Real-World Effectiveness and Safety of Oral Alitretinoin in Chronic Hand Eczema with Exploratory Off-Label...

Background and Objectives: Oral alitretinoin (9-cis-retinoic acid), a dual retinoic acid receptor/retinoid X receptor agonist, is approved for severe chronic hand eczema (CHE) refractory to potent topical corticosteroids but is also prescribed off-label in routine practice. Long-term real-world data on both uses are limited. We evaluated 10-year prescribing patterns, effectiveness, tolerability, and lipid changes at one Korean academic center. Materials and Methods: Patients prescribed oral alitretinoin between January 2016 and December 2025 were identified from the hospital prescribing database; those with an evaluable course of ≥1 month formed the effective-treatment cohort and underwent chart review. Treatment success was defined as final chart-derived Investigator Global Assessment (IGA) 0/1. Success by initial dose was compared using Fisher exact test; paired lipid changes using paired t-test and Wilcoxon signed-rank test. Results: Of 161 patients, 38 (23.6%) received a single prescription; 99 formed the effective-treatment cohort (50 women, 49 men; mean age 50.7 ± 16.0 years). CHE was the leading indication (70/99, 70.7%), followed by palmoplantar pustulosis (PPP, n = 14), mycosis fungoides (MF, n = 6), parapsoriasis, porokeratosis, palmoplantar keratoderma, and Darier disease. Overall success was 66.7% (66/99) over a mean treatment duration of 12.4 months, highest in CHE (77.1%) and more variable off-label (PPP 42.9%; MF 33.3%). Initiation at 30 mg was associated with higher success than 10 mg (71.1% vs. 43.8%; p = 0.044), but this association did not persist after restriction to patients maintained on their initial dose (62.2% vs. 50.0%; p = 0.498) or after Firth penalized logistic regression adjusting for age, sex, and indication (adjusted odds ratio 1.84; 95% CI 0.56-5.90; p = 0.309). Adverse events occurred in 21 patients (21.2%), most commonly dyslipidemia (n = 12) and headache (n = 7); mean triglyceride rose 42.1 mg/dL and total cholesterol 14.0 mg/dL (both p < 0.001), and new elevation above conventional thresholds occurred in 25.8% (triglyceride) and 27.5% (total cholesterol) of patients with normal baseline values. Thirty patients (30.3%) discontinued, most often for insufficient effectiveness. Conclusions: Alitretinoin showed favorable effectiveness in CHE and variable, exploratory responses off-label. The apparent advantage of 30 mg initiation was not independent of indication and dose adjustment. Lipid elevation was common, supporting routine surveillance. Off-label findings, particularly in PPP and MF, should be interpreted cautiously given small subgroups and non-standardized retrospective assessment.