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

Yoshiya Tanaka, Tsutomu Takeuchi, Masato Okada, Tomonori Ishii, Hiroshi Nakajima, Shinichi Kawai, Takao Nagashima, Nobuya Hayashi, Liangwei Wang, Raj Tummala

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish
JournalModern Rheumatology
DOIs
Publication statusPublished - 2019 Jan 1

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Interferon alpha-beta Receptor
Systemic Lupus Erythematosus
Monoclonal Antibodies
Safety
Pharmacokinetics
Interferons
Incidence

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 journalArticle

Tanaka, Yoshiya ; Takeuchi, Tsutomu ; Okada, Masato ; Ishii, Tomonori ; Nakajima, Hiroshi ; Kawai, Shinichi ; Nagashima, Takao ; Hayashi, Nobuya ; Wang, Liangwei ; Tummala, Raj. / 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. In: Modern Rheumatology. 2019.
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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.",
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AU - Okada, Masato

AU - Ishii, Tomonori

AU - Nakajima, Hiroshi

AU - Kawai, Shinichi

AU - Nagashima, Takao

AU - Hayashi, Nobuya

AU - Wang, Liangwei

AU - Tummala, Raj

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