Dupixent^® Chronic Spotaneous Urticaria (CSU)

IL-4 and IL-13 signaling may contribute to different aspects of mast cell activation and degranulation

Type 2 cytokines may amplify the inflammatory process of CSU, contributing to itch and hives¹⁷

^a Itch signals can, in turn, induce further immune activation and release of inflammatory mediators, creating a feedback loop.^5,17
b Skin infiltration in CSU is also influenced by the role of IL-5 in eosinophil maturation and survival.^5,10

CSU, chronic spontaneous urticaria; MOD, mechanism of disease.

Only DUPIXENT specifically targets IL-4Rα, inhibiting IL-4 and IL-13 signaling in CSU¹

CSU, chronic spontaneous urticaria; MOA, mechanism of action.

CUPID Study A

DUPIXENT patients achieved significant control over itch and hives (UAS7 reduction from baseline) vs placebo at Week 12 and Week 24^1,3,18,19

^a Patients with active AD were excluded from the study.
UAS7 is the weekly Urticaria Activity Score, a patient-reported outcome of urticaria severity. UAS7 is a composite of itch severity (ISS7) and hives severity (HSS7), derived by adding the daily ISS and HSS scores from the preceding 7 days, for a total UAS7 range of 0 to 42.⁶

AD, atopic dermatitis; HSS7, Hives Severity Score over 7 days; ISS7, Itch Severity Score over 7 days; LSM, least squares mean;
Q2W, once every 2 weeks; UAS7, Urticaria Activity Score over 7 days.

CUPID Study A

In CUPID Study A, a higher percentage of DUPIXENT patients achieved complete relief (UAS7=0) vs placebo at Week 24^3,6,19

• ≈60% of patients with moderate disease activity at baseline were well-controlled (UAS7 ≤6) at Week 24 vs 38% with placebo³
• 45% of patients with severe disease activity at baseline were well-controlled (UAS7 ≤6) at Week 24 vs 22% with placebo³

UAS7 is the weekly Urticaria Activity Score, a patient-reported outcome of urticaria severity. UAS7 is a composite of itch severity (ISS7) and hives severity (HSS7), derived by adding the daily ISS and HSS scores from the preceding 7 days, for a total UAS7 range of 0 to 42.⁶

HSS7, Hives Severity Score over 7 days; ISS7, Itch Severity Score over 7 days; Q2W, once every 2 weeks; UAS7, Urticaria Activity Score over 7 days.

DUPIXENT improved QoL at Week 24 as measured by DLQI (nominal P=0.0026)²

With CU-Q2oL, a CSU-specific instrument validated by global guideline organizations (EAACI, GA2LEN, and EDF) DUPIXENT patients achieved^20,21:
- 30-point improvement with DUPIXENT vs 21 points with placebo at Week 24 (nominal P=0.0049)²⁰

CU-Q2oL, Chronic Urticaria–Quality of Life Questionnaire; DLQI, Dermatology Life Quality Index; EAACI, European Academy of Allergy and Clinical Immunology; EDF, European Dermatology Forum; GA2LEN, Global Allergy and Asthma European Network; Q2W, once every 2 weeks.

Adverse reactions occurring in ≥2% of patients through Week 24 (pooled safety data across CUPID-A and CUPID-B)^1,a,b

Injection site reactions 4% (DUPIXENT) vs 2% (placebo)

Adverse reactions in clinical studies across all indications²³

• If a systemic hypersensitivity reaction (immediate or delayed) occurs, DUPIXENT should be discontinued immediately and appropriate therapy initiated²³
• Patients who develop conjunctivitis that does not resolve following standard treatment should undergo ophthalmological examination²³
• Patients with moderate-to-severe atopic dermatitis and comorbid asthma should not adjust or stop their asthma treatments without consulting their physicians. Monitor patients with comorbid asthma carefully following discontinuation of DUPIXENT²³
• Most patients experiencing conjunctivitis recovered or were recovering during the treatment period²³
• Treat any pre-existing helminth infections prior to initiating treatment with DUPIXENT²³
• If patients become infected while receiving treatment and do not respond to anti-helminth treatment, discontinue treatment until infection resolves²³

The safety of DUPIXENT has been demonstrated across 7 indications including in patients ≥6 months in AD¹

^a CUPID Study A was a 24-week, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of dupilumab in participants with CSU who remained symptomatic despite the use of H1-antihistamines and who were naïve to omalizumab. The efficacy of dupilumab was assessed based on the effect of dupilumab on the frequency/severity of itch and hives scored individually and through the composite Urticaria Activity Score, on urticaria control, and on participants’ healthrelated quality of life (HRQoL) and health status. CUPID Study A enrolled 138 patients of which 132 were adults, 4 were pediatric patients 12 to 17 years of age, and 2 were pediatric patients 6 to 11 years of age, randomized to receive either DUPIXENT 300 mg every two weeks (n=67), DUPIXENT 200 mg every two weeks (n=3), or placebo (n=68). The primary endpoint was change from baseline in Itch Severity Score over 7 days (ISS7) at Week 24. Key secondary endpoints included change from baseline in Urticaria Activity Score over 7 days (UAS7) at Week 24, and change from baseline in Hives Severity Score over 7 days (HSS7) at Week 24.^1,3

^b CUPID Study B contained a total of 108 adults and adolescents (12-17 years) with CSU inadequately controlled despite H1- antihistamine treatment that were randomized to DUPIXENT or placebo. All participants were inadequate responders or intolerant to anti-IgE therapy. This study had the same efficacy endpoints as CUPID Study A. In CUPID Study B, DUPIXENT did not meet statistical significance for reduction from baseline in the primary endpoint (ISS7) at Week 24, but demonstrated nominally significant improvements for secondary endpoints (UAS7 and HSS7) at Week 24.¹

^c Eye disorders and oral herpes occurred predominately in atopic dermatitis studies.

^d From postmarketing reporting.

^e The frequencies for eye pruritus, blepharitis, and dry eye were common, and ulcerative keratitis was uncommon in atopic dermatitis studies.

AD, atopic dermatitis; CSU, chronic spontaneous urticaria.