Biologics for Airway Disease
How targeted antibodies work, who benefits, and the trials behind them. Severe asthma, COPD with eosinophilic inflammation, nasal polyps, and EGPA.
1The physiology: Type 2 inflammation
Most severe asthma, and a subset of COPD, is driven by a single immune pathway. The airway lining senses a trigger, releases alarm signals, and recruits immune cells that make IL-4, IL-5, and IL-13. Each biologic cuts this chain at a different link.
Blocking TSLP quiets the whole cascade, so tezepelumab also helps people whose Type 2 markers are low. IL-33 sits at the same level and is the newest target, aimed at COPD in former smokers regardless of eosinophil count.
IL-4/IL-13 blockade lowers IgE, mucus, and FeNO and often raises FEV1. IL-5 blockade starves eosinophils of their growth signal.
Anti IgE stops allergic mast cell firing. Benralizumab removes eosinophils outright, often to near zero in blood.
2Reading the biomarkers
Three inexpensive tests tell us which part of the pathway is active and help match the drug to the patient.
Eosinophil count
≥150 cells/µL suggests Type 2 activity; ≥300 predicts the strongest response to IL-5 and IL-4R drugs. In COPD, ≥300 is the threshold used in the biologic trials. Counts vary, so repeat off oral steroids.
FeNO
≥25 ppb reflects IL-13 driven airway inflammation. High FeNO plus high eosinophils points strongly toward dupilumab or tezepelumab.
Total IgE and sensitization
Year round allergen sensitization with IgE in the dosing range (roughly 30 to 700 IU/mL) supports omalizumab for allergic asthma.
3Seven approved biologics, plus one on the way
All are injected under the skin except reslizumab (IV infusion). The last card is a new IL-33 drug still under FDA review. Trial names link to the original publications on PubMed.
Omalizumab Xolair
Target: IgE- Dosing
- Every 2 to 4 weeks, by weight and IgE level
- Pulm uses
- Moderate to severe allergic asthma (age 6+); nasal polyps
- Key finding
- About 25% fewer exacerbations; greatest benefit with higher eosinophils or FeNO
Mepolizumab Nucala
Target: IL-5- Dosing
- 100 mg every 4 weeks (300 mg in EGPA)
- Pulm uses
- Severe eosinophilic asthma (age 6+); COPD with eosinophilic phenotype; EGPA; nasal polyps; HES
- Key finding
- 53% fewer asthma attacks; halves oral steroid dose; 21% fewer COPD exacerbations
Reslizumab Cinqair
Target: IL-5- Dosing
- IV infusion, 3 mg/kg every 4 weeks
- Pulm uses
- Severe eosinophilic asthma (age 18+)
- Key finding
- 50 to 59% fewer exacerbations in patients with eosinophils ≥400
Benralizumab Fasenra
Target: IL-5 receptor α- Dosing
- 30 mg every 4 weeks × 3, then every 8 weeks
- Pulm uses
- Severe eosinophilic asthma (age 6+); EGPA
- Key finding
- Up to 51% fewer attacks; 75% median cut in oral steroid dose; matched mepolizumab in EGPA
Dupilumab Dupixent
Target: IL-4 receptor α- Dosing
- Every 2 weeks after a loading dose
- Pulm uses
- Moderate to severe eosinophilic or steroid dependent asthma (age 6+); COPD with eosinophils ≥300; nasal polyps
- Key finding
- 48% fewer attacks overall, more with high eos/FeNO; 30 to 34% fewer COPD exacerbations with about 80 mL FEV1 gain
Tezepelumab Tezspire
Target: TSLP- Dosing
- 210 mg every 4 weeks
- Pulm uses
- Severe asthma (age 12+) with no biomarker requirement; nasal polyps
- Key finding
- 56% fewer attacks overall, and benefit even with eosinophils below 300
Depemokimab Exdensur
Target: IL-5 (long acting)- Dosing
- 100 mg twice a year
- Pulm uses
- Severe asthma with eosinophilic phenotype (age 12+), FDA approved December 2025
- Key finding
- 54% fewer attacks (pooled) with only two injections per year
Tozorakimab AstraZeneca · not yet approved
Target: IL-33 (new)- Status
- Investigational. Under FDA review, decision expected early 2027
- Dosing
- 300 mg every 4 weeks in trials
- Studied in
- COPD with 2+ moderate or 1+ severe exacerbations in the past year, on inhaled maintenance therapy, with no eosinophil cutoff
- Key finding
- About 30% fewer exacerbations overall (29 to 34% in former smokers); larger effect with higher eosinophils
- How it works
- Blocks both forms of IL-33: the reduced form (via ST2, drives inflammation) and the oxidized form (via RAGE/EGFR, drives epithelial damage and mucus)
4The evidence at a glance
Reduction in the yearly rate of severe exacerbations versus placebo in each drug's pivotal trial.
These trials enrolled different populations and are not head to head comparisons. In QUEST, patients with eosinophils ≥300 saw about a 65% reduction.
*Investigational, not FDA approved; enrolled patients regardless of eosinophil count. The three approved drugs enrolled patients still having exacerbations on inhaled triple therapy (or double therapy if inhaled steroids were not appropriate) with blood eosinophils ≥300. Dupilumab also improved FEV1 by about 80 mL over placebo. Cross trial comparisons are not reliable because populations differ.
Reduction in daily oral steroid dose while keeping asthma controlled (placebo arms also fell with careful tapering: 25%, 42%, and 0% respectively). Tezepelumab did not meet this goal in SOURCE.
5FDA approved pulmonary indications
What each drug is labeled for in the United States, focused on conditions seen in pulmonary clinic.
| Biologic | Severe asthma | COPD | Nasal polyps | EGPA | Youngest age (asthma) |
|---|---|---|---|---|---|
| Omalizumab | · | · | 6 | ||
| Mepolizumab | 6 | ||||
| Reslizumab | · | · | · | 18 | |
| Benralizumab | · | · | 6 | ||
| Dupilumab | · | 6 | |||
| Tezepelumab | · | · | 12 | ||
| Depemokimab | · | · | · | 12 |
Mepolizumab is also approved for hypereosinophilic syndrome. Several drugs carry additional non pulmonary indications (for example atopic dermatitis and eosinophilic esophagitis for dupilumab). Always confirm against current prescribing information. Coming next: tozorakimab (IL-33) for COPD is under FDA review and not yet approved.
Two decades of progress
6From referral to response
How a pulmonary clinic typically decides whether a biologic makes sense, following the GINA severe asthma approach and the GOLD COPD report.
Confirm the diagnosis
Spirometry and history. Rule out look alikes such as vocal cord dysfunction or bronchiectasis.
Fix the basics
Check inhaler technique and adherence, treat reflux, sinus disease and sleep apnea, remove exposures, stop smoking.
Phenotype
Blood eosinophils, FeNO, IgE and allergy testing. Count exacerbations and oral steroid bursts over the past year.
Trial and reassess
Give a chosen biologic at least 4 months. Judge by attacks, steroid use, symptoms, and lung function. Switch class if the response is poor.
Matching the patient to the drug
A common starting framework. Individual choice also weighs other conditions, dosing schedule, and insurance coverage.
Beyond fewer attacks, the field now aims for clinical remission on treatment: no exacerbations, no oral steroids, well controlled symptoms, and stable lung function for at least 12 months.
Generally well tolerated. Omalizumab and reslizumab carry anaphylaxis warnings. Dupilumab can transiently raise blood eosinophils, so very high baseline counts need a careful look. Screen for parasites where relevant.
