comaprative efficacy treatment tinea corporis

8/2/2019 Comaprative Efficacy Treatment Tinea Corporis

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332 A. Singal et al.

A fungal culture was also performed in allpatients but a positive culture was not aprerequisite for inclusion in the study.

Pregnant and lactating females, patientswith extensive (w 20% of skin surface) tinea,concurrent skin diseases which couldinterfere with the clinical evaluation onsubsequent visits, or with other severesystemic diseases were excluded from thestudy. Patients with a history of treatmentwith other oral or topical antifungal drugs inthe previous 4 weeks or with knownhypersensitivity to allyalamines/imidazoleswere also excluded.

Eligible patients were randomized to

receive either butenafine (applied once dailyfor 2 weeks) or clotrimazole cream (twicedaily application for 4 weeks) in a double-blind manner. Individual drugs weredispensed in two identical containers of 5 gcapacity for morning and eveningapplication. As butenafine was to be appliedonce daily for 2 weeks, a placebo (vehicle)was supplied in a similar container forevening application for the initial 2 weeksand for twice daily application for the next 2weeks. For both groups, neither theinvestigators nor the patients were aware of

the composition of the drugs allocated. Aclinical nurse had the codes for the drugs,which were revealed only after completion ofthe study.

At the initial visit, all the study patientsunderwent detailed physical and cutaneousexamination. All clinical details wererecorded on a predesigned proforma. Thesymptoms and signs like erythema, scalingand pruritus were designated a scale of 0 to3 as follows: 05 none, 15 mild, 25moderateand 35severe. The individual symptomscores were added and a total score (clinicalassessment score) was recorded, with amaximum additive score of 9. Lesional skinscraping in 10% KOH was performed toconfirm the presence of hyphae. Fungalculture was done on Sebourauds dextroseagar medium to identify the fungal species.Laboratory tests including completehaemogram, liver and kidney function tests,random blood sugar and urine microscopywere done at the initial visit.

Patients were followed up after 1, 2, 4 andfinally 8 weeks (4 weeks after the cessation

of treatment). At each visit, clinicalexamination was carried out, clinicalassessment score was calculated and KOH

smear was repeated. Fungal culture wasrepeated at the second and fourth week.Blood tests were repeated at the fourth weekand whenever required. Adverse effects, ifany, were recorded at each visit.


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Table II. Profile of lesions among study population

(total580).Clinical cure was defined as aclinical assessment score of 0 or 1 at anytime during the 8-week study period.Mycological cure was defined as a negativeKOH smear at any follow-up visit. Relapse

was defined as a positive KOH smear at anypoint till 8 weeks, once it had becomenegative during the treatment.

2Results were analysed as per protocol. Thep value was calculated using the xtestand/or unpaired t test as appropriate. Thelevel of significance was set to 0.05.

Results Eighty patients fulfilled the inclusioncriteria during

the study period. Each patient was

randomized to either the butenafine or theclotrimazole group based on random tables.The baseline characteristics of the patientswere comparable (Table I). Twelve (30%)patients had a history of similar lesions inthe past in the same season and 11 (27.5%)patients had at least one family member withsimilar skin lesions, probably due to sharingof towels and clothes and the hot and humid

environment. In all, 50% of the patientsincluded in the study had tinea corporis and28.8% had both tinea corporis and crurisinfection simultaneously. Details of patientswith different types of lesions in both thetreatment groups are provided in Table II.

In the butenafine group, of the 40 patientsrecruited at baseline, 34, 31, 27 and 20patients were followed up after 1, 2, 4 and 8weeks, while in the clotrimazole group 34,32, 25 and 21 patients were followed atsimilar intervals. Others were lost to follow-up. Clinical assessment score wascalculated in both the treatment groups onall visits and mean score was calculated ateach time point. With treatment the scoredeclined significantly in both the treatmentgroups (Table III). In the butenafine

Table I. Baseline characteristics of patients in twotreatment groups.

Characteristics Butenafine (n540) Clotrimazole (n540)Males 30 (75%) 23 (57.5%)

3.68 3.92Females 10 (25%) 17 (42.5%) Age (years)28.7 10.46 29.311.52 KOH-positive 40 (100%) 40(100%) Positive culture 18 (45%) 20 (50%) Meanduration of disease (weeks)

Type of dermatophytosis Number of patients (% of total) Butenafine (n540) Clotrimazole (n540) T. cruris 17 (21.25) 107

T. corporis 40 (50) 18 22 T. cruris + T. corporis 23 (28.75) 12 11


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Butenafine and clotrimazole in tinea cruris and corporis 333

group, the mean score declined from 6.651.29 at baseline to 2.85 0.78 at week 1,1.00 0.63 at week 2, 0.56 0.51 at week 4,and 0.65 0.49 at week 8 (Figure 1). Themean reduction in the clinical assessmentscore from baseline was 5.90 1.04 at 2weeks and 6.56 1.12 at 4 weeks. In theclotrimazole group, the score reduced from amean of 6.45 1.28 at baseline to 3.12 0.84at week 1, 1.50 0.72 at week 2, 0.76 0.52at week 4 and 0.62 0.50 at week 8 (Figure1). The mean reduction in the clinicalassessment score from baseline at 2 weekswas 5.00 1.08 and at 4 weeks was 5.561.12.

The clinical assessment score in thebutenafine group was significantly less ascompared with the clotrimazole group at theend of 2 weeks of treatment (1.0 0.63 in thebutenafine group and 1.5 0.72 in theclotrimazole group, p50.005); however, atthe end of 4 weeks it became

Table III. Clinical assessment score.comparable in

the two treatment groups (0.56 0.51 inbutenafine group and 0.76 0.50 inclotrimazole group, p5 0.158) (Table III). Thereduction in the clinical assessment score at2 weeks as well as 4 weeks was significantlymore in the butenafine group than in theclotrimazole group (p5 0.001 at 2 weeks and0.002 at 4 weeks) (Table IV).

The number of patients achieving clinicalcure after treatment for 1 week and 2 weekswas significantly more in the butenafinegroup. However, this became statisticallycomparable at 4 as well as 8 weeks (Table

V). Similiarly, significantly more patientstreated with butenafine achievedmycological cure after treatment for 1 week;however, the number of patients achievingmycological cure became comparable after4 weeks (Table VI).

Eighteen patients in the butenafine groupand 20 in the clotrimazole group had apositive fungal culture at baseline. Allcultures were negative at 2

Post treatment

Pretreatment2 wks 4 wks 8 wks Butenafine6.651.29 (40) 1.00.63 (31) 0.560.51 (27) 0.650.49 (20)

Clotrimazole 6.451.28 (40) 1.50.72 (32) 0.760.52 (25) 0.620.50 (21) p value 0.489 0.005 0.158 0.842


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334 A. Singal et al.

Table IV. Reduction in clinical assessment score with treatment.

Week 2 Week 4

DrugNumber of patients Change in score* Number of patients Change in score** Butenafine 31 5.90 1.04 27 6.561.12

Clotrimazole 32 5.00 1.08 25 5.56 1.12

Butenafine vs clotrimazole *p value50.001, **pvalue50.002.

and 4 weeks in the butenafine group;however, three patients were culture-positivein the clotrimazole group at 2 weeks and oneat 4 weeks. T. rubrum was the mostcommonly isolated dermatophyte, grown in

29 of 38 isolates (76.3%), followed by E.floccosum in 7 (18.4%) and T.mentagrophytes in 2 (5.3%).

In the butenafine group, relapse was notobserved in any patient, while two patients inthe clotrimazole group became KOH-positiveagain at 8 weeks and one of them also hadevidence of clinical relapse. Two of 37patients complained of transient burningsensation at the application site in thebutenafine group in the first week but itresolved spontaneously while on treatmentand did not require discontinuation of

therapy. In the clotrimazole group, twopatients complained of increased pruritusand two had mild increase in the lesionalerythema and scaling during the first week ofapplication. There was no biochemical orhaematological alteration in any patient ineither of the groups.

Discussion The efficacy of butenafine hasnot been compared

with the established topical therapeuticagents like clotrimazole. The clinical cure

rate (26.5% vs 2.9%) as well as themycological cure rate (61.7% vs 17.6%) wassignificantly higher in the butenafine then inthe clotrimazole group at 1 week (Tables Vand VI). At follow-up in subsequent weeksthe mycological cure rates were again higherwith

Table V. Clinical cure.

Butenafine (%) Clotrimazole(%) p value 1 week 9/34(26.5) 1/34 (2.9) 0.000

2 weeks 24/31 (77.4) 18/32 (56.2) 0.006 4 weeks26/27 (96.2) 24/25 (96.0) 0.735 8 weeks 20/20 (100)20/21 (95.2) 0.512

Table VI. Mycological cure.

Butenafine (%) Clotrimazole(%) p value 1 week 21/34(61.7) 6/34 (17.6) 0.000


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2 weeks 30/31 (96.7) 26/32 (81.2) 0.057 4 weeks26/27 (96.2) 23/25 (92.0) 0.471 8 weeks 20/20 (100)

20/21 (95.2) 0.512butenafine; however, thedifference was not statistically significant(96.7% vs 81.2%, 96.2% vs 92%, 100% vs95.2% at weeks 2, 4 and 8, respectively(Table V). Thus butenafine achieved fastermycological cure, although cure rateswere comparable at 4 weeks. The clinicalassessment score was also significantlylower with butenafine as compared withclotrimazole at week 2 (Table III). Theclinical assessment score from baselineimproved significantly more withbutenafine at both weeks 2 and 4 (TableIV). This is because the fungicidal activityof butenafine (7) leads to rapid resolutionof clinical signs and symptoms, whileclotrimazole is only a fungistatic drug (3).

The efficacy of topical 1% butenafine inthe treatment of superficial fungal infectionshas been demonstrated in many studies.Butenafine was better than vehicle intreating interdigital tinea pedis (8) as well astinea corporis (9). Butenafine recipients hadsignificantly higher rates of mycological cureat day 7 (64% vs 9%) with continuedimprovement through day 42 (88% vs 17%)(9) The results of another vehicle-controlled,double-blind, randomized, parallel studyindicate that 1% butenafine applied once

daily for 2 weeks is safe and effective in thetreatment of tinea cruris and the proportionof patients cured increased between the endof treatment and 4 weeks post treatment (5).

Following antimycotic treatment, tineainfections often recur or relapse because

patients often discontinue therapyprematurely as their symptoms abate beforemycological cure is achieved, and somedrugs may only suppress the growth of thepathogen rather than fully eradicate it (7,10).Butenafine may have the potential toovercome these barriers, because of thefaster mycological cure, as seen in thepresent study. There was no relapse for atleast 4 weeks after the cessation of therapy;this is because butenafine demonstrates areservoir effect in the skin even afterelimination of the fungi (7).

Thus single daily application, faster reliefof symptoms, shorter durations of therapy, afavourable safety profile and absence ofrelapse make butenafine a preferredtherapeutic modality as compared withclotrimazole for superficial dermatophytosis.

References

1. Crissey JT. Common dermatophyte infections: asimple diagnostic test and current management.Postgrad Med. 1998;103:1912.


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Butenafine and clotrimazole in tinea cruris and corporis 335

2. Pierard GE, Arrese JE, Pierard-Franchimont C.Treatment and prophylaxis of tinea infections. Drugs.1996;52:20924.

3. Elewski BE. Mechanisms of action of systemicantifungal agents. J Am Acad Dermatol. 1993;28:S28S34.

4. McNeely W, Spencer CM. Butenafine. Drugs.1998;55: 40512.

5. Lesher JL Jr, Babel DE, Stewart DM, Jones TM,Kaminester L, Goldman M, et al. Butenafine 1% creamin the treatment of tinea cruris: a multicenter,vehiclecontrolled, double-blind trial. J Am AcadDeramatol. 1997;36:S20S24.

6. Arika J, Hase J, Yokoo M. Antitrichophytonmentagrophytes activity and percutaneous permeationof butenafine in guinea pigs. Antimicrob AgentsChemother. 1993;37:3635.

7. Arika T, Yokoo M, Hase T, Maeda T, Amemiya K,Yamaguchi H. Effects of butenafine hydrochloride, a

newbenzylamine derivative, on experimentaldermatophytosis in guinea pigs. Antimicrob AgentsChemother. 1990;34: 22503.

8. Savin R, De Villez RL, Elewski B, Hong S, Jones T,Lucky A, et al. One-week therapy with twice-dailybutenafine 1% cream versus vehicle in the treatment oftinea pedis: a multicenter, double-blind trial. J Am AcadDermatol. 1997;36: S15S19.

9. Greer DL, Weiss J, Rodriguez DA, Hebert AA,Swinehart JM. A randomized trial to assess once-dailytopical treatment of tinea corporis with butenafine, anew antifungal agent. J Am Acad Dermatol.1997;37:2315.

10. Berman B, Ellis C, Leyden J, Lowe N, Savin R,Shupack J. Efficacy of a 1-week twice-daily regimen of

terbinafine 1% cream in the treatment of interdigital tineapedis. J Am Acad Dermatol. 1992;26:95660.

comaprative efficacy treatment tinea corporis

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