Supplemental Material: Tolerability and Efficacy of Unorthodox Dosing Regimens of Tofacitinib and Baricitinib in Pediatric Patients with Moderate to Severe Alopecia Areata
Description
1. Research Hypothesis This study tested the core hypothesis: over a 24-week treatment period, tofacitinib and baricitinib, administered via unorthodox weight-stratified dosing regimens, would exhibit comparable efficacy and tolerability in pediatric patients aged 2–17 years with moderate-to-severe AA. 2. Notable Findings 2.1 Comparable Overall Efficacy with Subtle Differences Over 24 weeks, the two drugs showed no significant differences in primary efficacy endpoints (all P>0.05), supporting the hypothesis of comparable efficacy under unorthodox dosing. 2.2 Favorable Tolerability with Pediatric-Specific AE Profiles Both drugs were well-tolerated in pediatric patients, with no serious AEs and low discontinuation rates. 2.3 Limitations of Unorthodox Dosing for Baricitinib The unorthodox BID regimen for baricitinib (2 mg BID) resulted in a lower SALT ≤20 response rate in severe AA (30.77%) compared to the guideline-recommended 4 mg QD regimen (67.7% in literature). This suggests that deviating from guideline dosing may reduce efficacy, likely due to subtherapeutic peak drug concentrations from BID administration, which limits suppression of follicular inflammation. 3. Data Interpretation 3.1 Efficacy: Applicability and Limitations of Unorthodox Dosing Applicable scenarios: Unorthodox weight-stratified dosing can serve as a short-term (24-week) alternative for pediatric patients who cannot tolerate guideline-recommended doses (e.g., baricitinib 4 mg QD) or require matched dosing frequencies. Tofacitinib may be preferred for patients targeting "significant hair regrowth" (SALT 70 response), while baricitinib could be considered for those pursuing "near-complete regrowth" (given its numerical advantage in SALT 90 response). Limitations: The reduced efficacy of baricitinib’s unorthodox regimen highlights the priority of guideline-recommended dosing. Unorthodox dosing should only be used in special cases (e.g., poor tolerability in young children) and requires therapeutic drug monitoring (TDM) to adjust doses, ensuring trough concentrations match those of guideline regimens. 3.2 Safety: Risk Profile and Monitoring Priorities Risk profile: Short-term use of both JAK inhibitors is safe in children, with mild, manageable AEs (acne, transient hepatic enzyme elevations) and no increased risk of serious infections or cardiovascular events. Hematological AEs are less common in children than in adults, reducing concerns about blood-related safety risks. Monitoring focus: Clinicians should monitor acne in pubertal patients, conduct regular tests for hepatic enzymes, lipids, and creatine kinase (especially in the baricitinib group), and educate caregivers on recognizing mild AEs (e.g., upper respiratory tract infections). This dataset contains supplemental protocol, 1 supplemental figure, and 1 supplemental table.