Dupilumab receives FDA approval for AD with moderate-to-severe hand and foot involvement based on data from the LIBERTY-AD-HAFT trial

07 Feb 2024

Despite being approved for the treatment of moderate-to-severe atopic dermatitis (AD), dupilumab’s efficacy in treating patients with atopic hand and foot dermatitis had not been evaluated.1,2 The LIBERTY-AD-HAFT trial demonstrated dupilumab’s efficacy and safety in treating patients with AD with moderate-to-severe hand and foot involvement.3 Based on the study results, the United States (US) Food and Drug Administration (FDA) updated the label of dupilumab to include AD with moderate-to-severe hand and foot involvement.4

AD is a chronic, relapsing inflammatory disease characterized by skin lesions covering large body-surface areas, which cause significant and persistent itch that can be detrimental to the patient’s quality of life.5 In particular, AD of the hands and/or feet is a socially significant and difficult-to-treat disease due to its high prevalence, morbidity, and associated loss of work time due to sick leave.2 Dupilumab, a human monoclonal immunoglobulin G4 (IgG4) antibody that inhibits the key inflammatory drivers of type 2 inflammation, was the first FDA-approved human monoclonal antibody for the treatment of adult and pediatric patients aged ≥6 months with moderate-to-severe AD, whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.1,2 However, the biologic had not been evaluated for its clinical performance in treating AD on the hands and feet.2

The LIBERTY-AD-HAFT was a phase 3, randomized, double-blind study designed to assess the efficacy and safety of dupilumab in treating patients with atopic hand and foot dermatitis.3 A total of 133 patients who were aged ≥12 years, diagnosed with AD and chronic hand and/or foot eczema with an overall Investigator Global Assessment (IGA) score for hand and foot of 3 (moderate) or 4 (severe) and exhibited inadequate response or intolerance to topical corticosteroids on AD lesions of hand/foot were enrolled and randomized to receive either 200mg/300mg of dupilumab every 2 weeks (n=67) or placebo (n=66).3

The primary endpoint was the proportion of patients achieving a clear or almost clear skin of hand and feet eczema at 16 weeks, as measured by a score of 0 or 1 on the IGA scale.3 The key secondary endpoint was the proportion of patients with improvement in itch on hands and feet from baseline, defined as achieving a 4-point improvement in weekly average of daily hand and foot Peak Pruritis-Numeric Rating Scale (PP-NRS) over time.3 Additional secondary endpoints included the change in health-related quality of life, as measured by the quality of life in hand eczema questionnaire (QoLHEQ), skin pain reduction, as measured by the peak pain Numeric Rating Scale (NRS), and sleep improvement, as measured by the sleep quality NRS.3 The percentage change in modified total lesion symptom score (mTLSS), Hand Eczema Severity Index (HECSI), PP-NRS, as well as the proportion of patients who achieved a ≥75% improvement in HECSI score (HESCI-75) at week 16 were also measured.3

At week 16, the proportion of patients with a hand and foot IGA of 0/1 was significantly higher in the dupilumab group than in the placebo group (40.3% vs. 16.7%; p≤0.01).3 Moreover, patients who received dupilumab were significantly more likely to achieve a 4-point improvement in the weekly average of daily hand and foot PP-NRS compared to patients who received placebo (52.2% vs. 13.6%; p<0.0001).3 Compared with the placebo group, patients in the dupilumab group had a significantly greater improvement in QoLHEQ (p<0.0001), peak pain NRS (p<0.0001), and sleep quality NRS (p=0.0115).3 Significant improvements in the other secondary endpoints such as mTLSS (p<0.0001), HECSI (p<0.0001), and PP-NRS (p<0.0001) were also observed.3 Furthermore, the dupilumab group had a significantly higher achievement rate of HECSI-75 than the placebo group (46.9% vs. 21.5%; p=0.0028).3

Dupilumab also exhibited a manageable safety profile in the LIBERTY-AD-HAFT study.3 Treatment-emergent adverse events (TEAEs) occurred in 65.7% of dupilumab-treated patients and 74.2% of placebo-treated patients.1 Nasopharyngitis (16.4%), upper respiratory tract infection (9.0%), and increased blood creatine phosphokinase (6.0%) were the top 3 TEAEs observed in the dupilumab group.3 In addition, fewer patients in the dupilumab group experienced AE leading to treatment discontinuation compared to the placebo group (1.5% vs. 4.5%).3

In summary, dupilumab led to an early and significant improvement in the symptoms and quality of life in patients with atopic hand and foot dermatitis.3 Dupilumab had a tolerable safety profile which was consistent with the safety profile of dupilumab in the approved AD indications.1 Based on these results, the FDA has updated the US prescribing information label of dupilumab to support its use in AD with moderate-to-severe hand and foot involvement.4

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