Νεότερα δεδομένα στη θεραπεία των ονυχομυκητιάσεων Έλενα Σωτηρίου Επ.Καθηγήτρια Α’ Δερματολογική Κλινική Α.Π.Θ. Θεσσαλονίκη, Ιούνιος 2015.

Παρουσίαση με θέμα: "Νεότερα δεδομένα στη θεραπεία των ονυχομυκητιάσεων Έλενα Σωτηρίου Επ.Καθηγήτρια Α’ Δερματολογική Κλινική Α.Π.Θ. Θεσσαλονίκη, Ιούνιος 2015."— Μεταγράφημα παρουσίασης:

1 Νεότερα δεδομένα στη θεραπεία των ονυχομυκητιάσεων Έλενα Σωτηρίου Επ.Καθηγήτρια Α’ Δερματολογική Κλινική Α.Π.Θ. Θεσσαλονίκη, Ιούνιος 2015

2 tavaborole Νέας γενιάς αντιμυκητιασικός παράγοντας Καινοτόμος χημική δομή & μηχανισμός δράσης Στοχεύει & αναστέλλει τη δράση της leucyl-tRNA synthetase Ευρύ αντιμυκητιασικό φάσμα Χαμηλό μοριακό βάρος: μεγάλη διεισδυτικότητα στην ονυχαία πλάκα

3 Φάσης ΙΙΙ, διπλές-τυφλές, τυχαιοποιημένες, ελεγχόμενες με εικονικό φάρμακο μελέτες 1194 ασθενείς με DSO & 20-60% προσβολή του όνυχα Εφαρμογή μία φορά την ημέρα για 48 εβδ. Κύριο καταληκτικό σημείο αποτελεσματικότητας: Πλήρης ίαση την εβδ. 52 Κλινική εκτίμηση κάθε 6 εβδ., μυκητολογικός έλεγχος κάθε 12 εβδ. Καταγραφή ανεπιθύμητων ενεργειών σε όλη τη διάρκεια της μελέτης

4 Τοπικές ανεπιθύμητες αντιδράσεις: απολέπιση (2.7%), ερύθημα (1.6%), δερματίτιδα (1.3%)

5 Tavaborole 5% / KERYDIN Τοπικώς εφαρμοζόμενο διάλυμα FDA έγκριση: Ιούλιος 2014 Ένδειξη: ονυχομυκητίαση από T.rubrum ή T.mentagrophytes Εφαρμογή άπαξ ημερησίως για 48 εβδ.

6 J Pharm Sci. 2015 May Efinaconazole Topical Solution, 10%: Formulation Development Program of a New Topical Treatment of Toenail Onychomycosis. Transungual drug delivery of antifungals is considered highly desirable to treat common nail disorders such as onychomycosis, due to localized effects, and improved adherence resulting from minimal systemic adverse events. However, the development of effective topical therapies has been hampered by poor nail penetration. An effective topical antifungal must permeate through, and under the dense keratinized nail plate to the site of infection in the nail bed and nail matrix. We present here the formulation development program to provide effective transungual and subungual delivery of efinaconazole, the first topical broad spectrum triazole specifically developed for onychomycosis treatment. We discuss the important aspects encompassing the formulation development program for efinaconazole topical solution, 10%, focusing on its solubility in a number of solvents, in vitro penetration through the nail, and in vivo efficacy. Efinaconazole topical solution, 10% is a stable, non-lacquer, antifungal with a unique combination of ingredients added to an alcohol-based formulation to provide low surface tension and good wetting properties. This low surface tension is believed to affect effective transungual delivery of efinaconazole and believed to provide a dual mode of delivery by accessing the nail bed by wicking into the space between the nail and nail plate.

7 J Am Podiatr Med Assoc. 2014 Sep-Oct;104(5):479-85. Efinaconazole 10% solution in the treatment of onychomycosis of the toenails. Efinaconazole 10% solution is a new triazole antifungal agent developed for the topical treatment of onychomycosis. This article reviews the pooled results of the two pivotal clinical trials of this drug that have been performed in the United States, Canada, and Japan. METHODS: The two studies of 1,655 patients were both double- blind, vehicle-controlled, parallel-group, randomized, multicenter studies designed to determine the efficacy and safety of efinaconazole 10% solution in the treatment of mild-to-moderate onychomycosis of the toenails caused by dermatophytes. Treatment was provided once daily for 48 weeks, and the primary end point was at week 52. RESULTS The combined results show a 56% mycologic cure rate compared with 17% for vehicle at week 52. Clinical treatment success was achieved in 43% of patients treated with efinaconazole 10% solution at follow-up (week 52). As expected for a topical agent, the use of efinaconazole 10% solution was found to be safe, with mild, transient irritation at the site of application reported as the most common adverse event. CONCLUSIONS: The efficacy and safety profile of efinaconazole 10% solution suggests that it may represent an important advance in the topical treatment of onychomycosis. Further studies will help us better understand the role of this agent for the treatment of this widespread podiatric medical condition.

8 Eficonazole 10% /JUBLIA Τοπικώς εφαρμοζόμενο διάλυμα FDA έγκριση: Ιούνιος 2014 Ένδειξη: ονυχομυκητίαση από T.rubrum ή T.mentagrophytes Εφαρμογή άπαξ ημερησίως για 48 εβδ.

9 Tazarotene: αντιφλεγμονώδη & ανοσορρυθμιστική δράση 15 ασθενείς, DLSO Tazarotene gel 0.1%, άπαξ ημερησίως για 12 εβδομάδες Κύριο καταληκτικό σημείο αποτελεσματικότητας: κλινική και μυκητολογική ίαση Μυκητολογική ίαση: 40% των ασθενών σε 4 εβδομάδες Πλήρης ίαση: 100% των ασθενών σε 12 εβδομάδες Διατήρηση του αποτελέσματος στο follow-up των 6μηνών Ασφάλεια: Ήπιο ερύθημα παρωνυχίου σε 2 ασθενείς

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11 National Library of Medicine’s Pubmed Database 7 μελέτες 137 ασθενείς T. rubrum (T.mentagrophytes, E.floccosum, Candida sp.) Προετοιμασία με ουρία 20-40% ή/και απόξεση του όνυχα ALA, MAL, methylene blue dye, παράγωγο αιματοπορφυρίνης Διάρκεια κλειστής περίδεσης: 1-5h Κόκκινο φως (570-670nm) 18 – 100 J/cm² Αριθμός συνεδριών: 3 - 12

12 Μεγαλύτερη αποτελεσματικότητα σε ήπιας & μέσης βαρύτητας ΟΜ Περιορισμένη αποτελεσματικότητα σε σοβαρή ΟΜ Μεγάλα ποσοστά υποτροπών Άλγος & αίσθημα καύσου κατά τη διάρκεια της ακτινοβόλησης Ερύθημα, οίδημα (φυσαλίδες, διαβρώσεις) για 7-15 μέρες These studies show a great potential of PDT in onychomycosis without systemic side effects.

13 Υψηλό κόστος Μεγάλο χρονικό διάστημα προετοιμασίας και θεραπευτικής διαδικασίας Καθορισμός θεραπευτικών παραμέτρων ( ένταση, αριθμός συνεδριών, μεσοδιαστήματα συνεδριών…)

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15 J Dtsch Dermatol Ges. 2014 Apr;12(4):322-9. Treatment of onychomycosis using the 1 064 nm Nd:YAG laser: a clinical pilot study. 20 toe nails, T.rubrum Mean patient age: 69.4 years Two treatment sessions, 4 weeks apart Results: Mean pain intensity during treatment (scale 0-10): 4.4 Decrease of OSI-Score by 3.8, 4.8 and 2.9 points within 3, 6 and 9 months. Negative cultures after 9 months: 65%. Results suggest that treatment of onychomycosis with the Nd:YAG laser can lead to a temporary clinical improvement, a reduction of positive fungal cultures and an improvement of the Onychomycosis Severity Index. The treatment regimen should be optimized to be used as an effective antimycotic monotherapy.

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17 J Am Acad Dermatol. 2014 May;70(5):911-7. Lack of efficacy with 1064-nm neodymium:yttrium- aluminum-garnet laser for the treatment of onychomycosis: a randomized, controlled trial BACKGROUND: Laser therapies have been Food and Drug Administration approved for temporary nail plate clearance; however, there is minimal evidence of their long-term efficacy. OBJECTIVE: We sought to evaluate the clinical and mycological clearance of toenails treated with 1064-nm neodymium:yttrium-aluminum-garnet laser versus no treatment. METHODS: This was a randomized, controlled, single-center trial comparing 2 treatments with 1064-nm neodymium:yttrium-aluminum-garnet laser (fluence of 5 J/cm(2), rate of 6 Hz) spaced 2 weeks apart versus no treatment in 27 patients (N = 125 affected nails) with clinical and mycological diagnosis of onychomycosis. At 3 months, patients were assessed with mycological cultures and proximal nail plate measurements. Patients treated with laser were also assessed with proximal nail plate measurements at 12 months. RESULTS: At 3 months, 33% of patients treated with laser achieved a negative mycological culture compared with 20% of the control group (P =.49), and had more proximal nail plate clearance compared with control subjects (0.44 vs 0.15 mm, P =.18), which was not statistically significant. At 12 months, there was no difference in nail plate clearance between laser versus control subjects (0.24 vs 0.15 mm, P =.59). There was no significant mycological culture or clinical nail plate clearance with 1064-nm neodymium:yttrium-aluminum-garnet laser compared with control.

18 J Dermatolog Treat. 2015 Apr 17:1-5. Efficacy and safety of 1064-nm Nd:YAG laser in treatment of onychomycosis. 64 nails, 35 patients 3 treatment sessions, one week interval Results Cure rates at 1,3,6m follow-up visits: 63.5%, 57.7%, 52% Side effects: mild erythema & swelling after laser procedure Conclusions Long-pulsed 1064-nm Nd:YAG laser therapy is safe and effective for the treatment of onychomycosis. However, a larger sample and longer follow-up period are needed to confirm our findings.

19 Combined oral terbinafine and long-pulsed 1,064-nm Nd: YAG laser treatment is more effective for onychomycosis than either treatment alone. Dermatol Surg. 2014 Nov OBJECTIVE: To compare the efficacy and safety of combined treatment with a long-pulsed 1,064-nm Nd:YAG laser and oral terbinafine with those of either treatment alone. METHODS: We randomly divided 53 patients with a total of 90 infected nails into 3 treatment groups: the T group received oral terbinafine, the L group received long-pulsed Nd:YAG laser treatment, and the T + L group received both treatments. We evaluated the mycological clearance rate (MCR) and the clinical clearance rate (CCR) of the 3 groups at Weeks 4, 8, 12, 16, and 24. RESULTS: The MCR and CCR increased in all 3 groups in a time-dependent manner. The MCR and CCR of the T + L group were significantly higher than those of the T group and the L group at Weeks 8, 12, 16, and 24 (p <.05). CONCLUSION: These data indicate that 12 weeks of combined treatment with a long-pulsed Nd:YAG laser and oral terbinafine produce more rapid and effective mycological and clinical clearance in patients with onychomycosis than either treatment alone, without any obvious side effects.

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22 Ευχαριστώ!