An economic evaluation of the randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo (the HI-Light Vitiligo Trial).

BACKGROUND: Economic evidence for vitiligo treatments is absent. OBJECTIVES: To determine the cost-effectiveness of (i) handheld narrowband ultraviolet B (NB-UVB) and (ii) a combination of topical corticosteroid (TCS) and NB-UVB compared with TCS alone for localized vitiligo. METHODS: Cost-effectiveness analysis alongside a pragmatic, three-arm, placebo-controlled randomized controlled trial with 9 months' treatment. In total 517 adults and children (aged ≥ 5 years) with active vitiligo affecting < 10% of skin were recruited from secondary care and the community and were randomized 1: 1: 1 to receive TCS, NB-UVB or both. Cost per successful treatment (measured on the Vitiligo Noticeability Scale) was estimated. Secondary cost-utility analyses measured quality-adjusted life-years using the EuroQol 5 Dimensions 5 Levels for those aged ≥ 11 years and the Child Health Utility 9D for those aged 5 to < 18 years. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: The mean ± SD cost per participant was £775 ± 83·7 for NB-UVB, £813 ± 111.4 for combination treatment and £600 ± 96·2 for TCS. In analyses adjusted for age and target patch location, the incremental difference in cost for combination treatment compared with TCS was £211 (95% confidence interval 188-235), corresponding to a risk difference of 10·9% (number needed to treat = 9). The incremental cost was £1932 per successful treatment. The incremental difference in cost for NB-UVB compared with TCS was £173 (95% confidence interval 151-196), with a risk difference of 5·2% (number needed to treat = 19). The incremental cost was £3336 per successful treatment. CONCLUSIONS: Combination treatment, compared with TCS alone, has a lower incremental cost per additional successful treatment than NB-UVB only. Combination treatment would be considered cost-effective if decision makers are willing to pay £1932 per additional treatment success.

Randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo: results of the HI-Light Vitiligo Trial.

BACKGROUND: Evidence for the effectiveness of vitiligo treatments is limited. OBJECTIVES: To determine the effectiveness of (i) handheld narrowband UVB (NB-UVB) and (ii) a combination of potent topical corticosteroid (TCS) and NB-UVB, compared with TCS alone, for localized vitiligo. METHODS: A pragmatic, three-arm, placebo-controlled randomized controlled trial (9-month treatment, 12-month follow-up). Adults and children, recruited from secondary care and the community, aged ≥ 5 years and with active vitiligo affecting < 10% of skin, were randomized 1 : 1 : 1 to receive TCS (mometasone furoate 0·1% ointment + dummy NB-UVB), NB-UVB (NB-UVB + placebo TCS) or a combination (TCS + NB-UVB). TCS was applied once daily on alternating weeks; NB-UVB was administered on alternate days in escalating doses, adjusted for erythema. The primary outcome was treatment success at 9 months at a target patch assessed using the participant-reported Vitiligo Noticeability Scale, with multiple imputation for missing data. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: In total 517 participants were randomized to TCS (n = 173), NB-UVB (n = 169) and combination (n = 175). Primary outcome data were available for 370 (72%) participants. The proportions with target patch treatment success were 17% (TCS), 22% (NB-UVB) and 27% (combination). Combination treatment was superior to TCS: adjusted between-group difference 10·9% (95% confidence interval 1·0%-20·9%; P = 0·032; number needed to treat = 10). NB-UVB alone was not superior to TCS: adjusted between-group difference 5·2% (95% CI - 4·4% to 14·9%; P = 0·29; number needed to treat = 19). Participants using interventions with ≥ 75% expected adherence were more likely to achieve treatment success, but the effects were lost once treatment stopped. Localized grade 3 or 4 erythema was reported in 62 (12%) participants (including three with dummy light). Skin thinning was reported in 13 (2·5%) participants (including one with placebo ointment). CONCLUSIONS: Combination treatment with home-based handheld NB-UVB plus TCS is likely to be superior to TCS alone for treatment of localized vitiligo. Combination treatment was relatively safe and well tolerated but was successful in only around one-quarter of participants.

Which outcomes should we measure in vitiligo? Results of a systematic review and a survey among patients and clinicians on outcomes in vitiligo trials.

BACKGROUND: Relevant and reliable outcomes play a crucial role in the correct interpretation and comparison of the results of clinical trials. There is a lack of consensus around methods of assessment and outcome measures for vitiligo, which makes it difficult to compare results of randomized controlled trials (RCTs) and perform meta-analysis. OBJECTIVES: To describe the heterogeneity in outcome measures used in published RCTs of vitiligo treatments, and to report the most desirable outcomes from patients' and clinicians' perspectives. METHODS: We conducted a systematic review of outcome measures used in RCTs as well as a survey of the most desirable outcomes identified by patients and clinicians as part of a Vitiligo Priority Setting Partnership. RESULTS: Outcomes from 54 eligible trials were analysed and compared with outcomes suggested by patients and clinicians. In the systematic review, 25 different outcomes were reported. Only 22% of trials had clearly stated primary outcome measures. Repigmentation was the most frequently reported outcome in 96% of trials and was measured using 48 different scales. Only 9% of trials assessed quality of life. Thirteen per cent measured cessation of spreading of the disease and 17% of studies reported patients' opinions and satisfaction with the treatment. In contrast, out of 438 suggestions made by patients and clinicians, cosmetically acceptable repigmentation (rather than percentage of repigmentation) was the most desirable outcome (68%), followed by cessation of spread of vitiligo (15%), quality of life (8%) and maintenance of repigmentation (4%). CONCLUSIONS: We propose that future vitiligo trials should include repigmentation, cosmetic acceptability of results, global assessment of the disease, quality of life, maintenance of repigmentation, stabilization of vitiligo and side-effects. International consensus among clinicians, researchers and patients is needed to establish an agreed core outcome set for future vitiligo trials.

Future research into the treatment of vitiligo: where should our priorities lie? Results of the vitiligo priority setting partnership.

BACKGROUND: Vitiligo is the most frequent depigmentation disorder of the skin and is cosmetically and psychologically devastating. A recently updated Cochrane systematic review 'Interventions for vitiligo' showed that the research evidence for treatment of vitiligo is poor, making it difficult to make firm recommendations for clinical practice. OBJECTIVES: To stimulate and steer future research in the field of vitiligo treatment, by identifying the 10 most important research areas for patients and clinicians. METHODS: A vitiligo priority setting partnership was established including patients, healthcare professionals and researchers with an interest in vitiligo. Vitiligo treatment uncertainties were gathered from patients and clinicians, and then prioritized in a transparent process, using a methodology advocated by the James Lind Alliance. RESULTS: In total, 660 treatment uncertainties were submitted by 461 participants. These were reduced to a list of the 23 most popular topics through an online/paper voting process. The 23 were then prioritized at a face-to-face workshop in London. The final list of the top 10 treatment uncertainties included interventions such as systemic immunosuppressants, topical treatments, light therapy, melanocyte-stimulating hormone analogues, gene therapy, and the impact of psychological interventions on the quality of life of patients with vitiligo. CONCLUSIONS: The top 10 research areas for the treatment of vitiligo provide guidance for researchers and funding bodies, to ensure that future research answers questions that are important both to clinicians and to patients.

Guideline for the diagnosis and management of vitiligo.

This detailed and user-friendly guideline for the diagnosis and management of vitiligo in children and adults aims to give high quality clinical advice, based on the best available evidence and expert consensus, taking into account patient choice and clinical expertise. The guideline was devised by a structured process and is intended for use by dermatologists and as a resource for interested parties including patients. Recommendations and levels of evidence have been graded according to the method developed by the Scottish Inter-Collegiate Guidelines Network. Where evidence was lacking, research recommendations were made. The types of vitiligo, process of diagnosis in primary and secondary care, and investigation of vitiligo were assessed. Treatments considered include offering no treatment other than camouflage cosmetics and sunscreens, the use of topical potent or highly potent corticosteroids, of vitamin D analogues, and of topical calcineurin inhibitors, and depigmentation with p-(benzyloxy)phenol. The use of systemic treatment, e.g. corticosteroids, ciclosporin and other immunosuppressive agents was analyzed. Phototherapy was considered, including narrowband ultraviolet B (UVB), psoralen with ultraviolet A (UVA), and khellin with UVA or UVB, along with combinations of topical preparations and various forms of UV. Surgical treatments that were assessed include full-thickness and split skin grafting, mini (punch) grafts, autologous epidermal cell suspensions, and autologous skin equivalents. The effectiveness of cognitive therapy and psychological treatments was considered. Therapeutic algorithms using grades of recommendation and levels of evidence have been produced for children and for adults with vitiligo.

Interventions for vitiligo.

BACKGROUND: Around 1% of the world's population has vitiligo, which causes a loss of skin colour in patches. The methods currently available to treat vitiligo are largely unsatisfactory and vary widely between cultures and within health systems. OBJECTIVES: To assess the effects of interventions used to manage vitiligo. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED and other databases (last searched September 2004). Reference lists of articles and conference proceedings were searched. Authors of reviews were contacted. SELECTION CRITERIA: Randomised controlled trials (RCTs). DATA COLLECTION AND ANALYSIS: At least two reviewers independently assessed study eligibility and methodological quality and carried out data extraction. The included studies compared different interventions and used different outcome measures so we considered it inappropriate to combine their results. MAIN RESULTS: Nineteen trials with a total of 1350 participants were included. The RCTs generally had low numbers of participants and only RCTs of repigmentation and not other methods of managing vitiligo were able to be included. In one study, potent topical steroids resulted in better repigmentation than placebo and they were also better than oral psoralens plus sunlight in another study (RR 4.70 95% CI 1.14 to 19.39) although their long-term use is limited by adverse effects. Two studies suggested that topical calcipotriol enhanced repigmentation rates from PUVAsol and PUVA when compared with placebo. Another two studies showed higher repigmentation rates with oral PUVAsol versus placebo plus sunlight (RR 19.20 95% CI 1.21 to 304.50 in 79 adults and RR 2.29 95% CI 1.14 to 4.58 in a study of 50 children). The safety of these interventions was poorly described and none of the studies was able to demonstrate long term benefits. Very few studies were carried out on children or included segmental vitiligo. No trials evaluating micropigmentation, melanocyte transplantation, depigmentation or cosmetic camouflage could be found. Despite the fact that the main impact of vitiligo is psychosocial only one study on psychological therapy was found and it is awaiting assessment. AUTHORS' CONCLUSIONS: This review has found some evidence to support existing therapies for vitiligo, but the different designs and outcome measurements, lack of quality of life measures and adverse effect reporting in the studies limit the usefulness of their findings. There is a pressing need for high quality randomised trials using standardised measures of repigmentation and which address relevant clinical outcomes including quality of life.