Which systemic treatment offers the best balance of efficacy and safety for atopic dermatitis?

by Haroon Ahmad, MD 2025-01-01 00:00

PhysicianMedical

🔍 Key Finding

High-dose upadacitinib was most effective for multiple outcomes but carried higher risks, while dupilumab, lebrikizumab, and tralokinumab showed intermediate effectiveness with favorable safety profiles.

🔬 Methodology Overview:

Design: Systematic review and network meta-analysis of RCTs
Data Sources: MEDLINE, EMBASE, CENTRAL, Web of Science, GREAT databases (inception to Nov 29, 2022)
Study Selection: Randomized trials addressing systemic treatments and phototherapy for AD
Quality Assessment: Modified Cochrane Risk of Bias tool version 2
Statistical Analysis: Bayesian random-effects network meta-analyses using Markov chain Monte Carlo approaches

📊 Evidence

149 RCTs including 28,686 participants with moderate-to-severe AD
75 different treatments evaluated
High-dose upadacitinib showed greatest improvement in disease severity (MD -13.99 [95% CrI -16.62 to -11.37])
Dupilumab showed intermediate effectiveness (MD -10.72 [95% CrI -12.30 to -9.19])
JAK inhibitors had higher adverse event rates (upadacitinib: 108 more per 1000 patients [95% CI 72 to 141])

💡 Clinical Impact

Provides comprehensive evidence hierarchy for systemic treatment selection in moderate-to-severe AD, helping clinicians balance efficacy and safety when choosing between newer biologics and JAK inhibitors.

🤔 Limitations

Limited long-term safety data for JAK inhibitors
Many conventional immunosuppressants showed low-certainty evidence
Few studies addressed patient-reported outcomes
Limited data on serious adverse events in shorter trials

Consider patient values and risk factors when selecting systemic therapy: JAK inhibitors (like upadacitinib) for patients prioritizing efficacy who can accept higher risks, or biologics (like dupilumab) for those prioritizing safety with moderate efficacy.

Chu AWL, Wong MM, Rayner DG, Guyatt GH, Diaz Martinez JP, Ceccacci R, et al. Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials. J Allergy Clin Immunol 2023;152:1470-92.