Effectiveness and safety of systemic therapy for moderate-to-severe atopic dermatitis in children and adolescent patients: a systematic review

Abstract

Importance: Due to comorbidities and associated safety risks, the management of severe atopic dermatitis (AD) in pediatric and adolescent patients poses significant challenges.

Objective: To examine the efficacy and safety of systemic therapies for the treatment of moderate-to-severe atopic dermatitis in children and adolescents.

Evidence review: On Feb 29, 2024, a systematic literature search was conducted in Embase, PubMed, and the Cochrane Central Register of Controlled Trials (Central). No date restrictions were applied. Randomized clinical trials, cohort studies, large case series, and meta-analyses were assessed to evaluate the efficacy (or effectiveness) and/or safety of systemic treatments for moderate-to-severe atopic dermatitis in children and adolescents.

Findings: A preliminary search yielded 1457 results, from which 19 unique articles with a total of 3741 patients were included in the analysis. Overall, the available data for each systemic medication are limited, and the overall quality of the included studies on conventional systemic treatments is relatively low. When Dupilumab was used as a standalone treatment, 30%-40% of infants and toddlers aged 6 months to 2 years achieved EASI-75, while 50% of patients aged 2 to 6 years achieved EASI-75. In children aged 6 to 12 years, 33.0%-59.0% of atopic dermatitis patients achieved EASI-75, and when combined with topical corticosteroids (TCS), 69.7%-74.6% achieved EASI-75. Long-term data showed EASI-75 rates ranging from 75.0% to 94.0% for this age group. For adolescents aged 12 to 18 years, 40%-71% of patients achieved EASI-75 within 12 to 16 weeks, and by week 52, 80.8% of patients achieved EASI-75.Abrocitinib treatment resulted in 68.5%-72.0% of patients achieving EASI-75. Omalizumab treatment at week 24 showed a percentage change in SCORAD scores of -12.4%. In the Methotrexate treatment group, there was a SCORAD change of -26.25% at week 12, while the Cyclosporine A group had a SCORAD change of -25.01%. Patients treated with IVIG (Intravenous Immunoglobulin) showed a -34.4% change in SCORAD percentage scores at week 4, which further decreased by 47.12% at week 24. Patients receiving 4mg of Baricitinib and TCS had a 52.5% rate of EASI-75 at 16 weeks, and patients receiving different doses of upadacitinib had a 63-75% rate of EASI-75 at 16 weeks. The rate of EASI-75 at 16 weeks was around 28% in patients who received various doses of Tralokinumab.The most common adverse events observed were nasopharyngitis, respiratory events and dermatitis atopic.

Conclusions and relevance: Awareness of adverse events and concomitant medications is crucial, and appropriate dosing and frequent laboratory and clinical monitoring are also essential. More real-world evidence and prospective cohort studies analyzing the effectiveness and safety of systemic therapies in children and adolescents are of paramount importance for optimizing personalized, effective, and safe management of the growing population of patients with atopic dermatitis in this age group.

Keywords: adolescent; atopic dermatitis (AD); children; effectiveness & efficiency (E&E); safety; systemic therapy.

Figure 1

Flow Diagram of the literature Search.

Figure 2

Efficacy or Effectiveness in Children and Adolescent Patients at Induction Phase (Weeks 12-16). Each bar chart represents the change in SCORAD (Scoring Atopic Dermatitis) scores in pediatric and adolescent patients following the administration of systemic medications for atopic dermatitis. Patients with different treatment durations were excluded from this figure. The dataset exhibited significant heterogeneity, precluding a proper meta-analysis. The drugs IVIG and Abrocitinib were not included in the analysis presented in this figure. QW, quaque week; Q2W, quaque two weeks; Q4W, quaque quattuor weeks; Bid, bis in die; Qd, quaque die; TCS, Topical Corticosteroid.

Figure 3

Efficacy or Effectiveness of Dupilumab in children and adolescents during induction period (12-16 weeks). Each bar chart represents a percentage change of 75% in the eczema area and Severity Index (EASI75) in pediatric and adolescent patients treated with Dupilumab. Patients with different treatment duration and who did not use the EASI-75 score were excluded from this chart. The dataset showed significant heterogeneity, so a proper meta-analysis was not possible. QW, quaque week; Q2W, quaque two weeks; Q4W, quaque quattuor weeks; TCS, Topical Corticosteroid.