An evaluation of anifrolumab for use in adults with systemic lupus erythematosus

ABSTRACT

Introduction

Type 1 interferons play a key role in the pathogenesis of systemic lupus erythematosus (SLE). An important clinical question is whether inhibiting the type 1 interferon pathway reduce the disease activity in SLE patients. This review evaluates the safety and efficacy of the monoclonal antibody against the type 1 interferon alpha receptor, anifrolumab, in patients with SLE.

Areas covered

Key terms (SLE, type 1 interferon, anifrolumab) were used to query the PubMed database for phase 1, 2 and 3 clinical trials of anifrolumab for SLE patients. Phase 1 studies showed anifrolumab has non-linear pharmacokinetics and the optimal safe dose is 300 mg given intravenously every four weeks. The MUSE (phase 2) and the TULIP-2 (phase 3) trials showed that anifrolumab when added to standard therapy significantly reduced disease activity in SLE patients. Common adverse events associated with anifrolumab were upper respiratory and urinary infections as well as shingles.

Expert opinion

Anifrolumab is an exciting new therapeutic for SLE patients. Additional analyses of the combined TULIP-1 and TULIP-2 datasets as well as future studies with anifrolumab will generate yet more data in SLE. No doubt anifrolumab will be studied in other diseases where type I interferons play an important role.

KEYWORDS:

• Systemic lupus erythematosus
• type-1 interferon
• anifrolumab
• MUSE
• TULIP

Article highlights

• SLE patients have high levels of type 1 interferons (IFNs), which drive the pathologic disease process.

• Anifrolumab is a monoclonal antibody against the interferon alpha receptor (IFNAR).

• Anifrolumab inhibits the signaling pathway of type 1 IFNs thereby reducing the production of proinflammatory cytokines.

• An important clinical question is whether anifrolumab (through its inhibition of the type 1 IFN signaling pathway) be used to reduce the disease activity in SLE patients.

• This review evaluates the safety and efficacy of anifrolumab used for SLE patients using data from phase 1, 2 and 3 clinical trials.

• Data from phase 1 clinical trials show that anifrolumab has non-linear pharmacokinetics and the optimal safe dose is 300 mg given as an intravenous infusion every four weeks.

• Data from phase 2 and 3 clinical trials show that anifrolumab (in combination with background therapy) could successfully reduce overall SLE disease activity, improve serologic markers, reduce CLASI scores, reduce tender and swollen joint counts and reduce cumulative corticosteroid doses for SLE patients.

• The most frequent adverse events associated with anifrolumab are nasopharyngitis, upper respiratory tract infection (URI) and urinary tract infection (UTI).

• Anifrolumab is associated with higher herpes zoster infection events.

• There is no data in the published literature for the safety and efficacy of anifrolumab for lupus cerebritis, while only one trial (TULIP-LN, phase 2) included patients with lupus nephritis.

• A phase 3 trial of anifrolumab in patients with lupus nephritis (IRIS) is underway and is expected to produce valuable data in this important area.

• There is a theoretical risk of adverse outcomes with viral infections such as Covid-19 for patients taking anifrolumab, and there have been no clinical trials to date exploring this risk.

• Anifrolumab will be studied in the future for other diseases where type I interferons play an important role.

Declaration of interest

R Furie has served as a consultant to AstraZeneca. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

AstraZeneca provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This paper was not funded.