Cytokine pathway biologic blockade

Category: immune_innate

Overview

Therapeutic mAbs + fusion proteins target inflammatory cytokines + their receptors in autoimmune + atopic disease. TNF-α: etanercept (soluble TNF-R2-Fc), adalimumab, golimumab, certolizumab-pegol (Fab-PEG), infliximab — RA / IBD / psoriasis / AS. IL-17: secukinumab + ixekizumab (anti-IL-17A) — psoriasis / PsA / AS. IL-12/23: ustekinumab (shared p40) — psoriasis / IBD. IL-23: guselkumab + risankizumab (selective p19) — psoriasis. IL-4/13: dupilumab (IL-4Rα) — atopic dermatitis + asthma + nasal polyps + EoE. IgE: omalizumab — allergic asthma + chronic spontaneous urticaria. CGRP migraine biologics covered separately (IMM-2). Bone biologics covered in IMM-4.

Organ Systems

• immune-hematologic
• integumentary

Pathway Steps

1. cytokine-ligand → cytokine-receptor-activation — via biologic blocks the ligand-receptor engagement → downstream JAK-STAT / NF-κB suppression. Many inflammatory diseases are driven by specific cytokines binding their receptors to activate (often JAK-STAT) signaling. Biologics intercept this at the ligand or receptor — anti-TNF (adalimumab), anti-IL-6R (tocilizumab), anti-IL-17/IL-23 — a targeted alternative to broad immunosuppression that transformed rheumatology and dermatology.

Known Modulators

• etanercept (inhibitor) — TNF-α (soluble TNF-R2-Fc decoy). TNF-i; RA + AS + plaque psoriasis + PsA; SC; less effective in IBD vs antibody-class TNF-i (mechanism difference)
• certolizumab pegol (inhibitor) — TNF-α (Fab-PEG, no Fc). TNF-i; Fab fragment + PEGylation extends t½ without Fc-mediated effector functions; pregnancy-preferred (no placental Fc transfer)
• golimumab (inhibitor) — TNF-α (full IgG mAb). TNF-i; once-monthly SC; RA + PsA + AS + UC
• secukinumab (inhibitor) — IL-17A. plaque psoriasis + PsA + AS; rapid + deep skin clearance vs TNF-i; mucocutaneous candida tail (on-target Th17 effect)
• ixekizumab (inhibitor) — IL-17A. plaque psoriasis + PsA + axSpA; comparable clinical efficacy to secukinumab
• ustekinumab (inhibitor) — IL-12 + IL-23 p40 subunit (shared). psoriasis + PsA + IBD; targets shared p40 of IL-12 + IL-23; less specific than p19 agents
• guselkumab (inhibitor) — IL-23 p19 (selective). plaque psoriasis + PsA; p19 selectivity spares IL-12/Th1 — preserved infection defense
• risankizumab (inhibitor) — IL-23 p19. plaque psoriasis + PsA + Crohn's; q8-12week SC
• dupilumab (inhibitor) — IL-4Rα (blocks IL-4 + IL-13). atopic dermatitis + asthma (T2) + nasal polyps + EoE + prurigo nodularis; SC; conjunctivitis tail
• omalizumab (inhibitor) — IgE (free, in circulation). allergic asthma + chronic spontaneous urticaria + nasal polyps; binds free IgE → downregulates FcεRI on mast cells
• rituximab (inhibitor) — CD20 (B-cell depleter). anti-CD20 mAb; CLL + lymphoma + RA + MS + ANCA vasculitis; biosimilars widely available
• trastuzumab (inhibitor) — HER2 (ERBB2). first HER2 mAb; HER2+ breast cancer; cardiotoxicity (LVEF monitoring); biosimilars

References

• PMID 28612747