Anifrolumab, a monoclonal antibody to the type I interferon receptor subunit 1, for the treatment of systemic lupus erythematosus: an overview from clinical trials

Abstract

Chronic activation of the type I interferon (IFN) pathway plays a critical role in systemic lupus erythematosus (SLE) pathogenesis. Anifrolumab is a human monoclonal antibody to the type I IFN receptor subunit 1, which blocks the action of type I IFNs. Two phase 3 studies (TULIP-1 and TULIP-2) and a phase 2b study (MUSE) provide substantial evidence for the efficacy and safety of anifrolumab for moderately to severely active SLE. In all three studies, monthly intravenous anifrolumab 300 mg was associated with treatment differences >16% compared with placebo at Week 52 in British Isles Lupus Assessment Group-based Composite Lupus Assessment response rates. The combined data across a range of other clinically significant endpoints (e.g. oral corticosteroid reduction, improved skin disease, flare reduction) further support the efficacy of anifrolumab for SLE treatment. The safety profile of anifrolumab was generally similar across all studies; serious adverse events occurred in 8–16% and 16–19% of patients receiving anifrolumab and placebo, respectively. Herpes zoster incidence was greater with anifrolumab (≤7%) vs placebo (≤2%). Evidence from these clinical trials suggests that in patients with active SLE, anifrolumab is superior to placebo in achieving composite endpoints of disease activity response and oral corticosteroid reduction.

Keywords:

• Anifrolumab
• anti-interferon alpha receptor antibody
• systemic lupus erythematosus
• TULIP-1
• TULIP-2

Acknowledgments

The authors thank the patients, study sites, and investigators who participated in these clinical trials and also appreciate all members of the global academic steering committee and local steering committees. Writing and editing assistance was provided by Debra Scates, PhD, and Angela Cimmino, PharmD, of JK Associates Inc., a Fishawack Health Company. This support was funded by AstraZeneca.

Conflict of interest

Yoshiya Tanaka has received speaking fees and/or honoraria from Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol Myers Squibb, Eisai, Chugai, AbbVie, Astellas, Pfizer, Sanofi, Asahi Kasei, GSK, Mitsubishi-Tanabe, Gilead, and Janssen, and has received research grants from Mitsubishi-Tanabe, Chugai, AbbVie, Takeda, UCB, Daiichi-Sankyo, and Eisai. Raj Tummala is an employee of AstraZeneca.