Ameen M, Lear JT, Madan V, Mohd Mustapa MF, Richardson M.
British Association of Dermatologists' guidelines for the management of onychomycosis 2014.
Br J Dermatol. 2014 Nov;171(5):937-58. doi: 10.1111/bjd.13358.
Abstract/Text
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Guidelines of care for superficial mycotic infections of the skin: onychomycosis. Guidelines/Outcomes Committee. American Academy of Dermatology.
J Am Acad Dermatol. 1996 Jan;34(1):116-21. doi: 10.1016/s0190-9622(96)90843-9.
Abstract/Text
Watanabe S, Tsubouchi I, Okubo A.
Efficacy and safety of fosravuconazole L-lysine ethanolate, a novel oral triazole antifungal agent, for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study.
J Dermatol. 2018 Oct;45(10):1151-1159. doi: 10.1111/1346-8138.14607. Epub 2018 Aug 29.
Abstract/Text
Fosravuconazole L-lysine ethanolate (F-RVCZ) is a prodrug of ravuconazole, a novel triazole antifungal agent, exerting broad and potent antifungal activity. The efficacy and safety of F-RVCZ, compared with a placebo, were investigated in a multicenter, double-blind, randomized study of Japanese onychomycosis patients with 25% or more clinical involvement of the target toenail. Subjects (n = 153) were randomly assigned to receive F-RVCZ (100 mg RVCZ, n = 101) or placebo (n = 52) p.o. once daily for 12 weeks. The primary end-point was the rate of complete cure (clinical cure [0% clinical involvement of the target toenail] plus mycological cure [negative potassium hydroxide examination]) at week 48 (36-week post-treatment visit). Secondary end-points were changes over time in the efficacy and mycological effect of F-RVCZ. Safety was also evaluated. The complete cure rate at week 48 was significantly higher with F-RVCZ (59.4%, 60/101) than the placebo (5.8%, 3/52) in the full analysis set (P < 0.001). The mycological cure rate at week 48 was also significantly higher with F-RVCZ (82.0%, 73/89) than the placebo (20.0%, 10/50, P < 0.001). Regarding safety, adverse events were observed in 83.2% (84/101) and 80.8% (42/52), and adverse drug reactions (ADR) in 23.8% (24/101) and 3.8% (2/52) of F-RVCZ and placebo subjects, respectively. ADR were mild to moderate in severity, with none being serious. F-RVCZ (equivalent to 100 mg ravuconazole) administrated once daily for 12 weeks was more effective than placebo and tolerable in patients with onychomycosis, suggesting it to be a promising drug for onychomycosis treatment.
© 2018 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.
Sergeev AY, Gupta AK, Sergeev YV.
The Scoring Clinical Index for Onychomycosis (SCIO index).
Skin Therapy Lett. 2002;7 Suppl 1:6-7.
Abstract/Text
Onychomycosis is a common disease, and there are a number of factors that may affect the duration and dosage of treatment including the type of onychomycosis, the area and thickness of nail involvement, the age of the patient, and the location of the digit that is affected. We report a composite index, the Scoring Clinical Index for Onychomycosis (SCIO) that combines these factors to give an index of the overall severity of onychomycosis. The use of the SCIO may have treatment implications; by matching patients with similar SCIO scores, it may be possible to better compare the clinical response to therapy.
Odom RB, Aly R, Scher RK, Daniel CR 3rd, Elewski BE, Zaias N, DeVillez R, Jacko M, Oleka N, Moskovitz BL.
A multicenter, placebo-controlled, double-blind study of intermittent therapy with itraconazole for the treatment of onychomycosis of the fingernail.
J Am Acad Dermatol. 1997 Feb;36(2 Pt 1):231-5. doi: 10.1016/s0190-9622(97)70286-x.
Abstract/Text
BACKGROUND: Onychomycosis is the most frequent cause of nail disease and represents 30% of all mycotic infections of the skin.
OBJECTIVE: Our purpose was to compare the effectiveness and tolerability of intermittent dosing of itraconazole ("pulse therapy") with placebo in fingernail onychomycosis.
METHODS: Seventy-three patients with clinically and mycologically diagnosed fingernail onychomycosis were randomly selected to receive itraconazole, 200 mg twice daily, or placebo for the first week of each month for 2 consecutive months; patients were observed for 19 weeks. Seventy-one patients received the study medication and were included in the safety analysis. Efficacy of treatment was evaluated in 46 patients.
RESULTS: A significantly greater proportion of itraconazole-treated patients than placebo-treated patients achieved clinical success (77% vs 0%), mycologic success (73% vs 13%), and overall success (68% vs 0%). No itraconazole-treated patient had a clinical or mycologic relapse during the follow-up period. Ten itraconazole-treated patients (28%) and nine placebo-treated patients (26%) had adverse events. Three patients discontinued treatment for safety reasons.
CONCLUSION: Pulse therapy with itraconazole for 2 consecutive months produces significantly greater clinical, mycologic, and overall success than placebo. Short-term itraconazole pulse therapy for fingernail onychomycosis is effective and well tolerated.
Drake LA, Shear NH, Arlette JP, Cloutier R, Danby FW, Elewski BE, Garnis-Jones S, Giroux JM, Gratton D, Gulliver W, Hull P, Jones HE, Journet M, Krol AL, Leyden JJ, Maddin SC, Ross JB, Savin RC, Scher RK, Sibbald GR, Tawfik NH, Zaias N, Tolpin M, Evans S, Birnbaum JE.
Oral terbinafine in the treatment of toenail onychomycosis: North American multicenter trial.
J Am Acad Dermatol. 1997 Nov;37(5 Pt 1):740-5. doi: 10.1016/s0190-9622(97)70111-7.
Abstract/Text
BACKGROUND: Onychomycosis is an increasing problem with limited therapeutic options.
OBJECTIVE: We evaluated the safety and efficacy, of oral terbinafine, a new fungicidal antimycotic, in patients with toenail onychomycosis.
METHODS: A North American multicenter, double-blind, placebo-controlled study evaluated the mycologic and clinical efficacy of oral terbinafine 250 mg/day for 12 or 24 weeks in 358 patients with toenail onychomycosis.
RESULTS: A total of 74% of patients treated with 12 or 24 weeks of terbinafine achieved a successful clinical outcome. Approximately 11% of terbinafine responders showed evidence of relapse 18 of 21 months after cessation of treatment. Terbinafine was well tolerated; most adverse events were transient and mild to moderate in severity.
CONCLUSION: The results of this study confirm that oral terbinafine is a safe and effective therapy for the treatment of onychomycosis.
Baran R.
Topical amorolfine for 15 months combined with 12 weeks of oral terbinafine, a cost-effective treatment for onychomycosis.
Br J Dermatol. 2001 Oct;145 Suppl 60:15-9.
Abstract/Text
OBJECTIVE: This open randomized study examined the efficacy of a combination of oral terbinafine and topical amorolfine in the treatment of severe dermatophyte toenail onychomycosis with matrix area involvement.
PATIENTS/METHODS: A total of 147 patients were randomized to one of three treatment groups: 15 months of once-weekly topical amorolfine lacquer in combination with 6 weeks (Group AT6) or 12 weeks (Group AT12) of oral terbinafine, 250 mg once daily: or terbinafine monotherapy for 12 weeks (Group T12). Patients were followed for a total of 18 months. The primary efficacy variable was the result of mycological examination after 3 months of therapy; secondary efficacy variables were mycological and clinical examination at 3-monthly intervals, with an additional clinical evaluation at 18 months. Safety and tolerance were also assessed.
RESULTS: Negative mycological results, assessed at 3 months, were recorded for 14 of 40 patients (35%) in Group AT6, 11 of 44 (27.5%) in Group AT12 and 7 of 41 (17.1%) in Group T12. At 18 months, the global response (mycological and clinical cure) was seen in 22 of 50 patients (44%), 34 of 47 (72.3% and 18 of 48 (37.5%) in the AT6, AT12 and T12 groups, respectively.
CONCLUSIONS: These results suggest that a combination therapy regime with oral and systemic treatment is superior in efficacy to monotherapy with a systemic drug alone in the treatment of severe onychomycosis. In addition, the cost per cure ratio was better in the combination groups.
Elewski BE, Rich P, Pollak R, Pariser DM, Watanabe S, Senda H, Ieda C, Smith K, Pillai R, Ramakrishna T, Olin JT.
Efinaconazole 10% solution in the treatment of toenail onychomycosis: Two phase III multicenter, randomized, double-blind studies.
J Am Acad Dermatol. 2013 Apr;68(4):600-608. doi: 10.1016/j.jaad.2012.10.013. Epub 2012 Nov 20.
Abstract/Text
BACKGROUND: Onychomycosis is a common nail infection, often resulting in nail plate damage and deformity. Topical lacquer treatments have negligible efficacy. Oral treatments, although more efficacious, are limited by drug interactions and potential hepatotoxicity.
OBJECTIVE: We investigated the safety and efficacy of efinaconazole 10% solution (efinaconazole), the first triazole antifungal developed for distal lateral subungual onychomycosis.
METHODS: Two identical, multicenter, randomized, double-blind, vehicle-controlled studies were conducted in patients with toenail distal lateral subungual onychomycosis (20%-50% clinical involvement [study 1: N = 870, study 2: N = 785]). Patients were randomized (3:1) to efinaconazole or vehicle, once daily for 48 weeks, with 4-week posttreatment follow-up. Debridement was not performed. The primary end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52.
RESULTS: Mycologic cure rates were significantly greater with efinaconazole (study 1: 55.2%, study 2: 53.4%) compared with vehicle (P < .001). The primary end point, complete cure, was also significantly greater for efinaconazole (study 1: 17.8% vs 3.3%, study 2: 15.2% vs 5.5%, P < .001). Treatment success (percent affected target toenail [0%-≤10%]) for efinaconazole ranged from 21.3% to 44.8% in study 1 and from 17.9% to 40.2% in study 2, compared with 5.6% to 16.8% and 7.0% to 15.4%, respectively, with vehicle. Adverse events associated with efinaconazole were local site reactions (2%) and clinically similar to vehicle.
LIMITATIONS: A period of 52 weeks may be too brief to evaluate a clinical cure in onychomycosis.
CONCLUSIONS: Once daily topical efinaconazole appears to be a viable alternative to oral treatment options for onychomycosis.
Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
Watanabe S, Kishida H, Okubo A.
Efficacy and safety of luliconazole 5% nail solution for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study.
J Dermatol. 2017 Jul;44(7):753-759. doi: 10.1111/1346-8138.13816. Epub 2017 Mar 23.
Abstract/Text
Onychomycosis is a highly prevalent and intractable disease. The first-line treatment agents are oral preparations, but an effective topical medication has long been desired. The objective was to investigate the efficacy and safety of luliconazole 5% nail solution, an imidazole antifungal agent, for the treatment of patients with onychomycosis. A multicenter, double-blind, randomized phase III study was conducted in Japanese patients with distal lateral subungual onychomycosis affecting the great toenails, with 20-50% clinical involvement. Patients were randomized (2:1) to luliconazole or vehicle once daily for 48 weeks. The primary end-point was the complete cure rate (clinical cure [0% clinical involvement of the nail] plus mycological cure [negative results on direct microscopy]). The adverse event incidence was monitored to evaluate safety. The complete cure rate significantly favored luliconazole (14.9%, 29/194 subjects) versus vehicle (5.1%, 5/99) (P = 0.012). Similarly, the negative direct microscopy rate was significantly higher with luliconazole (45.4%, 79/174) than with vehicle (31.2%, 29/93) (P = 0.026). There were no serious adverse drug reactions. We conclude that once daily topical luliconazole 5% nail solution demonstrated clinical efficacy and was confirmed to be well tolerated.
© 2017 Japanese Dermatological Association.
