dupilumab

**Mechanism:** Dupilumab binds the alpha subunit of the IL-4 receptor (IL-4Rα), which is shared by two receptor complexes. The type I receptor (IL-4Rα + common gamma chain) binds IL-4 only. The type II receptor (IL-4Rα + IL-13Rα1) binds both IL-4 and IL-13. Blocking IL-4Rα inhibits both cytokines, which are the key drivers of type 2 (Th2) inflammation. Effects of blocking them: - Less Th2 differentiation. - Less B-cell class switching to IgE. - Less eosinophil recruitment (via eotaxin and VCAM-1). - Less mucus production and airway hyperresponsiveness. - Less skin barrier dysfunction (filaggrin downregulation).

**Indications (FDA-approved):** - Moderate-to-severe atopic dermatitis (adults and children, down to 6 months of age). It is often used when topical therapy fails. - Add-on maintenance for moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma. - Chronic rhinosinusitis with nasal polyps. - Eosinophilic esophagitis. - Prurigo nodularis. - COPD with an eosinophilic phenotype (add-on maintenance). - Other newer indications (e.g., chronic spontaneous urticaria, bullous pemphigoid) have been added or are under study. Verify current labeling.

**Administration:** Subcutaneous injection, usually every 2 weeks after a loading dose. Some indications allow every-4-week dosing.

**Adverse effects (high-yield):** - Conjunctivitis and keratitis. This is the classic AE, seen mostly in atopic dermatitis patients and less often in asthma patients. - Injection-site reactions. - Eosinophilia, which can be transient. Rarely, it progresses to eosinophilic vasculitis resembling EGPA, especially when systemic steroids are tapered in asthma. - Hypersensitivity reactions. - Oral herpes and other herpesvirus infections. - Arthralgia. - Possible new-onset or worsening psoriasis, and rare cutaneous T-cell lymphoma unmasking (reported in case series).

**Clinical pearls:** - Dupilumab is not a rescue therapy for acute bronchospasm or acute asthma exacerbations. - Avoid live vaccines. Inactivated vaccines are fine. - It is not broadly immunosuppressive, so there is no routine lab monitoring and no significant increase in serious infections. This is unlike JAK inhibitors (e.g., upadacitinib, abrocitinib) or cyclosporine. - It treats the atopic march (atopic dermatitis, allergic rhinitis, asthma, food allergy) via a shared Th2 mechanism.

**Comparison with related biologics (commonly tested):** - Omalizumab: anti-IgE. Used for allergic asthma and chronic urticaria. - Mepolizumab and reslizumab: anti-IL-5. Benralizumab: anti-IL-5Rα. These target eosinophilic asthma and EGPA. - Tezepelumab: anti-TSLP. It is effective in asthma regardless of phenotype. - Tralokinumab and lebrikizumab: anti-IL-13 only. Used for atopic dermatitis. - Nemolizumab: anti-IL-31 receptor. Used for prurigo nodularis and atopic dermatitis.

**Naming:** The "-mab" suffix means monoclonal antibody. The "-u-" infix means fully human. The "-li-" infix means immunomodulating (immune system target).