Systemic Therapies for Moderate-to-Severe Atopic Dermatitis in Children and Adolescents: A Systematic Review

Moderate-to-severe atopic dermatitis (AD) in children and adolescents imposes a significant burden, often requiring systemic therapy. With the recent development of targeted biologics and Janus kinase (JAK) inhibitors, the treatment landscape has evolved rapidly. This systematic review aims to critically evaluate the efficacy and safety of these advanced systemic therapies in the pediatric population. A systematic search of PubMed/MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov was conducted for randomized controlled trials (RCTs) published from 2020 onwards, yielding 250 records. Thirteen studies involving over 3,500 pediatric patients were included. Studies evaluating biologics or JAK inhibitors in children and adolescents (0-18 years) with moderate-to-severe AD were included. The Cochrane Risk of Bias 2 (ROB 2) tool was used for quality assessment. A narrative synthesis was performed due to clinical heterogeneity. Dupilumab and tralokinumab (biologics) demonstrated significant efficacy, with Eczema Area and Severity Index 75 (EASI-75) response rates of 43.3% at week 16 and sustained improvements in disease severity (SCORAD, IGA) and pruritus. The JAK inhibitors, abrocitinib and upadacitinib, showed rapid and high-magnitude efficacy, with EASI-75 and Validated Investigator Global Assessment (vIGA-AD) response rates frequently exceeding 70-90% by weeks 12-16 and providing rapid itch relief. Dupilumab's safety profile was favorable, with mostly mild-to-moderate adverse events (e.g., conjunctivitis). JAK inhibitors were associated with acne, nausea (abrocitinib), and herpes infections, necessitating routine monitoring. The overall risk of bias was low across most studies. Advanced systemic therapies are highly effective for moderate-to-severe pediatric AD. Biologics offer a well-established safety profile, while JAK inhibitors provide superior and faster efficacy, particularly for itch, but require careful safety monitoring. Treatment choice should be individualized based on disease severity, preference, and risk profile.