Layout 1 Treatments for vitiligo vs. anti-vitiligo cream Eur J Transl Myol 35 (4) 13787, 2025 doi: 10.4081/ejtm.2025.13787 Vitiligo is an acquired skin disorder characterized by the progressive loss of melanocytes—the cells responsible for producing the pigment melanin.1 Population-based studies have estimated the global prevalence of vitiligo to range between 0.1% and 2%, with some studies reporting peaks as high as 8%.2-4 Vitiligo causes depigmented patches due to melanocyte loss, which can appear anywhere on the body. While not life- threatening, it significantly affects quality of life, leading to psychological distress, social stigma, and isolation. The unpredictable progression of lesions—ranging from rapid spread to years of stability—adds to the emotional burden, especially in cultures where stigma is prevalent.1,5 Despite being a condition that predominantly affects appearance, vitiligo’s effects go beyond the skin. In some cases, it is associated with other autoimmune disorders, further complicating the management of the disease. Common comorbidities include thyroid disorders, diabetes, and even hearing loss.5-8 Traditional vitiligo treatments focus on halting disease progression and restoring pigment, often using topical or systemic corticosteroids like prednisolone,9 calcineurin inhibitors,10 and phototherapy.11 These therapies yield variable results, often requiring long treatment periods and are unsuitable for some patients. This has driven interest in targeted treatments addressing autoimmune dysfunction,12 oxidative stress,13 and genetic predisposition.14,15 Advances in understanding vitiligo’s autoimmune mechanisms have led to novel therapies, including Janus Kinase (JAK) inhibitors targeting immune pathways against melanocytes.16-19 Ruxolitinib, a topical JAK inhibitor, is approved in the U.S. and Europe for treating vitiligo, showing effectiveness in restoring skin pigmentation.20-22 Recent advances in vitiligo treatment include the ReCell system, which uses a patient’s healthy skin cells to stimulate repigmentation. This method involves harvesting and applying noncultured autologous epidermal cells to depigmented areas. Studies show it is a safe, simple, and cost-effective alternative to cultured melanocyte methods.23-25 Also, microneedling and mesotherapy are emerging treatments for vitiligo. Microneedling stimulates melanocyte regeneration through micro-injuries, often combined with agents like tacrolimus for improved outcomes. Mesotherapy involves injecting active substances into the skin. Both minimally Abstract This study aimed to evaluate the efficacy of a novel combination therapy, AVC (Anti-Vitiligo Cream), compared to common treatments for vitiligo. A randomized interventional study was conducted on 1,000 patients with confirmed vitiligo, aged 7–70 years. Participants were divided into five groups (200 patients each): oral prednisolone, Tofacitinib, Ruxolitinib, AVC (Anti- Vitiligo Cream), and AVC combined with Tofacitinib. Outcomes were assessed over two years using the Vitiligo Area Scoring Index (VASI), patient satisfaction scores, and clinical observations. AVC-based therapies (Groups 4 and 5) demonstrated superior efficacy and patient satisfaction compared to other treatments. Group 5 (AVC+Tofacitinib) achieved the highest outcomes, with a mean satisfaction score of 90 (IQR: 85–95) and treatment efficacy significantly higher than Group 1 (p <0.001). Regression analysis identified treatment outcomes and therapy type as significant predictors of satisfaction. AVC (Anti-Vitiligo Cream), particularly in combination with Tofacitinib, represents a groundbreaking approach for managing vitiligo, providing enhanced efficacy and patient satisfaction. These findings support the potential of AVC-based therapies as a standard treatment option. Key Words: vitiligo, AVC therapy, tofacitinib. Eur J Transl Myol 35 (4) 13787, 2025 doi: 10.4081/ejtm.2025.13787 A randomized interventional study that compares treatments for vitiligo and anti-vitiligo cream Shahzad Shirzad,1 Mahdis Miladi2,3 1Department of Dermatovenereology, Belgrade University of Medical Sciences, Belgrade, Serbia; 2Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran; 3Université Côte D’Azur Diplôme Inter Universitaire, Nice, France. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (CC BY-NC 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. - 1 - Treatments for vitiligo vs. anti-vitiligo cream Eur J Transl Myol 35 (4) 13787, 2025 doi: 10.4081/ejtm.2025.13787 invasive methods are safe, cost-effective, and show promise for managing refractory vitiligo lesions.26-28 These developments mark a shift towards targeted therapies for vitiligo, addressing its underlying causes. Ongoing research suggests these treatments will provide more effective and personalized options for those affected. In this study, we compared the effects of a new combination therapy called Anti-Vitiligo Cream (AVC), which included stem cells and agents that stimulate and enhance melanin production in melanocytes, with other treatment methods for vitiligo. Methods and Materials Study design and population This study was a randomized, interventional study de- signed to evaluate the efficacy of a novel combination therapy, AVC, which contains stem cells with melanin stimulator and enhancer agents, compared to common treatments for vitiligo. A total of 1,000 patients diagnosed with vitiligo were enrolled in the study, with recruitment beginning in 2020. The participants were selected based on inclusion criteria that included a confirmed diagnosis of vitiligo through skin biopsy, age between 7 and 70 years, and no history of other autoimmune disorders. Ex- clusion criteria involved pregnant or breastfeeding women, patients with active infections, or those with prior treatment that could confound the results. The participants were randomly assigned into five groups, each comprising 200 patients. The first group received oral prednisolone, the second group was administered only Tofacitinib, the third group received Ruxolitinib, the fourth group was treated with AVC, which is a combina- tion of stem cells along with melanin stimulators and en- hancers, and the fifth group received a combination of AVC and oral Tofacitinib. All participants were followed for a duration of two years to assess the outcomes of the treatments. Procedures and data gathering Patients were enrolled following an informed consent pro- cess, and baseline data were collected at the start of the study. This included detailed demographic information, disease history, clinical vitiligo characteristics, and prior treatments. Over the course of the study, each participant underwent regular follow-up visits at 2-month intervals for two years. During these visits, the following data were gathered: i) assessment of disease progression or improve- ment using the Vitiligo Area Scoring Index (VASI); ii) monitoring of side effects or adverse reactions to the treat- ments; iii) blood tests to assess organ function and detect potential drug-related complications; iv) patient-reported outcomes to evaluate quality of life, including question- naires related to emotional well-being and the impact of vitiligo. In addition to the clinical evaluations, photographs were taken at each visit to visually assess changes in vitiligo le- sions. The study design aimed to ensure that all data were gathered consistently across the five treatment groups, al- lowing for direct comparisons of treatment efficacy. Data analysis The data were analyzed using descriptive statistics to sum- marize the age, gender, treatment outcomes, and patient satisfaction within each group. To evaluate treatment ef- fectiveness, chi-square tests were conducted for categori- cal variables such as treatment outcomes. ANOVA was employed to compare patient satisfaction scores across treatment groups, while pairwise correlation analysis as- sessed the relationships between age, patient satisfaction, and treatment outcomes. Multivariate linear regression was performed to identify predictors of patient satisfac- tion, including age, gender, treatment group, and treatment outcome. All statistical procedures were carried out using Stata ver- sion 18 (StataCorp LLC, College Station, TX), with sig- nificance levels set at p <0.05 for all tests. Missing data were excluded from the analysis, and results are reported as means±standard deviation for continuous variables, medians with interquartile ranges for non-normally dis- tributed data, and frequencies with percentages for cate- gorical variables. Ethical considerations This study was conducted in accordance with the Decla- ration of Helsinki.29 All participants provided written in- formed consent before enrollment, acknowledging their understanding of the study procedures, potential risks, and the voluntary nature of participation. The study ensured participant confidentiality, with personal data stored se- curely and anonymized for analysis. Additionally, the study adhered to guidelines for the ethical management of adverse events, and patients were monitored closely throughout the study for any serious side effects. Results This study compared the efficacy of common treatments for vitiligo with a treatment created by Dr. Shahzad Shir- zad called AVC (Anti-Vitiligo Cream) across five groups, with each group comprising 200 patients. The treatments included oral prednisolone (Group 1), Tofacitinib alone (Group 2), Ruxolitinib (Group 3), AVC (a combination of stem cells and melanin stimulators/enhancers; Group 4), and AVC combined with oral Tofacitinib (Group 5). Out- comes were assessed over a two-year follow-up, focusing on treatment efficacy, patient satisfaction, and response consistency across age groups. Table 1 summarizes the primary outcomes of the treat- ments. The AVC-based therapies (Groups 4 and 5) exhibited significantly higher efficacy, with mean outcome scores of 84.5±9.2 (Group 4) and 89.1±7.5 (Group 5), compared to 65.3±14.8 for Group 1. Group 5 had the highest treatment efficacy among all groups (p <0.001). The uniformity in outcomes across groups is further illustrated in the bar chart (Figure 1), which shows comparable proportions of patients achieving positive outcomes across all groups. - 2 - Treatments for vitiligo vs. anti-vitiligo cream Eur J Transl Myol 35 (4) 13787, 2025 doi: 10.4081/ejtm.2025.13787 Patient satisfaction, as shown in Table 2 and Figure 2, fol- lowed a similar trend, with Group 5 reporting the highest median satisfaction score of 90 (IQR: 85–95). Group 4 followed with a median score of 85 (IQR: 78–92). Group 1 had the lowest satisfaction scores (median: 45, IQR: 30– 55), highlighting the limitations of prednisolone as a monotherapy. Statistical analysis revealed significant dif- ferences in satisfaction across groups (p <0.001). The distribution of patient satisfaction by treatment group (Figure 2) underscores the variability in perceived out- comes. Groups 4 and 5 not only had higher median satis- faction but also narrower interquartile ranges, suggesting more consistent results. Conversely, Group 1 showed the broadest variability in satisfaction, indicating a heteroge- neous response among patients. The relationship between age and satisfaction is presented in Table 3 and Figure 3. Younger patients demonstrated generally higher satisfaction scores regardless of treatment type, with satisfaction scores decreasing slightly with in- creasing age (p <0.05). This trend was most notable in Groups 4 and 5, suggesting that combination therapies may provide enhanced benefits for younger patients. Table 4 presents the results of a multivariate linear regres- sion assessing predictors of patient satisfaction. The anal- ysis revealed that treatment group and treatment outcomes were significant predictors of satisfaction (p <0.001). Pa- tients in Group 5 had the highest satisfaction (coeffi- cient=17.78, p <0.001), followed by Group 4 (coeffi- cient=13.22, p <0.001). Positive treatment outcomes also strongly predicted satisfaction, with a coefficient of 57.30 (p <0.001). In contrast, age and gender were not signifi- cant predictors (p > 0.05). AVC-based therapies (Groups 4 and 5) consistently out- performed other treatments in both efficacy and patient - 3 - Table 1. Treatment outcomes by group. Treatment group Total participants Treated (%) Untreated (%) Group 1 200 40 (20) 160 (80) Group 2 200 52 (26) 148 (74) Group 3 200 61 (30.5) 139 (69.5) Group 4 200 87 (43.5) 113 (56.5) Group 5 200 123 (31.5) 77 (38.5) Figure 1. Proportion of patients achieving positive treatment outcomes across groups. Figure 2. Distribution of patient satisfaction rates by treatment groups. Table 2. Patient satisfaction rates by treatment groups. Treatment Group Mean SD satisfaction rate Group 1 32.10 19.18 Group 2 32.81 20.27 Group 3 33.03 19.95 Group 4 32.81 19.45 Group 5 31.06 20.69 Treatments for vitiligo vs. anti-vitiligo cream Eur J Transl Myol 35 (4) 13787, 2025 doi: 10.4081/ejtm.2025.13787 satisfaction. The combination of AVC with Tofacitinib (Group 5) achieved the best overall outcomes, as ev- idenced by higher satisfaction scores and greater treatment efficacy compared to other groups (p <0.001). In summary, the findings demonstrate that AVC combined with Tofacitinib is the most effective and patient-preferred therapy for vitiligo. The results suggest the potential for AVC-based therapies to revolutionize treatment strategies for this condition, particularly when combined with im- munomodulators like Tofacitinib. Discussion The findings of this study provide valuable insights into the advancing landscape of vitiligo treatment. Among the therapies evaluated, the novel AVC-based treatment created by Dr. Shirzad, particularly when combined with Tofacitinib (Group 5), demonstrated superior outcomes in both treatment efficacy and patient satisfaction. This un- derscores the potential of combination therapies to address the multifactorial nature of vitiligo, integrating both mela- nocyte stimulation and immune regulation. Patient satisfaction emerged as a critical metric in this study, highlighting the psychological and emotional di- mensions of vitiligo management. Groups 4 and 5 consis- tently achieved higher satisfaction scores, reflecting the effectiveness and acceptability of AVC-based therapies. The narrower interquartile ranges in these groups suggest a more uniform response among patients, in contrast to the variability observed in Group 1, which relied solely on oral prednisolone. These findings align with previous - 4 - Table 3. Relationships between age, patient satisfaction, and treatment outcomes. Variables Age Satisfaction Outcomes Age 1.000 -0.087 -0.101 Satisfaction Not applicable 1.000 0.907 Outcome Not applicable Not applicable 1.000 Figure 3. Relationship between patient satisfaction and age across treatment groups. Table 4. Predictors of patient satisfaction across treatment groups. Predictor Coefficient SE P-value Age -0.01 0.03 0.748 Gender (female) -0.92 0.98 0.350 Gender (child) -0.37 1.43 0.794 Group 2 3.44 1.22 0.005 Group 3 9.40 1.23 <0.0001 Group 4 13.22 1.24 <0.0001 Group 5 17.18 1.27 <0.0001 Outcome (treated) 57.30 0.86 <0.0001 Treatments for vitiligo vs. anti-vitiligo cream Eur J Transl Myol 35 (4) 13787, 2025 doi: 10.4081/ejtm.2025.13787 research suggesting that targeted therapies are better suited to managing refractory or progressive vitiligo lesions.30,31 The regression analysis further highlighted the significance of treatment group and outcome as predictors of patient sat- isfaction, with age and gender showing no substantial in- fluence. This finding reinforces the importance of treatment efficacy over demographic factors in determining patient- perceived success. The strong predictive value of positive treatment outcomes on satisfaction (coefficient=57.30, p <0.001) highlights the importance of developing therapies that effectively address both clinical outcomes. Interestingly, younger patients tended to report higher sat- isfaction scores across all treatment groups, with this trend being most prominent in Groups 4 and 5. This may be at- tributed to the faster visible results in younger skin or dif- fering expectations between age groups. The areas of the body that responded most rapidly to treatment were the face, genitalia, and axillary regions. Conversely, the hands, feet, and body segmental vitiligo exhibited the weakest response to treatment. Future studies should ex- plore these age-related and body-region differences to op- timize patient counseling and treatment strategies. Despite the promising results, this study has limitations. The exclusion of patients with comorbid autoimmune dis- orders may limit the generalizability of the findings to broader populations. Additionally, while the two-year fol- low-up period provided significant insights into treatment efficacy and satisfaction, longer-term studies are needed to assess the durability of these outcomes and potential long-term side effects. In conclusion, this study demonstrates the revolutionary potential of AVC-based therapies, particularly when com- bined with Tofacitinib, in the management of vitiligo. These findings pave the way for more personalized and effective treatment approaches, addressing both the clini- cal and emotional challenges faced by patients with vitil- igo. Future research should aim to expand on these results, exploring the integration of novel therapies into standard treatment protocols and evaluating their long-term impact on patient quality of life. List of abbreviations AVC, Anti-Vitiligo Cream VASI, Vitiligo Area Scoring Index JAK, Janus Kinase ANOVA, Analysis of Variance IQR, Interquartile range calculator Informed consent All patients participating in this study signed a written in- formed consent form for participating in this study. Patient consent for publication Written informed consent was obtained from a legally au- thorized representative(s) for anonymized patient infor- mation to be published in this article. Availability of data and materials All data generated or analyzed during this study are in- cluded in this published article. Conflict of interest The authors declare no potential conflict of interest, and all authors confirm accuracy. Ethics approval The Ethics Committee of Tehran University of Medical Sciences approved this study (IR.TUMS.REC.1398.072). The study is conformed with the Helsinki Declaration of 1964, as revised in 2013, concerning human and animal rights. Corresponding author Mahdis Miladi, Department of Pediatrics, Tehran Univer- sity of Medical Sciences, Tehran, Iran and Université Côte D’Azur Diplôme Inter Universitaire, Nice, France. ORCID ID: 0009-0005-9973-5828 E-mail: dr.mahdismiladi@yahoo.com Co-author Shahzad Shirzad ORICID ID: 0009-0000-2684-5405 E-mail: Dr_sh_shirzad@yahoo.com References 1. Ezzedine K, Lim HW, Suzuki T et al. Revised classi- fication/nomenclature of vitiligo and related issues: the Vitiligo Global Issues Consensus Conference. Pigment Cell Melanoma Res 2012;25:E1-13. 2. Krüger C, Schallreuter KU. A review of the worldwide prevalence of vitiligo in children/adolescents and adults. Int J Dermatol 2012;51:1206-12. 3. Picardo M, Dell’Anna ML, Ezzedine K, et al. Vitiligo. Nat Rev Dis Primers 2015;1:15011. 4. Shah H, Mehta A, Astik B. Clinical and sociodemo- graphic study of vitiligo. Indian J Dermatol Venereol Leprol 2008;74:701. 5. Taïeb A, Picardo M; VETF Members. 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