Abstract
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.
| Original language | English |
|---|---|
| Journal | Modern Rheumatology |
| DOIs | |
| Publication status | Published - 2019 Jan 1 |
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Keywords
- Anifrolumab
- dose escalation
- intravenous
- safety
- systemic lupus erythematosus
ASJC Scopus subject areas
- Rheumatology
Cite this
Safety and tolerability of anifrolumab, a monoclonal antibody targeting type I interferon receptor, in Japanese patients with systemic lupus erythematosus : A multicenter, phase 2, open-label study. / Tanaka, Yoshiya; Takeuchi, Tsutomu; Okada, Masato; Ishii, Tomonori; Nakajima, Hiroshi; Kawai, Shinichi; Nagashima, Takao; Hayashi, Nobuya; Wang, Liangwei; Tummala, Raj.
In: Modern Rheumatology, 01.01.2019.Research output: Contribution to journal › Article
}
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
PY - 2019/1/1
Y1 - 2019/1/1
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
UR - http://www.scopus.com/inward/record.url?scp=85063133915&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063133915&partnerID=8YFLogxK
U2 - 10.1080/14397595.2019.1583833
DO - 10.1080/14397595.2019.1583833
M3 - Article
JO - Modern Rheumatology
JF - Modern Rheumatology
SN - 1439-7595
ER -