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.

Once-daily upadacitinib versus placebo in adults with extensive non-segmental vitiligo: a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study.

Background: Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, in adults with non-segmental vitiligo. Methods: This was a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study completed at 33 clinical centres in the United States, Canada, France, and Japan. Eligible patients were aged 18-65 years with non-segmental vitiligo and had a Facial Vitiligo Area Scoring Index (F-VASI) ≥0.5 and a Total Vitiligo Area Scoring Index (T-VASI) ≥5. Patients were randomly assigned (2:2:2:1:1) using an interactive response technology to receive upadacitinib 6 mg (UPA6), upadacitinib 11 mg (UPA11), upadacitinib 22 mg (UPA22), or placebo (PBO; preassigned to switch to either UPA11 or UPA22 in period 2) once daily for 24 weeks (period 1). For weeks 24-52 (period 2), patients randomly assigned to upadacitinib continued their treatment, and patients receiving PBO switched to their preassigned upadacitinib dose in a blinded fashion. The primary endpoint was the percent change from baseline in F-VASI at week 24. Efficacy was analysed in the intention-to-treat population, and safety was examined in all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT04927975. Findings: Between June 16, 2021, and June 27, 2022, 185 patients (including 115 [62%] who were female and 70 [38%] who were male) were randomly assigned to UPA6 (n = 49), UPA11 (n = 47), UPA22 (n = 43), or PBO (n = 46). At week 24, the LS mean difference versus PBO in the percent change from baseline in F-VASI was -7.60 (95% CI -22.18 to 6.97; p = 0.3037) for UPA6, -21.27 (95% CI -36.02 to -6.52; p = 0.0051) for UPA11, and -19.60 (95% CI -35.04 to -4.16; p = 0.0132) for UPA22. The LS mean difference versus PBO in the percent change from baseline in T-VASI was -7.45 (95% CI -16.86 to 1.96; p = 0.1198) for UPA6, -10.84 (95% CI -20.37 to -1.32; p = 0.0259) for UPA11 and -14.27 (95% CI -24.24 to -4.30; p = 0.0053) for UPA22. Ongoing treatment with upadacitinib induced continuous skin repigmentation over time without reaching a plateau through week 52. The rates for study drug discontinuation and serious treatment-emergent adverse events (TEAEs) were higher in the UPA22 group than in the UPA11 and UPA6 groups. Eight serious TEAEs, including one death of unknown cause and one case of infiltrating lobular breast carcinoma, were reported through 52 weeks; only two serious TEAEs (coronary artery arteriosclerosis [UPA6 (n = 1)] and non-fatal ischemic stroke [UPA11 (n = 1)]) were deemed by the investigator to have a reasonable possibility of being related to study drug. The one case of breast cancer in the UPA11 group was deemed unrelated to study drug, and the one death of unknown cause in the UPA22 group was reviewed and adjudicated and was deemed to be unrelated to study drug. The most common TEAEs were COVID-19, headache, acne, and fatigue. No new safety signals were observed. Interpretation: Upadacitinib monotherapy led to substantial repigmentation of both facial and total body vitiligo lesions and may offer an effective treatment option for adults with extensive non-segmental vitiligo. Based on these findings, upadacitinib 15 mg is being investigated in adults and adolescents with non-segmental vitiligo in an ongoing phase 3 randomised controlled trial. Funding: AbbVie Inc.

Economic Burden among Patients with Vitiligo in the United States: A Retrospective Database Claims Study.

Patients with vitiligo incur direct and indirect costs associated with their condition; however, data regarding the economic burden of vitiligo are scarce and outdated. In this retrospective cohort analysis of the Merative MarketScan Commercial Database, healthcare costs and healthcare resource utilization (HCRU) were evaluated among United States patients with vitiligo. Patients with vitiligo were matched (1:2) with individuals without vitiligo (controls) between January 2007 and December 2021. Outcomes included all-cause and vitiligo-related costs (2021 dollars) and all-cause HCRU, including mental health-related HCRU, during a 1-year postindex period. Subgroup analyses were completed for patients on vitiligo treatments with systemic effects (such as phototherapy and oral steroids) or a new mental health diagnosis. The analysis was focused solely on direct costs. Baseline demographics were well-balanced between matched vitiligo (49,512) and control (99,024) cohorts. Patients with vitiligo incurred significantly higher all-cause ($15,551 vs $7735) and vitiligo-related ($3490 vs $54) costs than controls (P < .0001). All-cause and mental health-related HCRU were also significantly higher among patients with vitiligo (P < .0001). Differences in all-cause and vitiligo-related healthcare costs remained significantly higher in patients on treatments with systemic effects/mental health diagnoses than in controls (P < .0001). Taken together, healthcare costs and HCRU were significantly higher among patients with vitiligo than among controls.

Comorbidity Burden Among Patients with Vitiligo in the United States: A Large-Scale Retrospective Claims Database Analysis.

INTRODUCTION: Vitiligo is often associated with comorbid conditions that may increase economic burden and affect patients' health-related quality of life. No large-scale study has been published to date using claims databases to evaluate the burden of comorbidities among patients with vitiligo. Herein, we evaluate the comorbidity burden among patients diagnosed with vitiligo from the US. METHODS: This retrospective cohort analysis used the Merative MarketScan Commercial Database. Eligible patients were diagnosed with vitiligo between January 2008 and December 2020 and matched 1:4 (vitiligo:control) with control subjects with no diagnosis of vitiligo between January 2007 and December 2021. Study outcomes were the incidence of comorbidities after matching, adjusted hazard ratios of comorbidity incidence among patients with vitiligo relative to matched control subjects, and time to comorbidity diagnosis or incidence. RESULTS: Baseline demographics were well balanced between matched vitiligo (n = 13,687) and control cohorts (n = 54,748). Incidence rates of comorbidities were higher among patients compared with control subjects (psychiatric, 28.4% vs 22.8%; autoimmune, 13.4% vs 5.1%; and non-autoimmune, 10.0% vs 7.0%). The most common psychiatric and autoimmune comorbidities in patients with vitiligo compared with control subjects included anxiety (14.3% vs 11.0%, respectively), sleep disturbance (9.1% vs 7.1%), depression (8.0% vs 6.3%), atopic dermatitis (3.1% vs 1.1%), psoriasis (2.7% vs 0.6%), and linear morphea (1.5% vs 0.1%). The risk of developing any psychiatric (hazard ratio 1.31; P < 0.01), autoimmune (hazard ratio 2.77; P < 0.01), or non-autoimmune (hazard ratio 1.45; P < 0.01) comorbidity was significantly higher among patients with vitiligo. Time to diagnosis of most vitiligo comorbidities was 1-3 years, although linear morphea was diagnosed at < 1 year. CONCLUSION: Results of this retrospective analysis demonstrated that patients were much more likely to be diagnosed with autoimmune or psychiatric comorbidities following a vitiligo diagnosis, which likely contributed to increased economic burden and lower quality of life.

Vitiligo, a long-lasting disorder in which patches of the skin lose color, is often associated with other medical conditions that may lower a patients' quality of life and increase the cost of caring for patients with the disorder. No large-scale studies are currently available that look at how other medical conditions affect patients with vitiligo. In this study, we determine the occurrence and timing of other medical conditions among patients from the US who have vitiligo. We used the Merative MarketScan Commercial Database, which captures medical and prescription drug data for 145.5 million people in the US. Patients in this study had vitiligo diagnosed between January 2008 and December 2020 and were matched with subjects who did not have vitiligo between January 2007 and December 2021. We looked at the occurrence of other medical conditions among patients with vitiligo compared with subjects without vitiligo and the time it took for another medical condition associated with vitiligo to happen. The authors found that among 13,687 patients with vitiligo and 54,748 subjects without vitiligo, patients with vitiligo were much more likely to have an autoimmune (disorders in which the body's immune system attacks healthy tissue) or psychiatric (mental, emotional, or behavioral) disorder, which likely contributed to the amount of money needed to care for the condition and reduced quality of life.

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.

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.

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.

Expert opinion about laser and intense pulsed light (IPL)-induced leukoderma or vitiligo: a cross-sectional survey study.

Vitiligo patients may desire laser hair removal, skin rejuvenation, vascular treatments, and other laser or intense pulsed light (IPL) assisted treatments. However, there is a risk of inducing new depigmented patches (Koebner phenomenon). In absence of guidelines on the safe use of laser or IPL in vitiligo patients, dermatologists tend to be reluctant to administer these treatments. The aim of this survey study was to provide an estimation of the occurrence and related risk factors of laser/IPL-induced leukoderma or vitiligo. A cross-sectional survey study was performed among 15 vitiligo experts from 11 countries, with 14 questions about affected patients, involved laser/IPL treatments and the physicians' approach. In a total of 11,300 vitiligo patients, laser/IPL-induced leukoderma or vitiligo was reported in 30 patients (0.27%). Of these, 12 (40%) patients had a medical history of vitiligo and seven (58%) of these patients had stable (> 12 months) vitiligo before the treatment. Most frequently reported were hair removal procedures and localization of the face and legs. Side effects like blistering, crusting, and erosions occurred in 56.7% of the cases. These vitiligo experts based their advice on the risk of the laser treatment on stability of the vitiligo (43%) and activity signs (50%), and 50% discuss the risks before starting a laser treatment. Relevant activity signs are the Koebner phenomenon (57.1%), confetti-like lesions (57.1%) and hypochromic borders (50%). Laser-induced leukoderma or vitiligo is an uncommon phenomenon. Remarkably, a minority had a medical history of vitiligo of which 58% were stable. Consequently, most cases could not have been prevented by not treating vitiligo patients. However, a majority had laser/IPL-induced skin damage. Therefore, caution is advised with aggressive settings and test-spots prior to the treatment are recommended. This study showed significant variation in the current recommendations and approach of vitiligo experts regarding laser/IPL-induced leukoderma or vitiligo.

Cultural Competence and Humility.

The increasing diversification of the United States has led to more racially and ethnically discordant visits between health care providers and patients; this is especially true in dermatology due to the lack of diversity in the field. Diversifying the health care workforce has been shown to reduce health care disparities and is an ongoing goal of dermatology. Improving cultural competence and humility among physicians is an important part of addressing health care inequities. This article reviews cultural competence, cultural humility, and practices dermatologists can incorporate to address this challenge.

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.

15-Year Diversity Trends Among Dermatology Resident Trainees Compared With Other Specialties.

This cross-sectional study examines racial and ethnic diversity trends among dermatology resident trainees and applicants compared with other specialties.

Structural Determinants of Indole-2-carboxamides: Identification of Lead Acetamides with Pan Antimycobacterial Activity.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is one of the leading causes of death in developing countries. Non-tuberculous mycobacteria (NTM) infections are rising and prey upon patients with structural lung diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis. All mycobacterial infections require lengthy treatment regimens with undesirable side effects. Therefore, new antimycobacterial compounds with novel mechanisms of action are urgently needed. Published indole-2-carboxamides (IC) with suggested inhibition of the essential transporter MmpL3 showed good potency against whole-cell M.tb, yet had poor aqueous solubility. This project focused on retaining the required MmpL3 inhibitory pharmacophore and increasing the molecular heteroatom percentage by reducing lipophilic atoms. We evaluated pyrrole, mandelic acid, imidazole, and acetamide functional groups coupled to lipophilic head groups, where lead acetamide-based compounds maintained high potency against mycobacterial pathogens, had improved in vitro ADME profiles over their indole-2-carboxamide analogs, were non-cytotoxic, and were determined to be MmpL3 inhibitors.

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.

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 Malignancy in Adrenal Nodules With Heterogeneous Microscopic Fat on Chemical-Shift MRI: A Multiinstitutional Study.

BACKGROUND. Homogeneous microscopic fat within adrenal nodules on chemical-shift MRI (CS-MRI) is diagnostic of benign adrenal adenoma, but the clinical relevance of heterogeneous microscopic fat is not well established. OBJECTIVE. This study sought to determine the prevalence of malignancy in adrenal nodules with heterogeneous microscopic fat on dual-echo T1-weighted CS-MRI. METHODS. We performed a retrospective study of adult patients with adrenal nodules detected on MRI performed between August 2007 and November 2020 at seven institutions. Eligible nodules had a short-axis diameter of 10 mm or larger with heterogeneous microscopic fat (defined by an area of signal loss of < 80% on opposed-phase CS-MRI). Two radiologists from each center, blinded to reference standard results, determined the signal loss pattern (diffuse, two distinct parts, speckling pattern, central loss, or peripheral loss) within the nodules. The reference standard used was available for 283 nodules (pathology for 21 nodules, ≥ 1 year of imaging follow-up for 245, and ≥ 5 years of clinical follow-up for 17) in 282 patients (171 women and 111 men; mean age, 60 ± 12 [SD] years); 30% (86/282) patients had prior malignancy. RESULTS. The mean long-axis diameter was 18.7 ± 7.9 mm (range, 10-80 mm). No malignant nodules were found in patients without prior cancer (0/197; 95% CI, 0-1.5%). Four of the 86 patients with prior malignancy (hepatocellular carcinoma [HCC], renal cell carcinoma [RCC], lung cancer, or both colon cancer and RCC) (4.7%; 95% CI, 1.3-11.5%) had metastatic nodules. Detected patterns were diffuse heterogeneous signal loss (40% [114/283]), speckling (28% [80/283]), two distinct parts (18% [51/283]), central loss (9% [26/283]), and peripheral loss (4% [12/283]). Two metastases from HCC and RCC showed diffuse heterogeneous signal loss. Lung cancer metastasis manifested as two distinct parts, and the metastasis in the patient with both colon cancer and RCC showed peripheral signal loss. CONCLUSION. Presence of heterogeneous microscopic fat in adrenal nodules on CS-MRI indicates a high likelihood of benignancy, particularly in patients without prior cancer. This finding is also commonly benign in patients with cancer; however, caution is warranted when primary malignancies may contain fat or if the morphologic pattern of signal loss may indicate a collision tumor. CLINICAL IMPACT. In the absence of prior cancer, adrenal nodules with heterogeneous microscopic fat do not require additional imaging evaluation.