Efficacy and safety of pioglitazone in lichen planopilaris in comparison with hydroxychloroquine: Prospective non‐inferiority study

BACKGROUND AND OBJECTIVES: Pioglitazone is an underused drug in lichen planopilaris (LPP) with limited prospective evidence. This study investigated the therapeutic efficacy and safety profile of pioglitazone compared with hydroxychloroquine. PATIENTS AND METHODS: This reviewer-blinded, prospective non-inferiority study was conducted at a tertiary university hospital in Belgrade, Serbia, between October 2023 and January 2025. Patients with LPP affecting < 20 % of the scalp received pioglitazone (exposed cohort), whereas those with > 20 % scalp involvement received hydroxychloroquine (HCQ; control cohort). Patients were evaluated at baseline and after 3 and 6 months. The primary outcome measures were the Lichen Planopilaris Activity Index (LPPAI) and Global Photographic Assessment (GPA). RESULTS: In total, 82 consecutive patients (42 pioglitazone, 40 HCQ) were enrolled. 66 patients (80.49 %) were analyzed using a per-protocol approach. The mean LPPAI at baseline and last session were 3.32 ± 1.23 and 0.95 ± 0.74 in the pioglitazone group and 3.64 ± 1.46 and 1.13 ± 0.9 in the hydroxychloroquine cohort, respectively. No significant difference in LPPAI reduction (p = 0.66) was observed between cohorts. Pioglitazone prevents disease progression in 87.5 % cases. No statistical difference between cohorts in GPA score was seen (p = 0.98). Both treatment options were well-tolerated (p = 0.73). CONCLUSIONS: This study provides the largest prospective pioglitazone cohort reported to date in LPP and demonstrates that pioglitazone is non-inferior to hydroxychloroquine as a first-line systemic treatment, while also exhibiting a strong safety profile.