SLE — SCE Rheumatology MCQ

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ModerateSLE & Antiphospholipid SyndromeSLESCE Rheumatology

A 42-year-old woman with systemic lupus erythematosus has persistent moderate extrarenal disease activity (SLEDAI-2K score 10) despite hydroxychloroquine and azathioprine. She has active cutaneous and musculoskeletal disease without renal involvement. Anifrolumab is being considered. What is its mechanism of action?

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Correct answer: A — Type I interferon receptor subunit 1 (IFNAR1) antagonism

Explanation lettering: C = shown as B · B = shown as C · E = shown as D · D = shown as E

Anifrolumab is a fully human monoclonal antibody directed against subunit 1 of the type I interferon receptor, IFNAR1. Binding promotes receptor internalisation and prevents formation of the functional IFNAR1–IFNAR2 signalling complex, thereby inhibiting signalling by multiple type I interferons, including IFN-α, IFN-β and IFN-ω. This distinguishes it from belimumab, which inhibits BLyS/BAFF (D), and rituximab, which depletes CD20-positive B cells (E). Calcineurin inhibitors such as tacrolimus and voclosporin act through intracellular phosphatase inhibition (B), while IL-6 receptor blockade is the mechanism of tocilizumab (C). The previous key was correct, but the teaching content has been revised because TULIP-1 did not meet its primary endpoint and a high interferon gene signature should not be presented as a requirement for treatment.

Reference: Riggs JM et al. Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus. Mechanistic and pharmacological characterisation. Lupus Science & Medicine. 2018. https://lupus.bmj.com/content/5/1/e000261