Skin infections during dupilumab monotherapy in moderate-to-severe atopic dermatitis – a meta-analysis of randomized clinical trials

ABSTRACT

Objective

Atopic dermatitis (AD) increases the risk of bacterial and viral cutaneous infections. This study assesses the risk of skin infections related to dupilumab monotherapy in moderate-to-severe AD.

Methods

We searched PubMed/Medline, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Library. For gray literature, Google Scholar was searched. A meta-analysis of randomized clinical trials (RCTs) for overall skin infections, eczema herpeticum, nonherpetic skin infections and subgroup meta-analysis based on overall herpetic infection type was performed.

Results

We observed a statistically significant (p < 0.005) lower incidence rate in the dupilumab group compared to placebo for overall skin infections (Risk Ratio [RR] = 0.59, 95% confidence interval [CI]: [0.47, 0.75], P < 0.0001) and nonherpetic skin infections (RR = 0.42, 95% CI: [0.27, 0.66], P = 0.0001). For herpetic infections in 2b phase studies a meta‐analysis demonstrated significantly higher events in dupilumab group compared to placebo (RR = 3.38, 95% CI: [1.98, 5.76], P < 0.00001, test for subgroup differences: P = 0.02, I² = 65.6%).

Conclusions

In moderate-to-severe AD, dupilumab in monotherapy may be an effective and safe therapeutic approach, not associated with an increased risk of overall skin infections and nonherpetic skin infections. Due to the lack of statistical significance in heterogeneity associated with potential confounders in some cases, results should be interpreted cautiously.

Registration

The meta-analysis was registered in PROSPERO, ID: CRD42023441346

KEYWORDS:

• Atopic dermatitis
• dupilumab
• meta-analysis
• monotherapy
• skin infections

Article highlights

• Dupilumab was the first approved biologic therapy that has revolutionized the treatment of moderate-to-severe atopic dermatitis (AD).

• AD patients are more susceptible to cutaneous and extracutaneous infections, among which Staphylococcus aureus (S. aureus) and herpes simplex virus (HSV) are the most frequently diagnosed.

• Skin infections cause significant morbidity in patients with AD. There is a need to understand the mechanisms and risk factors of infections in AD and what is related to the safety of the applied therapies.

• This study aims to provide a meta-analysis of the data from randomized clinical trials (RTCs) to assess whether dupilumab in monotherapy is associated with a risk of skin infections compared to placebo. A subgroup meta-analysis based on herpetic infection type was also performed.

• It can be concluded that monotherapy with dupilumab may be an effective and safe therapeutic approach, not associated with an increased risk of overall and nonherpetic skin infections.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Data availability statement

All information can be available in the manuscript.

Ethics approval informed consent to participate

This article is a meta-analysis. It does not use any patients or personal data that could be submitted to the evaluation of the Local Ethical Committee. Additionally, in this type of study, the informed consent of the participants is not required.

Author contributions

M Marko: data curation: lead, formal analysis: lead, investigation: lead, methodology: lead, writing original draft: lead, writing review and editing: equal. R Pawliczak: conceptualization: lead, funding acquisition: lead, project administration: lead, writing review and editing: equal

Additional information

Funding

This paper was funded by the Medical University of Lodz under Grant number [503/0-149-03/503-01-001-19-00].