Can Dupilumab Relieve the Itch and Inflammation of Diverse Skin Diseases?

🔍 Key Finding Dupilumab, an IL-4 and IL-13 inhibitor, shows efficacy in treating various inflammatory skin diseases beyond its approved indications for atopic dermatitis and prurigo nodularis, including eczema, chronic pruritus, bullous diseases, alopecia areata, chronic urticaria, and Netherton syndrome, often in patients refractory to other treatments. While generally safe, further research is needed to confirm efficacy, determine optimal dosing, and identify predictors of treatment response in these off-label uses.

🔬 Methodology Overview

• Design: Systematic review of dupilumab use in inflammatory skin diseases (excluding atopic dermatitis and prurigo nodularis in adults).
• Data Sources: PubMed/Medline, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov.
• Search Terms: (dermatology OR skin OR dermatitis) AND dupilumab. ClinicalTrials.gov was also queried using “dupilumab”.
• Selection Criteria: English language case reports, case series, retrospective clinical studies, or randomized controlled trials published before January 15, 2023, reporting clinical responses to off-label dupilumab use in dermatological conditions. Reviews, meeting abstracts, non-English articles, and reports solely on atopic dermatitis, prurigo nodularis in adults, or adverse events of in-label dupilumab treatment were excluded.
• Analysis Approach: Qualitative synthesis of reported clinical outcomes.
• Evidence Level Categorization: Adapted Oxford Centre for Evidence-Based Medicine (OCEBM) levels of evidence table.

📊 Results

• Eczema: Dupilumab showed significant improvement in nummular eczema (EASI -32.87 mean, itch NRS -7.17 mean) and contact dermatitis (85% mean BSA improvement) in patients refractory to other treatments. In chronic hand eczema, a prospective study showed 89% HECSI reduction over 52 weeks in 72 patients, with 62.9% achieving HECSI-90. However, hyperkeratotic CHE showed less response.

• Chronic Pruritus/Prurigo: Dupilumab reduced itch NRS by a mean of 7 points in 15 CPUO patients and by 8.75 points in another 4 CPUO patients. Efficacy was also seen in uremic and cholestatic pruritus.

• Bullous Pemphigoid: Dupilumab as add-on therapy led to shorter time to disease control, faster itch and BPDAI decline, and lower steroid/immunosuppressant doses compared to conventional therapy alone in a retrospective cohort study of 28 patients. Multiple case reports also showed efficacy, including in checkpoint inhibitor-induced BP.

• Alopecia Areata: A phase 2 RCT showed improvement in SALT scores at week 24 (p=0.049) and week 48 (p<0.0001) with dupilumab vs. placebo. SALT30 was achieved in 32.5% vs. 20% at week 48. High IgE and atopy history predicted better response. Case reports showed mixed results, with some complete regrowth but also non-responders.

• Chronic Spontaneous Urticaria: A phase 3 RCT showed an 8.5 point greater UAS7 reduction with dupilumab vs. placebo (p=0.0003) in antihistamine-refractory CSU. Case reports showed complete sustained resolutions in 10 of 14 patients.

• Netherton Syndrome: Dupilumab provided prompt itch and skin lesion resolution in 16 reported cases, with sustained responses in most.

• Other Hereditary Skin Diseases: Dupilumab showed efficacy in some cases of various conditions including dystrophic epidermolysis bullosa (itch improvement), Hailey-Hailey disease (skin lesion improvement), and Grovers disease (lesion and itch resolution).

💡 Clinical Impact Dupilumab demonstrates efficacy in a broad spectrum of inflammatory skin diseases beyond its approved indications for atopic dermatitis and prurigo nodularis, particularly in conditions driven by type 2 inflammation. This suggests that dupilumab may become a valuable treatment option for various refractory inflammatory skin diseases, potentially reducing reliance on systemic corticosteroids and other immunosuppressants.

🤔 Limitations

• Limited long-term efficacy and safety data for dupilumab in many off-label indications.
• Many studies are case reports or small case series, providing low-level evidence.
• Heterogeneity of patient populations and prior treatments makes comparisons difficult.
• Concomitant atopic dermatitis in many patients confounds efficacy assessment for other conditions.
• Lack of placebo-controlled trials for many indications.
• Potential for rare but serious adverse events, including new-onset skin conditions.
• Limited data on optimal dosing regimens and duration of therapy for off-label use.

✨ What It Means For You Dupilumab demonstrates efficacy in treating various inflammatory skin diseases beyond its approved indications, offering clinicians an additional treatment option for refractory cases of eczema, prurigo, bullous diseases, alopecia areata, and chronic urticaria. While generally safe, doctors should be aware of potential adverse events and consider individual patient characteristics, such as atopy and IgE levels, when prescribing dupilumab, as these may influence treatment response. Further research, particularly larger controlled trials, is needed to solidify optimal use and predict treatment outcomes in specific disease subtypes.

Reference Olbrich, H.; Sadik, C.D.; Ludwig, R.J.; Thaçi, D.; Boch, K. Dupilumab in Inflammatory Skin Diseases: A Systematic Review. Biomolecules. 2023;13:634. https://doi.org/10.3390/biom13040634