A comparative trial between the therapeutic efficacy of topical 2% sertaconazole cream and 1% terbinafine cream in the treatment of tinea cruris/tinea corporis

INTRODUCTION

Fungal skin diseases are very common and account for 6% of patients seen in our outpatient department. Dermatophytosis is a superficial fungal infection of skin, hair and nails caused by dermatophytes, a group of related fungi belonging to 3 genera namely Epidermophyton, Microsporum and Trichophyton. In India the most commonly occurring clinical type of dermatophytosis is tinea corporis and tinea cruris for adults, that is involvement of the glabrous skin of trunk and groin.^1,2 In spite of the increasing prevalence of these infections, specific guidelines on the management of tinea cruris and corporis are in fact two decades old.³ Updated Cochrane reviews on the use of topical therapies in tinea corporis and cruris have helped to bridge this gap.⁴

Topical antifungal agents belonging to groups such as azoles, polyenes and allylamines are available and are considered generally as first line therapy for dermatophytosis owing to their high efficacy and low potential for systemic side effects. Shadomy and colleagues reported Terbinafine to be 2 to 30 times more potent than Ketoconazole and 10 times more potent than Clotrimazole against common dermatophytes.⁵ The in vitro anti dermatophyte potency for topical antifungal agents in descending order of potency is Butenafine >Terbinafine >ciclopirox = naftifine >azoles.⁶

Terbinafine is a fungicidal allylamine that inhibits squalene epoxidase that results in intracellular accumulation of toxic squalene and causes fungal cell death. Azoles are mainly fungistatic as they block lanosterol 14-α demethylase which prevents the formation of ergosterol, the primary sterol component of the fungal cell membrane. Sertaconazole, a newer lipophilic benzothiophene imidazole derivative, not only blocks lanosterol 14-α demethylase but also binds to non-sterol cell membrane lipids leading to altered membrane permeability and leakage of intracellular contents. This dual mechanism means that depending on the exact organism and drug concentration, Sertaconazole can be either fungistatic or fungicidal.⁷

There is a paucity of studies regarding the clinical efficacy of Sertaconazole in the treatment of tinea corporis and cruris. Hence this study was carried out to compare the efficacy of Sertaconazole nitrate 2% and Terbinafine hydrochloride 1% creams in the treatment of localized tinea corporis and/or tinea cruris.

METHODS

Source of data

Clearance from institutional ethical committee was obtained and this prospective comparative study was conducted on 80 patients presenting to the dermatology department of SRM medical college hospital and Research Centre, Potheri from January 2012 to July 2014.

Inclusion criteria

All patients clinically diagnosed as tinea corporis and/or tinea cruris with less than 20% body surface area involvement and skin scraping positive for dermatophyte filaments on 10% KOH mount, were included in the study.

Exclusion criteria

Pregnant and lactating women and age <18 years, immune-compromised patients including HIV, uncontrolled diabetes, malignancies, cancer chemotherapy, and transplant recipients, Patients with prior history of intolerance or hypersensitivity to imidazole, allylamine compounds or vehicle, Patients using medications such as topical antifungal or topical steroid or topical steroid-antifungal combination in the treatment area within 2 weeks of baseline visit, systemic antifungal agents a within 4 weeks of baseline visit, systemic corticosteroids within 30 days of baseline visit, were excluded from the study.

Sample collection

80 consecutive patients satisfying the inclusion criteria were recruited and were alternatively assigned to two groups A and B of 40 patients each. Group A patients were treated with 2% Sertaconazole nitrate cream and Group B were treated with 1% Terbinafine hydrochloride cream. Both groups were advised to apply the cream twice daily on the affected sites for four weeks and were recalled at the end of 2^nd and 4^th weeks to note the clinical improvement and adverse effects like local erythema, swelling, stinging sensation or increased itching. Clinical photographs were taken at each visit. Clinical cure was assessed by clinical improvement in signs and symptoms of the parameters like pruritus, erythema, papules and scaling which was graded at 0, 2 and 4 weeks as shown below in Table 1.¹⁰

Cured: 0; Mild: <4; Severe: 4-8.

Mycological cure was assessed by doing skin scraping for 10% KOH mount and culture on Sabouraud’s dextrose agar with chloramphenicol and cycloheximide at 0, 2 and 4 weeks. Mycological cure was defined as negative KOH and culture. Complete cure was defined as mycological cure with complete absence of clinical signs and symptoms.

Statistical analysis

Descriptive and inferential statistical analysis was carried out in the study. Results on continuous measurements are presented on mean±SD (min-max) and results on categorical measurement are presented in numbers (%). Significance is assessed at 5% level of significance student T test has been used to find the significance of study parameters for continuous measurement and Chi square/Fisher exact test has been used for categorical measurement between the 2 groups.

RESULTS

The study population consisted of 80 patients including 51 males (63.7%) and 29 females (36.3%). The mean age of the population was 27.97 years. Students comprised a majority group accounting for 52% of the study population. The mean duration of symptoms in the two groups was 16.28±15.96 and 20.63±19.20 days. Though the duration is more in Terbinafine group it is not statistically significant. Tinea corporis was more common with 65% and 57.5% in the groups, while tinea cruris was seen in 35% and 40% of the 2 groups respectively. Both tinea cruris and tinea corporis was seen in 1 subject. 12 persons dropped out of the study, which included 7 in Sertaconazole group and 5 in Terbinafine group. Culture positivity was seen in 92.5% and 95.0%, 5.4% and 2.9%, 2.9% and 0% in group A and B respectively at baseline 2^nd and 4^th weeks. Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis and Microsporum gypseum were the culture isolates in the order of frequency in both groups. Clinical assessments at 2nd and 4th week are depicted below in Table 2.

At the end of the 2^nd week as well as the 4^th week, Terbinafine group showed higher cure rates. There were no severe cases at the end of the treatment period in the Terbinafine group while 10.8% of severe cases persisted at the end of the study period in the Sertaconazole group. Mycological assessment at the end of 2^nd and 4^th weeks is depicted below in Table 3.

At baseline KOH is positive in all patients and is negative in all the patients tested in both the groups at 4 weeks. However at 2 weeks KOH is negative in 91.9% of patients in group A as compared to 97.1% in group B. All patients in group B are culture negative at the end of 4 weeks where as one patient remained culture positive in group A. A majority of our patients in both the groups showed Trichophyton rubrum (53.75%) followed by T. mentagrophytes (36.25%) growth on culture.

DISCUSSION

In our prospective comparative study, we have studied the efficacy of topical 2% Sertaconazole cream and 1% Terbinafine cream in treatment of localised tinea corporis and tinea cruris. The majority of the total study population was between 20 to 30 years of age with a male preponderance. A male preponderance was also noted in a similar study done by Jerajani et al, where 65% were males and 35% were females.¹¹

We have assessed the response to treatment both by clinical observation (rating them by giving a scoring pattern), as well as with mycological study i.e. 10% KOH mount and culture which was done at base line ( zero day),end of 2 weeks & 4 weeks respectively for both the drug groups.¹⁰ Clinical cure i.e. clinical score equals to zero was achieved in 59.5% and 80% of patients in group A (Sertaconazole) as compared to 71.4% and 90.9% in group B (Terbinafine) at the end of two and four weeks respectively which is similar to a study done by Choudhary et al.¹⁴

Complete cure is clinical score =0 with KOH and culture negativity. In group A (Sertaconazole) complete cure was noted in 59.5%, and 80% of patients at the end of 2^nd and 4^th week of treatment, respectively. Significant P value was observed if the results were compared between baseline to 2^nd week (<0.001), baseline to 4^th week (<0.001) and 2^nd to 4^th week (0.008).

In group B (Terbinafine) complete cure was noted in 71.4% and 90.9% patients at the end of 2nd and 4th week of treatment, respectively. Significant P value was observed if the results were compared between baseline to 2^nd week (<0.001), baseline to 4^th week (<0.001) and 2^nd to 4^th week (0.016).

A comparison between Group A and Group B for complete cure is not statistically significant (at 2 weeks P value = 0.286, at 4 weeks P value = 0.307) even though the complete cure rate for Terbinafine was higher at the end of 2^nd and 4^th weeks. These observations indicate that in our study Sertaconazole nitrate 2% cream is similar in efficacy to Terbinafine hydrochloride 1% cream at the end of 2^nd and 4^th weeks.

Jerajani et al compared the efficacy and safety of Sertaconazole (2%) cream versus Terbinafine cream (1%) versus Luliconazole (1%) cream in tinea corporis and tinea cruris and showed that at the end of ‘treatment phase’, there was a greater reduction in mean total composite score in Sertaconazole group (97.1%) as compared to Terbinafine (91.2%). Composite score in their study was based on clinical symptoms and signs namely pruritus, erythema, vesicle and desquamation.¹¹ This study was in contrast to ours in which the clinical cure of Terbinafine (90.9%) was better than Sertaconazole (80%) at the end of 4 weeks of treatment. However in their study the ‘treatment phase’ was different for both the groups. Sertaconazole nitrate 2% cream was given twice daily for 4 weeks whereas Terbinafine 1% cream was given once daily for 2 weeks hence possibly the difference in efficacy.

Choudhary et al in their comparative study between the same two drugs in tinea cruris and corporis used Terbinafine hydrochloride 1% and Sertaconazole nitrate 2% cream twice daily for 3 weeks and observed statistically non-significant results when the two groups were compared for complete cure at the end of 1^st, 2^nd and 3^rd week. At the end of 2nd week, complete cure rate for Terbinafine was 80% as compared to 73.35% for Sertaconazole with no statistical significance.¹⁴ However in their study they observed a statistically significant difference in complete cure in Sertaconazole group when the results between 2nd and 3rd week was compared, which was not observed in Terbinafine group unlike our study in which statistically significant results were obtained within the group for both the groups when compared for complete cure between 2^nd and 4^th week.

Tamilselvan et al compared the efficacy of Sertaconazole, Luliconazole, Terbinafine, Amorolfine and Eberconazole and found that Sertaconazole showed higher efficacy with 93.3% as compared to Terbinafine which showed 80%. The treatment duration was only one week only but Sertaconazole showed greater clinical symptom relief as compared to Terbinafine.¹⁵ This is in contrast to our study as well as other studies where Terbinafine gives earlier and better results than Sertaconazole. Adverse reactions were not noted in any of the treated patients in both the groups.

CONCLUSION

This study showed that the clinical cure and complete cure rate was found to be higher in Terbinafine 1% compared to Sertaconazole 2%, though it is not statistically significant. Thus it can be said that topical Sertaconazole 2% cream is similar in efficacy to topical Terbinafine 1% cream in the treatment of tinea corporis and tinea cruris. The main drawback of this study was that there was no follow up phase to evaluate the recurrences.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the institutional ethics committee

REFERENCES

1. 1. Mohanty JC, Mohanty SK, Sahoo RC, Sahoo AS, Prahraj CH. Incidence of Dermatophytosis in Orissa. Indian J Med Microbiol. 1998;16:78-80.
2. 2. Singh S, Beena MP. Profile of Dermatophyte infections in Baroda. Indian J Dermatol Venereol Leprosy. 2003;69:281–3.
3. 3. Sahoo AK, Mahajan R. Management of Tinea Corporis, Tinea Cruris and Tinea Pedis: A Comprehensive review. Indian Dermatol online J. 2016;7:77-86.
4. 4. El – Gohary M, Van Zurren EJ, Fedorowickz Z, Burgess H, Doney L, Stuart B, et al. Topical antifungal treatments for tinea cruris and tinea corporis. Cochrane database system Rev. 2014;8:CD009992.
5. 5. Shadomy S, Esoingel Ingroff A, Gebhart RJ: Invitro studies with SF 86-327, a new orally active allylamine derivative. Sabouraudia 1985;23:125-32.
6. 6. Rhea MP, Theodore R. Topical antifungal agents. In: Wolverton SE. Comprehensive dermatologic drug therapy. 2nd edition. WB Saunders; 2001: 508-9.
7. 7. Croxtall JD, Plosker GL. Sertaconazole: A review of its use in superficial mycoses in dermatology and gynaecology. Drugs. 2009;69:339-59.
8. 8. Liebel F, Lyte P, Garay M, Babad J, Southall MD. Anti-inflammatory and anti-itch activity of Sertaconazole nitrate. Arch Dermatol Res. 2006;298:191-9.
9. 9. Lakshmi V, Bengalorkar GM, Kumar S. Clinical efficacy of topical terbinafine versus luliconazole in the treatment of Tinea corporis / Tinea cruris patients. Br J Pharmacol. 2013;3(4);1001-14.
10. 10. Budimulja U. Terbinafine 1% cream Vs Bifonazole 1% cream in the treatment of Tinea cruris. In J Dermatol. 1998;37:871-3.
11. 11. Jerajani HR, Janaki C, Kumar S, Phiske M. Comparative assessment of the efficacy and safety of Sertaconazole 2% cream versus Terbinafine 1% versus Luliconazole 1% cream in patients with Dermatophytoses: A pilot study. Indian J Dermatol. 2013;58:34–8.
12. 12. Rotta I, Ziegelmann PK, Otuki MF, Riveros BS, Bernardo NL, Correr CJ. Efficacy of topical antifungals in the treatment of Dermatophytosis. A mixed treatment comparison Meta-analysis involving 14 treatments. JAMA Dermatol. 2013;149:341-9.
13. 13. Sumitha A, Geetha M, Shashikala GH, HS Somashekar, KS chandarn. Efficacy and safety of 1% terbinafine hydrochloride versus 2% Sertaconazole cream in the treatment of tinea corporis. Int J Basic Clin Pharmacol. 2015;4:474–8.
14. 14. Chaudhary SV, Bisati S, Singh A, Koley S. Efficacy and safety of Terbinafine hydrochloride 1% cream Vs Sertaconazole nitrate 2 % Cruris: A comparative therapeutic trial. Indian J Dermatol. 2013;58:457-60.
15. 15. Tamilselvan A, Girisha G, Bhaskar V, Suthakaran R. Comparative evaluation of newer topical antifungal agents in the treatment of superficial fungal infections ( Tinea or Dermatophytic). Int Res J Pharm. 2013;4(6):224–8.