Efficacy and Safety of 0.05% Halometasone/1% Triclosan Cream Versus 0.1% Mometasone Furoate Cream in the Treatment of truncal vitiligo: A Retrospective Study

Shu-Zhen Qi, Xue-Si Zeng, Shu-Chang Hu

1STD Clinic, Hospital for Skin Diseases (Institute of Dermatology), Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu 210042, China;2Department of Pathology, Hospital for Skin Diseases (Institute of Dermatology),Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu 210042, China;3Department of Medical Record, Hangzhou Third Hospital, Hangzhou, Zhejiang 310009, China.

Abstract Objective:To retrospectively evaluate efficacy and safety of 0.05% halometasone/1% triclosan cream(Hal/TCS)in treating truncal vitiligo of children and adolescents.Methods:We retrospectively reviewed the records of children and adolescents with truncal vitiligo treated only with topical Hal/TCS twice daily or only with topical 0.1% mometasone furoate cream(mometasone)twice daily for at least 3months, and collected relevant data.Efficacy outcomes included patients’ mean repigmentation score after 1-and 3-month treatment calculated based on patients’repigmentation percentage,and effective rate(percentage of patients with ≥50% repigmentation).Subgroup analyses of patients’ mean repigmentation score based on their age, vitiligo stage, and duration were conducted.Rate of adverse events were calculated.Results:One hundred and twenty-two eligible patients were included,among them,63 and 59 patients were in the Hal/TCS group and the mometasone group, respectively.After 3months of treatment, the Hal/TCS group had significantly higher mean repigmentation score and effective rate than the mometasone group(53.49±28.33 vs.41.46±27.16,P=0.02;53.97%vs.35.59%,P=0.04,respectively).Patients with shorter disease duration(≤12months)and patients with progressive vitiligo responded significantly better to the Hal/TCS treatment than patients with longer disease duration and patients with stable vitiligo, respectively.Both treatments were well tolerated and the two treatment groups had comparable rates of adverse events.Conclusions:Short-term Hal/TCS treatment was effective,well-tolerated,and safe in treating vitiligo in the trunk of children and adolescents.

Keywords: 0.05% halometasone/1% triclosan cream, 0.1% mometasone furoate cream, adolescents, children,efficacy, safety, vitiligo

Introduction

Vitiligo is a depigmenting disease of the skin and hair,it is characterized by depigmented skin patches of different sizes and shapes and could affect up to 2.9% of worldwide population.1–3As about half of the patients with vitiligo have disease onset before the age of 20,it is a serious skin disorder in children and adolescents.3Although vitiligo is a benign disorder, the disfigurement due to vitiligo during childhood and adolescence could cause lasting psychological trauma.2,4

Vitiligo is the result of selective damage and destruction of epidermal melanocytes,leading to reduced or no pigmentation of the skin, hair, and/or mucous membranes.3-4The etiology of vitiligo is unclear and could be autoimmune,antotoxicity, and/or neural based.3-4Topical corticosteroids such as 0.1% mometasone furoate creamis considered the first-line treatment for vitiligo.2–4Other treatments include systemic corticosteroids, calcipotriol, calcineurin inhibitors,narrow band ultraviolet B,and phototherapy.4However, for children and adolescents with vitiligo,treatment options are limited due to adverse events (AEs)or poor efficacy.3Therefore, finding an effective and safe treatment for children and adolescents with vitiligo is important.

0.05% halometasone/1% triclosan cream (Hal/TCS) is used by many dermatologists in China to treat vitiligo.0.05% halometasone cream is a synthetic Class III topical corticosteroid with anti-inflammatory, anti-allergic, antiepidermoplastic, antipruritic, and anti-exudative properties.5-6It has been approved in many European countries and others for treating various types of dermatitis with proven efficacy,tolerability, and safety.5In addition, two studies reported that both adult and pediatric patients with vitiligo treated with topical halometasone in combination with 308-nm excimer laser had significantly higher repigmentation rate than patients receiving 308-excimer laser alone or patients receiving tacrolimus plus excimer laser,7-8suggesting that topical halometasone had efficacy in treating vitiligo.Triclosan is a broad-spectrum antibacterial and anti-inflammatory agent.9-10It has been reported that 1% triclosan had synergistic effect with corticosteroid in treating uninfected atopic dermatitis and was corticosteroid-sparing.10

In this retrospective study, we compared efficacy and safety of Hal/TCS with 0.1% mometasone furoate cream in treating vitiligo of the trunk in children and adolescents.

Materials and methods

Patients

In this retrospective study,we reviewed the medical records of children and adolescents with vitiligo limited to their trunk treated only with twice daily topical Hal/TCS(Novartis Pharma Schweiz, Shanghai, China, Approval Number:H20140161)(the Hal/TCS group)or twice daily topical 0.1% mometasone furoate cream (Mometasone,Shanghai Schering Plough Pharmaceutical Co., Ltd,Shanghai,China, CFDA Approval Number: H19991418)for at least 3months at our institute from June 1,2016 to May 31,2017.

Inclusion criteria: (1) patients who were 7–18years old diagnosed with mild vitiligo1limited to their trunks with a disease duration ≤2years with no repigmentation, (2)patients who had 1–4 patches of lesions constituting less than 1% of their body surface,each lesion with a diameter of 0.5–3.0cm, and (3) patients whose skin lesions were photographed before the treatment and after 1month and 3months of treatment.Both patients with progressive vitiligo (the area of skin lesions under a Wood lamp was larger than that observed by eyes)and patients with stable vitiligo(the area of skin lesions under a Wood lamp did not exceed that observed by eyes) were included.Exclusion criteria:(1)patients who received topical treatment within 2weeks before or during the Hal/TCS or mometasone treatment, patients who received systemic medication(s)for vitiligo such as corticosteroids or other immunomodulators within 4weeks before or during the Hal/TCS or mometasone treatment;(2) patients with autoimmune diseases,severe hepatic or renal impairment,or other skin diseases;and patients whose medical history was incomplete and insufficient for efficacy evaluation.

Medical records of included patients were further reviewed to extract their demographic and clinical characteristics such as their medical history,family history,duration,type and stage of vitiligo,location and area(cm2)of skin lesions, and also AEs.Patients’ area (cm2) of skin lesions before and after the 1-month and 3-month treatment were extracted from photographs taken before and after treatment.

This study was approved by the Institutional Review Board of Hospital for Skin Diseases (Institute of Dermatology), Chinese Academy of Medical Sciences,and Peking Union Medical College(2021 Linkuaishen 43).

Efficacy outcomes

Efficacy outcomes included patients’mean repigmentation score by the end of the 1- and 3-month treatment.Each patient’s area of lesions after the 1-and 3-month treatment was compared with his/her baseline area of lesions using the baseline and month 1 and 3 photographs to calculate the percentage of repigmentation.The repigmentation score was classified as follows:

Complete recovery: disappearance of 100% skin lesions and returning of normal skin color;Excellent effect: 75%–99% repigmentation;Marked effect: 50%–74% repigmentation;Moderate effect: 25%–49% repigmentation;and Minimal effect: 0–24% repigmentation.

Other efficacy outcomes included effective rate (the percentage of patients with ≥50% repigmentation)after 1 month and 3months of treatment;and subgroup analyses of patients’mean repigmentation score based on their age(7–12yearsvs.13–18years), disease duration (≤12 monthsvs.13–24months) and stage (progressivevs.stable)

Safety evaluations

AEs experienced by every patient were extracted from their medical records and rates of AEs were calculated.

Statistical analysis

SAS 9.4 for Windows(SAS Institute Inc.,Cary,NC,USA)was used for all statistical analyses, and data were presented as mean±SD.Categorical variables weredescribed with numbers (n) and percentages (%) while continuous variables were described with means±standard deviations.Inter-group comparisons were conducted using the independentttest for continuous variables and Chi-square test for categorical variables.All tests were two-tailed (α = 0.05), and statistical significance was achieved with aP<0.05.

Results

Patients’ demographics and baseline characteristics

One hundred and twenty-two patients were included in the study, among them, 63 and 59 patients were in the Hal/TCS group and the mometasone group, respectively.Patients in the 2 groups had comparable age, gender,vitiligo stage, and duration (allP>0.05) (Table 1).

Table 1Patient demographics and baseline characteristics.

Effects of Hal/TCS on treatment of truncal vitiligo compared with mometasone

Based on the numbers of patients in the 2 groups with a repigmentation score of 100,87,62,37,or 12 by the end of the 3-month treatment,patients in the HAL/TCS group had a significantly higher mean repigmentation score than patients in the mometasone group after 3months of treatment (53.49±28.33vs.41.46±27.16,P=0.02)(Table 2).In addition, after treatment for 1month,patients in the Hal/TCS group had a numerously though statistically insignificantly higher mean repigmentation score than patients in the mometasone group (32.24±23.27vs.26.83±20.82,P=0.18) (Table 2).

Although effective rate in the Hal/TCS group were numerically though statistically insignificantly higher than the mometasone group by the end of the 1-month treatment (22.22%vs.15.25%,P=0.33), after 3months of treatment,the Hal/TCS group had a significantly higher effective rate than the mometasone group (53.97%vs.35.59%,P=0.04) (Table 2).

Mean repigmentation scores and effective rates of both groups were significantly higher after the 3-month treatment than after the 1-month treatment (Table 2).

Subgroups analyses revealed that patients in the Hal/TCS group with a disease duration of ≤12months had a significantly higher mean repigmentation score than patients whose disease duration was 13–24months after 3months of treatment (62.79±25.99vs.43.27±27.65,P=0.01).Additionally, patients with progressive vitiligo responded significantly better to the 3-month Hal/TCS treatment than patients with stable vitiligo(62.03±26.80vs.44.68±27.55,P=0.01).However,patients who were 7–12years old had a comparable repigmentation score with patients who were 13–18years old (P=0.43) by the end of the 3-month Hal/TCS treatment (Table 3).

Table 2Mean repigmentation scores and effective rate of Hal/TCS and mometasone treatments.

Table 3Subgroup analyses of mean repigmentation score of patients treated with Hal/TCS after 3months of treatment.

Safety

Both treatments were well tolerated.A total of 11(17.46%) patients in the Hal/HCS groups and five(8.47%) patients in the mometasone group experienced AEs.Among them, five (7.94%) and 6 (9.52%) patients in the Hal/TCS group had mild telangiectasia and folliculitis (papules), respectively.As for the mometasone group,two (3.39%)and three (5.08%) patients had mildtelangiectasia and folliculitis (papules), respectively.The two groups had comparable rate of AEs(P=0.404).All of the AEs could be tolerated and partially resolved with symptomatic treatments.None of the patients experienced epidermal atrophy, hypertrichosis or serious AEs.

Discussion

In this first study on efficacy and safety of the Hal/TCS in treating vitiligo of the trunk in children and adolescents,we found that patients treated with Hal/TCS for 3months had significantly higher repigmentation score and effective rate than patients treated with topical 0.1% mometasone furoate cream.Subgroup analyses revealed that patients with shorter disease duration (≤12months) and patients with progressive vitiligo responded significantly better to the Hal/TCS than patients with longer disease duration(13–24months) and patients with stable vitiligo, respectively.Both treatments were well tolerated and had comparable rate of AEs.Mild telangiectasia and folliculitis(papules) were the only observed AEs.

As children’s body systems are not fully developed,some treatments for adult vitiligo may have intrinsic limitation in treating pediatric vitiligo due to efficacy or safety concerns or practical reasons.3,11Currently, topical corticosteroid treatment is the first-line treatment for pediatric vitiligo of the body,4,11while topical calcineurin inhibitors are recommended by the European Vitiligo Task Force to be the first-line treatment for childhood facial vitiligo, as high-potency topical corticosteroids could cause facial atrophy, dyspigmentation or telangiectasia since facial skin is thin.4,11

Our study found that patients treated with Hal/TCS for 3months had significantly higher repigmentation score and effective rate than patients treated with topical 0.1% mometasone furoate cream, a topical corticosteroid commonly used to treat vitiligo including childhood vitiligo.4,12-13Liet al.7-8reported an 80% effective rate(percentage of lesions with >50% repigmentation) when treating pediatric and adult patients with topical halometasone twice daily in combination with 308nm excimer laser twice per week for 12weeks.Our study showed that Hal/TCS treatment for 12weeks had a 53.97% effective rate (the percentage of patients with ≥50% repigmentation), difference in methods of calculating effective rates(patients-basedvs.lesions-based)made it hard to tell how much more effective the excimer laser - halometasone combination was than the Hal/TCS.In addition,Hal/TCS has the advantage of easy administration and could spare the time and effort needed for pediatric patients and their caregivers to go to their doctors for excimer laser treatment twice per week, and thus could greatly encourage compliance.

The 0.05% halometasone cream is a Class III topical corticosteroid with demonstrated anti-inflammatory properties.5-6Vitiligo is a disorder that heavily involves local inflammation.14-15Studies have suggested that accidental stimulation of paralesional CD8+cytotoxic T lymphocytes(CTLs)that recognize major histocompatibility complex Ibinding peptide derived from melanocyte protein in the context of local skin inflammation might be important in the development of vitiligo.14-15These CD8+CTLs’stimulation and expansion in vivo depend on CD4+T cells,and subsequently,local inflammation facilitates these CD8+CTLs to migrate and infiltrate into the epidermis and destruct melanocytes in the skin by producing proinflammatory cytokines such as interferon-gamma and tumor necrosis factor-alpha.14-15Zhuet al.16studied the effect of 0.05% halometasone cream on a mouse model of human vitiligo and found that topical administration of 0.05% halometasone cream led to significantly less skin depigmentation and significantly less local CD8+CTLs infiltration than control, suggesting that one possible mechanism underlying the efficacy of 0.05% halometasone cream in treating vitiligo is by inhibiting migration and infiltration of CD8+CTLs into the epidermis and therefore protecting melanocyte from destruction.

Another component of the Hal/TCS, triclosan, is a broad-spectrum antibacterial agent with anti-inflammatory property.9-10It has synergistic effect with corticosteroid and has corticosteroid-sparring effect in treating uninfected atopic dermatitis.9-10Additionally,it has been reported that triclosan could downregulate pro-inflammatory factors such as interferon-gamma and tumor necrosis factor-alpha,9both were produced by melanocytesdestructing CD8+CTLs.14-15

Consistent with prior studies,17-18we found that patients with progressive vitiligo had significantly better response to Hal/TCS treatment than patients with stable vitiligo.We also found that patients with disease duration of ≤12months responded significantly better to the treatment than patients with longer disease duration while patients 7–12years of age and patients 13–18years of age had comparable response to the treatment.Previous studies on whether disease duration or age affected a vitiligo patient’s response to a particular treatment produced inconsistent results.1,18–20More studies are needed to elucidate factors affecting a patient’s response to the Hal/TCS treatment.

We acknowledge certain limitations to our study.First,only patients with mild vitiligo limited to their trunk whose lesions constituting <1% of their body surface were included in our study, therefore, the efficacy of Hal/TCS treatment on patients with more severe vitiligo was not studied.Secondly, no follow-up was performed after the treatment.Thirdly, it was a retrospective study, and therefore,might be more prone to bias than a prospectively study.

In conclusion,this first study on the safety and efficacy of Hal/TCS treatment showed that short-term Hal/TCS treatment was effective,well-tolerated,and safe in treating vitiligo in the trunk of children and adolescents.Shorter disease duration was associated with better treatment response,and patients with progressive vitiligo responded better to the treatment than patients with stable vitiligo.