Home interventions and light therapy for treatment of vitiligo (HI-Light Vitiligo Trial): study protocol for a randomized controlled trial

Vitiligo is a condition resulting in white patches on the skin. People with vitiligo can suffer from low self-esteem, psychological disturbance and diminished quality of life. Vitiligo is often poorly managed, partly due to lack of high quality evidence to inform clinical care. We describe here a large, independent, randomised controlled trial (RCT) assessing the comparative effectiveness of potent topical corticosteroid, home-based hand-held narrowband ultraviolet B-light (NB-UVB) or combination of the two, for the management of vitiligo. Methods and Analysis The HI-Light Vitiligo Trial is a multi-centre, three-arm, parallel group, pragmatic, placebo-controlled RCT. 516 adults and children with actively spreading, but limited, vitiligo are randomised (1:1:1) to one of three groups: mometasone furoate 0.1% ointment plus dummy NB-UVB light, vehicle ointment plus NB-UVB light, or mometasone furoate 0.1% ointment plus NB-UVB light. Treatment of up to three patches of vitiligo is continued for up to 9 months with clinic visits at baseline, 3, 6 and 9 months and four post treatment questionnaires. The HI-Light Vitiligo Trial assesses outcomes included in the vitiligo core outcome set and places emphasis on participants’ views of treatment success. The primary outcome is proportion of participants achieving treatment success (patient-rated Vitiligo Noticeability Scale) for a target patch of vitiligo at 9 months with further independent blinded assessment using digital images of the target lesion before and after treatment. Secondary outcomes include time to onset of treatment response, treatment success by body region, percentage repigmentation, quality of life, time-burden of treatment, maintenance of response, safety, and within-trial cost effectiveness. Ethics and Dissemination Approvals were granted by East Midlands–Derby Research Ethics Committee (14/EM/1173) and the MHRA (EudraCT 2014-003473-42). The trial was registered 8th January 2015 ISRCTN (17160087). Results will be published in full as open access in the NIHR Journal library and elsewhere

Home-based narrowband UVB, topical corticosteroid or combination for children and adults with vitiligo: HI-Light Vitiligo three-arm RCT

BACKGROUND: Systematic reviews suggest that narrowband ultraviolet B light combined with treatments such as topical corticosteroids may be more effective than monotherapy for vitiligo. OBJECTIVE: To explore the clinical effectiveness and cost-effectiveness of topical corticosteroid monotherapy compared with (1) hand-held narrowband ultraviolet B light monotherapy and (2) hand-held narrowband ultraviolet B light/topical corticosteroid combination treatment for localised vitiligo. DESIGN: Pragmatic, three-arm, randomised controlled trial with 9 months of treatment and a 12-month follow-up. SETTING: Sixteen UK hospitals - participants were recruited from primary and secondary care and the community. PARTICIPANTS: Adults and children (aged ≥ 5 years) with active non-segmental vitiligo affecting ≤ 10% of their body area. INTERVENTIONS: Topical corticosteroids [mometasone furoate 0.1% (Elocon®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) plus dummy narrowband ultraviolet B light]; narrowband ultraviolet B light (narrowband ultraviolet B light plus placebo topical corticosteroids); or combination (topical corticosteroids plus narrowband ultraviolet B light). Topical corticosteroids were applied once daily on alternate weeks and narrowband ultraviolet B light was administered every other day in escalating doses, with a dose adjustment for erythema. All treatments were home based. MAIN OUTCOME MEASURES: The primary outcome was self-assessed treatment success for a chosen target patch after 9 months of treatment ('a lot less noticeable' or 'no longer noticeable' on the Vitiligo Noticeability Scale). Secondary outcomes included blinded assessment of primary outcome and percentage repigmentation, onset and maintenance of treatment response, quality of life, side effects, treatment burden and cost-effectiveness (cost per additional successful treatment). RESULTS: In total, 517 participants were randomised (adults, n = 398; and children, n =  119; 52% male; 57% paler skin types I-III, 43% darker skin types IV-VI). At the end of 9 months of treatment, 370 (72%) participants provided primary outcome data. The median percentage of narrowband ultraviolet B light treatment-days (actual/allocated) was 81% for topical corticosteroids, 77% for narrowband ultraviolet B light and 74% for combination groups; and for ointment was 79% for topical corticosteroids, 83% for narrowband ultraviolet B light and 77% for combination. Target patch location was head and neck (31%), hands and feet (32%), and rest of the body (37%). Target patch treatment 'success' was 20 out of 119 (17%) for topical corticosteroids, 27 out of 123 (22%) for narrowband ultraviolet B light and 34 out of 128 (27%) for combination. Combination treatment was superior to topical corticosteroids (adjusted risk difference 10.9%, 95% confidence interval 1.0% to 20.9%; p = 0.032; number needed to treat = 10). Narrowband ultraviolet B light was not superior to topical corticosteroids (adjusted risk difference 5.2%, 95% confidence interval -4.4% to 14.9%; p = 0.290; number needed to treat = 19). The secondary outcomes supported the primary analysis. Quality of life did not differ between the groups. Participants who adhered to the interventions for > 75% of the expected treatment protocol were more likely to achieve treatment success. Over 40% of participants had lost treatment response after 1 year with no treatment. Grade 3 or 4 erythema was experienced by 62 participants (12%) (three of whom were using the dummy) and transient skin thinning by 13 participants (2.5%) (two of whom were using the placebo). We observed no serious adverse treatment effects. For combination treatment compared with topical corticosteroids, the unadjusted incremental cost-effectiveness ratio was £2328.56 (adjusted £1932) per additional successful treatment (from an NHS perspective). LIMITATIONS: Relatively high loss to follow-up limits the interpretation of the trial findings, especially during the post-intervention follow-up phase. CONCLUSION: Hand-held narrowband ultraviolet B light plus topical corticosteroid combination treatment is superior to topical corticosteroids alone for treatment of localised vitiligo. Combination treatment was relatively safe and well tolerated, but was effective in around one-quarter of participants only. Whether or not combination treatment is cost-effective depends on how much decision-makers are willing to pay for the benefits observed. FUTURE WORK: Development and testing of new vitiligo treatments with a greater treatment response and longer-lasting effects are needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN17160087. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 64. See the NIHR Journals Library website for further project information

Prescribing and using vitiligo treatments – lessons from a nested Process Evaluation within the HI-Light Vitiligo Randomised Controlled Trial

BackgroundThe HI-Light Trial demonstrated that for active, limited vitiligo, combination treatment with potent topical corticosteroid (TCS) and hand-held narrowband UVB offers a better treatment response than potent TCS alone. However, it is unclear how to implement these findings.ObjectivesWe sought to answer three questions: i. Can combination treatment be used safely and effectively by people with vitiligo? ii. Should combination treatment should be made available as routine clinical care? iii. Can combination treatment be integrated within current healthcare provision? MethodsMixed-methods process evaluation, including semi-structured interviews with a purposive sample of trial participants, structured interviews with commissioners, and an online survey and focus groups with trial staff. Transcripts were coded by framework analysis, with thematic development by multiple researchers.ResultsParticipants found individual treatments easy to use, but combination treatment was complicated, and required nurse support. Participants and site investigators felt that combination treatment should be made available, although commissioners were less certain. Combination treatment was not suitable for all people. There was support for the development of services offering combination treatment, although this might not be prioritised above treatment for other conditions. A ‘mixed economy’ model was suggested, involving patients purchasing their own devices, although concerns regarding the safe use of treatments mean that training, monitoring and ongoing support are essential. The need for medical physics support may mean that a regional service is more practical. ConclusionsCombination treatment should be offered, although this should include careful selection and training of recipients, and medical physics support