Nipponkayaku Co.Ltd., and Novartis Pharma K.K., 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., and Novartis Pharma K.K., and 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. Y. Tanaka has received speaking fees and/or honoraria from Daiichi-Sankyo, Astellas, Pfizer, Mitsubishi-Tanabe, Bristol-Myers, Chugai, YL Biologics, Eli Lilly, Sanofi, Janssen, and UCB, and has received research grants from Mitsubishi-Tanabe, Takeda, Bristol-Myers, Chugai, Astellas, AbbVie, MSD, Daiichi-Sankyo, Pfizer, Kyowa-Kirin and Eisai, Ono. R. Matsumura has received research grants from Mitsubishi-Tanabe Pharma Co., Asahi Kasei Medical Co. Ltd., Bristol-Myers Squibb Co., and AbbVie Inc. T. Atsumi has received consulting fees from Chugai, Eli Lily Japan K.K., GlaxoSmithKline K.K., Pfizer Inc. and UCB Japan Co. Ltd, and has received speaking fees from Takeda Pharmaceutical Co. Ltd, Chugai Pharmaceutical Co. Ltd., AbbVie Inc., Bristol-Myers Squibb Co., Daiichi Sankyo Co. Ltd., Astellas Pharma Inc., AYUMI Pharmaceutical Co., UCB Japan Co. Ltd, Novartis Co. Ltd, Janssen Pharmaceutical K.K., Asahi Kasei Pharma Corporation, Eisai Co. Ltd, Alexion Inc., Janssen Pharmaceutical K.K., and Mitsubishi Tanabe Pharma Co. K. Saito, M. Yoshimura, K. Amano, and E. Suematsu declare that they have no conflicts of interest to disclose. N. Hayashi is an employee of AstraZeneca K.K. L. Wang and R. Tummala are employees of AstraZeneca Pharmaceuticals.