Efficacy and Safety of Hydroxychloroquine Combined With Doxycycline for the Treatment of Patients With Rosacea: A Randomized, Double‐Blind, Double‐Dummy Clinical Trial

Purpose: While the 2021 Chinese rosacea guidelines recommend hydroxychloroquine (HCQ) and doxycycline as A‐level treatments for erythema, monotherapy with these agents has shown suboptimal clinical efficacy against both erythema and flushing symptoms. This study aimed to evaluate whether combination therapy could enhance therapeutic outcomes without increasing adverse effects (AEs). Methods: In this randomized, double‐blind, placebo‐controlled trial conducted at Guizhou Provincial People’s Hospital (January 2022–January 2024), 73 moderate‐to‐severe rosacea patients were randomized to receive either (1) HCQ 200 mg bid plus doxycycline 100 mg qd (intervention group, n = 36) or (2) placebo plus doxycycline 100 mg qd (control group, n = 37). Treatment duration was 8 weeks with follow‐up assessments at Weeks 0, 4, 8, and 12. Results: Among 58 completers (29 per group), the intervention group demonstrated significantly higher clinical efficacy at Week 8: erythema improvement rates (89.67% vs. 68.97%, p < 0.05), flushing reduction (68.97% vs. 44.83%, p < 0.05), and greater quality‐of‐life improvement (RosQoL score Δ23.66 vs. Δ17.00, p < 0.05). Investigator’s Global Assessment showed comparable results (72.22% vs. 65%, p > 0.05). Both regimens were well tolerated with no severe AEs reported. Conclusion: The HCQ–doxycycline combination demonstrates superior efficacy over doxycycline monotherapy for improving erythema, flushing symptoms, and quality of life in moderate‐to‐severe rosacea patients, with comparable safety profiles. Trial Registration: Chinese Clinical Trial Register: ChiCTR2400089784