|Year : 2022 | Volume
| Issue : 3 | Page : 210-219
A comparative study of efficacy and safety of topical 10% phenylalanine gel versus 0.1% mometasone furoate cream in limited nonsegmental vitiligo
Abhishek Kumar, Ramachandran Ramakrishnan, Murali Narasimhan, N. Jegadish
Department of Dermatology, Venereology and Leprosy, SRM Medical College Hospital and Research Centre, Kattankulathur, Chengalpattu, Tamilnadu, India
|Date of Submission||02-Jul-2021|
|Date of Decision||03-Nov-2021|
|Date of Acceptance||29-Nov-2021|
|Date of Web Publication||30-Nov-2022|
Dr. Murali Narasimhan
Department of Dermatology, Venereology and Leprosy, SRM Medical College Hospital and Research Centre, Kattankulathur, Chengalpattu 603203, Tamilnadu
Source of Support: None, Conflict of Interest: None
Background: Among various therapeutic options for treating vitiligo, the search for an effective agent to minimize disease progression and achieve repigmentation continues. Topical phenylalanine 10% gel has shown promising results, and hence this study was carried out in patients with limited vitiligo. Aim: To compare the efficacy and safety of topical 10% phenylalanine gel versus topical 0.1% mometasone furoate cream in patients with limited nonsegmental vitiligo. Materials and methods: This study included 74 participants diagnosed as limited nonsegmental vitiligo (≤5 skin lesions). Group A received topical 10% phenylalanine gel (twice daily application), whereas Group B received topical 0.1% mometasone furoate cream (once daily application) for a period of 16 weeks. Clinical improvement based on vitiligo area severity index (VASI) scoring was assessed at intervals of 4 weeks until the end of the study duration. Physician’s global improvement assessment was calculated at the end of the study based on VASI scores. Results: Group A participants showed improvement of 24% when compared with 30.7% in group B at end of 16 weeks. Reduction in VASI scores and clinically visible improvement were noted in both groups after 8 weeks. Adverse events were not noted in any of the groups. Lesions over hands and feet were 11.3 times less likely to show response to treatment when compared with other sites. Conclusion: Both phenylalanine and mometasone were able to achieve significant repigmentation in the participants without any adverse effects. Mometasone achieved marked to excellent response in a higher percentage of participants. The overall efficacy of topical mometasone cream was better than topical phenylalanine gel.
Keywords: Mometasone, phenylalanine, vitiligo
|How to cite this article:|
Kumar A, Ramakrishnan R, Narasimhan M, Jegadish N. A comparative study of efficacy and safety of topical 10% phenylalanine gel versus 0.1% mometasone furoate cream in limited nonsegmental vitiligo. Pigment Int 2022;9:210-9
|How to cite this URL:|
Kumar A, Ramakrishnan R, Narasimhan M, Jegadish N. A comparative study of efficacy and safety of topical 10% phenylalanine gel versus 0.1% mometasone furoate cream in limited nonsegmental vitiligo. Pigment Int [serial online] 2022 [cited 2023 Mar 27];9:210-9. Available from: https://www.pigmentinternational.com/text.asp?2022/9/3/210/362400
| Introduction|| |
Vitiligo is a multifactorial, polygenic disorder with a complex pathogenesis. Various theories such as autoimmunity, oxidative stress, autocytotoxicity, melanocytorrhagy, neurohumoral hypothesis, vitamin D deficiency, hyperhomocysteinemia, and convergence theory have been proposed as pathogenetic mechanisms for the development of vitiligo.
The worldwide prevalence of vitiligo ranges from 0.06% to 2.28%. India followed by Mexico and Japan has the highest number of vitiligo cases in the world.
The vitiligo global issues consensus conference classification proposed by Ezzedine et al. in 2012 includes four main types, namely nonsegmental, segmental, mixed and unclassified forms of vitiligo.
Treatment of vitiligo is aimed at minimizing or preventing disease progression and attaining repigmentation with satisfactory cosmetic improvement. Although various medical and surgical methods are available, the first-line therapy for nonsegmental vitiligo is usually a topical corticosteroid or calcineurin inhibitor, whereas other options such as vitamin D analogs and phenylalanine either alone or in combination with phototherapy can be used.
Clobetasol propionate or mometasone furoate is usually the preferred topical agents of choice, but they may cause skin atrophy, striae, and telangiectasia on prolonged use. Topical calcineurin inhibitors are safer in this regard but are relatively expensive. Phenylalanine 10% gel, as a topical medication, produces improved tolerance to sun exposure and prevents sunburns in vitiligo patches and also enhances UVA-induced repigmentation. Topical phenylalanine as a stand-alone treatment produced excellent response in 29.3% patients, marked response in 8.1% patients, moderate response in 55% patients, and minimal response in 7.6% patients.
Hence this study was undertaken to compare the efficacy and safety of topical 10% phenylalanine gel with a commonly used topical steroid, namely mometasone furoate, in the treatment of nonsegmental vitiligo, with focal or limited involvement.
| Materials and Methods|| |
This was a randomized, interventional, nonblinded two-arm study to compare the safety and efficacy of topical 10% phenylalanine gel with that of 0.1% mometasone furoate cream. The study population was sourced from the dermatology outpatient department of a tertiary care hospital from November 2017 to April 2019. Institutional ethics committee clearance was obtained before recruiting the participants for the study.
Consenting adults of either sex, aged between 18 and 65 years with focal or multifocal nonsegmental vitiligo having limited involvement (less than 5 lesions) were included.
All other types of vitiligo and those who were on other forms of treatment in the past 3 months were excluded from the study.
Demographic and clinical details such as age, sex, duration of lesions, and sites involved were recorded in a case record form. Vitiligo area severity index (VASI) scores were noted at baseline. The participants were randomized into groups A and B based on a computer-generated sequence.
Participants in group A were advised to apply 10% phenylalanine gel topically over the lesions in the morning and at night. Group B participants were advised once daily topical application of 0.1% mometasone furoate cream in the morning. The applications were continued for 16 weeks. The persons missing the application for a continuous period of 2 weeks were excluded from the study. No other adjuvant treatments were administered.
Clinical photographs and VASI scores were taken during subsequent follow-up visits at 4, 8, 12, and 16 weeks. At the end of the study, physician’s global improvement assessment (PGA) was performed and rated on a 5-point scale based on percentage improvement in VASI score from baseline to 16 weeks: improvement of 76% to 100% from baseline is considered as excellent response; 51% to 75% improvement as marked response; 26% to 50% improvement as definite improvement; 1% to 25% improvement as minimal improvement; and 0% improvement as no change. Increase in VASI score was considered as negative improvement in the analysis.
For the purpose of analysis, the study population was divided in to three groups, namely those with recent onset vitiligo, stable vitiligo, and unstable vitiligo. As per the Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) task force guidelines for vitiligo surgery, a patient reporting no new lesions, no progression of existing lesions, and absence of Koebner phenomenon during the past 1 yearwas considered stable vitiligo, and others with a disease duration of more than 1 year showing above signs of activity were considered as unstable. All participants with a disease duration of less than 1 year were classified as recent onset vitiligo.
Statistical analysis was carried out using IBM SPSS Statistics software version 23.0. Chi-squared test was used to compare categorical variables between the study groups. Independent t test was used to find out the association between mean scores of each group. Repeated measure of analysis of variance (ANOVA) test was used to find out the association between the mean scores of each visit.
| Observations and Results|| |
A total of 81 participants were recruited for the study of whom 74 completed the study and were included in the analysis. The baseline characteristics of the study population are summarized in [Table 1].
The age of participants ranged from 18 to 60 years. The mean age in group A was 38 years, whereas in group B, it was 41.14 years. Males accounted for 43.2% and 54.1%, whereas females accounted for 56.8% and 45.9%, in groups A and B, respectively.
The mean duration of illness was 14.4 and 11.54 months in groups A and B, respectively. A majority of participants had recent onset vitiligo in both the groups.
Pearson Chi-squared test was used to find P-values for the groups. It was observed at the start of the study that there was no statistical difference between the groups in terms of age, gender, duration of symptoms, sites involved, and disease activity.
Statistically significant improvement was observed within the two groups at each follow-up visit in terms of reduction of VASI scores [Table 2]. The same was established using paired T test and Wilks lambda test for repeated measures ANOVA. Both the groups showed a linear decrease in mean VASI with time [Figure 1]. At the end of the study period, there was an overall VASI score reduction of 24% and 30.7% in groups A and B, respectively. However, this difference was not statistically significant [Table 2].
|Figure 1 Percentage decrease in vitiligo area severity index (VASI) score with time between the two groups.|
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Based on the PGA score, excellent improvement was observed in one (2.7%) patient of group A and in three (8.1%) patients of group B [Table 3]. All three patients showing excellent response in group B had complete resolution of lesions [Figure 2].
|Table 3 Association between activity levels and physician global assessment|
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Marked improvement was reported in three (8.1%) and four (10.8%) patients in groups A and B, respectively [Figure 3] and [Figure 4]. Group A showed definitive improvement in 7 (18.9%) patients, whereas in group B, the same was observed in 11 (29.7%) patients. Minimal improvement was reported in 16 (43.2%) and 8 (21.6%) patients in groups A and B, respectively.
More than half of the study participants [21 (56.8%) in group A and 20 (54.1%) in group B] had recent onset vitiligo. The Chi-squared values for the association between PGA score and activity of vitiligo in groups A and B are 8.71 and 4.14, respectively, and the P-values were insignificant [Table 3].
In unstable vitiligo group, mometasone showed greater VASI score reduction (35.1%) when compared with phenylalanine (9.7%) [Table 2].
Variations in efficacy were observed within both groups depending on the site of involvement [Table 4]. The improvements in VASI score in the respective groups A and B were 36.6% and 44.5% for head and neck, 28.9% and 46.2% for forearms and arms, 18.5% and 9.5% for hands and feet.
|Table 4 Comparison of percentage improvement from baseline according to site of lesions in phenylalanine group and mometasone group|
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Earliest response was noted at 4 weeks in a few patients. Minimal improvement in PGA score was evident at 8 weeks in both groups. Group B showed higher percentage of repigmentation in the head, neck, face, proximal limbs, and trunk lesions at 12 and 16 weeks. Group A (18.5%) showed higher percentage of repigmentation than group B (9.5%) in the hands and feet.
Nil response to treatment at the end of the study period was noted in 10 (27%) and 11 (29.7%) patients in groups A and B, respectively. Lesions over the hands and feet were 11.3 times more likely to have no change in PGA score when compared with other sites, and this association was statistically significant. None of the participants in both groups developed worsening of lesions or development of new lesions during the study period. Adverse events were not noted in any of the study participants.
| Discussion|| |
Despite the availability of numerous therapies of proven efficacy for treatment, newer unconventional drugs have been continuously added to the therapeutic armamentarium of vitiligo. Szczurko and Boon did a systematic review of natural health product treatment for vitiligo and concluded that most of the studies were of poor quality and only L-phenylalanine used with phototherapy and oral Ginkgo biloba as monotherapy showed promise and warrant further investigation. The rationale for using phenylalanine in the treatment of vitiligo stems from the suggestion that melanocytes of patients with vitiligo demonstrate decreased calcium-dependant L-phenylalanine uptake and turnover compared to healthy control cells. Camacho and Mazuecos suggested that phenylalanine could stop autoantibodies and allows solar radiation to stimulate melanocytes from other areas to migrate into damaged areas.
Currently recommended first-line topical therapies for focal vitiligo include topical corticosteroids such as clobetasol or mometasone, tacrolimus, and narrow band ultraviolet B (NB-UVB) phototherapy.
This study explored the efficacy and safety of 10% topical phenylalanine gel vis-à-vis 0.1% mometasone furoate cream in patients with limited, nonsegmental vitiligo. (To the best of our knowledge, there are no head-to-head studies comparing these two agents.)
Mometasone furoate has been compared in various studies with agents such as tacrolimus, pimecrolimus, and placental extract.,,,
Patients with vitiligo are usually anxious and expect improvement in a short time. Most of the vitiligo therapies take a minimum of 2 to 3 months to show response and treatments should be discontinued or changed if there is no visible improvement in the above time frame.
In our study, repigmentation although insignificant was noted at 4 weeks. Clinically significant reduction in mean VASI scores was evident only at the end of 8 weeks. At every subsequent visit, mometasone-treated group showed a higher percentage of reduction in VASI scores when compared with phenylalanine till the end of the study period [Table 2]. The overall VASI score reduction from baseline to the end of study period was higher in the mometasone-treated group, but was not statistically significant.
Camacho and Mazuecos reported a total response of 56.7% with oral and topical phenylalanine after a treatment period of 3 years. This study included several types of vitiligo unlike our study on limited and focal types.
Previous studies with mometasone have shown to give excellent response in 11% to 15%, moderate to marked improvement in 33% to 55% and minimal or no improvement in 0% to 33%.,
The response rates are similar in our study. The biggest problem however in comparing such studies is the wide variation in methodology of selecting patients as well as treatment protocols.
On comparing the two groups in our study, we found that mometasone was able to achieve a marked to excellent response (i.e., >50% repigmentation) on PGA scale in seven (18.92%) participants when compared with four (10.81%) participants in the phenylalanine group [Table 3]. It is important to observe here that 26 (70.3%) participants in phenylalanine group had no or minimal improvement when compared with 19 (50%) participants in mometasone group. Given that this study did not have a placebo arm, the treatment response in some of the participants could have been due to spontaneous repigmentation.
It is a well-documented fact that vitiligo lesions over face, neck, trunk, and mid extremities show good response, whereas the lips, genitals, and acral lesions show poor response to treatment. Highest efficacy in the phenylalanine group was reported in the head, neck, face, and mid extremities. The only site where phenylalanine scored over mometasone was the hands and feet [Table 4]. We presume that the higher efficacy at this site may be due to other confounding factors scuh as exposure to sun and disease activity. Acral lesions formed the majority of nonresponders to treatment.
There was no difference in treatment response in both groups among patients with recent onset and stable vitiligo. It is also worth noting that nearly two-thirds of unstable patients with vitiligo in phenylalanine group did not respond to treatment, whereas one-third showed only minimal response. However, mometasone achieved higher repigmentation in unstable vitiligo. However, no meaningful statistical significance can be derived from this observation as the sample size of this subgroup is small.
Adverse effects were not reported in any of our study participants in both groups.
Mid potency topical corticosteroids such as mometasone are largely devoid of side effects such as telangiectasia, atrophy, hypertrichosis, and acneiform eruptions. Some authors like Kose et al. have reported atrophy, telengiectasias, and erythema in patients with vitiligo getting mometasone for 3 months, whereas some like Masuria et al. and Wazir et al. have not reported any adverse effects even after 6 months of use.,, Adverse effects were not noted in patients treated with combinations of oral and topical phenylalanine with UVA exposure.
In our study, none of the participants showed any evidence of adverse reactions, implying the good safety profile of phenylalanine and mometasone.
There are many patients whom we encounter in clinical practice having aversion or apprehension toward topical steroid use. Phenylalanine can thus be considered as a therapeutic option in the long-term treatment of these patients, either alone or in combination with other modalities.
| Conclusion|| |
Both phenylalanine and mometasone were able to achieve significant repigmentation in the participants without any adverse effects in patients with limited and focal vitiligo. Topical mometasone achieved higher reduction in VASI scores than phenylalanine, although results are not statistically significant. Lesions over hands and feet were less likely to show response to treatment when compared with other sites. Further long-term studies with phenylalanine as an adjuvant to topical steroids, calcineurin inhibitors, and phototherapy can be contemplated, for exploring the full therapeutic potential of this drug in various forms of vitiligo.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]