|Year : 2022 | Volume
| Issue : 2 | Page : 66-72
A retrospective analysis of real-world data to evaluate the safety and effectiveness of topical amorolfine in tinea infection
Devendra Jain1, Pradeep Kumar2, Sanjib Chowdhuri3, Hitesh Doshi4, Umesh Jain5, Savitha L Beergouder6, Krishnasree Maganti7, Rashmi Rani8, Bhagyashree Mohod9, Ashok Jaiswal9
1 Prathama Skin and Hair Care Center, Virar, Maharashtra, India
2 Skin Care Center, Gandhinagar, Ghaziabad, Uttar Pradesh, India
3 Fortis Hospital, Anandapur & Wizderm Skin & Hair Clinics, Kolkata, West Bengal, India
4 Sardar Smarak Hospital & Muslim Trust Hospital, Surat, Gujarat, India
5 Dermacure Advanced Skin and Hair Clinic, Mayur Vihar, Delhi, India
6 Anagha Skin and Hair Clinic, Bagalkot, Karnataka, India
7 Maganti Hospital, Gudivada, Andhra Pradesh, India
8 Sadar Hospital, Jamuhar, Bihar, India
9 Medical Affairs Department, Zydus Healthcare Ltd., Mumbai, Maharashtra, India
|Date of Submission||07-May-2022|
|Date of Decision||14-Sep-2022|
|Date of Acceptance||21-Nov-2022|
|Date of Web Publication||5-Jan-2023|
Medical Affairs Department, Zydus Healthcare, ‘Zydus Tower’ CTS No. 460/6,Village Pahadi, Off I. B. Patel Road, Goregaon East, Mumbai 400063, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Conventional antifungals are becoming resistant against dermatophytosis due to development of recalcitrant tinea. These patients may get benefit from newer topical antifungals or combination therapy. Topical antifungal therapy is the mainstay in the treatment of dermatophytosis. Aims/Objectives: To evaluate the safety and effectiveness of topical amorolfine in tinea infection in real-world settings. Materials and Methods: This was a real-world retrospective study; data was collected from 106 centers across India on the usage of amorolfine in the management of tinea infections. The treatment response was evaluated at the end of 2 and 4 week. It was determined by the reduction in severity of the classic symptoms of disease viz. pruritus, burning sensation, erythema, and scaling and crusting at Week 2 and Week 4 of treatment. The severity of symptoms was classified and quantified as mild (1), moderate (2), and severe (3). Safety was determined based on the occurrence of any adverse events during the treatment. Results: An improvement in symptoms score was observed for all the classic symptoms of infection viz. pruritus, burning sensation, erythema, and scaling and crusting at Week 2 and Week 4 compared to baseline. Mean total symptom score (TSS) was reduced to 0.88 ± 1.19 from 7.18 ± 2.84 at week 4 (P < 0.05). Only 10 (0.73%) patients out of 1358 showed mild and non-treatment-related adverse events. Conclusion: Amorolfine alone or in combination therapy with oral antifungals in real world clinical setting represents an improved treatment strategy for patients with tinea infections.
Keywords: Dermatophytosis, itraconazole, real-world study, symptoms score, topical amorolfine
|How to cite this article:|
Jain D, Kumar P, Chowdhuri S, Doshi H, Jain U, Beergouder SL, Maganti K, Rani R, Mohod B, Jaiswal A. A retrospective analysis of real-world data to evaluate the safety and effectiveness of topical amorolfine in tinea infection. Indian J Drugs Dermatol 2022;8:66-72
|How to cite this URL:|
Jain D, Kumar P, Chowdhuri S, Doshi H, Jain U, Beergouder SL, Maganti K, Rani R, Mohod B, Jaiswal A. A retrospective analysis of real-world data to evaluate the safety and effectiveness of topical amorolfine in tinea infection. Indian J Drugs Dermatol [serial online] 2022 [cited 2023 Oct 1];8:66-72. Available from: https://www.ijdd.in/text.asp?2022/8/2/66/367126
| Introduction|| |
Superficial dermatophytosis is the commonest fungal infection observed in clinical practice. Fungal infections are prevalent in tropical areas with a hot and humid atmosphere, such as India. Dermatophytes are fungi that colonize the keratinized layers of the epidermis of the skin, hair, and nail, causing infection., Dermatophytes are classified into three major genera, Trichophyton, Microsporum and Epidermophyton in which Trichophyton rubrum, Trichophyton mentagrophytes are the most prevalent dermatophytes. However, according to recent multicentric study, Trichophyton mentagrophytes/ Trichophyton interdigitale complex is on rise. World Health Organization survey on the prevalence of dermatophytes infection shown that 20–25% of patients are suffering from cutaneous fungal infections globally. India is also facing challenge of similar alarming condition. According to the current report, prevalence in India falls in a very wide range of 6.09–61.5%. Studies from south India have found a prevalence of 6.09% to 27.65%, while a north Indian study found the prevalence of 61.55%.
In current scenario, dermatophytosis is treated with oral or topical antifungal drugs or a combination of both, depending on the extent and severity, site of infection, and causative organism. Commonly used therapeutic agents include the allylamine and benzylamine class (i.e. butenafine, terbinafine), azole class of medications (i.e. Sertaconazole, Luliconazole, Itraconazole, fluconazole etc.), Morpholines (i.e. Amorolfine) and newer class like Hydroxypyridone (i.e. Ciclopirox).
Amorolfine is a morpholine derivative and topically active antifungal agent with a unique structure and possesses both fungistatic and fungicidal activity in vitro. It has broad antifungal activity against dermatophytes, yeasts, dimorphic fungi, and molds and is fungicidal against most species. Six weeks of treatment of amorolfine 0.25% cream has reported 85 to 90% of overall cure and improvement rate in superficial dermatomycoses. It can be a better topical adjuvant in the present scenario of recalcitrant dermatophytosis.
The burden of the disease i.e. dermatophytosis is exponentially increasing in India, which respond poorly to the standard treatment recommendations due to rise of recalcitrant cases, the emergence of resistance to drugs and patient incompliance. This makes the combination therapy approach particularly of interest. Clinical data has also indicated that combination of systemic plus topic antifungal agents is effective and useful in increasing the clinical and microbiological cure of a superficial fungal infection.
It is recommended that drugs from two different class should be used for wider coverage, synergistic or additive action and to reduce the chance of resistance. Combination of itraconazole and amorolfine has reported to have better antifungal activity due to the sequential inhibition of 14 α demethylase by itraconazole and inhibition of delta-14-reductase and delta-7, 8-isomerase by amorolfine. This results in more complete suppression of ergosterol synthesis and gives better antifungal activity. In literature also, it is reported that combination of amorolfine with azoles has 100% synergistic interaction against many Trichophyton spp. Therefore, the objective behind this study was to evaluate the safety and effectiveness of topical amorolfine with or without oral antifungal agents in tinea infection in real world settings.
| Materials and Methods|| |
This is retrospective analysis of data from patients who have used amorolfine topically for the management of tinea infection. Total 106 centers of dermatology outpatient across the India were selected and provided them a case record form to collect the data. The diagnosis was identified according to physical signs and symptoms as per available medical records. Data of Male and non-pregnant female patients above 18 years of age with new or recurrent tinea pedia/cruris/corporis infection were collected. Data of Pregnant or nursing females and patients with malignancy, renal or hepatic dysfunction were excluded.
Data of demographic profile, History of comorbid condition and previous treatment, family history, current ongoing treatment and adverse events were collected from their medical database. A total of 1358 patients’ data was analysed. The patients were treated with topical amorolfine with or without other commonly used oral anti-fungal agent as per the requirement.
The treatment response evaluated at the end of 2 and 4 week of the therapy. Moreover, treatment response was determined by the reduction of severity of the classical signs and symptoms of infection. As per the medical records, total symptom score included scoring of pruritus, burning sensation, erythema, and scaling. Each symptom/sign was scored on 4-point scale (0 to 3) which were recorded at baseline and at the end 2 weeks and 4 weeks. Severity of symptoms were classified and quantified as no sign/symptom (0), mild (1), moderate (2) andsevere (3).
Data analysis was performed using IBM SPSS ver. 20 software. A frequency distribution was performed to obtain the frequency of each response. Quantitative data were expressed as mean and standard deviation, whereas categorical data were expressed as numbers and percentages.
| Results|| |
Data were collected from total 1358 patients of tinea infection from 106 centers in the present study. Out of this, 55.7% were males and 44.3% were females. Out of 1358 patients 894 (65.83%) of patients were of new tinea infection and 416 (30.63%) patients were of recurrent tinea infection. A recurrence rate of 45.47% was observed in patients with positive family history whereas recurrence rate was 22.99% in patients with negative family history [Figure 1]. Majority of the patients received systemic anti-fungal therapy along with topical amorolfine therapy. The demographics and baseline parameters of the study patients are listed in [Table 1].
Distribution of patients according to treatment given showed that out of the 1358 patients, 146 (10.8%) received topical monotherapy (amorolfine 0.25%) and 1212 (89.2%) received topical amorolfine 0.25% in combination with systemic antifungal therapy. Out of the 1212 patients who received combination with systemic antifungal therapy, majority were prescribed amorolfine in combination with Itraconazole (79.8%) followed by combination of amorolfine with terbinafine (17.9%) and amorolfine with griseofulvin (2.2%).
At week 4, data of total 1158 patients included to analyze the change in severity of pruritus as per the record. At baseline, 51.97% of the patients suffered from severe pruritus, while 39.46% had moderate severity. 7.57% of patients scored the severity of pruritus as mild whereas, 1% did not present pruritus at the start. At week 4, an improvement in pruritus symptoms was observed, a majority had no pruritus (58.03%), and 39.12% had mild symptoms. None of the patients had severe symptoms, and only 2.85% had moderate symptoms [Figure 2].
|Figure 2: Percentage of patients with severity of pruritus at baseline, week 2 and week 4 (n = 1158)|
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At week 4, data of total 1196 patients included to analyze the change in severity of burning sensation as per the record. At baseline, 20.34% of the patients suffered from severe burning sensation, while 38.56% had moderate severity. There were 28.27% of patients who scored the severity of burning sensation as mild, whereas 12.83% did not present burning sensation. At week 4, an improvement in burning sensation was observed as the majority had no burning sensation (83.6%), and 15.68% had mild symptoms. None of the patients had severe symptoms, and only 0.72% had moderate symptoms [Figure 3].
|Figure 3: Percentage patients with severity of burning sensation at baseline, week 2 and week 4 (n = 1196)|
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At week 4, data of total 1086 patients included to analyze the change in severity of scaling/crusting as per the record. At baseline, 20.5% of the patients suffered severe scaling crusting, while 35.58% had moderate severity. There were 34.59% of patients who scored the severity of scaling, crusting as mild whereas, 9.33% did not present scaling, crusting at the start. At week 4, an improvement in scaling crusting was observed, a majority had no scaling, crusting (77.9%), and 21.18% had mild symptoms. None of the patients had severe symptoms at the end of week 4 [Figure 4].
|Figure 4: Percentage patients with severity of scaling and crusting at baseline, week 2 and week 4 (n = 1086)|
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At week 4, data of total 1122 patients included to analyze the change in severity of erythema as per the record. At baseline, 23.55% of the patients suffered from severe erythema, while 45.34% had moderate severity. There were 26.61% of patients who scored the severity of erythema as mild whereas, 4.5% did not present erythema at the start. At week 4, an improvement in erythema was observed as the majority had no erythema (80.75%), and 18.18% had mild symptoms. None of the patients had severe symptoms. [Figure 5].
|Figure 5: Percentage patients with severity of erythema at baseline, week 2 and week 4 (n = 1122)|
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In total patient population, the mean total symptom score (TSS) was reduced to 0.88 ± 1.19 at week 4 from 7.18 ± 2.84 at baseline (P < 0.001) [Figure 6]. Among the patients treated with topical amorolfine monotherapy, the TSS at baseline and at week 4 follow-up were available from 90 patients and in this cohort, the mean TSS was significantly reduced from 7.40 ± 2.35 at baseline to 0.88 ± 1.29 at week 4 follow-up (P = 0.0001). Among the patients treated with combination of topical amorolfine and systemic antifungal, the TSS at baseline and week 4 follow-up were available from 852 patients and in this cohort, the mean TSS was significantly reduced from 8.21 ± 2.33 at baseline to 1.06 ± 1.34 at week 4 follow-up (P = 0.0001) [Table 2]. Only 10 (0.73%) patients out of 1358 showed mild and non-treatment-related adverse events. The most common was irritation (0.22%) followed by redness (0.22%) [Table 3].
|Table 2: Change in total symptom score in patients with topical amorolfine monotherapy and in patients with topical amorolfine in combination with systemic antifungals|
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| Discussion|| |
Dermatophytosis is a superficial fungal infection, common ailment among dermatology outpatient department. The mainstay objective of treatment of dermatophytosis is complete symptom control. However, due to the advancing recalcitrant lesions, there has been change in management of dermatophytosis in terms of combination of topical and oral antifungal drugs.,
In contrast to imidazoles, amorolfine is a novel class of antifungal agents with a novel mechanism of action. Amorolfine is a powerful fungicide and fungistatic agent because of its dual mechanism of action. The lowest MIC of any topical antifungal agent, according to an in vitro study, was found in a topical amorolfine formulation against several strains of dermatophytes. Amorolfine has been shown to increase fungistatic activity against T. mentagrophytes when combined with other antifungal agents like ketoconazole, terbinafine, itraconazole, and fluconazole. The efficacy of amorolfine in treating onychomycosis has been demonstrated in numerous studies.,,
In this real world scenario, amorolfine alone or in combination with oral antifungal agents found to be safe and effective in tinea infections. Improvement was observed in total symptoms score from baseline to week 2 and 4. Severity of symptoms were classified and quantified as no sign/symptom (0), mild (1), moderate (2) and severe (3). An improvement was noted in the severity of individual symptoms such as pruritus, burning sensation, erythema, and scaling and crusting over the period of 4 weeks. A similar study from Kolkata by Banerjee et al. reported the effectiveness of amorolfine as a topical antifungal in tinea corporis, and the clinical improvement was observed on day 14.
In current study, 10.8% of the patients received amorolfine monotherapy and 89.2% received combination with systemic antifungal therapy. The analysis showed an improvement in pruritus, burning sensation, erythema, and scaling and crusting over a period of week 4. A study conducted by Vishwanath et al. reported the outcome from 66 patients with multi-site tinea infection who failed to respond to previous combination therapy. Those 66 patients were treated with 6 weeks of antifungal therapy (combination of oral itraconazole and topical amorolfine). After 6 weeks of combination therapy, 75.75% patients achieved complete cure and 86.36% of the patients showed complete resolution of symptoms (erythema, scaling, pruritus, and incrustation).
Study reported by Sahoo et al. and Murlidhar et al. suggested that usage of a combination therapy showed improvement in the prominent lesions or persistent tinea infections. While using combination therapy, the author has recommended that drugs from two distinct classes should be chosen to achieve broader coverage, synergistic or additive activity, and minimize the risk of resistance., Some in-vitro studies have demonstrated the synergistic efficacy of itraconazole and amorolfine when taken together., Inhibition of 14 demethylases sequentially with itraconazole and delta-14 reductase and delta-7, 8-isomerase with amorolfine may completely suppress ergosterol production, resulting in increased antifungal efficacy.
Limitations of our study include that the data is collected retrospectively and lack of randomization. The fungal culture and sensitivity could not be done due to non-feasibility.
| Conclusion|| |
This is a real-world study providing evidence that the commonly used treatment strategy of topical and systemic antifungal drugs is efficacious and safe in managing tinea infections. Results of the study confirm that amorolfine alone or in combination with oral antifungal agent found to be safe and effective in managing tinea infection. This study truly demonstrates the effect of combination of two different antifungal drugs is associated with improved antifungal activity.
Financial support and sponsorship
Conflicts of Interest
Dr. Bhagyashree Mohod and Dr Ashok Jaiswal are part of medical services team of Zydus Healthcare Ltd.
Manuscript has been read and approved by all the authors, the requirements for authorship as stated earlier in this document have been met, and each author believes that the manuscript represents honest work.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3]