Psoriasis — SCE Dermatology MCQ

Correct answer: B — IL-23 p19 subunit

Tildrakizumab (option B, IL-23 p19 subunit) is a humanised monoclonal antibody that selectively binds the p19 subunit unique to interleukin-23, blocking IL-23 signalling without affecting IL-12. This places it in the IL-23 inhibitor class alongside guselkumab and risankizumab. IL-23 is the key upstream cytokine sustaining pathogenic Th17 cells in plaque psoriasis, so selective p19 blockade interrupts the core inflammatory axis while sparing IL-12-dependent Th1 immunity, giving a favourable long-term safety profile. NICE has approved tildrakizumab (Ilumetri) for moderate to severe plaque psoriasis, dosed at 100 mg subcutaneously at weeks 0 and 4 then every 12 weeks thereafter, one of the least frequent dosing schedules among licensed psoriasis biologics. Why the other options are wrong: A. IL-12/23 p40 subunit: this is the shared subunit targeted by ustekinumab, which blocks both IL-12 and IL-23 rather than IL-23 selectively. E. IL-17A: this cytokine, downstream of IL-23 signalling, is the target of secukinumab and ixekizumab, not tildrakizumab. D. IL-4Rα: this receptor subunit is blocked by dupilumab, used in atopic dermatitis and asthma, and has no role in psoriasis treatment. C. TNF-alpha: this is the target of adalimumab, etanercept and infliximab, an older biologic class acting further upstream of the IL-23/Th17 axis than tildrakizumab. Key point: Tildrakizumab is a selective IL-23 p19 inhibitor, distinguishing it from p40 inhibitors (ustekinumab) that also block IL-12.

Reference: NICE Technology Appraisal Guidance TA575, Tildrakizumab for treating moderate to severe plaque psoriasis, 2019, https://www.nice.org.uk/guidance/ta575