Assessing the trends of outcome measures and quality of life instruments in vitiligo: A systematic review

In recent years, there has been a significant increase in the number of instruments aimed at quantifying vitiligo outcomes.1 In this study, we describe trends in physician-reported outcome measures, patient-reported outcome measures (PROMs) and QoL instruments in vitiligo-related randomized controlled trials (RCTs) published between January 1964 and October 2021. Using PubMed and Embase databases, comprehensive searches of the literature were conducted on November 1, 2021. Search terms included: ‘vitiligo’, ‘hypopigmentation’, ‘outcome measures’, ‘randomized controlled trials’, ‘quality of life instruments’. The literature search was conducted according to the framework established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses2 and was prospectively registered with PROSPERO. References from published studies and systematic reviews were also searched. All human subject RCTs investigating vitiligo treatments published in English, between 1964 and October 2021 were included. Both outcomes and outcome measures reported in the eligible studies were retrieved. Screening and full-text review were independently assessed by two reviewers (JM, RS). Of the 514 reports, 132 (25.7%) met the eligibility criteria (Figure 1). A total of 53 physician-reported outcome measures were identified in this review (Table 1). Repigmentation was measured using a diverse assortment of scales (e.g. percentages, quartiles/quintiles, categories). Repigmentation was commonly measured using a percentage repigmentation scale (e.g. 0–30%, 31%–50%), which was identified in 83 (62.8%) studies. The Vitiligo Area Scoring Index (VASI), along with its modified version, was the most frequently used disease severity instrument identified in our study (27/132, 20.5%). VASI use increased from the year 2010 onward. Of the 54 published and ongoing RCTs since 2010, more than half (n = 32; 59.3%) used the VASI as an outcome measure (Table 1). Fourteen studies used biochemical markers as a measure of disease severity. Of the 22 PROMs identified, 17 (77%) were used in only 1 study. Patient satisfaction was assessed in 10 RCTs, closely followed by the Vitiligo Disease Activity Index, Patient's Global Assessment Scale (n = 6) and Vitiligo Noticeability Scale (n = 3). Six (33%) used more than one QoL measure. The proportion of RCTs that assessed QoL peaked between 2020 and 2021. The dermatology life quality index was used in nine RCTs, followed by the vitiligo QoL (VitiQoL, n = 3) and Vitiligo Impact Patient Scale (VIPs, n = 1). Although percentage repigmentation was the most frequently used scale to measure repigmentation, there were significant differences in the definition of percentages, making inter-study comparison challenging. Currently, the Vitiligo Group International Consensus Guidelines group recommends using a percentage of repigmentation quartiles scale to assess repigmentation. and VNS for assessing cosmetic acceptability.3, 4 However, only three studies identified in this review used VNS as an outcome measure. Both the VASI and Vitiligo European Task Force (VETFa) are considered to be reliable and accurate tools for disease extent (e.g. BSA) assessment.5 Despite being developed and validated in 2007, VETFa was only reported in two RCTs. Recently, the amount of change in BSA (e.g. responsiveness to treatment) has also been validated for the vitiligo extent score (VES) and its modified version (VESplus). As with disease severity instruments, QoL instruments also demonstrate significant heterogeneity and are non-specific. The VitiQoL was the most frequently used vitiligo-specific instrument identified in this review; it consists of 16 items divided into 3 domains: participation limitation, stigma and behaviour. However, the VitiQoL does not address other aspects of QoL (e.g. economic constraints, impact of vitiligo on relationships and sexuality). As such, the VitiQoL can be complemented by additional vitiligo-specific QoL instruments, such as VIS.8 This systematic review highlights the heterogeneity of outcome measures used to measure core domains of vitiligo. To date, there continues to be a need to standardize outcome measures to assess the core outcome domains. These efforts will help improve the quality and comparability of clinical trials. No funding was provided to the authors of this study. Tasneem Mohammad is an investigator for Clinuvel, Incyte Corporation, Pfizer, Avita, Arcutis, Pierre Fabre, Estee Lauder, Unigen Inc., Ferndale Healthcare Inc. and Allergan. Iltefat Hamzavi is an investigator for PCORI, Incyte Corporation, AVITA medical, L'Oréal, Beiersdorf, Estee Lauder, Unigen Inc., Ferndale Healthcare Inc., Pfizer, Allergan and Johnson & Johnson and has served as a consultant for Pfizer, Johnson and Johnson and Beiersdorf. Dr. Ezzedine reports serving as a consultant for Incyte, La Roche-Posay, Pfizer, Pierre Fabre, Sanofi and Viela Bio. Dr. Maghfour is a sub-investigator for Clinuvel, Incyte Corporation and Avita. Ms. Shoukfeh has no conflicts of interest to disclose. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.