ORIGINAL ARTICLES

Efinaconazole Topical Solution, 10%

Efficacy in Patients with Onychomycosis and Coexisting Tinea Pedis
Bryan Markinson, DPM*
Bryan Caldwell, DPM†

Background: We sought to evaluate the efficacy of efinaconazole topical solution, 10%,

in patients with onychomycosis and coexisting tinea pedis.
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,
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 ¼ .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%. (J Am Podiatr Med Assoc 105(5): 407-411, 2015)

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 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.
*Division of Podiatric Medicine and Surgery, Leni and
Peter W. May Department of 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:
Bryan.Markinson@mountsinai.org)
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 onychomy-
cosis 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 Onycho-
mycosis 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

Journal of the American Podiatric Medical Association  Vol 105  No 5  September/October 2015 407
 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 onycho-
mycosis 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 simulta-
neously.15
Tinea pedis may precede toenail onychomyco-
sis.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 52-week prospective, multi-
center, 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
408 September/October 2015  Vol 105  No 5  Journal of the American Podiatric Medical Association
mild-to-moderate toenail onychomycosis. Detailed
methods have already been reported, and a brief
summary is provided 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 dermatol-
ogists) examined both feet for the presence of tinea
pedis and were allowed to treat interdigital tinea
pedis with an investigator-approved topical antifun-
gal agent. Patients were categorized based on the
presence of tinea pedis and whether their tinea
pedis was treated. All investigators received identi-
cal 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 (10% clinical involvement of the
target toenail), complete or almost complete cure
(5% 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 who were
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 using the
last-observation-carried-forward method.
Results
Of 1,655 patients with onychomycosis, 352 (21.3%)
reported having interdigital tinea pedis. Of these,
215 patients (61.1%) were treated for their tinea
pedis with investigator-approved topical antifungal
drug therapy in addition to receiving efinaconazole
topical solution, 10%, or vehicle for their onycho-
mycosis. The most widely used antifungal agents to
treat tinea pedis were topical butenafine (64
patients), luliconazole (52 patients), and ketocona-
zole (23 patients). Overall, 1,436 patients (86.8%)
completed the 48-week treatment with efinacona-
zole 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, ony-
chomycosis complete cure rates were 29.4% (40 of
136) with efinaconazole treatment and 7.8% (5 of
64) with vehicle use (P ¼ .003). When patients’
tinea pedis was not treated, 16.1% (15 of 93) had a
complete cure with efinaconazole treatment com-
pared with 0% with vehicle use (P ¼ .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)
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 ¼ .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 ¼ .005). When
their tinea pedis was not treated, only 23.7% of
patients (22 of 93) achieved a complete or almost
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.
complete cure with efinaconazole use, and no
patients had a complete or almost complete cure
with vehicle use (P ¼ .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).
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 knowl-
edge, this is the first study to investigate the
resultant clinical benefit in terms of treatment
success.

Journal of the American Podiatric Medical Association  Vol 105  No 5  September/October 2015 409
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.
The safety and efficacy of efinaconazole topical
solution, 10%, in treating mild-to-moderate onycho-
mycosis 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 solu-
tion, 10%, was more effective than vehicle in
treating onychomycosis, irrespective of the coexis-
tence 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 onychomyco-
sis 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
410 September/October 2015  Vol 105  No 5  Journal of the American Podiatric Medical Association
Figure 3. Comparison of treatment success at week
52 in the observed case, intention-to-treat popula-
tion. Treatment success is defined as 10% or less
clinical involvement of the target toenail.
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.
It was noted that efficacy results with efinacona-
zole 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 treat-
ment of tinea pedis; therefore, this could be a
confounder.
The studies were not designed to address
whether the treatment of both coexisting onycho-
mycosis 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 Pharma-
ceuticals North America LLC.
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