Anifrolumab Mechanism — SCE Rheumatology MCQ

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ModerateSLE & Antiphospholipid SyndromeAnifrolumab MechanismSCE Rheumatology

A 50-year-old man with systemic lupus erythematosus has persistent inflammatory skin and joint disease despite hydroxychloroquine and mycophenolate mofetil. Anifrolumab is added to his treatment. Which molecular target and downstream effect best describe its mechanism of action?

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Correct answer: E — IFNAR1, inhibiting type I interferon signalling

Anifrolumab is a fully human monoclonal antibody directed against subunit 1 of the type I interferon receptor, IFNAR1. Binding promotes receptor internalisation and prevents signalling by type I interferons through the shared IFNAR complex, including downstream STAT1 phosphorylation and interferon-stimulated gene expression. This targets the dysregulated type I interferon pathway characteristic of SLE. Anti-BLyS therapy describes belimumab, while anti-CD20 therapy describes agents such as rituximab. IL-6 receptor blockade is the mechanism of tocilizumab and related agents, not anifrolumab. Complement C5 inhibition is exemplified by eculizumab and ravulizumab. Therefore, IFNAR1 blockade with inhibition of type I interferon signalling is the single best answer.

Reference: Riggs JM et al. Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus. Lupus Science & Medicine. 2018. https://pubmed.ncbi.nlm.nih.gov/29644082/