Skin therapy letter.
`v. 21, no. 6 (Nov-Dec 2016)
`General Collection
`W1 SKSQQP
`2017-01-27 06:07:13
`
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`indexed by the US National Library of Medicine and PubMed
`
`Volume 21- Number 6 - November-December 2016
`
`EDITOR: DR. RICHARD THOMAS
`
`
`
`A Review of Ixekizumab, an Anti-lnterleukin-1 7A Monoclonal
`
`Antibody, for Moderate-to-Severe Plaque Psoriasis
`Andrew J. Peranteau, MD‘; Ashley E.Turkeltaub2; Yun Tong,” MD3; Zeena Nawas, MD“;
`Stephen K. Tyring, MD, PhD”
`‘Cenfer for Ciinicai Studies, Houston, TX, USA
`zBaylor Coiiege ofMedicine, Houston, TX, USA
`
`inepartment ofDermatology, University of California San Diego, San Diego, CA, USA
`‘Department of Dermatology. University of Texas Health Science Center at Houston, Houston, TX, USA
`Conflicts of Interest: Dr. Tyring has been an investigator for clinical trials sponsored by Abbvie, Amgen. Boehringer lngelheim, Celgene, Coherus, Contravir,
`Cutanea. Dermira, Galderma, Genocea, Innovaderm. Janssen, Eli Lilly and Company, Leo Pharma, Merck, MSD, Medimmune, Novan, Novartis, Pfizer, Promius,
`Regeneroni Tolmar, Vitae. Watson-Actavis, and Xoma. Drs. Peranteau. Tong, and Nawas have been sub-investigators on clinical trials sponsored by the some
`companies listed above. Ashley Turkeitaub has no conflicts of interest to declare.
`
`ABSTRACT
`
`
`
`Psoriasis is a ninitifirctoriol chronic skin disease that can have Significant detrimental cflccts on patients" pin/sicni, mental, and
`psychosocial wcllbeing. Patients ofrcn suflcrfiom a decreased quality of life along with ironicaan cinnorbidilics. Rcceni advances
`in our understanding of the innate and adaptive inmronc systems have led to the identification ol'inrcricultin (NJ-l7 as a key
`pradlfilmrnnniory nmdiator in psoriasis. This knowledge has in turn led to tire dcrciopnrcni ofnc wci' biologic agents that franc bccn
`shown to be more reflective than traditional therapies. In this article, we review phase 1-3 clinical rriois rifdm onti—IL--i7 monoclomd
`antibody, ixekizmnoh for treatment ofmodcmrc-ro-screrc ploqnc psoriasis.
`
`
`
`
`
`
`
`
`
`
`Key words: IL— ] 7, intcrlcukin - l 7. inlcrleuk in— 1 7A, monoclonal antibody, ch ronic plaque psoriasis, Talia“
`
`intrcid uction
`
`Psoriasis is a chronic imrmincrmediated inflammatory skin
`disease characterized by inflamed. thickened. scaly, and pruritic
`plaques1 Although prevalence estimates vary by study. about
`2—3% of the world’s population — approximately 125 million
`people — are affected by psoriasis? " While topical theta-pics alone
`are generally sufficient to control mild psoriasis, patients with
`moderatcuto-scvcrc disease typically require systcmic therapy.“
`
`Systemic treatments target specific immunological pathways
`implicated in the pathogenesis of psoriasis.“ This includes
`biologics such as ctancrccpt. adalimumab. and mllnnmab
`— inhibitors of tumor necrosis factor alpha (’I‘Nl'ltx)." Use of
`these biologics is often preferer due to nun-compliance and
`frustration caused by the lack of efficacy with traditional topical
`therapies and phototbcrapy.“ Moreover, topical-treatments and
`phototherapy do not address the undcrlyingjotni disease sccn
`in psoriatic arthritis, which can affect up to 30% olpaticnts with
`psoriasis.”
`Despite the advantages of 'l'NFot lrcatmcnt. some palicnls
`experience insufficient response,
`loss of efficacy, or side
`effects that preclude them from using these drugs long-l‘crm.
`Additionally, newer trials with biologics targeting interleukin
`
`(lid—12:23 and 1L-l7 have shown increased efficacy in a gl‘catcr
`proportion of pal icnts,5 prompting further investigations of these
`lhcrapcutic options.”
`
`Rationale for IL-17 Inhibition in Psoriasis
`
`[)ysrcgulalion ol'bolh the innate and adaptive immune systems
`has long been implicated in psoriasis. Early studies indicaled
`that 'l‘NFu—producing 'l‘-bclpcr {'l‘h)l cells drives much of
`the inflammatory cyclc, as cvidcnccd by the favorable clinical
`response in TNth antagonists.‘ in rcccnl years. however, novel
`pathways have been discovered that implicate the p40 subunit of
`li,—12 and ll.—23 in the induction oiiniloiinnmnity. H.423 has also
`been foqu to bc a key driver of'l'h 17 cells, a 'l'—ccll subset dist inct
`from both 'l'h] and ’l‘h2 cclls. 'I‘his subgroup of (334+ T cells
`provides protection against extracellular bacterial and fungal
`pathogens, anti are now understood to play a ccntral role in the
`pathogenesis ol‘ p.st1riasis.5‘l‘I
`
`in the psorialic pathway, activated dendritic cells act as antigen
`presenting cells that produce an array of inflammatory cytokincs.
`including 'l'Nliot and lL—23.
`[1,—23 drives activation of TI) | 7
`cells, which in turn produce 11.717, HA), TM“, and other pro-
`inllannnatory cytokincs.” 'l‘hoso cylokincs induce changes in
`kcratinocytcs and the slain vasculature through production of
`
`
`
`Mission for-tho Treatment of anchomycosis (page 7)
`
`
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`Page 1 of 7
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`Kaken Exhibit 20 84
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`Acrux V. Kaken
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`IPR2017-00190
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`

`

`Update on Efinaconazole 1 0% Topical Solution for the
`
`Treatment of Onychomycosis
`
`Aditya K Gupta, MD, PhD, FRCPC"2 and Catherine Studholme, PhD:
`'Department ofMedr’cine, University of Toronto, Toronto, ON, Canada
`’Medr'probe Research Inc, London, ON, Canada
`Conflicts of interest: Aditya Gupta has been a clinical trials investigator torValeant Canada. Nuvolase, Bristol Meyers Squibb. Eli Lilly, Merck, Novartis, lanssen
`and Allergen; and has served as a speaker or consultant for Valeant Canada. Janssen, Novartis, Sandoz, Moberg Pharma, and Bayer.
`Catherine Studholme was an employee of Mediprobe Research inc. which conducts clinical trials under the supervision of Aditya Gupta.
`
`
`ABSTRACT
`
`
`
`Efirraconazole l0% nail solution is a novel topical antifimgal drug for the treatment of onychoniycosr's. Two Phase Ill trials were
`completed using efinaconazole 10% nail solution, where 17.8% and 5.2% ofpatients achieved complete cure, and 55.2% and 53.4%
`achieved mycological cure. Several post hoc analyses were carried out using data from Phase lt‘lr trials to determine the eflicacy of
`efinaconnzole with respect to disease duration, dismse progression, and comorbidities ofdiabetes or tinea paths with onychomycosis.
`Eflnaconazolc produced higher rflrcocy rates with patients presenting orwchonnlcosis in a small portion of the toenail (525%) for
`a shorter duration of time (<l year and 15 years). When patients prerenting with both ornrchornycosis and tinea pedis underwent
`concurrent treatment, efiicrtcy of efinaconazole increased from 16.1% to 29.4%, suggesting corrrlaination therapyJ improved
`results. Most interestingly there was no diflierence in cfinoconazole efficacy between diabetic and non—diabetic groups, indicating
`efinaconazole could he a safe and moreform oftreatmentfor diabetics. Orerall, efinoconazolc 10% unit solution shows potential
`as an antifrrngal therapyfor the treatment ofonychornycosis.
`
`
`
`
`
`
`
`
`
`Keir words: flmifllngal agent, efinaconazole, fungal nail infection, Inbliu®, onychomycosis, topical triazole
`
`
`
`
`
`
`
`
`
`
`
`
`
`Introduction
`
`Onychomycosis is a fungal infection of the nail unit caused
`by dermatophytcs, yeasts, and nondermatophyte molds.l
`Onychomycosis affects toenails more frequently than fingernails
`and accounts for 50% of nail disease.2-’Althorrgh this infection
`can be perceived as merely a cosmetic issue of thickening and
`discoloration of the nail plate, onychOmycosis can result in
`numerous side effects that can impede the use of shoes and make
`walking difficult in general, leading to decreased quality of life.“-5
`Additional risks include bacterial infections, foot ulcers, and
`gangrene." As a commonly occurring disease, it affects 243% of
`the general population, with prevalence of up to 50% in patients
`aged 70 years or higher.7 Along with advanced age, there are
`several other risk factors including diabetes. peripheral arterial
`disease, immunosupprcssion, and other preexisting nail diseases
`like psoriasis.“ Due to an increased chance of comorbiditY With
`onychomycosis, most recent investigational interests have focusad
`on topical antifungals, which have a lower risk of adverse effects
`and drug-drug interactions.
`
`The goal of onychomycosis treatment is restoring the nail to a
`normal appearance and complete eradication of fungus. This
`can be difficult to achieve as the nail plate acts as a barrier for
`tOPical treatmenw, and poor circulation in the elderly can prevent
`systemic treatments from reaching their target. Although some
`therapies can resalt in complete clinical and mycologiCal cure. the
`rates are low (35-50%), and risk of relapse is high (10—53%)?
`Currently, there are five classes of drugs approved for the
`treatment of onychomycosis: aliylamines, azoles, morpholines,
`hydroxypyridinones, and benzoxaboroles.'”'“ Historically,
`systemic therapies have been the most effective, with the oral
`allylamine terbinafine being the current gold standard with a
`complete cure rate of 38% and mycological cure rate of 74%.”"3
`
`The recommended dose of terbinafine for toenail onychomycosis
`is 250 mg daily for 12 weeks. Patients who are high risk for adverse
`effects from oral autifungals are prescribed topical agents. in the
`US there are three topical therapies approved for the treatment
`of onychomycosis: ciclopirox 8% nail solution, tavaborole 5%
`solution, and efinaconazole 10% solution. Given the challenges of
`transungual delivery. there is a need for novel topical antifungals
`that can increase penetrance, are potent, and carry minimal side
`effects.
`
`Efinaconazole 10% solution is a novel topical antifungal of the
`azole class that was US FDA approved for the treatment of toenail
`onychornycosis in June 2014.“ Efinaconazole has demonstrated
`a broad spectrum of activity against dermatophytcs and yeasts
`in vitro,ls and has uniquely low keratin affinity, allowing drug
`release from keratin and enhanced penetration through the nail
`plate compared to ciciopirox and amorolftnc.” Due to the unique
`formulation of efinaconazole, both transungual and subungual
`routes of delivery are achieved as the drug penetrates through
`the nail plate into the underlying nail bed, as well as via spreading
`around and under the nail plate through the air gap to reach
`the fungal infection.1m Recently, a human cadaver nail study
`demonstrated that efmaconazole is able to penetrate the nail
`even in the presence of nail polish,“’ which may be a potential
`advantage for patients concerned with hiding nail abnormalities
`while at the some time using a topical treatment. Efinaconazole
`works by inhibiting the synthesis of ergosterol, an essential
`structural component of fungal cell membranes?“2L Its inhibition
`results in a loss of cell membrane integrity, thus preventing fungal
`cell growthm'
`
`Previously, two identical, randomized, double-blind, vehicle-
`controlled Phase II] studies were performed using 1655
`patients with mild to moderate toenail onychomycosis.22 The
`
`Skin “Empylreflc’r‘ - Editor: Dr. RlChard Thomas -Volume 21, Number 6 o November—December 20l6
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`7
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`Page 2 of 7
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`treatment course was once daily application of efinaconaaole
`10% nail solution to the affected toenail and underside, as well
`as surrounding skin, for 48 weelts followed by a 4 week washout
`period.23 At week 52, 17.8% and 15.2% of patients achieved
`complete cure,antl 55.2% and 53.4% achieved mycological cure.“
`Interestingly, female patients demonstrated high er efficacies than
`males (27.1% vs 15.8%, respectively, P=0.001), where the only
`notable difference between genders were mean weight (73.3 kg
`and 90.2 kg).22 Further subgroup analyses were completed using
`Phase III data to elucidate the differences in treatment efficacy
`in patients with concurrent tinea pedis or diabetes, as well as
`duration and severity of diseased-5'3”
`
`Clinical Efficacy
`
`Consistent with previous findings,” 21.3% (352/1655) of
`patients from Phase III clinical trials reported onychomycosis
`with concurrent tinea pedis, and 61.1% (215352) underwent
`concomitant treatment for tinea pedis with an investigator-
`approved topical antifiingal.i"-"’ Butenafine, luliconazole, and
`ketoconazole were the most commonly used topical antifungal
`agents for tinea pedis treatment; used by 64, 52, and 23 patients,
`respectively.” With concomitant treatment of onychomycosis
`(efinaconazole) and tinea pedis, complete and mycological cure
`rates were 29.4% and 56.2%, respectively (7.8% and 26.6%
`vehicle, P:0.003 and P<0.001, respectively). When tinea pedis
`was left untreated, complete and mycological cure rates were
`16.1% and 45.2% (0% and 12.5% vehicle, l’=0.045 and P:0.007,
`respectively). Efinaconazole treatment was superior to all vehicle
`outcomes, and concurrent treatment for tinea pedis was superior
`to untreated tinea pedis measures. Moreover, patients treated with
`efinaconazole achieved a higher complete or almost complete
`cure and higher treatment success, compared with vehicle (data
`summarized in Table 1). Complete or almost complete cure was
`defined as 55% clinical involvement of the target toenail plus
`mycologic cure. Treatment success was defined as 510% clinical
`involvement of the target toenail.
`
`0f the 1655 patients from Phase III clinical trials, 112 patients
`had coexistent onychotnycosis and diabetes.25 Only patients
`whose diabetes was under control (N296) were included in the
`study. Diabetic (N269) and nonrdiabetic (N=993) patients had
`similar efficacies when treated with efinaconazole, with complete
`cure rates of 13% and 18.8%. respectively and mycological
`cure rates of 56.5% and 56.3%, respectively. These values were
`significantly higher than vehicle (N =27) for complete cure (3.7%
`and 4.7%, P<0.001 for both) and mycological cure (14.8%,
`P:0.016, and approximately 17.4%, P<0.001) for diabetic and
`nonrdiabetic patients, respectively. Moreover, patients receiving
`efinaconazole treatment had greater success achieving complete
`or almost complete cures as well as treatment success at
`week 52 (data summarized in Table 2). All secondary endpoints
`were identical to those defined above.
`
`Of all patients ( 1655) from Phase 11] trials, 1526 were categorized
`based on disease duration: <1 year (74 patients), 1—5 years (682
`patients), and >5 years (770 patients)” Complete cure rates of
`42.6%, 17.1%, and 16.2% were observed in efinaconazolertreated
`patients with <1 year, 1—5 years, and >5 years disease duration,
`respectively. Complete cure rates with efinaconazole treatment
`were significantly improved over vehicle for patients w1th baseline
`disease durations of 1-5 years (17.1% vs. 4.4%, P<0.001) and >5
`years (16.2% vs. 2.5%, P<0.001), however, this was not the case
`for patients presenting with onychomycosis for <1 year-(42.6%
`vs. 16.7%, not significant). It is possible that non—significance
`may be due to the small sample size (N=33 efinaconazole).
`Furthermore, 66.0%, 59.0%, and 53.8% of patients achieved
`mycological cure with disease duration of <1 year, 1—5 years, and
`>5 years, respectively. Similar to complete cure, the latter two
`durations were significantly different from vehicle (P <0.001).
`Lastly, while not significant for any duration, patients recelvmg
`efinaconazole treatment did show numerically higher complete
`or almost complete cure rates, as well as treatment success, for
`disease durations of<1 year (Figure 1), 175 years (Figure 2), or
`>5 years (Figure 3).All secondary endpoints are Identical to those
`defined above.
`
`
`
`
`
`Patients without
`- Tinea pedis-reported
`ifiéa lie-dis "mauled I
`
`
`,
`r’and treated
`'
`'
`“"93 Pad”
`but not treated
`
`
`
`
`{Vehicle .
`Efinaconazole
`Vehicle
`.: "..‘.’:.' Efi,'ia€0fi's.!ole.
`Efinaconazole
`Vehicle
`15/93
`0124
`1411333
`111255
`401136
`5164
`Complete cure
`(29.4%“
`(18%)
`(161%);
`(0%)
`(163%)c
`(4.3%)
`.
`771137
`171’64
`42193
`3124
`4801834
`3712255
`M I
`1
`you ogrca cure
`(56.2%)6
`(26.6%)
`(45.2%)”
`(115%)
`(516%);
`(14.5%)
`Completelalmost
`511136
`9164
`22:93
`0124
`_
`——
`complete cure
`(37.5%)”
`(14.1%)
`(23.7% )‘1
`(0%)
`T
`3351842
`sense
`17164
`41:94
`1124
`451258
`
`
`
`
`
`
`reatrnent success (17.4%) (58.8%), (ms-6%) (43.6%)c (4.2%) (453%):
`Table 1: Efficacy of efinaconazole in patients with concurrent tinea pedis, with or without concomitant treatment (Phase III studies].m"
`‘ P<0.05; b P<0.01;‘ P<0.00‘J efinaconazole significantly different from vehicle
`For Tables 1 to 3 and Figures 1 to 3:
`- Complete cure is defined as 0% clinical involvement ofthe target toenail plus negative potassium hydroxide [KOH) preparation and negative fungal culture.
`- Myeologlcal cure is defined as negative KOH preparation and negative fungal culture.
`- Completelalmost complete cure is defined as 35% clinical involvement ofthe target toenail and mycologic cure.
`- Treatment success is defined as 510% clinical involvement of the target toenail.
`
`w 8
`
`Skin mempylerrer‘ - Editor: Dr. Richard Thomas - Volume 21. Number 6 - NovembereDecember 2016
`
`Page 3 of 7
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`

`

`1. . urn—1...». .>.-‘.71-...r.-_1-.... Juan'u mum-4.1 pneumaem.:._.-.:.u.:...;.«_u_p_-..4_.c_
`.. cum-ch I...qu 4:4...“ tun—gun-» 1....)
`mun-Jam:MATT-25.5%. a.) M.» m. .-_.x..-.-.-..1nae-mu.».~\: . -a_..:-.
`
`
`
`
`
`
`
`
`
` Proportianstilpatientslit
`
`
` 1
`Complete cute Wcolugicalcure Completefalmust
`Treatment
`complete cure
`success
`
`m Elinaconazole
`I: Vehicle
`
`Figure 1: Summary of cure rates for patients with baseline disease
`duration of <1 year with efinaconazole."
`While cure rates are numerically higher for all efficacy outcomes.
`efinaconazole cure rates were not significantly greater than vehicle.
`
`
`
`
`
`
`
`DJ Efinaconazole
`El Vehicle
`
`
` Proportionsofpatientsit
`
`
`
`Non-diabetic
`
`
`patients '
`patients
`
`_
`
`
`Complete
`cure
`Mycological
`cure
`
`9169
`(13.11%)b
`39159
`(56.5%)a
`
`1127
`(3.7%)
`4127
`(14.8%)
`
`11171993
`(13.11%)b
`513111995b
`(56.3%)
`
`151316
`(4.7%)
`
`(17.4%)
`
`11.1111,
`
`_
`
`'
`
`ssnmnmtt
`
`Vuhkta
`
`17169
`:‘lflflete’
`completeww (24.6%)
`
`2127
`(7.4%)
`
`2771993
`(27.9%)
`
`4
`
`Treatment
`success
`
`29171
`(40.3%)
`
`5127
`(13.5%)
`
`47711001
`(47.7%)b
`
`581319
`(13.2%)
`
`Table 2: Efficacy of efinaconazole in diabetic vs non-diabetic
`patients Phase II] studies)”
`a P<D.05; b P<0.001 efinaconazole significantly different from vehicle
`
`Finally, effectiveness of efinaconazole based on disease severity
`was measured using 414. patients with mild onychomycosis
`(325% nail involvement), and 1237 patients with moderately
`severe onychomycosis (>25% nail involvement).23 Patients
`presenting with mild onychomycosis had complete and
`mycological cure rates of 25.8% and 58.2%, respectively, which are
`significantly higher than vehicle cure rates of 11.3% (P=0.006)
`and 25.0% (P<0.001), respectively. Patients with moderately
`severe onychomycosis had complete and mycological cure rates
`of 15.9% and 55.6%, respectively, again demonstrating significant
`Improvement over vehicle cure rates of 2.7% and 14.1% (P<0.001
`for both), respectively. Moreover, all patients with efinaconazole
`treatment had significantly higher complete or almost complete
`Cure rates and treatment success compare to vehicle (summarized
`in Table 3, P<0.001 for all).All secondary endpoints were identical
`to those defined above.
`
` '
`
`_ Moderately severe :
`onyehomycosis
`{225% toenail
`
`Involvement}
`'
`‘iPifi-mén.“
`
`ran-men'-
`"M-
`..
`
`
` ass-.911 (sass; t-
`
`81312
`1471925
`121103
`801311
`(2.7%)
`(15.9%)b
`(11.3%)
`(25.11%)1
`Compl‘itecure
`441312
`5141925
`261103
`1811311
`Mycological
`(14.1%)
`(55.6%)”
`(25.11%)
`(58.2%)b
`cure
`151312
`22519251)
`131103
`1171311
`Effliew
`I.)
`(4.9%)
`(24.3%)
`(17.5%)
`completecm (37.5%)
`381312
`3761925
`391103
`Treatment
`2041311
`
`(12.1%)
`success
`(65.7%)b
`(37.3%)
`(40.7%)”
`Table 3: Efficacy of efinaconazole in patients with varying severity
`of disease (Phase III studies)?“
`a P<0.0l; b P<D.001 efinaconazole significantlydifferent from vehicle
`
`
`
`
`
`Complete cure Mycologiral cure Completehlmost
`complete cute
`
`treatment
`success
`
`Figure 2: Summary of cure rates for patients with baseline disease
`duration of 1-5 years with efinaconazoie?’
`'P<0.00! compared to vehicle
`
`
`
`‘16
`
`Prepsrtionsofpatients
`
`Complete curt: Mycologioal cure Complelefalrnost
`complete cure
`
`Treatment
`success
`
`to Efinaconazole
`9 Vehicle
`
`Figure 3: Summary of cure rates for patients with baseline disease
`duration of >5 years with efinaconazole."
`'P<D.Utli compared to vehicle
`
`
`
`Skin Therapyletter‘ - Editor: Dr. Richard Thomas - Volume 2|. Number 6 - November-December 2016
`
`9
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`Page 4 of 7
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`

`"M'J‘i'H-l-‘J'uo mu'- .-=nr ‘MVI‘I-i'm-a"vi-1.11.1.- a a na Linc-l.'atu‘..u'.4—241am at...was.LamaumAAWHsguawu-wuuwo
`
`Discussion
`
`References
`
`:- wo-wwumqumuy-um.h'l'u'-.W5-1.9:u an"..- .m...
`
`
`
`
`
`
`The data from two Phase III clinical trials have been analyzed and
`the efficacy of efinaconazole with respect to concurrent treatment
`for tinea pedis, diabetic patients, disease duration, and severity
`of disease shows promise. Efficacies were highest among patients
`with less severe (325% nail involvement) and shorter disease
`duration {<1 year and 1-5 years) compared to vehicle.
`Efinaconazole treatment was more effective than vehicle for the
`treatment of onychomycosis with or without concurrent treatment
`of tinea pedis. Since one—third of onychomycosis patients also
`have tinea pedis, it is recommended that patients are examined
`for concomitant dermatomycoses, and treatment for both fungal
`infections (if present) be sought, as pathogens that cause tinea
`pedis can also lead to onychomycosis.1m Although concurrent
`treatment for tinea pedis and onychomycosis {efinaconazole)
`improved complete cure rates from 16.1% to 29.4%, there was
`no information about the severity of tinea pedis, or the success
`of tinea pedis treatment. Therefore, further testing would need
`to be completed to confirm whether combination therapy could
`increase treatment efficacy of both fungal infections.
`
`Onychomycosis in diabetic patients is extremely difficult to treat
`with traditional antifungals due to hyperglycemia and problematic
`foot hygiene." Moreover, onychomycosis left untreated poses a
`significant risk for further complications that can potentially lead
`to loss of limb?“ The findings that the efficacy of efinaconazole
`was comparable between diabetic and non-diabetic patients
`and cure rates for both groups were significantly higher than
`respective vehicle groups, indicate that diabetics can now receive
`safe and effective treatment for onyehomyc05is.
`In summary, good responders to efinaconazole treatment are
`more likely to be patients with mild (525% clinical toenail
`involvement) onychomycosis and have a low number of non-
`target nail involvement,23 with early or baseline onychomycosis
`(<1 year or 1—5 years, respectively)? who receive concurrent
`treatment for tinea pedis (if present),2'3‘3° are female,22 and weigh
`<84.4 kg.“ Most interestingly, whether patients were diabetic
`or non-diabetic had no effect on the efficacy of etinaconazole
`treatment.
`
`Efinaconazole 10% topical solution is an effective topical
`treatment for onychomycosis with favorable clinical and
`mycological efflcacies, low risk of drug-drug interactions, and a
`minimal side effect profile.“ With complete cure rates of 17.8%
`and 15.2%,21-34 and a favorable safety profile, efinaconazole also
`looks promising for use in Children and in combination therapy.
`Moreover, since levels of efinaconazole reach a steady state in
`the nail after 2 weeks of daily application, and remain at high
`concentrations well above the minimum inhibitory concentration
`for dermatophytes for at least 2 Weeks off therapy,55 it is possible
`that efinaconazole may be used twice Weekly as a maintenance
`regime. This strategy may be considered after the completion of
`the 48 week treatment period in order to prevent relapse; however,
`maintenance studies have yet to be conducted. Taken together,
`efinaconazole 10% topical solution is an easy to use, safe, and
`effective therapy for the treatment of onychomycosis.
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`filestlamisil_tablets.pclf Accessed September 26, 2016.
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`14. Elewski 11E, Rich P. Pollak R. et al. Efinaconaeole 10% solution in the treatment
`of toenail onychomycosis: two phase [II multicentcr, randomized, doubleblind
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`17. Gupta AK, Pillai R.The presence of an air gap between the nail plate and nail bed
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`13. Gupta AK, Simpson FC. Routes of drug delivery into the nail apparatus:
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`,l Dcrmntolog item. 2016 27(1):2—4.
`l9. Zeichner IA, Stein Goid 1., Korotzcr A. Penetration of ((14)C)7efinaconazole
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`labellZDI 4i203563’3000lblpdf. Accessed September 26, 2016.
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`H 1
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`Skin ThempyLetrer' - Editor: Dr. Richard Thomas - Volume 21, Number 6 - November-December 2016
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`Emmi! “nu-l: 16.4.1-55;.Julexam-uaiarmuwryug
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`
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`
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`24.
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`Lipner SR, Scher RK. Efinaconazole in the treatment of onychomycosis. infect
`Drug Resist. 2015 8:163—72.
`Vlahovic TC, Ioseph W3. Efinaconaaole topical, 10% for the treatment of
`toenail onychomycosis in patients with diabetes. ,1 Drugs Dermatol. 2014
`0ct;13(10):1136—90.
`Lipner SR, Scher RK. Management of onychomycosis and co-existing tinea
`pedis. l Drugs Dermatol. 2015 May;14(5):492—4.
`the benefits of
`Rich P. Efinaconazole topical
`solution, 10%:
`onychomycosis early. I Drugs Dermatol. 2015 lan;14(1):58-62.
`Rodriguez DA. Efinaconaaole topical solution, 10%. for the treatment ofmild and
`moderate toenail onychomycosisJ Clin Aesthet Dermatol. 2015 Inn;8(6):24—9.
`Seepietowski 1C, Reich A, Garlowska E, et a1, Onychomycosis Epidemiology Study
`Group. Factors influencing coexistence of toenail onychomycosis with tinea
`pedis and other dermatomycoses: a survey of2761 patients. Arch Dermatol. 2006
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`treating
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`with onychomycosis and coexisting tinea pedis. I Am Podiatr Merl Assoc. 2015
`Sep;105{5):407~11.
`infections of the feet in patients with
`Tan ]3, Ioseph WS. Common fungal
`diabetes mellitus. Drugs Aging. 2004 21(211101-12.
`Gupta AK, Humke S. The prevalence and management of onychomycosis in
`diabetic patients. Eur J Dermatol. 2000 ]ul-rtug:10(5):3?9-34.
`l’apini M, Cicoletti M, Fabriai V, et .11. Skin and nail mycnses in patients with
`diabetic foot. G Ital Dermatol Venereol. 2013 Dec;148{6):603-8.
`Lipner SR, Scher RK. Efinaconaanle 10% topical solution for the topical
`treatment of onychomycosis of the toenail. Expert Rev Clin Pitarmrtcol. 2015
`8(6):?19—31.
`Sakamoto M, Sugimoto N, Kawabata H, et al. Transnngnal delivery of
`efinaconazolc: its deposition in the nail of onychomycosis patients and in vitro
`fungicidal activity in human nails. l Drugs Dermatol. 2014 Nov;13(111:1388—92.
`
`an}
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`Skin ThempyLettef
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`http:/lwwws kinthera pyletterco mfipad lsupporthtmi
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`Available for iPad, Phone and iPod touch
`Provides instant access to all articles published to date.
`Powerful search functionality and intuitive navigation tools allow the user to find relevant information quickly.
`The application is updated automatically to include the most recently published articles.
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`Content 3: instructions can be found at:
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`Skinfliempylmer' - Editor: Dr. Richard Thomas - Votume 2|, Number 6 - November—December 2016
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`-————
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`
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`Biosimilar of
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`NATIONAL LIBRARY OF MEDICINE
`uDW-m,
` “111‘
`EDITOR-lN-CHIEF
`13491141995.
`
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`it
`Richard Thomas, MD
`
`SidraMedlcaland Research Center.Doha.Qatar
`_-
`_
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`‘
`ASSOCIATE EDITORS
`.
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`NL M [I 5 11 ‘7 j, 5 Li 1 5
`Hugo Degteef‘mntphn
`Brodalumab forSC The Ministry of Health, Labour and I
`filfl‘ii’lz'g'sflmgmmBelgium
`approved this fully human anti-interleukin tiny—i; LULLFtUr i,
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`UniversityofBritishColumbia,Vancouver.Canada
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`antibody in Iuly 2016 as a second-line treatment for psoriasis
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`EqDlTOdiiAlgLAE‘ngORY BOARD
`Kiowa Hakko Kim! vulgaris, psoriatic arthritis, pustular psoriasis, and psoriatic
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`m,
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`HakeemUnnamuwedtcatschootgkagwg
`erythroderma. Brodalumab binds With high affinity to 11,-17
`KennethA. Amdt, MD
`receptor A, thereby inhibiting several pro-inflammatory cytokines
`Harvard MeduulSchoolJostonmSA
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`pathoPhySIOIogy associatedWltl'l psoriasis.
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`Jan D.Bos,
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`UniversityofAmsterdam.Amsterdam-Holland
`In August 2016, the US FDA approved ErelziTM (etanercept-szzs),
`Etanercept—szzs for
`filfi‘rflgfgfifflgfifl:Vancouwr_camda_
`a tumor necrosis factor (TNi‘) blocker .biosimil'ar to Enbrel®
`SCinjection
`BryceCowan, MD, PhD
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`(etanercept, Amgen Inc.) for all indications Included In the reference
`“"‘W’S‘h‘MBm‘h ‘°'""‘b"’-”“"‘°“"°“Ca"ada
`Sandoz Inc,
`product label, including moderate to severe rheumatoid arthritis,
`moderate to severe poiyarticular juvenile idiopathic arthritis,
`Jeffrey 5. Dover, MD
`a Novartis division
`
`We University Sch not of Medlcine. New Haven. USA
`active psoriatic arthritis, active ankylosing spondylitis, and chronic
`Dartmouth Medlca'l School. Ha