Anti-IL5 and Anti-IL4R Drugs
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Direct answer
Severe asthma biologics are sorted by the cell you intend to starve: eosinophils run on IL-5, and type-2 inflammation speaks through IL-4 and IL-13. Against IL-5 sit mepolizumab (100 mg subcutaneously every 4 weeks), reslizumab (intravenous) and benralizumab — which binds the IL-5 receptor alpha and clears eosinophils through antibody-dependent cell cytotoxicity. Dupilumab blocks the IL-4 receptor alpha, switching off both IL-4 and IL-13 signalling, and treats atopic dermatitis (300 mg fortnightly), asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis. Tezepelumab, anti-TSLP, stands upstream of the whole cascade. Selection is phenotypic — blood eosinophils, exacerbations, atopic burden — and dupilumab's signature quirks are conjunctivitis and a transient eosinophilia that can be striking at initiation.
What you must remember
- Mepolizumab (anti-IL5): 100 mg SC every 4 weeks for severe eosinophilic asthma; 300 mg for eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss); also licensed in hypereosinophilic syndrome.
- Benralizumab (anti-IL5Rα): binds CD125 on eosinophils and recruits natural killer cells via ADCC to deplete them; every 4 weeks for three doses, then every 8 weeks.
- Reslizumab (anti-IL5, IV): 3 mg/kg monthly — anaphylaxis risk means post-dose observation; intravenous route distinguishes it.
- Dupilumab (IL-4Rα): blocks IL-4 and IL-13 signalling; atopic dermatitis 300 mg every 2 weeks, plus asthma, CRSwNP, eosinophilic oesophagitis, prurigo nodularis, bullous pemphigoid; conjunctivitis in a sizeable minority; transient, occasionally marked eosinophilia on starting.
- Tezepelumab (anti-TSLP): blocks the epithelial alarmin upstream of type-2 inflammation; works across phenotypes without needing an eosinophil threshold.
- Selection: blood eosinophils roughly 150–300/μL and above with exacerbations favour anti-IL5/IL5R; atopic dermatitis comorbidity or nasal polyps favour dupilumab; EGPA means mepolizumab.
- The confused companion: omalizumab is anti-IgE — same clinic, different target; distinguishing the four targets (IgE, IL-5, IL-4Rα, TSLP) is the core exam ask.
- Practical points: screen for helminths before IL-4/IL-13 blockade (dupilumab can unmask parasitic infection); injection reactions are few; biologics layer on top of inhaled therapy, never replace it.
Matching two patients to two pathways
Patient one: 46-year-old woman, severe asthma despite high-dose inhaled combination, five exacerbations last year, blood eosinophils 420/μL, chronic rhinosinusitis with polyps on CT. The eosinophil number nominates IL-5 blockade, but the polyps pull the other way — dupilumab treats both the asthma and the polyp disease, with the conjunctivitis caveat discussed before the first dose. Patient two: 31-year-old man with lifelong atopic dermatitis covering most of his body, moderate asthma, eosinophils 250/μL. Here the skin rules: dupilumab again, with the expectation of visible eczema response in weeks and the asthma following. Had patient two instead carried EGPA — asthma with neuropathy, sinus disease and eosinophils above 1500 — mepolizumab at 300 mg becomes the disease-modifying answer, in some protocols replacing chronic prednisone. The practical algorithm is four questions: eosinophils how high, polyps or eczema present, vasculitic features, and is there a need to treat beyond type-2 biology (where tezepelumab's upstream reach helps). Answer them in order and the injection writes itself.
Where students slip
The first slip is the ligand-versus-receptor trap: mepolizumab and reslizumab block IL-5 itself, benralizumab blocks the receptor and adds ADCC-mediated killing — same pathway, different pharmacology, and examiners ask precisely this. The second is dupilumab's breadth: students file it under "asthma biologic" and miss that IL-4Rα blockade covers eczema, nasal polyps, eosinophilic oesophagitis and even bullous pemphigoid. Third, the initiation eosinophilia: dupilumab can transiently raise eosinophil counts dramatically in the first weeks — alarming on a report, usually benign, and the classic "what do you do?" answer is observe unless clinical features appear. Fourth, conjunctivitis is dupilumab's signature adverse effect and belongs in every consent conversation. Fifth, omalizumab gets dragged into IL-5 discussions — it is anti-IgE, selected by allergen sensitisation and total IgE, not by eosinophils. Finally, tezepelumab's claim to fame — efficacy without a biomarker threshold — is the modern addition that elevates an answer above the standard list.
Frequently asked questions
How does benralizumab differ from mepolizumab?
Mepolizumab neutralises IL-5 itself; benralizumab binds the IL-5 receptor alpha on eosinophils and depletes them via antibody-dependent cell cytotoxicity, allowing every-8-week dosing.
Why does dupilumab treat both eczema and asthma?
IL-4 receptor alpha blockade switches off IL-4 and IL-13, the central type-2 cytokines driving atopic dermatitis, asthma and nasal polyposis alike.
What is the significance of dupilumab-induced eosinophilia?
A transient rise in blood eosinophils can occur in the first weeks, occasionally marked — usually benign and monitored rather than treated.
Which biologic treats EGPA?
Mepolizumab 300 mg every 4 weeks — reducing flares and corticosteroid dependence in eosinophilic granulomatosis with polyangiitis.
How is tezepelumab different from the others?
It blocks TSLP, an epithelial alarmin upstream of the entire type-2 cascade, and works across phenotypes without an eosinophil or IgE threshold.