Chronic spontaneous urticaria (CSU) is a chronic inflammatory skin disease associated with recurrent itch and hives that can significantly impair quality of life.¹ While H1 antihistamines (H1AH) remain the standard first-line treatment, disease control remains suboptimal in some patients despite therapy.¹ Recently, the US Food and Drug Administration (FDA) approved dupilumab for children aged 2-11 years with CSU who remain symptomatic despite H1AH treatment, extending the indication to a younger pediatric population and establishing dupilumab as the first biologic approved for CSU in children as young as two years of age.²

CSU is driven in part by type 2 inflammation, with interleukin (IL)-4 and IL-13 recognized as key mediators involved in disease pathophysiology.³ Dupilumab is a fully human monoclonal antibody that inhibits IL-4 and IL-13 signaling, thereby targeting central drivers of type 2 inflammation.³ The recent FDA approval represents the latest expansion of dupilumab’s clinical utility across type 2 inflammatory diseases and marks the fifth such indication approved for children younger than 12 years of age.²

The FDA approval was supported by evidence from the phase 3 LIBERTY-CSU CUPID clinical development program.² Efficacy data were derived from randomized, double-blind, placebo-controlled phase 3 trials evaluating dupilumab as add-on therapy to standard-of-care H1AH in patients with CSU who remained symptomatic despite treatment.^4,5 In parallel, pharmacokinetic data from the phase 3 CUPIDKids study provided supportive evidence for extrapolation in children aged 2-11 years with uncontrolled CSU.²

The LIBERTY-CSU CUPID program included replicate phase 3 trials (Study A and Study C) in anti-IgE-naïve patients aged ≥6 years, and a separate study (Study B) in patients aged ≥12 years who were inadequate responders or intolerant to anti-IgE therapy, with all controlled trials conducted over a 24-week treatment period vs. placebo.^4,5 Across these studies, dupilumab demonstrated improvements in disease activity vs. placebo, including reductions in itch severity (weekly itch severity score [ISS7]) and urticaria activity (weekly urticaria activity score [UAS7]).^4,5 In Study A and Study C, treatment was also associated with higher proportions of patients achieving well-controlled disease (UAS7 ≤6) and complete response (UAS7=0).^4,5

The CUPIDKids phase 3 study was a single-arm pharmacokinetic and exposure-response trial evaluating weight- and age-based dupilumab dosing in children aged 2-11 years with CSU who remained symptomatic despite antihistamine therapy.² Over a 24-week treatment period, dupilumab was administered using age- and weight-adjusted regimens, with pharmacokinetic assessment as the primary objective, including serial serum concentrations and trough levels (C_trough) at weeks 12 and 24.² These pharmacokinetic data contributed to the extrapolation of efficacy to the pediatric CSU population, while safety in children aged 2-11 years with CSU was supported by data from pediatric patients across other approved indications.²

The safety profile of dupilumab in CSU was generally consistent with that observed across its approved dermatologic indications.^2,4,5 The most commonly reported adverse event occurring more frequently with dupilumab than placebo was injection-site reactions.^2,5 No new safety signals were identified across the CSU clinical development program, and no new adverse reactions were observed in children aged 2-11 years.^2,5

In conclusion, the FDA approval of dupilumab extends a targeted treatment option to children with CSU whose disease remains inadequately controlled despite antihistamine therapy.² As the first biologic approved for children as young as two years of age with CSU, dupilumab addresses an important unmet need and further supports the role of type 2 inflammatory pathways as therapeutic targets in this chronic disease.²