Psoriasis — SCE Dermatology MCQ

Correct answer: E — IL-23 (p19 subunit)

The correct answer is E, IL-23 (p19 subunit). Guselkumab is a fully human monoclonal antibody engineered to bind selectively to the p19 subunit of interleukin-23, blocking IL-23 signalling without affecting IL-12, which shares only the p40 subunit with IL-23. This selective upstream blockade interrupts the IL-23/Th17 axis that drives keratinocyte proliferation and neutrophil recruitment in plaque psoriasis, and NICE TA521 approved guselkumab on this basis for moderate to severe plaque psoriasis in adults. The p19 selectivity is the defining pharmacological feature that distinguishes guselkumab from the older IL-12/23 inhibitors and is the exact discriminator being tested in this stem. Why the other options are wrong: B. IL-17A: This is the target of secukinumab and ixekizumab, downstream effector cytokines produced as a result of IL-23 driven Th17 differentiation, not guselkumab's target. C. IL-17A and IL-17F: This dual IL-17 blockade describes bimekizumab's mechanism, a distinct downstream biologic class rather than an IL-23 inhibitor. A. IL-12 and IL-23 (p40 subunit): This describes ustekinumab, which binds the shared p40 subunit and therefore blocks both IL-12 and IL-23, unlike guselkumab's selective p19 approach. D. TNF-alpha: This is the target of adalimumab, etanercept, infliximab and certolizumab pegol, an entirely different upstream inflammatory pathway used in earlier lines of psoriasis biologic therapy. Key point: Guselkumab selectively blocks the p19 subunit of IL-23 (sparing IL-12), which differentiates it from ustekinumab's dual p40-mediated IL-12/23 blockade.

Reference: NICE Technology Appraisal TA521, Guselkumab for treating moderate to severe plaque psoriasis (2018), www.nice.org.uk/guidance/ta521