Comparative Efficacy of Ritlecitinib, Baricitinib, and Upadacitinib in Adolescents With Severe Alopecia Areata: A Bayesian Network Meta‑Analysis

Severe alopecia areata (AA) in adolescents carries a substantial physical, psychological, social, and economic burden.Three Janus kinase (JAK) inhibitors, ritlecitinib, baricitinib, and upadacitinib, are now authorized in the European Union (EU) for the treatment of severe AA in both adults and adolescents, although only ritlecitinib and baricitinib are currently approved for adolescents in the United States (US).Current clinical experience in adolescents remains limited, particularly for upadacitinib and baricitinib, given their very recent introduction in the EU and US.Upadacitinib is currently under review by the US Food and Drug Administration (FDA) for adolescent AA.With multiple oral JAK inhibitors newly available or nearing approval for adolescents with severe AA, comparative evidence is needed to guide treatment selection, particularly in the context of FDA boxed safety warnings and European Medicines Agency (EMA) safety monitoring requirements.This study evaluated the relative efficacy of ritlecitinib, baricitinib, and upadacitinib in adolescents with severe AA.A systematic review and Bayesian network meta-analysis of randomized, placebo-controlled trials was conducted.Adolescent data (ages 12 to 17) were extracted from eligible studies evaluating ritlecitinib, baricitinib, or upadacitinib.The primary outcome was achievement of a Severity of Alopecia Tool (SALT) score ≤20 at Week 24.Odds ratios (ORs) with 95% credible intervals (CrIs) were estimated using a fixed-effect Bayesian model, and Week 24 SALT ≤20 responder rates were compared across trials.Four placebo-controlled trials were included, comprising one study each for ritlecitinib and baricitinib and two studies for upadacitinib.Data for ritlecitinib and upadacitinib were derived from predominantly adult trials with smaller adolescent subgroups, whereas data for baricitinib were derived from a dedicated pediatric study.Compared with placebo, upadacitinib 30 mg demonstrated the highest and most stable efficacy (OR: 174.13, 95% CrI: 21.17 to 4520.81), followed by upadacitinib 15 mg (OR: 48.09, 95% CrI: 6.40 to 1304.38), baricitinib 4 mg (OR: 15.30, 95% CrI: 4.73 to 68.45), and baricitinib 2 mg (OR: 6.46, 95% CrI: 1.85 to 29.90).Indirect comparisons showed clear dose-response relationships: upadacitinib 30 mg exceeded upadacitinib 15 mg (OR: 3.42, 95% CrI: 1.38 to 9.26), and baricitinib 4 mg exceeded baricitinib 2 mg (OR: 2.37, 95% CrI: 1.14 to 5.01).Week 24 responder rates were directionally consistent across studies: 56% to 57% and 72% to 85% of adolescents achieved SALT ≤20 with upadacitinib 15 mg and 30 mg across two studies, respectively, compared with 17% and 32% with baricitinib 2 mg and 4 mg, and 25% with ritlecitinib 50 mg.Ritlecitinib estimates were unstable because of sparse adolescent data and near-zero placebo response rates, resulting in wide CrIs and substantial uncertainty.Oral JAK inhibitors improved outcomes in adolescents with severe AA.Upadacitinib demonstrated a distinctly superior efficacy profile, with Week 24 responder rates far exceeding those historically observed with currently approved JAK inhibitors and markedly higher than those observed with baricitinib or ritlecitinib in this analysis.Baricitinib and ritlecitinib produced more modest and broadly similar responder rates.These findings suggest that upadacitinib may represent a higher-efficacy tier within the JAK inhibitor class.