Dear editor
The article by Labib et alCitation1 provides a valuable review of prurigo nodularis (PN). Dupilumab, recently approved by the U.S. Food and Drug Administration as the only systemic therapy for the treatment of PN, is mentioned among novel immunotherapies under investigation. Dupilumab safety is reviewed based on clinical trial data for atopic dermatitis (AD). However, the article cites skin infections as adverse reactions more commonly associated with dupilumab relative to placebo, a point that we believe warrants clarification.
Eichenfield et alCitation2 analyzed pooled data from 7 randomized, placebo-controlled trials in adults with AD and found that the exposure-adjusted proportion of patients with treatment-emergent non-herpetic adjudicated skin infections was significantly lower with dupilumab than with placebo (14.5% vs 26.6%, p < 0.001). In the same study, the incidence of herpetic infections was non-significantly higher with dupilumab (12.7% vs 10.4%, p = 0.24), while eczema herpeticum and herpes zoster were significantly less frequent with dupilumab versus placebo (1.1% vs 3.6%, p = 0.004). Similarly, in a pooled analysis of 2 randomized, placebo-controlled trials in children aged 6–17 years with AD, Paller et alCitation3 reported significantly lower exposure-adjusted proportions of patients with total and non-herpetic skin infections in the dupilumab group versus placebo (respectively, 35.9% vs 67.0%, p = 0.001 and 27.8% vs 56.9%, p = 0.004), while herpes viral infections did not differ significantly (total herpes infections, 8.9% vs 14.7%, p = 0.262; eczema herpeticum, 0.8% vs 1.6%, p = 0.628; herpes zoster, 0.8% vs 0, p = 1.0). Additionally, Blauvelt et alCitation4 analyzed treatment-emergent infections over 4 years of dupilumab treatment in an AD open-label study and found that the cumulative number of patients with serious or severe infections, non-herpetic or herpetic infections, and total skin infections, decreased yearly with continued treatment.
In PN, subsequent to the publication of Labib et al,Citation1 results from Phase 3 randomized LIBERTY-PN PRIME and PRIME2 trials showed, similarly to AD trials, that non-herpetic skin infections occurred less frequently in patients treated with dupilumab versus placebo (2.7% vs 9.3% in PRIME, and 5.2% vs 6.1% in PRIME2); herpetic skin infections did not occur in PRIME and were more frequent with dupilumab in PRIME2 (5.2% vs 0).Citation5
AD patients are highly susceptible to non-herpetic skin infections, usually with Gram-positive bacteria, and dupilumab was shown to decrease abundance of Staphylococcus aureus in both AD lesional and non-lesional skin,Citation6 results further supported by comprehensive evidence from clinical trials and post-marketing studies. Herpes infections are a known adverse drug reaction in both AD and PN and included in the U.S. prescribing information.Citation7
In conclusion, evidence from AD and PN trials demonstrates that dupilumab treatment does not increase the risk of skin infections overall, and is associated with fewer non-herpetic skin infections compared with placebo.
Disclosure
Simmi Wiggins is a Sanofi employee and may hold stock and/or stock options in the company; Noah A. Levit was a Regeneron Pharmaceuticals Inc. employee and shareholder at the time this letter was written and reports compensation as non-promotional speaker from Sanofi, outside the submitted work.
Acknowledgments
Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Medical writing/editorial assistance was provided by Iulia Oprea, MD, PhD, of Excerpta Medica, and was funded by Sanofi and Regeneron Pharmaceuticals Inc., according to the Good Publication Practice guideline.
References
- Labib A, Ju T, Vander Does A, Yosipovitch G. Immunotargets and therapy for prurigo nodularis. Immunotargets Ther. 2022;11:11–21. doi:10.2147/ITT.S316602
- Eichenfield LF, Bieber T, Beck LA, et al. Infections in dupilumab clinical trials in atopic dermatitis: a comprehensive pooled analysis. Am J Clin Dermatol. 2019;20(3):443–456. doi:10.1007/s40257-019-00445-7
- Paller AS, Beck LA, Blauvelt A, et al. Infections in adolescents and children treated with dupilumab in pediatric clinical trials for atopic dermatitis – a pooled analysis of trial data. Pediatr Dermatol. 2022;39(2):187–196. doi:10.1111/pde.14909
- Blauvelt A, Wollenberg A, Eichenfield LF, et al. No increased risk of overall infection in adults with moderate-to-severe atopic dermatitis treated for up to 4 years with dupilumab. Adv Ther. 2023;40:367–380. doi:10.1007/s12325-022-02322-y
- Yosipovitch G, Mollanazar N, Ständer S, et al. Dupilumab in patients with prurigo nodularis: two randomized, double-blind, placebo-controlled phase 3 trials. Nat Med. 2023. doi:10.1038/s41591-023-02320-9
- Callewaert C, Nakatsuji T, Knight R, et al. IL-4Rα blockade by dupilumab decreases Staphylococcus aureus colonization and increases microbial diversity in atopic dermatitis. J Invest Dermatol. 2020;140(1):191–202. doi:10.1016/j.jid.2019.05.024
- Dupixent®. U.S. Food and Drug Administration. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761055s044lbl.pdf. Accessed May 15, 2023.