Comparative efficacy and safety of systemic therapies for moderate-to-severe atopic dermatitis in adults: a systematic review of randomized controlled trials
Abstract
BackgroundAtopic dermatitis (AD) is a common, chronic inflammatory skin condition, and patients with moderate-to-severe disease often require systemic therapy. Since 2017, targeted systemic agents, biologics and Janus kinase (JAK) inhibitors, have expanded treatment options available, but comparative evidence remains limited by heterogeneous trial design, outcome reporting, and follow-up duration.ObjectiveTo systematically review the efficacy and safety of European Medicines Agency (EMA)-approved systemic therapies for moderate-to-severe AD in adults.MethodsFollowing PRISMA 2020 guidelines, we searched PubMed/MEDLINE, Embase and Web of Science for randomized controlled trials evaluating EMA-approved biologics (dupilumab, tralokinumab, lebrikizumab, nemolizumab) and JAK inhibitors (upadacitinib, abrocitinib, baricitinib) at recommended adult doses. The primary outcome was the proportion of patients achieving EASI-75 at the primary trial endpoint (12–16 weeks). Due to substantial clinical and methodological heterogeneity, a structured narrative synthesis was conducted rather than a meta-analysis.ResultsTwenty-five RCTs met inclusion criteria. At EMA-recommended doses, EASI-75 responses ranged from 44% to 69% for dupilumab, 60.6% for lebrikizumab, 25-64% for tralokinumab, and 49.1% for nemolizumab (combination-therapy data only). Among JAK inhibitors, upadacitinib showed the highest observed response rate (73.0% at 16 weeks), followed by abrocitinib (64.6% at 12 weeks) and baricitinib (17.9-48.0%). Placebo response rates ranged from 6% to 36% and were consistently higher in combination-therapy trials. Any adverse event occurred in 45.2% (abrocitinib 100 mg) to 82.46% (nemolizumab) of patients, with serious adverse events generally low across therapies.ConclusionEMA-approved systemic therapies for moderate-to-severe AD demonstrate meaningful short-term efficacy and acceptable safety. However, treatment selection should remain individualized given cross-trial heterogeneity and the current absence of long-term comparative data. Further head-to-head trials and real-world evidence are needed to optimize treatment sequencing.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251102911
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BibTeX
@article{pikoula2026comparative,
title = {{Comparative efficacy and safety of systemic therapies for moderate-to-severe atopic dermatitis in adults: a systematic review of randomized controlled trials}},
author = {Vasiliki Pikoula and Efterpi Zafiriou and Anthony Bewley and Andrea Carugno and Ignasi Figueras Nart and Emily Kelly and Nina Magnolo and Julia-Tatjana Maul and Marta Szepietowska and Jacek C. Szepietowski and Tiago Torres and Alexander Zink and Filomena Russo and Emanuele Scala and Maria-Angeliki Gkini},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1985846},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1985846},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comparative efficacy and safety of systemic therapies for moderate-to-severe atopic dermatitis in adults: a systematic review of randomized controlled trials
AU - Vasiliki Pikoula
AU - Efterpi Zafiriou
AU - Anthony Bewley
AU - Andrea Carugno
AU - Ignasi Figueras Nart
AU - Emily Kelly
AU - Nina Magnolo
AU - Julia-Tatjana Maul
AU - Marta Szepietowska
AU - Jacek C. Szepietowski
AU - Tiago Torres
AU - Alexander Zink
AU - Filomena Russo
AU - Emanuele Scala
AU - Maria-Angeliki Gkini
PY - 2026
DA - 2026/10/30
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1985846
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1985846
AB - BackgroundAtopic dermatitis (AD) is a common, chronic inflammatory skin condition, and patients with moderate-to-severe disease often require systemic therapy. Since 2017, targeted systemic agents, biologics and Janus kinase (JAK) inhibitors, have expanded treatment options available, but comparative evidence remains limited by heterogeneous trial design, outcome reporting, and follow-up duration.ObjectiveTo systematically review the efficacy and safety of European Medicines Agency (EMA)-approved systemic therapies for moderate-to-severe AD in adults.MethodsFollowing PRISMA 2020 guidelines, we searched PubMed/MEDLINE, Embase and Web of Science for randomized controlled trials evaluating EMA-approved biologics (dupilumab, tralokinumab, lebrikizumab, nemolizumab) and JAK inhibitors (upadacitinib, abrocitinib, baricitinib) at recommended adult doses. The primary outcome was the proportion of patients achieving EASI-75 at the primary trial endpoint (12–16 weeks). Due to substantial clinical and methodological heterogeneity, a structured narrative synthesis was conducted rather than a meta-analysis.ResultsTwenty-five RCTs met inclusion criteria. At EMA-recommended doses, EASI-75 responses ranged from 44% to 69% for dupilumab, 60.6% for lebrikizumab, 25-64% for tralokinumab, and 49.1% for nemolizumab (combination-therapy data only). Among JAK inhibitors, upadacitinib showed the highest observed response rate (73.0% at 16 weeks), followed by abrocitinib (64.6% at 12 weeks) and baricitinib (17.9-48.0%). Placebo response rates ranged from 6% to 36% and were consistently higher in combination-therapy trials. Any adverse event occurred in 45.2% (abrocitinib 100 mg) to 82.46% (nemolizumab) of patients, with serious adverse events generally low across therapies.ConclusionEMA-approved systemic therapies for moderate-to-severe AD demonstrate meaningful short-term efficacy and acceptable safety. However, treatment selection should remain individualized given cross-trial heterogeneity and the current absence of long-term comparative data. Further head-to-head trials and real-world evidence are needed to optimize treatment sequencing.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251102911
SN - 1664-3224
ER -