Maintenance of remission following successful treatment of papulopustular rosacea with ivermectin 1% cream vs. metronidazole 0.75% cream: 36‐week extension of the <scp>ATTRACT</scp> randomized study

Taı̈eb, Alain; Khemis, A.; Ruzicka, Thomas; Barańska‐Rybak, Wioletta; Berth‐Jones, J.; Schauber, Jürgen; Briantais, Philippe; Jacovella, Jean; Passeron, Thierry

doi:10.1111/jdv.13537

Cited by 45 publications

(64 citation statements)

References 22 publications

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“…The results of this study showed that initial successful treatment with ivermectin cream 10 mg/g significantly extended the remission of rosacea compared with metronidazole cream when treatment was stopped [28]. The effects of ivermectin on KLK5 and CAMP gene expression ex vivo could explain the increased remission time seen with ivermectin treatment versus metronidazole, and this could indicate an impact of this agent on the course of the disease.…”

Section: Discussionmentioning

confidence: 99%

Topical Treatment of Rosacea with Ivermectin Inhibits Gene Expression of Cathelicidin Innate Immune Mediators, LL-37 and KLK5, in Reconstructed and Ex Vivo Skin Models

Ménonville

Rosignoli

Soares

et al. 2017

Dermatol Ther (Heidelb)

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IntroductionNumerous intrinsic and extrinsic factors have been associated with the pathophysiology of rosacea, including dysregulation of innate immunity. A high level of cathelicidin antimicrobial peptides (e.g., LL-37) has been shown in the facial skin of patients with rosacea. Excessive production of both LL-37 and KLK5, the serine protease responsible for its cleavage, has been suggested to play a role in the pathophysiology of rosacea. Ivermectin 10 mg/g cream, indicated for the treatment of inflammatory lesions of rosacea, is reported to have dual anti-parasitic and anti-inflammatory properties. However, the exact mechanism of action of ivermectin cream in the treatment of rosacea is unknown.MethodsThis study aimed to evaluate the effect of ivermectin on the expression of KLK5 and the subsequent effect on the maturation process of cathelicidins. Experimental studies were performed either on normal human epidermal keratinocytes (NHEK), reconstructed human epidermis (RHE) or on human skin ex vivo stimulated with calcitriol (1α,25-dihydroxyvitamin D3), which is known to induce KLK5 and LL-37 expression.ResultsThe results show that ivermectin is able to inhibit KLK5 and CAMP gene expression and protein secretion in NHEK cells stimulated with calcitriol. Those results were confirmed in 3D models of the skin (RHE and skin ex vivo). The anti-inflammatory effects of ivermectin were associated with an inhibition of IL-8, IL-6 and MCP-1 (CCL2) secretion from NHEK cells.ConclusionsThese results suggest that ivermectin can prevent the inflammatory effects of rosacea triggered by abnormal LL-37 processing, through the inhibition of KLK5 gene expression in the epidermis. Funding: Nestlé Skin Health R&D.Electronic supplementary materialThe online version of this article (doi:10.1007/s13555-017-0176-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Topical Treatment of Rosacea with Ivermectin Inhibits Gene Expression of Cathelicidin Innate Immune Mediators, LL-37 and KLK5, in Reconstructed and Ex Vivo Skin Models

Ménonville

Rosignoli

Soares

et al. 2017

Dermatol Ther (Heidelb)

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“…Maintenance of remission following a successful initial treatment with ivermectin 1 % cream or metronidazole 0.75 % cream over 16 weeks as described above was analysed in an extension period over 36 weeks . The results of this remission study showed that an initial successful treatment with ivermectin 1 % cream once daily significantly extended remission of rosacea compared with initial treatment with metronidazole 0.75 % cream twice daily following treatment discontinuation.…”

Section: Approved Topical Therapiesmentioning

confidence: 99%

Rosacea Management: Update on general measures and topical treatment options

Schaller

Schöfer

Homey

et al. 2016

J Deutsche Derma Gesell

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SummaryAlthough there is presently no cure for rosacea, there are several recommended treatment options available to control many of the symptoms and to prevent them from getting worse. In addition to self-help measures like avoidance of trigger factors and proper skin care, rosacea management should include topical medications as one of the first-line choices for patients with erythematous and mild to severe papulopustular rosacea. Since mixed forms of characteristic rosacea symptoms are more common, medical treatment must be symptom-tailored for each individual case and will often involve a combination therapy. Approved topical agents for the major symptoms of rosacea encompass brimonidine for erythema and ivermectin, metronidazole or azelaic acid for inflammatory lesions, all of which have shown their efficacy in numerous valid, well-controlled trials. In addition, there are several other, not approved topical treatments which are possible options that require further validation in larger well-controlled studies.

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“…Jeszcze ciekawsze okazały się wyniki ostatnio opu-blikowanych badań, w których stwierdzono bardzo korzystny wpływ iwermektyny na czas remisji w rosacea. Po zaprzestaniu 16-tygodniowej terapii remisja po aplikacji iwermektyny była istotnie statystycznie dłuższa niż po zastosowaniu 0,75% metronidazolu (odpowiednio 196 vs 169 dni) [60].…”

Section: Glikokortykosteroidyunclassified

Rosacea – new data on pathogenesis and treatment

Placek¹,

Wolska²

2016

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StreSzczenieTrądzik różowaty jest częstą dermatozą, występującą przeważnie u kobiet i mającą istotny niekorzystny wpływ na jakość życia pacjentów. Obecnie przyjmuje się, że w jego przebiegu mogą przeważać zmiany rumieniowe lub zapalne, a w niektórych przypadkach przerostowe, niekoniecznie stanowiące kolejne etapy nasilenia choroby. Badania ostatnich lat wskazują, że podstawową rolę w rozwoju rosacea odgrywają zaburzona wrodzona odpowiedź immunologiczna i patologie w obrębie ukła-du naczyniowego skóry. Uwzględnia się również podłoże genetyczne i rolę skórnych, ale nie tylko, patogenów (np. Helicobacter pylori, Demodex). W związku z powyższym zalecane metody terapii uwzględniają działanie zarówno przeciwzapalne, jak i ukierunkowane na pasożyty skórne. Podstawowymi preparatami w terapii miejscowej są metronidazol, kwas azelainowy, antybiotyki, leki przeciwpasożytnicze, takie jak iwermektyna, oraz leki oddziałujące wybiórczo na zmiany naczyniowe. W cięższych przypadkach za leki z wyboru uznaje się obecnie tetracykliny, alternatywnie makrolidy, a w skrajnie ciężkich postaciach izotretynoinę. W związku z bezsprzeczną, co najmniej pogarszającą chorobę rolą promieniowania ultrafioletowego (UV) zaleca się rygorystyczną ochronę przed UV, a także -co również wynika z obserwacji klinicznych -odpowiednią dietę. Wraz z postępem techniki coraz większe znaczenie w leczeniu rosacea mają różnego typu terapie świetlne. AbStrActRosacea is a common dermatosis more prevalent in females, significantly impairing quality of life. Currently erythematous, papulo-pustular and phymatous subtypes are distinguished, which do not necessarily represent consecutive stages. Recent findings indicate in the pathogenesis of rosacea the role of the impaired innate immune system and vascular abnormalities. Additionally, the role of genetic and infectious factors is suggested. The therapy of rosacea is directed not only against inflammatory changes but also anti-parasitic. In topical treatment the most commonly used are metronidazole and azelaic acid. Other drugs are topical antibiotics, antiparasitic agents such as ivermectin and preparations directly influencing erythema. In more severe cases tetracyclines or macrolides are used, and in the most severe cases, isotretinoine. As ultraviolet light is a recognized trigger for rosacea, regular sunscreen use is necessary. Also, proper diet is indicated. Presently in the treatment of rosacea more and more techniques using different lights are employed.

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Maintenance of remission following successful treatment of papulopustular rosacea with ivermectin 1% cream vs. metronidazole 0.75% cream: 36‐week extension of the ATTRACT randomized study

Abstract: The results of this relapse study showed that an initial successful treatment with ivermectin 1% cream QD significantly extended remission of rosacea compared with initial treatment with metronidazole 0.75% cream BID following treatment cessation.

Cited by 45 publications

References 22 publications

Topical Treatment of Rosacea with Ivermectin Inhibits Gene Expression of Cathelicidin Innate Immune Mediators, LL-37 and KLK5, in Reconstructed and Ex Vivo Skin Models

Topical Treatment of Rosacea with Ivermectin Inhibits Gene Expression of Cathelicidin Innate Immune Mediators, LL-37 and KLK5, in Reconstructed and Ex Vivo Skin Models

Rosacea Management: Update on general measures and topical treatment options

Rosacea – new data on pathogenesis and treatment

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