asthma biologics

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comparison

	Omalizumab	Mepolizumab	Benralizumab	Dupilumab	Tezepelumab
Brand	Xolair	Nucala	Fasenra	Dupixent	Tezspire
Target	IgE	IL-5	IL-5Rα	IL-4Rα (IL-4 + IL-13)	TSLP
Route	SC	SC	SC	SC	SC
Dose	75–375 mg q2–4wk (weight + IgE-based)	100 mg q4wk	30 mg q4wk ×3, then q8wk	200 or 300 mg q2wk	210 mg q4wk
Key biomarker	Total IgE 30–1500 + allergen sensitisation	Blood eos ≥ 0.15	Blood eos ≥ 0.3	Blood eos ≥ 0.15 or FeNO ≥ 25	Broadest — all phenotypes
Self-injectable	Some formulations	Yes (auto-injector)	Yes (auto-injector)	Yes (pen)	Yes (auto-injector)
Onset of action	12–16 weeks	4 weeks	4 weeks	2–4 weeks	4 weeks
Age approval	≥ 6y	≥ 6y	≥ 12y (≥ 6y some regions)	≥ 6y	≥ 12y

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mechanism — where each agent acts

Allergen / Irritant
       ↓
  Epithelial TSLP ← ── TEZEPELUMAB blocks here (most upstream)
       ↓
  Th2 / ILC2 activation
       ↓
  ┌────┴────┐
  IL-4/IL-13    IL-5
  ↓              ↓
  DUPILUMAB     MEPOLIZUMAB (binds IL-5)
  blocks both   BENRALIZUMAB (binds IL-5Rα → depletes eosinophils)
  ↓              ↓
  IgE class      Eosinophil
  switching      recruitment
  ↓
  OMALIZUMAB
  (binds free IgE)

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dosing details

omalizumab (Xolair)

• Dose determined by body weight and baseline total IgE (dosing table in product monograph)
• IgE 30–1500 IU/mL; weight 20–150 kg
• SC injection q2wk or q4wk depending on calculated dose
• First doses should be administered in clinic (anaphylaxis risk ~0.1%)
• Do not recheck IgE to guide dosing after initiation (drug-bound IgE elevates total IgE)

mepolizumab (Nucala)

• 100 mg SC q4wk (fixed dose in adults)
• Also approved for EGPA (300 mg SC q4wk)
• Screen for Strongyloides in at-risk patients before starting

benralizumab (Fasenra)

• 30 mg SC q4wk ×3 doses, then q8wk (convenient maintenance schedule)
• Depletes eosinophils via antibody-dependent cell-mediated cytotoxicity (ADCC) — near-complete eosinophil depletion
• Screen for Strongyloides before starting

dupilumab (Dupixent)

• Loading dose: 400 mg or 600 mg SC ×1 (depends on indication/dose)
• Maintenance: 200 mg or 300 mg SC q2wk
• Multi-indication: also approved for atopic dermatitis, nasal polyposis, eosinophilic oesophagitis, prurigo nodularis — advantageous in patients with overlapping conditions

tezepelumab (Tezspire)

• 210 mg SC q4wk (fixed dose)
• Most upstream target (TSLP) → effective across T2-high and T2-low phenotypes
• The only biologic with demonstrated efficacy in patients with low eosinophils and low FeNO
• Rigorous non-T2 definition (BEC < 0.15, FeNO < 25 ppb, negative perennial allergy skin tests) — trend toward benefit but not statistically significant in NAVIGATOR/PATHWAY re-analysis (N=96) (CADTH 2024)

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adverse effects

Agent	Common AEs	Notable risks
Omalizumab	Injection site reaction, headache	Anaphylaxis (~0.1%; observe 30 min after first 3 doses, then 15 min)
Mepolizumab	Injection site reaction, headache, back pain	Herpes zoster (reactivation); Strongyloides hyperinfection
Benralizumab	Injection site reaction, pharyngitis	Strongyloides hyperinfection (near-total eosinophil depletion)
Dupilumab	Injection site reaction, conjunctivitis, eosinophilia	Transient eosinophilia (can be marked; usually resolves in weeks; monitor if eos > 3.0). Conjunctivitis in ~5–15%
Tezepelumab	Injection site reaction, pharyngitis, arthralgia	No unique safety signals to date

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monitoring

Parameter	Frequency	Notes
Symptom control	Every visit	Asthma control questionnaire
Exacerbation rate	q3–6 months	Compare to pre-biologic baseline
Blood eosinophils	Baseline, q3–6 months	Expect near-zero on anti-IL-5/5Rα; transient rise on dupilumab
FeNO	Baseline, q3–6 months (if available)	Useful for dupilumab and tezepelumab response assessment
OCS dose	Every visit	Taper systematically; goal = elimination
FEV1	q3–6 months	Expect improvement, especially with dupilumab
Response assessment	4–6 months	Switch biologic if inadequate response (CHEST 2025)

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key points

• All biologics reduce exacerbations by ~50% in appropriately selected patients
• None are curative — exacerbations return if discontinued; consider a trial off biologic only after ≥ 12 months of complete control + OCS elimination
• Cost is substantial — coverage request documentation should include: confirmed severe asthma, biomarkers, adherence confirmation, failed step 4–5 therapy, exacerbation history
• Concurrent biologics are not reimbursed under Canadian public plans; some provinces restrict coverage for active smokers (CADTH 2024)
• Pregnancy: limited data for all agents; omalizumab has the longest safety track record. Continue biologic if asthma is well-controlled and risk of exacerbation outweighs theoretical risk

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Canadian reimbursement criteria (CDEC)

Specific thresholds used by most public drug plans — varies slightly by province (CADTH 2024):

Agent	Biomarker threshold for coverage	Additional requirements
Omalizumab	Total IgE 30–1500 IU/mL + confirmed allergen sensitisation	Weight-based dosing table
Mepolizumab	Blood eos ≥ 0.3 (or ≥ 0.15 at initiation if ≥ 0.3 in past 12 months)	≥ 2 exacerbations in past year
Benralizumab	Blood eos ≥ 0.3 AND ≥ 2 exacerbations in past year, OR eos ≥ 0.15 if on chronic OCS	—
Dupilumab	Blood eos ≥ 0.15 or FeNO ≥ 25 ppb	≥ 2 exacerbations in past year
Tezepelumab	No specific biomarker threshold	≥ 2 exacerbations in past year