What is the appropriate treatment and dosage of Dupixent (dupilumab) for a patient with a history of atopic dermatitis, asthma, or chronic rhinosinusitis with nasal polyposis?

Dupixent (Dupilumab) Treatment and Dosing

For chronic rhinosinusitis with nasal polyps (CRSwNP), administer dupilumab 300 mg subcutaneously every 2 weeks in adults and adolescents ≥12 years, which significantly reduces polyp size, nasal congestion, and improves quality of life while reducing the need for systemic corticosteroids and surgery. 1, 2

Dosing by Indication

Chronic Rhinosinusitis with Nasal Polyps

• Adults and adolescents ≥12 years: 300 mg subcutaneously every 2 weeks (no loading dose required) 2
• Continue concurrent intranasal mometasone furoate 100 μg in each nostril twice daily as standard of care 1
• This regimen produces clinically meaningful improvements in SNOT-22 scores (mean difference -19.61 points), nasal polyp scores (mean difference -1.80 to -2.06), Lund-Mackay CT scores (mean difference -5.13 to -7.44), and sense of smell (UPSIT improvement of 14.8 points) at 24 weeks 1, 3, 4

Atopic Dermatitis

• Adults: 600 mg loading dose (two 300 mg injections at different sites), then 300 mg every 2 weeks 2
• Children 6-17 years:
  • 15 to <30 kg: 600 mg loading dose, then 300 mg every 4 weeks 2
  • 30 to <60 kg: 400 mg loading dose, then 200 mg every 2 weeks 2
  • ≥60 kg: 600 mg loading dose, then 300 mg every 2 weeks 2
• Children 6 months to 5 years:
  • 5 to <15 kg: 200 mg every 4 weeks (no loading dose) 2
  • 15 to <30 kg: 300 mg every 4 weeks (no loading dose) 2

Asthma

• Adults and adolescents ≥12 years:
  • Standard: 400 mg loading dose, then 200 mg every 2 weeks OR 600 mg loading dose, then 300 mg every 2 weeks 2
  • For oral corticosteroid-dependent asthma or comorbid moderate-to-severe atopic dermatitis or CRSwNP: 600 mg loading dose, then 300 mg every 2 weeks 2
• Children 6-11 years:
  • 15 to <30 kg: 300 mg every 4 weeks (no loading dose) 2
  • ≥30 kg: 200 mg every 2 weeks (no loading dose) 2

Evidence for CRSwNP Efficacy

The SINUS-24 and SINUS-52 trials demonstrated robust efficacy across all major outcomes in patients with severe CRSwNP refractory to intranasal corticosteroids. 1, 4

Key Outcomes at 24 Weeks:

• Quality of life: SNOT-22 improved by 19.61 points (95% CI -22.53 to -16.69) versus placebo 1
• Nasal congestion: Reduced by 0.86-0.89 points on severity scale versus placebo 1, 4
• Sense of smell: UPSIT scores improved by 14.8 points (95% CI 10.9 to 18.7) versus placebo 3
• Polyp burden: Nasal polyp score decreased by 1.80-2.06 points versus placebo 1, 4
• Sinus opacification: Lund-Mackay CT scores improved by 5.13-8.8 points versus placebo 1, 3
• Lung function in comorbid asthma: FEV1 significantly improved regardless of baseline eosinophil count 1, 5

Sustained Efficacy:

• Benefits maintained through 52 weeks with continued every-2-week dosing 1, 4
• Reduced need for systemic corticosteroids and nasal polyp surgery 5, 4
• Effective regardless of comorbid asthma, NSAID-exacerbated respiratory disease, or previous nasal polyp surgery 5, 4

Administration Technique

• Inject subcutaneously into thigh or abdomen (avoid 2 inches around navel), or upper arm if caregiver administers 2
• Rotate injection sites with each administration 2
• Remove from refrigerator 45 minutes before injection (300 mg formulation) or 30 minutes (200 mg formulation) to reach room temperature 2
• For loading doses requiring two injections, administer at different injection sites 2
• Pre-filled pen approved for ages ≥2 years; pre-filled syringe approved for ages ≥6 months 2

Important Safety Considerations

Ocular Surface Disorders

• Dupilumab-related ocular surface disorders (DROSD) occur in 8-42% of atopic dermatitis patients but are NOT observed at increased rates in CRSwNP or asthma patients. 1
• Risk factors for DROSD in AD patients include pre-existing dry eye disease with keratitis (OR 6.3, CI 1.3-31.6) and eyelid eczema (OR 8.7, CI 1.8-40.6) 1
• Prophylactic artificial tears may reduce DROSD risk in high-risk AD patients 1
• This concern is specific to atopic dermatitis and should not deter use in CRSwNP 1

Pre-Treatment Vaccination

• Complete all age-appropriate vaccinations per current immunization guidelines before initiating dupilumab 2

Concomitant Medications

• Intranasal corticosteroids (mometasone) are routinely combined without interaction concerns 1, 6
• Leukotriene modifiers (montelukast, zafirlukast, zileuton) can be safely combined and may provide additive benefit for patients with both nasal polyps and asthma 1, 6
• Modern second-generation antihistamines (cetirizine, loratadine, desloratadine, fexofenadine) have no significant interactions 6

Missed Dose Management

• Every 2 weeks dosing: If missed, administer within 7 days and resume original schedule; if >7 days, wait until next scheduled dose 2
• Every 4 weeks dosing: If missed, administer within 7 days and resume original schedule; if >7 days, administer dose and start new schedule from that date 2
• Weekly dosing: Administer as soon as possible and start new weekly schedule from date of last dose 2

Common Pitfalls to Avoid

• Do not discontinue intranasal corticosteroids when initiating dupilumab for CRSwNP—these are complementary therapies 1
• Do not inject into tender, damaged, bruised, or scarred skin 2
• Do not use if stored at room temperature for >14 days after removal from refrigerator 2
• Do not assume ocular side effects are equally problematic across all indications—the risk is specific to atopic dermatitis patients 1
• For patients with excellent response, interval extension to every 4 weeks (and potentially every 6 weeks) may be considered after 7-31 months of control, though this diverges from FDA approval 7