Biologic Agents in Severe Asthma
Type 2 high phenotypes, biomarker-guided drug selection, and approved biologic targets
Type 2 High Biomarkers
Biomarker 1
Blood Eosinophils
- ≥150 cells/µL: anti-IL-5 eligible
- ≥300 cells/µL: strongest response
- Guides anti-IL-5 agent selection
Biomarker 2
Fractional Exhaled NO
- ≥25 ppb: T2-high likely
- ≥50 ppb: strong IL-4/IL-13 signal
- Guides dupilumab selection
Biomarker 3
Serum Total IgE
- Required for omalizumab dosing
- Dose = IgE level × body weight table
- Too high or too low: ineligible
Approved Biologics: Comparison
|
Omalizumab |
Mepolizumab |
Benralizumab |
Dupilumab |
| Target | IgE | Interleukin-5 | IL-5Rα | IL-4Rα |
| Key biomarker | IgE + allergy | Eos ≥150/µL | Eos ≥150/µL | FeNO or Eos |
| Route | Subcutaneous | Subcutaneous | Subcutaneous | Subcutaneous |
| Frequency | q2w or q4w | q4w | q4w ×3 then q8w | q2w |
| Also treats | Urticaria | EGPA, HES | EGPA | AD, CRSwNP, EoE |
Biologic Selection Framework
Step 1: Confirm T2-high disease (eos, FeNO, or IgE elevated).
Step 2: Check comorbidities — atopic dermatitis or nasal polyps favor dupilumab.
Step 3: Match dominant biomarker to agent. All require failure of step 4 inhaled therapy first.