Consistent efficacy and safety in four double-blind vehicle-controlled studies of ivermectin 1% cream in the treatment of moderate to severe papulopustular rosacea

Introduction: Papulopustular rosacea (PPR) is characterized by facial papules, pustules, and persistent erythema. The pathogenesis of PPR is not yet completely understood; however, current studies indicate that underlying causes may include dysregulation of the innate immune system, overgrowth of commensal skin organisms, aberrant neurovascular signaling, and the production of inflammatory mediators in facial skin. Furthermore, inflammation may impair the barrier function of skin, leading to increased skin sensitivity, burning sensation, dryness, itching, and pain. Ivermectin 1% cream is a safe and effective topical therapy approved to treat the inflammatory lesions of rosacea. Methods and results: This analysis examined the variability of efficacy and safety in 4 (2 phase 2 and 2 phase 3) 12-week vehicle-controlled studies (n = 1,683) that were conducted during the development of ivermectin 1% cream. Efficacy assessments included the Investigator’s Global Assessment (IGA; 0-4 scale) of disease severity, and inflammatory lesion counts. Adverse events (AEs) were tracked in each study. Tolerability (stinging/burning, dryness, itching) was evaluated in both phase 3 and one of the phase 2 studies (4-point scale, 0-3). All 4 studies confirmed the statistical superiority of ivermectin 1% cream vs. vehicle with respect to success rate and lesion counts. In all studies where tolerability was examined, significantly more subjects in the Ivermectin 1% cream groups than in the vehicle groups showed improved stinging/burning, dryness and itching sensations. Furthermore, there was a large overlap of confidence intervals, indicating high inter study similarity in these observations. No serious adverse event related to ivermectin 1% cream was observed in any of the 4 studies. Summary: This analysis confirms that ivermectin 1% cream was safe and effective, and that these results were highly consistent in 4 vehicle-controlled studies conducted during the development of the drug