Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo.

BACKGROUND: Vitiligo is a chronic autoimmune disease that causes skin depigmentation. A cream formulation of ruxolitinib (an inhibitor of Janus kinase 1 and 2) resulted in repigmentation in a phase 2 trial involving adults with vitiligo. METHODS: We conducted two phase 3, double-blind, vehicle-controlled trials (Topical Ruxolitinib Evaluation in Vitiligo Study 1 [TRuE-V1] and 2 [TRuE-V2]) in North America and Europe that involved patients 12 years of age or older who had nonsegmental vitiligo with depigmentation covering 10% or less of total body-surface area. Patients were randomly assigned in a 2:1 ratio to apply 1.5% ruxolitinib cream or vehicle control twice daily for 24 weeks to all vitiligo areas on the face and body, after which all patients could apply 1.5% ruxolitinib cream through week 52. The primary end point was a decrease (improvement) of at least 75% from baseline in the facial Vitiligo Area Scoring Index (F-VASI; range, 0 to 3, with higher scores indicating a greater area of facial depigmentation), or F-VASI75 response, at week 24. There were five key secondary end points, including improved responses on the Vitiligo Noticeability Scale. RESULTS: A total of 674 patients were enrolled, 330 in TRuE-V1 and 344 in TRuE-V2. In TRuE-V1, the percentage of patients with an F-VASI75 response at week 24 was 29.8% in the ruxolitinib-cream group and 7.4% in the vehicle group (relative risk, 4.0; 95% confidence interval [CI], 1.9 to 8.4; P<0.001). In TRuE-V2, the percentages were 30.9% and 11.4%, respectively (relative risk, 2.7; 95% CI, 1.5 to 4.9; P<0.001). The results for key secondary end points showed superiority of ruxolitinib cream over vehicle control. Among patients who applied ruxolitinib cream throughout 52 weeks, adverse events occurred in 54.8% in TRuE-V1 and 62.3% in TRuE-V2; the most common adverse events were application-site acne (6.3% and 6.6%, respectively), nasopharyngitis (5.4% and 6.1%), and application-site pruritus (5.4% and 5.3%). CONCLUSIONS: In two phase 3 trials, application of ruxolitinib cream resulted in greater repigmentation of vitiligo lesions than vehicle control through 52 weeks, but it was associated with acne and pruritus at the application site. Larger and longer trials are required to determine the effect and safety of ruxolitinib cream in patients with vitiligo. (Funded by Incyte; TRuE-V1 and TRuE-V2 ClinicalTrials.gov numbers, NCT04052425 and NCT04057573.).

Racial and Ethnic Diversity in Vitiligo Clinical Trials: A Retrospective Cross-Sectional Study Assessing Demographic Reporting of Participants.

BACKGROUND: While the prevalence of vitiligo is similar across racial and ethnic groups, the effects of vitiligo vary by demographic group, culture, and skin color, with darker-skinned individuals facing greater stigma due to increased visibility of the disease.1,2 The recruitment of diverse participants that are representative of the United States (US) population is crucial to ensuring the generalizability of findings and understanding the impacts of vitiligo across diverse patient groups.   Objectives: This study aimed to determine demographic reporting trends in US vitiligo clinical trials and to determine whether participants are representative of the US population. METHODS: A search for US vitiligo clinical trials was conducted on clinicaltrials.gov. Trials conducted between 2006 to September 5, 2023, were included if they intended to treat vitiligo, were conducted in the US, and were completed or terminated.  Results: Of the 15 trials meeting inclusion criteria, only 60% (n=9) reported participant race/ethnicity. These 9 studies included 1,510 participants, of which only 25.43% (n=384) were non-White and 20.40% were Hispanic. There was disproportionately low representation of racial minorities, particularly Black, Native American, and Native Hawaiian groups.   Limitations: Limitations of our study include small sample size, variations in demographic reporting between trials, and undercounting of minority groups by the US Census.  Conclusions: Racial and ethnic minority groups remain underrepresented in US vitiligo clinical trials. Given that the impact of vitiligo can vary by the affected individual’s demographic group and skin color, investigators must be intentional about including a more diverse and representative population in vitiligo clinical trials.  J Drugs Dermatol. 2024;23(7):e164-e166. doi:10.36849/JDD.8117e.

Reliability and agreement testing of a new automated measurement method to determine facial vitiligo extent using standardized ultraviolet images and a dedicated algorithm.

BACKGROUND: Facial repigmentation is the primary outcome measure for most vitiligo trials. The Facial Vitiligo Area Scoring Index (F-VASI) score is often chosen as the primary outcome measure to assess the efficacy of treatments for facial vitiligo. Although useful, this scoring system remains subjective and has several limitations. OBJECTIVES: To assess the agreement and reliability of an algorithmic method to measure the percentage depigmentation of vitiligo on the face. METHODS: We developed a dedicated algorithm called Vitil-IA® to assess depigmentation on standardized facial ultraviolet (UV) pictures. We then conducted a cross-sectional study using the framework of the ERASE trial (NCT04843059) in 22 consecutive patients attending a tertiary care centre for vitiligo. Depigmentation was analysed before any treatment and, for 7 of them, after 3 and 6 months of narrowband UVB treatment combined with 16 mg methylprednisolone, both used twice weekly. Interoperator and interacquisition repeatability measures were assessed for the algorithm. The results of the algorithmic measurement were then compared with the F-VASI and the percentage of depigmented skin scores assessed by 13 raters, including 7 experts in the grading of vitiligo lesions. RESULTS: Thirty-one sets of pictures were analysed with the algorithmic method. Internal validation showed excellent reproducibility, with a variation of < 3%. The percentage of depigmentation assessed by the system showed high agreement with the percentage of depigmentation assessed by raters [mean error (ME) -11.94 and mean absolute error (MAE) 12.71 for the nonexpert group; ME 0.43 and MAE 5.57 for the expert group]. The intraclass correlation coefficient (ICC) for F-VASI was 0.45 [95% confidence interval (CI) 0.29-0.62] and 0.52 (95% CI 0.37-0.68) for nonexperts and experts, respectively. When the results were analysed separately for homogeneous and heterogeneous depigmentation, the ICC for homogeneous depigmentation was 0.47 (95% CI 0.31-0.77) and 0.85 (95% CI 0.72-0.94) for nonexperts and experts, respectively. When grading heterogeneous depigmentation, the ICC was 0.19 (95% CI 0.05-0.43) and 0.38 (95% CI 0.20-0.62) for nonexperts and experts, respectively. CONCLUSIONS: We demonstrated that the Vitil-IA algorithm provides a reliable assessment of facial involvement in vitiligo. The study underlines the limitations of the F-VASI score when performed by nonexperts for homogeneous vitiligo depigmentation, and in all raters when depigmentation is heterogeneous.

Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: A randomized phase 2b clinical trial.

BACKGROUND: Vitiligo is a chronic autoimmune disorder characterized by depigmented patches of the skin. OBJECTIVE: To evaluate the efficacy and safety of ritlecitinib, an oral JAK3 (Janus kinase)/TEC (tyrosine kinase expressed in hepatocelluar carcinoma) inhibitor, in patients with active nonsegmental vitiligo in a phase 2b trial (NCT03715829). METHODS: Patients were randomized to once-daily oral ritlecitinib ± 4-week loading dose (200/50 mg, 100/50 mg, 30 mg, or 10 mg) or placebo for 24 weeks (dose-ranging period). Patients subsequently received ritlecitinib 200/50 mg daily in a 24-week extension period. The primary efficacy endpoint was percent change from baseline in Facial-Vitiligo Area Scoring Index at week 24. RESULTS: A total of 364 patients were treated in the dose-ranging period. Significant differences from placebo in percent change from baseline in Facial-Vitiligo Area Scoring Index were observed for the ritlecitinib 50 mg groups with (-21.2 vs 2.1; P < .001) or without (-18.5 vs 2.1; P < .001) a loading dose and ritlecitinib 30 mg group (-14.6 vs 2.1; P = .01). Accelerated improvement was observed after treatment with ritlecitinib 200/50 mg in the extension period (n = 187). No dose-dependent trends in treatment-emergent or serious adverse events were observed across the 48-week treatment. LIMITATIONS: Patients with stable vitiligo only were excluded. CONCLUSIONS: Oral ritlecitinib was effective and well tolerated over 48 weeks in patients with active nonsegmental vitiligo.

Prevalence of Vitiligo among Children and Adolescents in the United States.

BACKGROUND: Vitiligo is an autoimmune disorder that causes patchy loss of skin pigmentation. Up to 2.16% of pediatric patients may have vitiligo. This study estimated vitiligo point prevalence in children and adolescents (ages: 4-11 and 12-17 years) in the United States (US). METHODS: An online, population-based survey of a nationally representative sample of individuals based on 2017 US Census Bureau estimates for age, race, Hispanic origin, income, and geographic region was conducted from December 2019 to March 2020. Parent/legal guardian proxies responded on behalf of their children or adolescents to vitiligo screening questions. Proxy-reported vitiligo status was adjudicated by expert dermatologists who reviewed photographs of vitiligo lesions uploaded by proxies using a teledermatology application. Estimated point prevalence (including diagnosed and undiagnosed vitiligo and its subtypes) was calculated for proxy-reported and clinician-adjudicated vitiligo. RESULTS: There were 9,118 eligible proxy responses (5,209 children, mean age 7.7 years; 3,909 adolescents, mean age 14.4 years). The proxy-reported vitiligo prevalence (95% confidence interval) for children and adolescents was 1.52% (1.11-1.93) and 2.16% (1.66-2.65), respectively. The clinician-adjudicated prevalence (sensitivity analysis bounds) was 0.84% (0.83-1.23) and 1.19% (1.18-1.74), respectively. Approximately 69% of children and 65% of adolescents had nonsegmental vitiligo (clinician adjudicated) and up to 50% may be undiagnosed. CONCLUSION: Based on the clinician-adjudicated prevalence estimates, there were more than 591,000 cases of vitiligo in children and adolescents in the US in 2020. More than two-thirds had nonsegmental vitiligo and nearly half may be undiagnosed. Future studies should confirm these findings.

Clinician-reported outcome measures for the assessment of vitiligo: A scoping review.

Clinician-reported outcome measures (ClinROMs) are essential for assessment of vitiligo in clinical trials and daily practice. Several instruments have been developed and tested to measure, for example, vitiligo extent, repigmentation and activity. The goal of this review was to identify all introductory publications of ClinROMs for vitiligo that include at least some aspects of validation and to describe the instruments' characteristics, intention for use and practical strengths and limitations. A search strategy was conducted in PubMed, Embase and Cochrane Library (CENTRAL) from inception to July 2022. Based on the literature search (n = 2860), 10 articles were identified, describing 14 different ClinROMs. Six ClinRoms measured disease extent and/or repigmentation, seven evaluated disease activity and one was a composite score. The Vitiligo Area Scoring Index (VASI), and Vitiligo Extent Score (VES and VESplus) measure overall disease extent and/or repigmentation. The VASI relies on hand units (1% body surface area), whereas the VES and VESplus use a picture-based scoring technique. The Vitiligo Extent Score for a Target Area (VESTA) measures repigmentation percentage for target lesions. One global assessment score for extent has been validated. Vitiligo disease activity scores included a static measure of clinical activity signs (Vitiligo Signs of Activity Score [VSAS]) and two measures assessing dynamic evolution (Vitiligo Disease Activity Score [VDAS] and Vitiligo Disease Improvement Score [VDIS]). The Vitiligo European Task Force assessment tool (VETFa) is a composite score. Depending on the practical strengths and limitations as well as the research question and setting (clinical trials vs. daily practice), the choice of an appropriate ClinROM may differ. Fourteen ClinROMs in vitiligo were identified to measure vitiligo extent, repigmentation, and activity. Further research evaluating the validity, reliability, and responsiveness of each instrument and worldwide consensus on which instrument to use for a specific outcome (domain) is greatly needed.

Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations.

BACKGROUND: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking. OBJECTIVES: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed. CONCLUSIONS: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.

Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the International Vitiligo Task Force Part 1: towards a new management algorithm.

BACKGROUND: The treatment of vitiligo can be challenging and depends on several factors such as the subtype, disease activity, vitiligo extent, and treatment goals. Vitiligo usually requires a long-term approach. To improve the management of vitiligo worldwide, a clear and up-to-date guide based on international consensus with uniform stepwise recommendations is needed. OBJECTIVES: To reach an international consensus on the nomenclature and to develop a management algorithm for the diagnosis, assessment, and treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence of topics included in the algorithms. A survey was utilized to resolve remaining issues among a core group of eight experts. Subsequently, the unanimous recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The algorithms highlight the importance of shared decision-making. Dermatologists are encouraged to provide patients with detailed explanations of the prognosis and expected therapeutic outcomes based on clinical examination. The treatment goal should be discussed and clearly emphasized to patients given the different approaches for disease stabilization and repigmentation. The evaluation of disease activity remains a cornerstone in the tailor-made approach to vitiligo patients. CONCLUSIONS: These new treatment algorithms are intended to guide clinical decision-making in clinical practice. Promising novel therapies for vitiligo are on the horizon, further highlighting the need for reliable outcome measurement instruments and greater emphasis on shared decision-making.

Efficacy of a lay community health worker (promotoras de salud) program to improve adherence to emollients in Spanish-speaking Latin American pediatric patients in the United States with atopic dermatitis: A randomized, controlled, evaluator-blinded study.

BACKGROUND: Latin American patients in the United States experience significant health disparities. Community health workers (promotoras de salud) reduce disparities by providing culturally appropriate education. While educational interventions have been studied in atopic dermatitis (AD), a chronic dermatologic condition affecting children, none have evaluated the use of promotoras in Spanish-speaking pediatric patients in the United States. OBJECTIVE: To create and evaluate a promotora-led education program for Spanish-speaking caregivers of Latin American, pediatric patients with AD through a randomized, controlled, evaluator-blinded study. METHODS: Children with moderate/severe AD (n = 48) were recruited from the pediatric dermatology clinic at Children's Health℠ in Dallas, TX and randomized to receive clinic education (n = 26) or clinic education plus promotora home visits (n = 22). The primary outcome was overall adherence to topical emollients over the 12-week study, quantified by MEMSCap™ devices; several secondary endpoints were evaluated. RESULTS: Intention-to-treat analysis revealed a trend toward increased overall adherence to emollients over the 12-week study period in promotora (median [interquartile range, IQR]: 43% [26%-61%]) versus non-promotora (median [IQR]: 20% [11%-49%]) (p = .09) groups. SCORAD, AD knowledge, and Spanish-language Parental Quality of Life Questionnaire for AD (Sp-PIQoL-AD) improved in both groups, although there was no statistically significant difference between groups. There was a trend toward increased AD knowledge at Week 4 (p = .06) in the promotora group. CONCLUSIONS: A promotora-led educational intervention is a promising approach in increasing caregiver medication adherence in pediatric, Latin American patients with AD in the United States. Further research using creative and culturally appropriate strategies to increase medication adherence is necessary to reduce health disparities in other racial and ethnic minority populations in the United States.

Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial.

BACKGROUND: Vitiligo is a chronic autoimmune disease resulting in skin depigmentation and reduced quality of life. There is no approved treatment for vitiligo repigmentation and current off-label therapies have limited efficacy, emphasising the need for improved treatment options. We investigated the therapeutic potential of ruxolitinib cream in patients with vitiligo and report the efficacy and safety results up to 52 weeks of double-blind treatment. METHODS: We did a multicentre, randomised, double-blind, phase 2 study for adult patients with vitiligo in 26 US hospitals and medical centres in 18 states. Patients with depigmentation of 0·5% or more of their facial body surface area (BSA) and 3% or more of their non-facial BSA were randomly assigned (1:1:1:1:1) by use of an interactive response technology system to receive ruxolitinib cream (1·5% twice daily, 1·5% once daily, 0·5% once daily, or 0·15% once daily) or vehicle (control group) twice daily on lesions constituting 20% or less of their total BSA for 24 weeks. Patients in the control group in addition to patients in the 0·15% once daily group who did not show a 25% or higher improvement from baseline in facial Vitiligo Area Scoring Index (F-VASI) at week 24 were re-randomised to one of three higher ruxolitinib cream doses (0·5% once daily, 1·5% once daily, 1·5% twice daily). Patients in the 0·5% once daily, 1·5% once daily, or 1·5% twice daily groups remained at their original dose up to week 52. Patients, investigators, and the study sponsor (except members of the interim analysis and primary endpoint analysis data monitoring teams) remained masked to treatment assignment throughout the study. The primary endpoint was the proportion of patients achieving a 50% or higher improvement from baseline in F-VASI (F-VASI50) at week 24, assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03099304. FINDINGS: Between June 7, 2017, and March 21, 2018, 205 patients were screened for eligibility, 48 were excluded and 157 patients (mean age, 48·3 years [SD 12·9]; 73 [46%] male and 84 [54%] female) were randomly assigned to either an intervention group or the control group. 32 (20%) of 157 were assigned to the control group, 31 (20%) to the 0·15% once daily group, 31 (20%) to the 0·5% once daily group, 30 (19%) to the 1·5% once daily group, and 33 (21%) to the 1·5% twice daily group. F-VASI50 at week 24 was reached by significantly more patients given ruxolitinib cream at 1·5% twice daily (15 [45%] of 33) and 1·5% once daily (15 [50%] of 30) than were treated with vehicle (one [3%] of 32). Four patients had serious treatment-emergent adverse events (one patient in the 1·5% twice daily group developed subdural haematoma; one patient in the 1·5% once daily group had a seizure; one patient in the 0·5% once daily group had coronary artery occlusion; and one patient in the 0·5% once daily group had oesophageal achalasia), all of which were unrelated to study treatment. Application site pruritus was the most common treatment-related adverse event among patients given ruxolitinib cream (one [3%] of 33 in the 1·5% twice daily group; three [10%] of 30 in the 1·5% once daily group; three [10%] of 31 in the 0·5% once daily group; and six [19%] of 31 in the 0·15% once daily group)with three [9%] of 32 patients showing application site pruritis in the control group. Acne was noted as a treatment-related adverse event in 13 (10%) of 125 patients who received ruxolitinib cream and one (3%) of 32 patients who received vehicle cream. All treatment-related adverse events were mild or moderate in severity and similar across treatment groups. INTERPRETATION: Treatment with ruxolitinib cream was associated with substantial repigmentation of vitiligo lesions up to 52 weeks of treatment, and all doses were well tolerated. These data suggest that ruxolitinib cream might be an effective treatment option for patients with vitiligo. FUNDING: Incyte.

Standardizing serial photography for assessing and monitoring vitiligo: A core set of international recommendations for essential clinical and technical specifications.

BACKGROUND: Clinical photography is an important component of the initial assessment and follow-up of patients with vitiligo in clinical practice and research settings. Standardization of this photographic process is essential to achieve useful, high-quality, and comparable photographs over time. OBJECTIVE: The aim is to develop an international consensus for a core set of recommendations for standardized vitiligo clinical photography. METHODS: Based an international meeting of vitiligo experts, a standard operating procedure was developed for vitiligo photography in daily practice and research settings. This protocol was subsequently reviewed by 20 vitiligo experts until agreement was reached. RESULTS: The resulting protocol includes a set of 10 and 15 photographs for clinical practice and research purposes, respectively. The photographic series are based on anatomic units included in the Vitiligo Extent Score. Furthermore, graphic representations of standardized positioning and suggestions for guidelines to standardize the process (background color, lighting, position marking, scales, materials, instruments) for both color and ultraviolet photographs are described. CONCLUSIONS: This consensus-based protocol for vitiligo photography will harmonize imaging for both clinical practice, translational research, and clinical trials. It can improve outcome assessment, foster multicenter collaboration, and promote better communication with patients regarding outcomes of treatment.

Randomised, controlled, double-blind study of combination therapy of oral tranexamic acid and topical hydroquinone in the treatment of melasma.

BACKGROUND/OBJECTIVES: Melasma is a common pigmentary disorder for which oral tranexamic acid has shown some efficacy in previous studies. The aim of this study was to assess the effectiveness of oral tranexamic acid in combination with hydroquinone cream in the treatment of melasma. METHODS: Subjects with moderate-to-severe melasma were enrolled. Group A received hydroquinone 4% cream, sunscreen and oral tranexamic acid, while Group B received hydroquinone 4% cream, sunscreen and placebo capsules for 3 months. All subjects had an additional 3-month follow-up visit on sunscreen alone. The primary outcome measure was change in modified Melasma Area and Severity Index (mMASI) score. In addition, the melanin index was measured using a mexameter. RESULTS: Fifty subjects were enrolled, and all completed the study. There was a 55% reduction in mMASI after 3 months from mean 8.96 (SD 2.45) to 4.0 (SD 1.6) in Group A compared to 10.9% from mean 8.53 (SD 2.04) to 7.6 (SD 2.0) in Group B. Three months after oral and topical therapy was discontinued, there was a 42% decrease in mMASI compared to baseline in Group A (mean 5.1 SD 1.7) vs. 4.7% in Group B (mean 8.1 SD 2.0). No serious adverse events were observed. CONCLUSIONS: A combination of oral tranexamic acid and topical hydroquinone is more effective than hydroquinone alone in the treatment of melasma.

Disorders of Hypopigmentation

Hypopigmentation and depigmentation of the skin can be due to multiple causes and has a broad differential diagnosis. The most common cause of depigmentation worldwide is vitiligo. This disorder affects 1-2% of the world's population and is seen in all races. Vitiligo is an autoimmune disorder in which the predominant cause is an attack by CD8+ cytotoxic T cells on melanocytes in the epidermis. This condition can have a significant negative impact on the quality of life of affected individuals. Treatment options currently include psychological counseling, topical therapy, systemic therapy, phototherapy, surgical therapy, and depigmentation. In patients with stable, refractory disease, successful repigmentation has been achieved using mini-punch grafting, blister grafting, and non-cultured epidermal suspension (NCES) grafting. Emerging therapies include the Janus kinase (JAK) inhibitors ruxolitinib and tofacitinib. Further studies exploring the pathogenesis of vitiligo are warranted in order to optimize treatment for affected patients. J Drugs Dermatol. 2019;18(3 Suppl):s115-116.

Diversity in dermatology: Roadmap for improvement.

The American Academy of Dermatology has taken an active stance in addressing the lack of racial and ethnic diversity in the specialty. At the American Academy of Dermatology President's Conference on Diversity in Dermatology, which was held on August 5, 2017, key action items to increase the number of practicing board-certified dermatologists who are under-represented in medicine (UIM) were identified in 3 main areas. The action items include increasing the pipeline of UIM students applying to medical school, increasing UIM medical students' exposure to the field of dermatology and their level of interest in it, and increasing the number of UIM students recruited into dermatology residency programs.

Randomized, placebo-controlled, double-blind study of oral tranexamic acid in the treatment of moderate-to-severe melasma.

BACKGROUND: Melasma is a common pigmentary disorder that is often difficult to treat. Tranexamic acid (TA) has emerged as a promising treatment for melasma; however, few controlled studies exist. OBJECTIVE: To determine the efficacy of oral TA in patients with moderate-to-severe melasma. METHODS: Patients with moderate-to-severe melasma were treated with 250 mg of TA or placebo capsules twice daily for 3 months and sunscreen followed by 3 months of treatment with sunscreen only. The primary outcome measure was the modified Melasma Area and Severity Index (mMASI) score. RESULTS: A total of 44 patients were enrolled and 39 completed the study. At 3 months, there was a 49% reduction in mMASI score in the TA group versus 18% in the control group. Patients with severe melasma improved more than those with moderate melasma. Three months after treatment was stopped, there was a 26% reduction in mMASI score in the TA group compared with the baseline visit versus a 19% reduction in the placebo arm. No serious adverse events were noted in either group. LIMITATIONS: Single-center study enrolling predominantly Hispanic women. CONCLUSIONS: Oral TA appears to be an effective treatment for moderate-to-severe melasma with minimal side effects.

Oral Tranexamic Acid for the Treatment of Melasma: A Review.

BACKGROUND: Melasma is a common acquired disorder of hyperpigmentation that commonly affects those with skin of color. Tranexamic acid (TXA) is a novel treatment for melasma that has a multimodal mechanism of action. OBJECTIVE: To provide a comprehensive review of the literature regarding the evidence on the mode of action, safety profile, and efficacy of TXA in the treatment of melasma. MATERIALS AND METHODS: The literature was searched for publications on TXA in the treatment of melasma using MEDLINE, Scopus, and Google Scholar. RESULTS: Oral TXA has clearly demonstrated the efficacy for melasma in Asian skin, even in low doses (e.g., 500 mg daily) over short periods (8-12 weeks). It is also a safe therapeutic option, which is easy to administer with few and mild side effects. Studies have shown that TXA does not increase the thromboembolic risk, although patients should be screened carefully for contraindications and risk factors prior to commencement of the therapy. CONCLUSION: Oral TXA is a safe and efficacious treatment for refractory melasma. It should be considered in cases that are unresponsive to topical hydroquinone and combination topical therapy over a period of approximately 12 weeks and without contraindications to oral TXA.