Expert: mAb targeting IL-23 p19 subunit (selective over IL-12 p40). Depletes pathogenic tissue-resident memory Th17 (TRM17) cells by removing their IL-23-dependent survival signal. Science Immunology (2023): local IL-23 required for skin-resident memory Th17 proliferation; anti-IL-23R therapy depleted TRM17 from lesional skin. KNOCKOUT trial: high-dose risankizumab normalized CD8+ TRM counts and pathogenic cytokines to non-lesional levels by Wk52. Disease modification evidence: some patients maintained PASI 90 for 84 weeks post-discontinuation. No candidiasis signal: mucosal IL-17 production maintained by IL-23-independent innate sources (gamma-delta T cells responding to IL-1beta/IL-18, ILC3s activated by IL-1beta+IL-2). Risankizumab epitope 2400 A-sq (R-sq=0.9969 correlation with PASI 90), half-life ~28d, bioavailability ~89%, silenced Fc (no FcgR binding). Guselkumab epitope 2240 A-sq, half-life ~17d, bioavailability ~49%, native Fc enables CD64-mediated docking on IL-23-producing myeloid cells.

Everyday: Blocks IL-23, the upstream commander signal that keeps pathogenic Th17 cells alive in skin. This achieves TRUE DISEASE MODIFICATION — not just symptom suppression. IN HEALTHY PEOPLE: IL-23 is produced by dendritic cells and macrophages. It tells a specific type of immune cell (Th17 cells) to survive, multiply, and produce IL-17. In healthy skin, this pathway helps fight infections. IN PSORIASIS: IL-23 is massively overproduced, driving an army of pathogenic Th17 cells that pump out IL-17A and IL-17F, causing chronic inflammation. Critically, psoriasis creates "immunological scar tissue" — tissue-resident memory T cells (TRM17) that hide in previously affected skin and cause relapse at the same spots. IL-23 is the SURVIVAL SIGNAL for these TRM17 cells. HOW IL-23 BLOCKADE WORKS: By cutting off IL-23, the pathogenic Th17 cells in skin are starved of their survival signal. Over months, they die off — including the TRM17 memory cells. This is why response DEEPENS over time: PASI 90 goes from ~75% at week 16 to ~82% at week 52. Some patients maintain PASI 90 for 84 WEEKS after stopping treatment — because the immunological memory driving psoriasis has been substantially erased. WHY NO CANDIDIASIS: This is the elegant part. Your mouth's defense against yeast relies on DIFFERENT cells — gamma-delta T cells and ILC3s — that produce IL-17 WITHOUT needing IL-23 (they respond to IL-1beta, IL-18, IL-6 instead). So blocking IL-23 kills the pathogenic skin army while leaving mouth defense intact. Candidiasis rates equal placebo. SKYRIZI vs TREMFYA: Both target IL-23's p19 subunit but differ pharmacologically. Skyrizi has larger epitope (2400 vs 2240 Angstrom-sq), longer half-life (~28 vs ~17 days), higher bioavailability (~89% vs ~49%), enabling q12w vs q8w dosing. Skyrizi's Fc is mutated (silenced) — pure cytokine interceptor. Tremfya's Fc is native — can anchor to IL-23-producing myeloid cells via CD64, intercepting IL-23 at the source.

Targets: ["IL-23"]

Primary EP: [{"id":"pasi90-w16","name":"PASI 90 at Week 16","type":"PRIMARY","unit":"%","results":[{"value":75.3,"arm_id":"risnk-arm","p_value":0.001},{"value":42,"arm_id":"ust-arm"},{"value":4.9,"arm_id":"pbo-ar

Skyrizi - Psoriasis - H2H vs Deucravacitinib 2026

IL-23 (p19) inhibitor with BEST-IN-CLASS durability and CLEANEST safety profile. True disease modification: depletes tissue-resident memory Th17 (TRM17) cells over time. PASI 90 75% Wk16 deepening to 82% Wk52. PASI 100 ~40% Wk16 → 56-60% Wk52. No candidiasis (=placebo). Some patients maintain PASI 90 for 84 WEEKS after stopping — TRM17 depletion. Beat Stelara (UltIMMa), Humira (IMMvent), Cosentyx (IMMerge). Longest dosing interval (q12w). Largest epitope on p19 (2400 A-sq), longest half-life (~28d), highest bioavailability (~89%). Mutated (silenced) Fc. Commercial juggernaut: $17.56B in 2025. AbbVie guides $20B by 2027. Approved: PsO (2019), CD (2022), UC (2024). US LOE ~2033.

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