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 - 11/12/19

Doi : 10.1016/j.jaad.2019.05.063

Martin Schaller, MD ^a,^⁎ , Lajos Kemény, MD, PhD, DSc ^b, Blanka Havlickova, MD, PhD ^c, J. Mark Jackson, MD ^d,^e, Marcin Ambroziak, MD ^f, Charles Lynde, MD ^g, Melinda Gooderham, MD ^h, Eva Remenyik, MD, PhD, DSc ⁱ, James Del Rosso, DO ^j, Jolanta Weglowska, MD ^k, Rajeev Chavda, MD ^l, Nabil Kerrouche, MSc ^m, Thomas Dirschka, MD ^n,^o, Sandra Johnson, MD ^p
^a Department of Dermatology, Tübingen University Hospital, Tübingen, Germany
^b Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary
^c Dermatology Center, Prague, Czech Republic
^d Division of Dermatology, University of Louisville, Louisville, Kentucky
^e Forefront Dermatology, Louisville, Kentucky
^f Ambroziak Clinic, Warsaw, Poland
^g Department of Medicine, University of Toronto, Toronto, Ontario, Canada
^h SKiN Centre for Dermatology, Peterborough, Ontario, Canada
ⁱ Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
^j JDR Dermatology Research/Thomas Dermatology, Las Vegas, Nevada
^k Niepubliczny Zakład Opieki Zdrowotnej multiMedica, Wrocław, Poland
^l Medical Evidence, Galderma S.A., Vevey, Switzerland
^m Galderma R&D, Sophia Antipolis, France
ⁿ CentroDerm-Clinic, Wuppertal, Germany
^o Faculty of Health, University of Witten-Herdecke, Witten, Germany
^p Johnson Dermatology, Fort Smith, Arkansas

^∗Reprint requests: Martin Schaller, MD, Department of Dermatology, Eberhard Karls University Tübingen, Liebermeisterstrasse 25, 72076 Tübingen, Germany.Department of DermatologyEberhard Karls University TübingenLiebermeisterstrasse 25Tübingen72076Germany

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Wednesday 11 December 2019
Cet article a été publié dans un numéro de la revue, cliquez ici pour y accéder

Abstract

Background

Randomized controlled studies of combination therapies in rosacea are limited.

Objective

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.

Methods

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).

Results

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.

Limitations

The duration of the study prevented evaluation of potential recurrences or further improvements.

Conclusion

Combining IVM and DMR can produce faster responses, improve response rates, and increase patient satisfaction in cases of severe rosacea.

Le texte complet de cet article est disponible en PDF.

Key words : clear, combination therapy, concomitant use, doxycycline, individualized treatment, ivermectin, rosacea, rosacea treatment, severe rosacea

Abbreviations used : AE, CEA, DLQI, DMR, IGA, ITT, IVM, LOCF, PBO, SD

Plan

Methods

Study design and randomization

Patient-reported outcomes

Safety

Discussion

Funding sources: Supported by Galderma.

Disclosure: Dr Schaller is a Galderma and Marpinion advisory board member; speaker for AbbVie, Bayer Healthcare, Galderma, and La Roche-Posay; recipient of research grants from Galderma and Bayer HealthCare; and investigator for GSK and Galderma. Dr Johnson is a Galderma advisory board member; Allermed/Greer/Nielsen, Regeneron and Sanofi Genzyme advisor; national speaker for Celgene, Allergan, and Candela Syneron; speaker for Galderma, Regeneron, and Sanofi Genzyme; and investigator for Galderma, Leo, Eli Lilly and Company, BMS, Foamix, and Gage. Dr Jackson is a Galderma investigator and advisor and Accuitis advisor. Dr Kemény is an investigator for Galderma and a Janssen, Abbvie, Novartis, and Eli Lilly and Company advisory board member. Dr Remenyik is a Galderma investigator. Dr Del Rosso is a researcher for Galderma, BiopharmX, Foamix, and Leo Pharma (Bayer Dermatology); Galderma advisory board member; speaker for Galderma, Leo Pharma (Bayer Dermatology), Mayne Pharma, and Almirall; and consultant for Leo Pharma (Bayer Dermatology), Mayne Pharma, Almirall, and Hovione. Dr Weglowska is an investigator for Galderma, Amgen, Sun Pharma, UCB, Regeneron, Leo Pharma, and Dermira and a Galderma advisory board member. Dr Gooderham is an investigator, speaker, and advisory board member for Galderma, Leo Pharma, and Valeant. Dr Ambroziak is an investigator for Galderma. Dr Lynde is an investigator, speaker, and advisory board member for Galderma, Leo Pharma, and Valeant/Bausch Health. Dr Havlickova is an investigator for Galderma. Dr Dirschka is an investigator for Galderma and has received research support from Almirall, Biofrontera, Galderma, Meda, and Schulze & Böhm GmbH. Dr Chavda is an employee of Galderma. Mr Kerrouche is a former employee of Galderma. No other conflicts of interest were declared.