What newly FDA‑approved medications are available for patients aged 12 years and older with chronic spontaneous urticaria that remains uncontrolled despite optimized H1‑antihistamine therapy?

Recently Approved Drugs for Chronic Spontaneous Urticaria

Dupilumab (Dupixent) was FDA-approved in April 2025 for chronic spontaneous urticaria in patients aged 12 years and older who remain symptomatic despite H1-antihistamine treatment, representing the first new biologic option beyond omalizumab for this indication. 1

FDA-Approved Dosing for Dupilumab in CSU

Adults (18 years and older)

• Initial loading dose: 600 mg (two 300 mg subcutaneous injections) 1
• Maintenance: 300 mg subcutaneously every 2 weeks 1

Adolescents (12-17 years)

• Body weight 30 to <60 kg:
  • Initial: 400 mg (two 200 mg injections)
  • Maintenance: 200 mg every 2 weeks 1
• Body weight ≥60 kg:
  • Initial: 600 mg (two 300 mg injections)
  • Maintenance: 300 mg every 2 weeks 1

Clinical Evidence Supporting Dupilumab

Phase 3 trial data (LIBERTY-CSU CUPID Study A) demonstrated that dupilumab significantly reduced urticaria activity in omalizumab-naive patients with CSU uncontrolled by H1-antihistamines. 2

• In omalizumab-naive patients, dupilumab reduced UAS7 by an additional 8.5 points versus placebo (P=0.0003) and ISS7 by 4.2 points (P=0.0005) at week 24 2
• The safety profile was consistent with dupilumab's known profile across other type 2 inflammatory conditions 2

Important limitation: In patients who were omalizumab-intolerant or incomplete responders (Study B), dupilumab showed smaller effects, with the primary endpoint not reaching statistical significance for ISS7 2

Treatment Algorithm: When to Use Dupilumab vs. Omalizumab

First-Line Biologic: Omalizumab Remains Preferred

Omalizumab 300 mg subcutaneously every 4 weeks should be the first biologic choice for patients with CSU inadequately controlled by up-dosed H1-antihistamines (up to 4-fold standard dose). 3, 4

• Allow up to 6 months of continuous omalizumab therapy to assess response before considering treatment failure 3, 4
• Omalizumab 300 mg demonstrated superior efficacy across all endpoints in phase 3 trials, with 35.8% achieving complete response (UAS7=0) versus 8.8% with placebo 5
• Onset of effect occurs within 1-2 weeks 6

When to Consider Dupilumab

Dupilumab should be considered for omalizumab-naive patients who:

• Have contraindications to omalizumab (e.g., documented anaphylaxis risk intolerance) 1, 2
• Have concurrent type 2 inflammatory conditions already being treated with dupilumab (e.g., atopic dermatitis, asthma, eosinophilic esophagitis) 1
• Prefer less frequent monitoring (dupilumab does not require the 30-minute post-injection observation mandated for omalizumab) 3, 1

For patients who fail omalizumab after 6 months:

• Dupilumab showed only modest benefit in omalizumab-incomplete responders (UAS7 reduction of 5.8 points, P=0.0390) 2
• Cyclosporine (up to 5 mg/kg/day) remains the evidence-based fourth-line option with 65-70% efficacy in autoimmune CSU 3, 4
• Consider dupilumab only if cyclosporine is contraindicated or not tolerated 2

Critical Safety Considerations

Omalizumab Monitoring Requirements

• First 3 doses: 2-hour observation period for anaphylaxis risk (0.2% incidence) 3
• Subsequent doses: 30-minute observation 3
• All patients must be prescribed and trained in epinephrine autoinjector use 3
• Administration must occur in settings equipped to manage anaphylaxis 3

Dupilumab Safety Profile

• No anaphylaxis risk requiring extended observation 1, 2
• Most common adverse events: conjunctivitis and injection site reactions (consistent with other dupilumab indications) 1, 2
• Monitor for conjunctivitis and keratitis, particularly in patients with history of atopic eye disease 1

Real-World Treatment Gaps

Despite guideline recommendations, many patients with poorly controlled CSU do not receive appropriate treatment escalation. 7

• Only 28.4% of patients escalated from H1-antihistamines to omalizumab achieved complete response (UCT=16 with ≥3-point increase) 7
• 28.6% of patients clinically eligible for escalation (UCT <12) did not receive step-up treatment or were inappropriately stepped down 7
• Factors associated with lack of escalation included younger age, shorter disease duration, and treatment with up-dosed antihistamines 7

This highlights the need for systematic use of validated tools like the Urticaria Control Test (UCT) to objectively document inadequate control and trigger timely escalation. 3, 7

Common Pitfalls to Avoid

• Do not delay biologic therapy while continuing to increase antihistamine doses beyond 4-fold standard dose—this provides diminishing returns 3
• Do not use long-term oral corticosteroids for chronic urticaria management; restrict to short courses (3-10 days) for severe acute exacerbations only 4, 8
• Do not assume dupilumab is equivalent to omalizumab in omalizumab-naive patients—omalizumab has stronger efficacy data and should remain first-line 5, 6, 2
• Do not prescribe dupilumab for other forms of urticaria—the FDA indication is limited to chronic spontaneous urticaria 1