Baricitinib, Ritlecitinib, Deuruxolitinib: Comparative Efficacy in AA

Alopecia areata affects approximately 2% of the population and manifests as patchy AA, alopecia totalis, or alopecia universalis. Severe AA is associated with profound psychosocial, economic, and physical burdens. Traditional treatments, including corticosteroids, immunomodulators, minoxidil, and systemic immunosuppressants, often yield incomplete responses, with frequent relapse.¹

Identification of the JAK–STAT pathway as a central mediator in AA pathogenesis has led to the development of targeted therapies. Oral JAKIs—baricitinib (JAK1/JAK2), ritlecitinib (JAK3/TEC family), and deuruxolitinib (JAK1/JAK2)—are now approved in the US, Europe, and UK for severe AA, providing the first disease-specific systemic therapies. However, head-to-head randomized trials comparing these agents are lacking. As authors behind a recent meta-analysis note, “In view of their relatively recent introduction and the absence of head-to-head non-inferiority RCTs…indirect statistical methods are required to provide a hierarchy of treatments for severe AA.”²

Methods
The systematic review of RCTs was conducted following PRISMA 2020 guidelines. Eligible studies enrolled adults with severe AA (≥50% scalp hair loss) and evaluated FDA-, EMA-, or MHRA-approved oral JAKIs with week 24 outcomes. Interventions included baricitinib 2 and 4 mg QD, ritlecitinib 50 mg QD, and deuruxolitinib 8 mg BID. Only placebo-controlled trials were included for primary network meta-analysis (NMA). Bayesian NMA estimated odds ratios (ORs) with 95% credible intervals (CrIs) for SALT ≤10 and ≤20 endpoints.

Results
Seven RCTs were included: BRAVE-AA1/AA2 (baricitinib), ALLEGRO Phase 2a/2b–3 (ritlecitinib), and THRIVE-AA/AA1/AA2 (deuruxolitinib), encompassing over 3,000 adults with severe AA. Baseline SALT scores ranged from 84–93, with substantial representation of alopecia universalis. Risk of bias was low overall, except for limited methodological reporting in BRAVE-AA1.

Bayesian NMA showed that deuruxolitinib 8 mg BID had superior efficacy versus baricitinib 2 mg for SALT ≤10 (OR = 0.36; 95% CrI: 0.46–19.94) and a favorable trend versus baricitinib 4 mg (OR = 0.45; 95% CrI: 0.16–1.00). Comparisons with ritlecitinib 50 mg were non-significant but consistently favored deuruxolitinib. ML-NMR adjusted analyses confirmed the robustness of these findings across covariates, with ORs remaining favorable for deuruxolitinib.

Unanchored MAIC analyses reinforced the efficacy advantage of deuruxolitinib. In the fully adjusted model for SALT ≤10, ORs were 13.42 (95% CI: 4.61–40.57) versus baricitinib 2 mg and 13.33 (95% CI: 5.66–34.70) versus ritlecitinib 50 mg. SUCRA rankings placed deuruxolitinib highest for both SALT ≤10 and ≤20, with baricitinib 4 mg intermediate and baricitinib 2 mg and ritlecitinib 50 mg lowest.

Discussion
This analysis establishes a provisional hierarchy among approved oral JAKIs in severe AA, consistently highlighting deuruxolitinib 8 mg BID as the most effective agent at week 24. As the authors state, “this study fills a critical evidence gap by offering a focused, methodologically rigorous indirect comparison that establishes deuruxolitinib 8 mg BID as the most effective approved treatment option for severe AA.”

Limitations include reliance on indirect comparisons, short-term follow-up, and potential residual confounding despite MAIC adjustment. Safety considerations remain paramount, as all oral JAKIs carry black-box warnings for infection, malignancy, cardiovascular events, and thrombosis. Deuruxolitinib’s BID dosing may affect adherence compared to QD regimens.

Conclusion
Bayesian NMA, ML-NMR, and MAIC analyses suggest that among FDA-, EMA-, and MHRA-approved oral JAKIs, deuruxolitinib 8 mg BID demonstrates the highest likelihood of achieving clinically meaningful hair regrowth in severe AA at week 24. These findings provide timely guidance for evidence-based treatment selection while emphasizing individualized consideration of safety, tolerability, and dosing convenience. Future studies should focus on long-term efficacy, safety, and direct head-to-head comparisons to confirm these results.

References

1. Ungar B, Renert-Yuval Y, Dlova NC, et al. Alopecia areata. Nat Rev Dis Primers. 2025;11(1):77. Published 2025 Nov 6. doi:10.1038/s41572-025-00664-9
2. Babul A, Mehta D, Soliman Y, Hussain M, Babul N. Comparative efficacy of janus kinase inhibitors indicated for severe alopecia areata: A bayesian network meta-analysis and matching-adjusted indirect comparison. J Dermatol. Published online October 11, 2025. doi:10.1111/1346-8138.17959