Upadacitinib Leads in Efficacy: A Bayesian Network Meta-Analysis of Four JAK Inhibitors in Moderate-To-Severe Atopic...

Janus kinase inhibitors (JAKis) have revolutionized the management of moderate-to-severe atopic dermatitis (AD). Although agents approved by the United States Food and Drug Administration (FDA), such as upadacitinib and abrocitinib, are widely used, and baricitinib and ivarmacitinib are under investigation, direct head-to-head randomized clinical trials (RCTs) comparing these agents are lacking.

Our aim was to rank the short-term efficacy of four oral JAKis, upadacitinib (15/30 mg), abrocitinib (100/200 mg), baricitinib (2/4 mg), and ivarmacitinib (4/8 mg), in moderate-to-severe AD using a Bayesian Network Meta-Analysis (BNMA).

Conducted per PRISMA 2020 guidelines and registered in PROSPERO (CRD420251116775), this study systematically reviewed phase 2 and 3 RCTs evaluating JAKi monotherapy in adults with moderate-to-severe AD. Primary endpoints included: (1) ≥ 75% improvement in Eczema Area and Severity Index (EASI-75), (2) Investigator's Global Assessment (IGA-AD 0/1), and (3) ≥ 4-point reduction in itch numeric rating scale (Itch NRS) at 12-16 weeks. Bayesian hierarchical modeling estimated odds ratios (ORs) with 95% credible intervals (CrIs), and surface under the cumulative ranking curve (SUCRA) probabilities defined the treatment hierarchy.

Nine RCTs (n = 4261) were included. Upadacitinib 30 mg demonstrated the greatest efficacy across all endpoints, EASI-75 (OR = 12.3; 95% CrI 7.9-18.7), IGA-AD 0/1 (OR = 18.9; 95% CrI 12.0-29.7), and Itch NRS (OR = 11.1; 95% CrI 7.2-17.5), followed by upadacitinib 15 mg, abrocitinib 200 mg, and ivarmacitinib 8 mg. Baricitinib 2 mg and 4 mg consistently ranked lowest. SUCRA values confirmed upadacitinib 30 mg as the top performer (97%-98%).

Among oral JAKis, upadacitinib 30 mg, followed by upadacitinib 15 mg, achieved the most consistent short-term efficacy, providing superior skin clearance and itch relief. Abrocitinib 200 mg and ivarmacitinib 8 mg showed intermediate benefits, whereas baricitinib displayed modest effects. These findings support a provisional efficacy preference for upadacitinib in managing moderate-to-severe AD unresponsive to biologic or topical therapies.