Efficacy and safety of supramolecular salicylic acid in the treatment of papulopustular rosacea: a multicentre randomized, double-blind, placebo-controlled superiority study

Abstract Background Rosacea is a chronic inflammatory skin disorder with a complex aetiology involving genetic, immunological and environmental factors. Although various treatments are available, managing papulopustular lesions remains challenging. Salicylic acid, known for its anti-inflammatory properties, has been used in dermatology for decades, but its efficacy in treating rosacea needs further exploration. Objectives To investigate the effectiveness and safety of 30% supramolecular salicylic acid (SSA) in treating papulopustular rosacea. Methods We conducted a prospective multicentre, randomized, double-blind, placebo-controlled trial involving 480 patients aged 18–60 years with papulopustular rosacea. Participants were randomized 1 : 1 to receive either 30% SSA or placebo every 2 weeks for 6 weeks, with follow-up assessments up to week 8. The study assessed primary and secondary efficacy endpoints, including lesion reduction rates, Investigator’s Global Assessment (IGA) and Investigator’s Severity Assessment (ISA) scores, VISIA® red area improvements and skin barrier functions, and evaluated safety and tolerability. Results The SSA group showed a significant improvement in the primary efficacy endpoint at week 8, with efficacy rates of 51.3% [full-analysis set (FAS)] and 59.9% [per-protocol set (PPS)], compared with 18.3% (FAS) and 20.5% (PPS) in the placebo group (P < 0.001 for both). Secondary endpoints also favoured SSA, demonstrating improved lesion reduction, IGA and ISA scores, and skin condition. Safety profiles were comparable between the SSA and placebo groups, with no significant difference in adverse event rates. Conclusions Our findings highlight the superior efficacy of 30% SSA in improving papulopustular rosacea symptoms compared with a placebo, coupled with a favourable safety and tolerability profile.