Efficacy of Dupilumab in Treating Atopic Hand and Foot Dermatitis

Atopic hand and foot dermatitis (AHFD) presents significant challenges in clinical management, with symptoms ranging from chronic dry fissured skin to hyperkeratotic lesions. Recent advancements have highlighted the potential of dupilumab (Dupixent; Sanofi and Regeneron), a monoclonal antibody targeting the IL-4 and IL-13 pathways, in treating moderate to severe atopic dermatitis (AD). A poster presentation at the 2024 Fall Clinical Dermatology Conference for PAs and NPs in Scottsdale, Arizona delves into the efficacy of dupilumab across different morphological subtypes of AHFD, as demonstrated in the phase 3, randomized, double-blind, placebo-controlled LIBERTY-AD-HAFT trial (NCT04417894).¹

Study Overview

The LIBERTY-AD-HAFT trial enrolled patients aged 12 and older with moderate to severe AHFD, characterized by an Investigator’s Global Assessment (IGA) score of 3 or 4. Participants were randomized to receive either dupilumab (300 mg every two weeks for adults, 200/300 mg every two weeks for adolescents based on weight) or placebo for 16 weeks. The primary endpoint was the percent change from baseline in the modified total lesion sign score (mTLSS), a composite measure of lesion severity. 

The trial’s primary objective was to evaluate the efficacy of dupilumab in reducing the severity of AHFD lesions, categorized into 3 morphological subtypes: chronic dry fissured, hyperkeratotic (palmar/plantar), and other. The analysis focused on the percent change from baseline in mTLSS at week 16, with secondary assessments at weeks 8 and 12. Safety profiles were monitored to ensure consistency with known dupilumab-related adverse events.

Results

The results from the LIBERTY-AD-HAFT trial indicated 3 significant improvements across all AHFD subtypes with dupilumab treatment compared to placebo.

1. Chronic Dry Fissured Subtype: Patients receiving dupilumab experienced a 65.5% reduction in mTLSS at Week 16, compared to a 31.5% reduction in the placebo group. The treatment effect difference was 34.1% (95% CI, -49.74 to -18.41), favoring dupilumab.

2. Hyperkeratotic Subtype (Palmar/Plantar): Dupilumab-treated patients showed a 58.2% reduction in mTLSS, whereas the placebo group had an 11.8% reduction. The difference in treatment effect was 46.4% (95% CI, -67.73 to -24.99), significantly favoring dupilumab.

3. Other Subtypes: For other morphological subtypes, dupilumab resulted in a 64.5% reduction in mTLSS, in contrast to a 29.9% reduction with placebo. The treatment effect difference was 34.6% (95% CI, -63.29 to -5.83), again favoring dupilumab.

The safety profile of dupilumab in this study was consistent with previous reports. Common adverse events included conjunctivitis and injection site reactions, but no new safety signals were identified. This consistency reaffirms the well-established safety profile of dupilumab in treating AD.^2-3

Clinical Considerations

The trial demonstrates that dupilumab significantly reduces lesion severity across various AHFD morphological subtypes. The consistent efficacy across different lesion types underscores the broad therapeutic potential of dupilumab in managing AHFD. These findings align with previous studies indicating dupilumab’s effectiveness in treating AD more broadly, suggesting that targeting the IL-4 and IL-13 pathways can substantially alleviate symptoms in patients with chronic, severe hand and foot dermatitis.^2-3 

The Phase 3 LIBERTY-AD-HAFT trial provides evidence supporting the efficacy of dupilumab in treating moderate to severe AHFD across different morphological subtypes. Investigators noted that dupilumab not only offered improvements in lesion severity but also maintained a favorable safety profile, making it a viable treatment option for clinicians managing patients with challenging AHFD presentations. Future research will continue to explore long-term outcomes and the potential for dupilumab to address other difficult-to-treat AD subtypes.

References

1. Worm M, Simpson E, Honari G, et al. Efficacy of dupilumab treatment in atopic hand and foot dermatitis across morphological subtypes: results from a phase 3, randomized, double-blind, placebo-controlled trial. Poster presented at: 2024 Fall Clinical Dermatology Conference for PAs and NPs; May 31-June 2, 2024; Scottsdale, AZ.

2. Simpson EL, Silverberg JI, Worm M, et al. Dupilumab treatment improves signs, symptoms, quality of life, and work productivity in patients with atopic hand and foot dermatitis: Results from a phase 3, randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2024. doi:10.1016/j.jaad.2023.12.066.

3. Voorberg AN, Kamphuis E, Christoffers WA, Schuttelaar MLA. Efficacy and safety of dupilumab in patients with severe chronic hand eczema with inadequate response or intolerance to alitretinoin: a randomized, double-blind, placebo-controlled phase IIb proof-of-concept study. Br J Dermatol. 2023;189(4):400–409. doi:10.1093/bjd/ljad156.