🔍 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