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IL-23 vs IL-12/23 Inhibition — SCE Rheumatology MCQ

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HardSpondyloarthropathyIL-23 vs IL-12/23 InhibitionSCE Rheumatology

A 42-year-old woman with psoriatic arthritis has completed an adequate trial of ustekinumab. Her psoriasis has responded well, but she continues to have clinically active peripheral synovitis. Guselkumab and risankizumab are being considered as alternative treatments. Which statement most accurately distinguishes these agents and interprets the available comparative evidence?

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Correct answer: E — Ustekinumab inhibits the p40 subunit shared by IL-12 and IL-23, whereas guselkumab and risankizumab selectively inhibit IL-23 p19; target selectivity alone does not establish superior joint efficacy.

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

Ustekinumab binds p40, the subunit shared by IL-12 and IL-23, and therefore inhibits both pathways. Guselkumab and risankizumab selectively target the IL-23-specific p19 subunit and do not directly inhibit IL-12. This is the relevant pharmacological distinction, but it should not be presented as proof that p19 inhibition is intrinsically superior for peripheral arthritis: PsA efficacy evidence is largely derived from separate placebo-controlled programmes and indirect comparisons rather than definitive head-to-head trials. Persistent synovitis despite skin improvement represents an inadequate musculoskeletal response, not evidence of a universal mechanistic disadvantage. Options B and C reverse or misassign the cytokine subunits. Option D incorrectly states that all three target p40 and that direct comparative trials establish equivalence. Option E is false because ustekinumab is licensed for active PsA.

Reference: Fragoulis GE, Siebert S. The role of IL-23 and the use of IL-23 inhibitors in psoriatic arthritis. 2022. https://www.medicines.org.uk/emc/product/15189/smpc