A Bayesian network meta-analysis comparing four oral JAK inhibitors-upadacitinib, abrocitinib, baricitinib, and ivarmacitinib-in moderate-to-severe atopic dermatitis has found that upadacitinib demonstrated superior short-term efficacy, particularly at the 30 mg dose, across multiple clinical endpoints. The analysis ranked upadacitinib highest for short-term effectiveness, suggesting it may be a preferred option in early treatment decisions, while noting that direct head-to-head trials are still needed to confirm comparative benefits.
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.
The 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.
Results: 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.
Reference:
A. Babul, D. Mehta, Y. Soliman, M. Hussain, and N. Babul, “ Upadacitinib Leads in Efficacy: A Bayesian Network Meta-Analysis of Four JAK Inhibitors in Moderate-To-Severe Atopic Dermatitis,” International Journal of Dermatology (2026): 1–15, https://doi.org/10.1111/ijd.70228.
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