JAPMA Article In Press This article has undergone peer review, copyediting, and author review but is not a final version and may differ from the published version.
ORIGINAL ARTICLE Efinaconazole Topical Solution, 10% Efficacy in Patients with Onychomycosis and Coexisting Tinea Pedis
Bryan Markinson, DPM* Bryan Caldwell, DPM†
*Division of Podiatric Medicine and Surgery, Leni and Peter W. May Department͒of Orthopedic Surgery, Mount Sinai School of Medicine, New York, NY. †Department of Clinical Education and Clinic Operations, College of Podiatric Medicine, Kent State University, Independence, OH.
Corresponding author: Bryan Markinson, DPM, Mount Sinai School of Medicine in New York, NY 10029. (E-mail: [email protected])
[Abstract] Background: We sought to evaluate the efficacy of efinaconazole topical solution, 10%, in patients with onychomycosis and coexisting tinea pedis.
1
Methods: We analyzed 1,655 patients, aged 18 to 70 years, randomized (3:1) to receive efinaconazole topical solution, 10%, or vehicle from two identical multicenter, double-blind, vehicle-controlled 48-week studies evaluating safety and efficacy. The primary end point was complete cure rate (0% clinical involvement of the target toenail and negative potassium hydroxide examination and fungal culture findings) at week 52. Three groups were compared: patients with onychomycosis and coexisting interdigital tinea pedis on-study (treated or left untreated) and those with no coexisting tinea pedis. Results: Treatment with efinaconazole topical solution, 10%, was significantly more effective than vehicle use irrespective of the coexistence of tinea pedis or its treatment. Overall, 352 patients with onychomycosis (21.3%) had coexisting interdigital tinea pedis at baseline, with 215 of these patients (61.1%) receiving investigator-approved topical antifungal agents for their tinea pedis in addition to their randomized onychomycosis treatment. At week 52, efinaconazole complete cure rates of 29.4% were reported in patients with onychomycosis when coexisting tinea pedis was treated compared with 16.1% when coexisting tinea pedis was not treated. Both cure rates were significant compared with vehicle (P = .003 and .045, respectively), and in the latter subgroup, no patients treated with vehicle achieved a complete cure. Conclusions: Treatment of coexisting tinea pedis in patients with onychomycosis enhances the efficacy of once-daily topical treatment with efinaconazole topical solution, 10%.
Onychomycosis is a progressive fungal infection of the nail bed, matrix, or plate; it leads to destruction and deformity of the toenails and (less frequently) fingernails.1,2 It represents up to 50% of all nail disorders and is usually associated with tinea pedis.1,3 Toenail onychomycosis
2
frequently involves several nails4 and can be more challenging to treat because of the nail’s slower growth rate and coexisting nail infection.5,6 It is well recognized in podiatric medical practice that onychomycosis and tinea pedis coexist, that tinea pedis can lead to onychomycosis, and that it is important to evaluate and treat both diseases. Onychomycosis represents more than half of all the nail disease we see, and more than a third of these patients also have tinea pedis. Treating their tinea pedis is important for preventing onychomycosis recurrence because the fungal pathogens infecting the skin may act as a reservoir for reinfection of the nail. The true prevalence of coexisting onychomycosis and tinea pedis is unknown. Neither are life-threatening diseases, and studies suggest that patients do not always seek medical advice unless their quality of life is significantly affected.7,8 This may be one reason why we see differences in prevalence rates among various studies. Other factors could include differences in methods, population sample (healthy general population or dermatologic patients), and study size.8,9 Onychomycosis and tinea pedis prevalence rates are also reported to be affected by social status, occupation, climate, travel, living environment, age, and several predisposing factors.3,7-9 The large Achilles screening project revealed that 56% to 62% of dermatologic patients had foot disease independent of their presenting medical concerns.10,11 Onychomycosis and tinea pedis were the most commonly diagnosed foot diseases; in some cases, they can coexist. In a large study of more than 2,700 patients with onychomycosis, approximately a third of them (33.8%) also had tinea pedis, with interdigital tinea pedis being the most common (in 22.1% of patients).12 These data were similar to previously reported prevalence rates of coexisting disease.13,14 Generally, both disorders are more common in men,10,11,13 with the coexistence of toenail
3
onychomycosis and tinea pedis being more prevalent in this sex (P < .001). Concomitant tinea pedis was more often observed in patients with recurrent toenail onychomycosis (P < .001), more advanced toenail onychomycosis (ie, in patients with bilateral toenail onychomycosis) (P < .001), and those with a higher number of affected toenails (P < .001).12 The coexistence of toenail onychomycosis and tinea pedis has also been reported to increase with age, and it is estimated that 25.7% of elderly individuals have both types of infection simultaneously.15 Tinea pedis may precede toenail onychomycosis.16 Many patients with toenail onychomycosis or tinea pedis are not aware that they have a fungal infection, and such patients pose a special challenge for physicians to detect and treat their disease.8,17,18 Although it is well recognized that the two diseases coexist and that tinea pedis can lead to onychomycosis, there are no data comparing the outcomes of treating patients with onychomycosis and coexisting tinea pedis where both diseases are treated. Two identical 52week prospective, multicenter, randomized, double-blind studies in 1,655 patients (aged 18–70 years) assessed the safety and efficacy of efinaconazole topical solution, 10%, in the treatment of onychomycosis.19 We provide an analysis of efficacy in patients with coexisting tinea pedis who were treated for both diseases. We also compare data with those not treated for their tinea pedis and the remaining study population without coexisting disease.
Methods Two multicenter, randomized, double-blind, vehicle-controlled studies were designed to evaluate the efficacy, safety, and tolerability of efinaconazole topical solution, 10%, relative to its vehicle in 1,655 male and female patients aged 18 to 70 years with mild-to-moderate toenail onychomycosis. Detailed methods have already been reported, and a brief summary is provided
4
herein.19 Patients who presented with 20% to 50% clinical involvement of the target toenail were randomized (3:1) to receive efinaconazole topical solution, 10%, or vehicle applied once daily to the toenails for 48 weeks, with 4-week posttreatment follow-up. Investigators (podiatric physicians and dermatologists) examined both feet for the presence of tinea pedis and were allowed to treat interdigital tinea pedis with an investigatorapproved topical antifungal agent. Patients were categorized based on the presence of tinea pedis and whether their tinea pedis was treated. All investigators received identical training within and across investigational centers and used standardized scales and tools to measure and report efficacy variables.
Efficacy Evaluation Efficacy evaluations were performed at baseline, at 12-week intervals after baseline (ie, weeks 12, 24, 36, and 48), and at the final visit (week 52). The primary end point was complete cure rate (0% clinical involvement of the target toenail and negative potassium hydroxide examination and fungal culture findings) at week 52. Secondary end points were mycologic cure (negative potassium hydroxide examination and fungal culture findings), treatment success FOLQLFDOLQYROYHPHQWRIWKHWDUJHWWRHQDLO FRPSOHWHRUDOPRVWFRPSOHWHFXUH clinical involvement and mycologic cure), and unaffected toenail growth (change from baseline). All of the secondary end points were assessed at week 52. The intention-to-treat population included all patients randomized to receive and dispensed study drug. Efficacy end points were compared using Cochran-Mantel-Haenszel tests (stratified by analysis center) at a 5% significance level. Missing efficacy data were imputed
5
using the last-observation-carried-forward method.
Results Of 1,655 patients with onychomycosis, 352 (21.3%) reported having interdigital tinea pedis at baseline. Of these, 215 patients (61.1%) were treated for their tinea pedis with investigatorapproved topical antifungal drug therapy in addition to receiving efinaconazole topical solution, 10%, or vehicle for their onychomycosis. The most widely used antifungal agents to treat tinea pedis were topical butenafine (64 patients), luliconazole (52 patients), and ketoconazole (23 patients). Overall, 1,436 patients (86.8%) completed the 48-week treatment with efinaconazole or vehicle and 1,420 patients (85.8%) completed the 4-week follow-up.19
Primary Efficacy End Point (Observed Case)
Efinaconazole topical solution, 10%, was more effective than vehicle in treating onychomycosis, irrespective of the coexistence of interdigital tinea pedis or its treatment. At week 52, 24.0% of patients with onychomycosis and coexisting tinea pedis on-study (55 of 229) had a complete cure with efinaconazole treatment compared with 5.7% (5 of 88) with vehicle use (P < .001). When coexisting tinea pedis was treated, onychomycosis complete cure rates were 29.4% (40 of 136) with efinaconazole treatment and 7.8% (5 of 64) with vehicle use (P = .003). When patients’ tinea pedis was not treated, 16.1% (15 of 93) had a complete cure with efinaconazole treatment compared with 0% with vehicle use (P = .045) (Fig. 1). This contrasted with complete cure rates of 16.9% (141 of 833) and 4.3% (11 of 255), respectively (P < .001), at week 52 in patients without tinea pedis.
Supportive and Secondary Efficacy End Points (Observed Case)
6
At week 52, 51.7% of patients with onychomycosis and coexisting tinea pedis on-study (119 of 230) achieved a mycologic cure with efinaconazole treatment compared with 22.7% (20 of 88) being treated with vehicle (P < .001). When coexisting tinea pedis was treated, 56.2% of patients with onychomycosis (77 of 137) had a mycologic cure with efinaconazole use compared with 26.6% (17 of 64) taking vehicle (P < .001). When tinea pedis was not treated, 45.2% of patients (42 of 93) had a mycologic cure with efinaconazole use compared with 12.5% (3 of 24) with vehicle use (P = .007) (Fig. 2). These data compared with 57.6% (480 of 834) and 14.5% (37 of 255), respectively, in patients with onychomycosis where no tinea pedis was reported (P < .001). In addition, more patients with onychomycosis achieved a complete or almost complete cure at week 52 when their coexisting tinea pedis was treated: 37.5% (51 of 136) with efinaconazole use and 14.1% (9 of 64) with vehicle use (P = .005). When their tinea pedis was not treated, only 23.7% of patients (22 of 93) achieved a complete or almost complete cure with efinaconazole use, and no patients had a complete or almost complete cure with vehicle use (P = .011). Most patients (52.6%) treated with efinaconazole were considered treatment successes at week 52 compared with 20.5% being treated with vehicle (P < .001). When their tinea pedis was treated, 58.8% of patients (80 of 136) were considered treatment successes with efinaconazole use compared with 26.6% (17 of 64) being treated with vehicle (P < .001). When not treated, only 43.6% of patients (41 of 94) were considered treatment successes with efinaconazole use compared with 4.2% (1 of 24) being treated with vehicle (P .001). This compared with 45.7% (385 of 842) and 17.4% (45 of 258), respectively, for patients without coexisting tinea pedis (P < .001) (Fig. 3).
7
Discussion The coexistence of onychomycosis and tinea pedis is commonplace in podiatric medical practice. The need to diagnose and treat both diseases when present is well recognized; however, to our knowledge, this is the first study to investigate the resultant clinical benefit in terms of treatment success. The safety and efficacy of efinaconazole topical solution, 10%, in treating mild-tomoderate onychomycosis has been reported elsewhere.19 Overall, more than 21% of patients reported coexisting interdigital tinea pedis on-study. These findings were similar to the prevalence reported in the literature.12 In the present study, efinaconazole topical solution, 10%, was more effective than vehicle in treating onychomycosis, irrespective of the coexistence of tinea pedis and, especially, whether the tinea pedis was treated. Onychomycosis complete cure rates with efinaconazole treatment in patients with coexisting tinea pedis that was treated were almost twice those seen in patients with coexisting tinea pedis that was not treated, with almost 60% of patients considered a treatment success by week 52. The benefits of treating coexisting tinea pedis on onychomycosis outcomes were further illustrated in the vehicle group; no patients were completely or almost completely cured of their onychomycosis by week 52 when coexisting tinea pedis was left untreated. More than 60% of the patients with onychomycosis and tinea pedis on-study were treated for their coexisting disease, and the better onychomycosis efficacy results reported confirm best practice. However, no information exists on the success of their tinea pedis treatment, and there is no detailed appreciation of the severity of disease. In addition, it was unclear why some patients with coexisting tinea pedis on-study did not have their infection treated.
8
It was noted that efficacy results with efinaconazole and vehicle were higher in patients with onychomycosis where coexisting tinea pedis was treated compared with those where no tinea pedis was reported. Although we believe that the effect was due to combination therapy, we lack data to substantiate patient compliance rates for the treatment of tinea pedis; therefore, this could be a confounder. The studies were not designed to address whether the treatment of both coexisting onychomycosis and tinea pedis improves patient outcomes; however, the results of the post hoc analysis support the importance of treating both diseases.
Acknowledgment: Brian Bulley, MSc, of Inergy Limited for medical writing support. Financial Disclosure: Valeant Pharmaceuticals North America LLC funded Inergy’s activities pertaining to this work. Conflict of Interest: Drs. Markinson and Caldwell have served as paid consultants to Valeant Pharmaceuticals North America LLC.
References 1.
Scher RK, Coppa LM: Advances in the diagnosis and treatment of onychomycosis. Hosp
Med 34: 11, 1998. 2.
Crissey JT: Common dermatophyte infections: a simple diagnostic test and current
management. Postgrad Med 103: 191, 1998. 3.
Gupta AK, Jain HC, Lynde CW, et al: Prevalence and epidemiology of onychomycosis in
patients visiting physicians’ offices: a multicenter Canadian survey of 15,000 patients. J Am Acad Dermatol 43: 244, 2000.
9
4.
Roberts DT: Onychomycosis: current treatment and future challenges. Br J Dermatol 141
(suppl 56): 1, 1999. 5.
Finch JJ, Warshaw EM: Toenail onychomycosis: current and future treatment options.
Dermatol Ther 20: 31, 2007. 6.
Kumar S, Kimball AB: New antifungal therapies for the treatment of onychomycosis.
Expert Opin Investig Drugs 18: 727, 2009. 7.
Jesudanam TH, Rao RG, Lakshmi DJ, et al: Onychomycosis: a significant medical
problem. Indian J Dermatol Venereol Leprol 68: 326, 2002. 8.
Ogasawara YM, Hiruma M, Muto H, et al: Clinical and mycological study of occult tinea
pedis and tinea unguium in dermatological patients from Tokyo. Mycoses 46: 114, 2003. 9.
Perea S, Ramos MJ, Garau M, et al: Prevalence and risk factors of tinea unguium and
tinea pedis in the general population in Spain. J Clin Microbiol 38: 3226, 2000. 10.
Roseeuw D: Achilles foot screening project: preliminary results of patients screened by
dermatologists. J Eur Acad Dermatol Venereol 12 (suppl 1): S6, 1999. 11.
Haneke E, Roseeuw D: The scope of onychomycosis: epidemiology and clinical features.
Int J Dermatol 38 (suppl 2): 7, 1999. 12.
Szepietowski JC, Reich A, Garlowska E, et al: Factors influencing coexistence of toenail
onychomycosis with tinea pedis and other dermatomycoses: a survey of 2761 patients. Arch Dermatol 142: 1279, 2006. 13.
Ungpakorn R, Lohaprathan S, Reangchainam S: Prevalence of foot diseases in
outpatients attending the Institute of Dermatology, Bangkok, Thailand. Clin Exp Dermatol 29: 87, 2004. 14.
Szepietowski JC: Selected clinical aspects of onychomycosis. Mikol Lek 11: 119, 2004.
10
15.
Pierard G: Onychomycosis and other superficial fungal infections of the foot in the
elderly: a pan-European survey. Dermatology 202: 220, 2001. 16.
Zaias N, Rebell G: Chronic dermatophytosis caused by Trichophyton rubrum. J Am Acad
Dermatol 35: S17, 1996. 17.
Pau M, Aste N, Biggio P: Unsuspected tinea pedis in a normal population. Micol
Dermatol 5: 75, 1991. 18.
Ingordo V, Naldi L, Fracchiola S, et al: Prevalence and risk factors for superficial fungal
infections among Italian navy cadets. Dermatology 209: 190, 2004. 19.
Elewski BE, Rich P, Pollak R, et al: Efinaconazole 10% solution in the treatment of
toenail onychomycosis: two phase 3 multicenter, randomized, double-blind studies. J Am Acad Dermatol 68: 600, 2013.
11
Figure 1. Comparison of complete cure rates at week 52 in the observed case, intention-to-treat population. Complete cure is defined as 0% clinical involvement of the target toenail and negative potassium hydroxide examination and fungal culture findings.
12
Figure 2. Comparison of mycologic cure rates at week 52 in the observed case, intention-to-treat population. Mycologic cure is defined as negative potassium hydroxide examination and fungal culture findings.
13
Figure 3. Comparison of treatment success at week 52 in the observed case, intention-to-treat population. Treatment success is defined as 10% or less clinical involvement of the target toenail.
14
ORIGINAL ARTICLE Efinaconazole Topical Solution, 10% Efficacy in Patients with Onychomycosis and Coexisting Tinea Pedis
Bryan Markinson, DPM* Bryan Caldwell, DPM†
*Division of Podiatric Medicine and Surgery, Leni and Peter W. May Department͒of Orthopedic Surgery, Mount Sinai School of Medicine, New York, NY. †Department of Clinical Education and Clinic Operations, College of Podiatric Medicine, Kent State University, Independence, OH.
Corresponding author: Bryan Markinson, DPM, Mount Sinai School of Medicine in New York, NY 10029. (E-mail: [email protected])
[Abstract] Background: We sought to evaluate the efficacy of efinaconazole topical solution, 10%, in patients with onychomycosis and coexisting tinea pedis.
1
Methods: We analyzed 1,655 patients, aged 18 to 70 years, randomized (3:1) to receive efinaconazole topical solution, 10%, or vehicle from two identical multicenter, double-blind, vehicle-controlled 48-week studies evaluating safety and efficacy. The primary end point was complete cure rate (0% clinical involvement of the target toenail and negative potassium hydroxide examination and fungal culture findings) at week 52. Three groups were compared: patients with onychomycosis and coexisting interdigital tinea pedis on-study (treated or left untreated) and those with no coexisting tinea pedis. Results: Treatment with efinaconazole topical solution, 10%, was significantly more effective than vehicle use irrespective of the coexistence of tinea pedis or its treatment. Overall, 352 patients with onychomycosis (21.3%) had coexisting interdigital tinea pedis at baseline, with 215 of these patients (61.1%) receiving investigator-approved topical antifungal agents for their tinea pedis in addition to their randomized onychomycosis treatment. At week 52, efinaconazole complete cure rates of 29.4% were reported in patients with onychomycosis when coexisting tinea pedis was treated compared with 16.1% when coexisting tinea pedis was not treated. Both cure rates were significant compared with vehicle (P = .003 and .045, respectively), and in the latter subgroup, no patients treated with vehicle achieved a complete cure. Conclusions: Treatment of coexisting tinea pedis in patients with onychomycosis enhances the efficacy of once-daily topical treatment with efinaconazole topical solution, 10%.
Onychomycosis is a progressive fungal infection of the nail bed, matrix, or plate; it leads to destruction and deformity of the toenails and (less frequently) fingernails.1,2 It represents up to 50% of all nail disorders and is usually associated with tinea pedis.1,3 Toenail onychomycosis
2
frequently involves several nails4 and can be more challenging to treat because of the nail’s slower growth rate and coexisting nail infection.5,6 It is well recognized in podiatric medical practice that onychomycosis and tinea pedis coexist, that tinea pedis can lead to onychomycosis, and that it is important to evaluate and treat both diseases. Onychomycosis represents more than half of all the nail disease we see, and more than a third of these patients also have tinea pedis. Treating their tinea pedis is important for preventing onychomycosis recurrence because the fungal pathogens infecting the skin may act as a reservoir for reinfection of the nail. The true prevalence of coexisting onychomycosis and tinea pedis is unknown. Neither are life-threatening diseases, and studies suggest that patients do not always seek medical advice unless their quality of life is significantly affected.7,8 This may be one reason why we see differences in prevalence rates among various studies. Other factors could include differences in methods, population sample (healthy general population or dermatologic patients), and study size.8,9 Onychomycosis and tinea pedis prevalence rates are also reported to be affected by social status, occupation, climate, travel, living environment, age, and several predisposing factors.3,7-9 The large Achilles screening project revealed that 56% to 62% of dermatologic patients had foot disease independent of their presenting medical concerns.10,11 Onychomycosis and tinea pedis were the most commonly diagnosed foot diseases; in some cases, they can coexist. In a large study of more than 2,700 patients with onychomycosis, approximately a third of them (33.8%) also had tinea pedis, with interdigital tinea pedis being the most common (in 22.1% of patients).12 These data were similar to previously reported prevalence rates of coexisting disease.13,14 Generally, both disorders are more common in men,10,11,13 with the coexistence of toenail
3
onychomycosis and tinea pedis being more prevalent in this sex (P < .001). Concomitant tinea pedis was more often observed in patients with recurrent toenail onychomycosis (P < .001), more advanced toenail onychomycosis (ie, in patients with bilateral toenail onychomycosis) (P < .001), and those with a higher number of affected toenails (P < .001).12 The coexistence of toenail onychomycosis and tinea pedis has also been reported to increase with age, and it is estimated that 25.7% of elderly individuals have both types of infection simultaneously.15 Tinea pedis may precede toenail onychomycosis.16 Many patients with toenail onychomycosis or tinea pedis are not aware that they have a fungal infection, and such patients pose a special challenge for physicians to detect and treat their disease.8,17,18 Although it is well recognized that the two diseases coexist and that tinea pedis can lead to onychomycosis, there are no data comparing the outcomes of treating patients with onychomycosis and coexisting tinea pedis where both diseases are treated. Two identical 52week prospective, multicenter, randomized, double-blind studies in 1,655 patients (aged 18–70 years) assessed the safety and efficacy of efinaconazole topical solution, 10%, in the treatment of onychomycosis.19 We provide an analysis of efficacy in patients with coexisting tinea pedis who were treated for both diseases. We also compare data with those not treated for their tinea pedis and the remaining study population without coexisting disease.
Methods Two multicenter, randomized, double-blind, vehicle-controlled studies were designed to evaluate the efficacy, safety, and tolerability of efinaconazole topical solution, 10%, relative to its vehicle in 1,655 male and female patients aged 18 to 70 years with mild-to-moderate toenail onychomycosis. Detailed methods have already been reported, and a brief summary is provided
4
herein.19 Patients who presented with 20% to 50% clinical involvement of the target toenail were randomized (3:1) to receive efinaconazole topical solution, 10%, or vehicle applied once daily to the toenails for 48 weeks, with 4-week posttreatment follow-up. Investigators (podiatric physicians and dermatologists) examined both feet for the presence of tinea pedis and were allowed to treat interdigital tinea pedis with an investigatorapproved topical antifungal agent. Patients were categorized based on the presence of tinea pedis and whether their tinea pedis was treated. All investigators received identical training within and across investigational centers and used standardized scales and tools to measure and report efficacy variables.
Efficacy Evaluation Efficacy evaluations were performed at baseline, at 12-week intervals after baseline (ie, weeks 12, 24, 36, and 48), and at the final visit (week 52). The primary end point was complete cure rate (0% clinical involvement of the target toenail and negative potassium hydroxide examination and fungal culture findings) at week 52. Secondary end points were mycologic cure (negative potassium hydroxide examination and fungal culture findings), treatment success FOLQLFDOLQYROYHPHQWRIWKHWDUJHWWRHQDLO FRPSOHWHRUDOPRVWFRPSOHWHFXUH clinical involvement and mycologic cure), and unaffected toenail growth (change from baseline). All of the secondary end points were assessed at week 52. The intention-to-treat population included all patients randomized to receive and dispensed study drug. Efficacy end points were compared using Cochran-Mantel-Haenszel tests (stratified by analysis center) at a 5% significance level. Missing efficacy data were imputed
5
using the last-observation-carried-forward method.
Results Of 1,655 patients with onychomycosis, 352 (21.3%) reported having interdigital tinea pedis at baseline. Of these, 215 patients (61.1%) were treated for their tinea pedis with investigatorapproved topical antifungal drug therapy in addition to receiving efinaconazole topical solution, 10%, or vehicle for their onychomycosis. The most widely used antifungal agents to treat tinea pedis were topical butenafine (64 patients), luliconazole (52 patients), and ketoconazole (23 patients). Overall, 1,436 patients (86.8%) completed the 48-week treatment with efinaconazole or vehicle and 1,420 patients (85.8%) completed the 4-week follow-up.19
Primary Efficacy End Point (Observed Case)
Efinaconazole topical solution, 10%, was more effective than vehicle in treating onychomycosis, irrespective of the coexistence of interdigital tinea pedis or its treatment. At week 52, 24.0% of patients with onychomycosis and coexisting tinea pedis on-study (55 of 229) had a complete cure with efinaconazole treatment compared with 5.7% (5 of 88) with vehicle use (P < .001). When coexisting tinea pedis was treated, onychomycosis complete cure rates were 29.4% (40 of 136) with efinaconazole treatment and 7.8% (5 of 64) with vehicle use (P = .003). When patients’ tinea pedis was not treated, 16.1% (15 of 93) had a complete cure with efinaconazole treatment compared with 0% with vehicle use (P = .045) (Fig. 1). This contrasted with complete cure rates of 16.9% (141 of 833) and 4.3% (11 of 255), respectively (P < .001), at week 52 in patients without tinea pedis.
Supportive and Secondary Efficacy End Points (Observed Case)
6
At week 52, 51.7% of patients with onychomycosis and coexisting tinea pedis on-study (119 of 230) achieved a mycologic cure with efinaconazole treatment compared with 22.7% (20 of 88) being treated with vehicle (P < .001). When coexisting tinea pedis was treated, 56.2% of patients with onychomycosis (77 of 137) had a mycologic cure with efinaconazole use compared with 26.6% (17 of 64) taking vehicle (P < .001). When tinea pedis was not treated, 45.2% of patients (42 of 93) had a mycologic cure with efinaconazole use compared with 12.5% (3 of 24) with vehicle use (P = .007) (Fig. 2). These data compared with 57.6% (480 of 834) and 14.5% (37 of 255), respectively, in patients with onychomycosis where no tinea pedis was reported (P < .001). In addition, more patients with onychomycosis achieved a complete or almost complete cure at week 52 when their coexisting tinea pedis was treated: 37.5% (51 of 136) with efinaconazole use and 14.1% (9 of 64) with vehicle use (P = .005). When their tinea pedis was not treated, only 23.7% of patients (22 of 93) achieved a complete or almost complete cure with efinaconazole use, and no patients had a complete or almost complete cure with vehicle use (P = .011). Most patients (52.6%) treated with efinaconazole were considered treatment successes at week 52 compared with 20.5% being treated with vehicle (P < .001). When their tinea pedis was treated, 58.8% of patients (80 of 136) were considered treatment successes with efinaconazole use compared with 26.6% (17 of 64) being treated with vehicle (P < .001). When not treated, only 43.6% of patients (41 of 94) were considered treatment successes with efinaconazole use compared with 4.2% (1 of 24) being treated with vehicle (P .001). This compared with 45.7% (385 of 842) and 17.4% (45 of 258), respectively, for patients without coexisting tinea pedis (P < .001) (Fig. 3).
7
Discussion The coexistence of onychomycosis and tinea pedis is commonplace in podiatric medical practice. The need to diagnose and treat both diseases when present is well recognized; however, to our knowledge, this is the first study to investigate the resultant clinical benefit in terms of treatment success. The safety and efficacy of efinaconazole topical solution, 10%, in treating mild-tomoderate onychomycosis has been reported elsewhere.19 Overall, more than 21% of patients reported coexisting interdigital tinea pedis on-study. These findings were similar to the prevalence reported in the literature.12 In the present study, efinaconazole topical solution, 10%, was more effective than vehicle in treating onychomycosis, irrespective of the coexistence of tinea pedis and, especially, whether the tinea pedis was treated. Onychomycosis complete cure rates with efinaconazole treatment in patients with coexisting tinea pedis that was treated were almost twice those seen in patients with coexisting tinea pedis that was not treated, with almost 60% of patients considered a treatment success by week 52. The benefits of treating coexisting tinea pedis on onychomycosis outcomes were further illustrated in the vehicle group; no patients were completely or almost completely cured of their onychomycosis by week 52 when coexisting tinea pedis was left untreated. More than 60% of the patients with onychomycosis and tinea pedis on-study were treated for their coexisting disease, and the better onychomycosis efficacy results reported confirm best practice. However, no information exists on the success of their tinea pedis treatment, and there is no detailed appreciation of the severity of disease. In addition, it was unclear why some patients with coexisting tinea pedis on-study did not have their infection treated.
8
It was noted that efficacy results with efinaconazole and vehicle were higher in patients with onychomycosis where coexisting tinea pedis was treated compared with those where no tinea pedis was reported. Although we believe that the effect was due to combination therapy, we lack data to substantiate patient compliance rates for the treatment of tinea pedis; therefore, this could be a confounder. The studies were not designed to address whether the treatment of both coexisting onychomycosis and tinea pedis improves patient outcomes; however, the results of the post hoc analysis support the importance of treating both diseases.
Acknowledgment: Brian Bulley, MSc, of Inergy Limited for medical writing support. Financial Disclosure: Valeant Pharmaceuticals North America LLC funded Inergy’s activities pertaining to this work. Conflict of Interest: Drs. Markinson and Caldwell have served as paid consultants to Valeant Pharmaceuticals North America LLC.
References 1.
Scher RK, Coppa LM: Advances in the diagnosis and treatment of onychomycosis. Hosp
Med 34: 11, 1998. 2.
Crissey JT: Common dermatophyte infections: a simple diagnostic test and current
management. Postgrad Med 103: 191, 1998. 3.
Gupta AK, Jain HC, Lynde CW, et al: Prevalence and epidemiology of onychomycosis in
patients visiting physicians’ offices: a multicenter Canadian survey of 15,000 patients. J Am Acad Dermatol 43: 244, 2000.
9
4.
Roberts DT: Onychomycosis: current treatment and future challenges. Br J Dermatol 141
(suppl 56): 1, 1999. 5.
Finch JJ, Warshaw EM: Toenail onychomycosis: current and future treatment options.
Dermatol Ther 20: 31, 2007. 6.
Kumar S, Kimball AB: New antifungal therapies for the treatment of onychomycosis.
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Figure 1. Comparison of complete cure rates at week 52 in the observed case, intention-to-treat population. Complete cure is defined as 0% clinical involvement of the target toenail and negative potassium hydroxide examination and fungal culture findings.
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Figure 2. Comparison of mycologic cure rates at week 52 in the observed case, intention-to-treat population. Mycologic cure is defined as negative potassium hydroxide examination and fungal culture findings.
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Figure 3. Comparison of treatment success at week 52 in the observed case, intention-to-treat population. Treatment success is defined as 10% or less clinical involvement of the target toenail.
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