A randomized phase 3b/4 study to evaluate concomitant use of topical ivermectin 1% cream and doxycycline 40-mg modified-release capsules, versus topical ivermectin 1% cream and placebo in the treatment of severe rosacea

• Published in: Journal of the American Academy of Dermatology Vol. 82; no. 2; pp. 336 - 343
• Main Authors: Schaller, Martin, Kemény, Lajos, Havlickova, Blanka, Jackson, J. Mark, Ambroziak, Marcin, Lynde, Charles, Gooderham, Melinda, Remenyik, Eva, Del Rosso, James, Weglowska, Jolanta, Chavda, Rajeev, Kerrouche, Nabil, Dirschka, Thomas, Johnson, Sandra
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2020
• Subjects: Administration, Oral; Adult; Capsules; clear; combination therapy; concomitant use; Delayed-Action Preparations - administration & dosage; doxycycline; Doxycycline - administration & dosage; Drug Therapy, Combination - methods; Female; Humans; individualized treatment; ivermectin; Ivermectin - administration & dosage; Male; Patient Satisfaction; Placebos - administration & dosage; Quality of Life; rosacea; Rosacea - complications; Rosacea - diagnosis; Rosacea - drug therapy; rosacea treatment; severe rosacea; Severity of Illness Index; Skin Cream - administration & dosage; Time Factors; Treatment Outcome; DLQI; IVM; IGA; rosacea treatment; AE; LOCF; rosacea; clear; DMR; ITT; doxycycline; ivermectin; SD; severe rosacea; concomitant use; individualized treatment; combination therapy; PBO; CEA
• ISSN: 0190-9622; 1097-6787; 1097-6787
• DOI: 10.1016/j.jaad.2019.05.063

Randomized controlled studies of combination therapies in rosacea are limited. Evaluate the efficacy and safety of combining ivermectin 1% cream (IVM) and doxycycline 40-mg modified-release capsules (ie, 30-mg immediate-release and 10-mg delayed-release beads) (DMR) versus IVM and placebo for treatment of severe rosacea. This 12-week, multicenter, randomized, investigator-blinded, parallel-group comparative study randomized adult subjects with severe rosacea (Investigator's Global Assessment [IGA] score, 4) to receive either IVM and DMR (combination arm) or IVM and placebo (monotherapy). A total of 273 subjects participated. IVM and DMR displayed superior efficacy in reduction of inflammatory lesions (–80.3% vs –73.6% for monotherapy [P = .032]) and IGA score (P = .032). Combination therapy had a faster onset of action as of week 4; it significantly increased the number of subjects achieving an IGA score of 0 (11.9% vs 5.1% [P = .043]) and 100% lesion reduction (17.8% vs 7.2% [P = .006]) at week 12. Both treatments reduced the Clinician's Erythema Assessment score, stinging/burning, flushing episodes, Dermatology Life Quality Index score, and ocular signs/symptoms and were well tolerated. The duration of the study prevented evaluation of potential recurrences or further improvements. Combining IVM and DMR can produce faster responses, improve response rates, and increase patient satisfaction in cases of severe rosacea.