Could Efinaconazole 10% Have An Impact For Onychomycosis?
Can an emerging topical hold promise for onychomycosis? This author takes a closer look in this case study of a 24-year-old patient with distal lateral subungual onychomycosis.
Onychomycosis is the most frequent nail disease affecting some 35 million people in the United States.1,2 It is the number one diagnosed and treated disease by podiatrists today.3
Although oral treatment is generally required, patients express concerns about oral therapies. In addition, few podiatrists use these modalities routinely.4,5 Not only are there safety concerns (such as hepatotoxicity) but oral antifungals can also cause rashes and hypogeusia. Potential drug interactions limit the use of oral therapies in many patients, especially the elderly in whom onychomycosis and the use of concomitant medications are most common.6,7
Our onychomycosis patients would prefer a topical treatment. However, reported cure rates of available topical therapies are much lower than those with systemic treatments.8 To date, ciclopirox nail lacquer (Penlac, Sanofi-Aventis) is the only topical treatment approved by the Food and Drug Administration (FDA) for the treatment of onychomycosis in the United States.10 Unfortunately, ciclopirox nail lacquer has reported complete cure rates of 5.5-8.5 percent, requires frequent nail debridement and patients have to use alcohol to remove excess buildup of lacquer from the ventral aspect of the nail plate to avoid additional infection.9,10
The main challenge in the development of topicals for onychomycosis has been to formulate a drug that can penetrate through the nail plate and reach the site of infection in the nail bed in a high enough concentration.
Accordingly, I would like to present a clinical case of distal lateral subungual onychomycosis and effective topical treatment with efinaconazole 10% solution, the first topical triazole antifungal developed specifically for the treatment of onychomycosis. The patient was enrolled in one of 2 phase 3 multicenter, randomized, double-blind studies on efinaconazole 10% solution, the full details of which are reported elsewhere.11
When A Patient Presents With Distal Lateral Subungual Onychomycosis Of The Great Toenail
A 24 year-old man presented at our clinic with distal lateral subungual onychomycosis of the great toenail. He had suffered from the disease for over 10 years. Forty-five percent of the great toenail was affected and laboratory results from the baseline fungal culture were positive for Trichophyton rubrum. The patient had five infected toenails.
The patient used efinaconazole 10% solution once a day for 48 weeks. The patient applied efinaconazole 10% solution to the clean, dry nail plate surface, lateral and proximal nail folds, hyponychium, and the undersurface of the nail plate. The patient was assessed for efficacy and safety at 12-week intervals post-baseline (i.e., Weeks 12, 24, 36. 48) and at follow-up (Week 52). I noted progressive improvement over the treatment period and at follow-up. By Week 12, the percentage of the affected nail had decreased to 30 percent and down to 10 percent at Week 24. The KOH was positive and the fungal culture was negative at this visit.
By Week 48 (the end of treatment), the great toenail had 0 percent involvement. Three other toenails were still affected. Both KOH and fungal cultures were negative from Week 36. At the week 52 follow-up visit, the patient’s onychomycosis was not completely cleared (5 percent involvement). However, the KOH and fungal cultures were still negative, and one of the other affected toenails was clear.
Any new topical product for onychomycosis must not cause irritation or contact dermatitis. The patient reported no redness, swelling, burning, itching or vesiculation during treatment. There were no adverse events relating to efinaconazole use.
In addition to the reported clinical results, the patient assessed his satisfaction in terms of improvement and appearance of his toenails. At baseline, he noted yellowing or discoloration of his toenails, and found his condition very bothersome. Being embarrassed by the appearance of his nails, feeling self-conscious and wearing shoes were all very much problems. At the 52 week follow-up visit, he deemed his condition as only ‘slightly bothersome,’ presumably because other nails continued to be affected, but embarrassment, pain or discomfort had ceased to be problems. Overall, he was very satisfied with the improvement in the condition of his toenails.
Onychomycosis is notoriously difficult to treat and requires a long-term management program. The key aims are to eradicate the pathogens, restore a healthy nail and minimize recurrence. The slow growth of the toenail impacts the ability to assess clinical effectiveness quickly.12,13 Mycological cure is considered an important precursor in evaluating treatment success as it precedes clinical cure, often by several months.14 In this clinical case, mycological cure was apparent from Week 36 whereas I only saw complete cure (0% involvement of the target nail and mycologic cure) at Week 48 (the end of treatment).
There is a reluctance to treat onychomycosis with topical agents because we do not have anything that is effective. Often our patients, like the one in this case, have suffered with the disease for many years. In addition, a number of nails are usually affected. The results of this case report using efinaconazole 10% solution are encouraging both in terms of mycologic and complete cure, and the patient’s self assessment of improvement. An effective topical antifungal for the treatment of onychomycosis will satisfy an unmet need in the management of onychomycosis, and we await more extensive data from the clinical program.
Dr. Pollak is in private practice in San Antonio. Dr. Pollak has disclosed that he is an advisor to Valeant Dermatology, a subsidiary of Valeant Pharmaceuticals North America LLC, and was an investigator in the Phase 3 clinical trials of efinaconazole. Dr. Pollak thanks Brian Bulley, MSc, of Inergy Limited, for his assistance with this case study.
1. Scher RK, Coppa LM. Advances in the diagnosis and treatment of onychomycosis. Hosp Med 1998;34:11-20.
2. Ghannoum MA, Hajjeh RA, Scher R et al. A large-scale North American study of fungal isolates from nails: the frequency of onychomycosis, fungal distribution, and antifungal susceptibility patterns. J Am Acad Dermatol 2000;43 (4):641-648.
3. Mozena J. A guide to treatments for onychomycosis. Podiatry Today 2003;16(8);61-67.
4. Sciandra J. A closer look at onychomycosis. Podiatry Management. 2001;20(6):121-132.
5. Schein JR, Gouse D, Stier DM, et al. Onychomycosis: baseline results of an observational study. J Am Podiatr Med Assoc. 1997;87(11):512-519.
6. Baran R, Sigurgeirsson B, de Berker D et al. A multicentre, randomized, controlled study of the efficacy, safety and cost-effectiveness of a combination therapy with amorolfine nail lacquer and oral terbinafine compared with oral terbinafine alone for the treatment of onychomycosis with matrix involvement. Br J Dermatol 2007; 157(1): 149–157.
7. (No authors listed). Fungal nail infections: diagnosis and management (editorial). Prescrire Int 2009;18(99): 26–30.
8. de Berker D. Fungal nail disease. N Engl J Med 2009;360(3):2108 –16.
9. Piraccini BM, Sisti A, Tosti A. Long-term follow-up of toenail onychomycosis caused by dermatophytes after successful treatment with systemic antifungal agents. J Am Acad Dermatol 2010;62(3):411–414.
10. Sparavigna A, Setaro M, Frisenda L. Physical and microbiological properties of a new nail protective medical device. J Plastic Dermatol 2008;4:5-12.
11. Elewski BE, Rich P, Pollak R, Pariser DM, et.al. Efinaconazole 10% solution in the treatment of toenail onychomycosis: two phase 3 multicenter, randomized, double-blind studies. J Am Acad Dermatol. http://www.jaad.org/article/S0190-9622%2812%2901140-1/fulltext. Published online November 22, 2012. Accessed January 21, 2013.
12. De Cuyper C, Hindryckx PH. Long-term outcomes in the treatment of toenail onychomycosis. Br J Dermatol 1999;141(Suppl 56):15–20.
13. Werschler WP, Bondar G, Armstrong D. Assessing treatment outcomes in toenail onychomycosis clinical trials. Am J Clin Dermatol 2004; 5(3):145–152.
14. Elewski BE, Ghannoum MA, Mayser P, Gupta AK, et al. Efficacy, safety and tolerability of topical terbinafine nail solution in patients with mild-to-moderate toenail onychomycosis: results from three randomized studies using double-blind vehicle-controlled and open-label active-controlled designs. J Eur Acad Dermatol Venereol. http://onlinelibrary.wiley.com/doi/10.1111/j.1468-3083.2011.04373.x/full . Published online December 20, 2011. Accessed January 21, 2013.