Prescribing and using vitiligo treatments: lessons from a nested process evaluation within the HI-Light vitiligo randomized controlled trial.

BACKGROUND: The HI-Light Trial demonstrated that for active, limited vitiligo, combination treatment with potent topical corticosteroid (TCS) and handheld narrowband ultraviolet B offers a better treatment response than potent TCS alone. However, it is unclear how to implement these findings. AIM: We sought to answer three questions: (i) Can combination treatment be used safely and effectively by people with vitiligo?; (ii) Should combination treatment be made available as routine clinical care?; and (iii) Can combination treatment be integrated within current healthcare provision? METHODS: This was a mixed-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. RESULTS: Participants found individual treatments easy to use, but the combination treatment was complicated and required nurse support. Both participants and site investigators felt that combination treatment should be made available, although commissioners were less certain. There was support for the development of services offering combination treatment, although this might not be prioritized 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. CONCLUSION: Combination treatment should be made available for people seeking treatment for vitiligo, but services require partnership with medical physics and ongoing training and support for patients.

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.

The Home Interventions and Light therapy for the treatment of vitiligo (HI-Light Vitiligo) trial aimed to find out whether or not treating vitiligo at home with a narrowband ultraviolet B light, either by itself or with a steroid ointment, is better than treatment using a steroid ointment only. We enrolled 517 children (aged ≥ 5 years) and adults who had small, active (i.e. recently changing) patches of vitiligo into the study. Participants received one of three possible treatment options: steroid ointment (plus dummy light), hand-held narrowband ultraviolet B light therapy (plus placebo ointment) or both treatments used together. We asked participants to judge how noticeable their target vitiligo patch was after 9 months of treatment. We considered the treatment to be successful if the participants' responses were either 'a lot less noticeable' or 'no longer noticeable'. The results showed that using both treatments together was better than using a steroid ointment on its own. Around one-quarter of participants (27%) who used both treatments together said that their vitiligo was either 'no longer noticeable' or 'a lot less noticeable' after 9 months of treatment. This was compared with 17% of those using steroid ointment on its own and 22% of those using narrowband ultraviolet B light on its own. All treatments were able to stop the vitiligo from spreading. Patches on the hands and feet were less likely to respond to treatment than patches on other parts of the body. The trial found that the vitiligo tended to return once treatments were stopped, so ongoing intermittent treatment may be needed to maintain the treatment response. The treatments were found to be relatively safe and easy to use, but light treatment required a considerable time commitment (approximately 20 minutes per session, two or three times per week). This trial showed that using steroid ointment and narrowband ultraviolet B light together is likely to be better than steroid ointment alone for people with small patches of vitiligo. Steroid ointment alone can still be effective for some people and remains a useful treatment that is able to stop vitiligo from spreading. The challenge is to make hand-held narrowband ultraviolet B light treatment available as normal care in the NHS for people with vitiligo.

Interventions for vitiligo.

BACKGROUND: Vitiligo is a chronic skin disorder characterised by patchy loss of skin colour. Some people experience itching before the appearance of a new patch. It affects people of any age or ethnicity, more than half of whom develop it before the age of 20 years. There are two main types: generalised vitiligo, the common symmetrical form, and segmental, affecting only one side of the body. Around 1% of the world's population has vitiligo, a disease causing white patches on the skin. Several treatments are available. Some can restore pigment but none can cure the disease. OBJECTIVES: To assess the effects of all therapeutic interventions used in the management of vitiligo. SEARCH METHODS: We updated our searches of the following databases to October 2013: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2013, Issue 10), MEDLINE, Embase, AMED, PsycINFO, CINAHL and LILACS. We also searched five trials databases, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing the effects of treatments for vitiligo. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed study eligibility and methodological quality, and extracted data. MAIN RESULTS: This update of the 2010 review includes 96 studies, 57 from the previous update and 39 new studies, totalling 4512 participants. Most of the studies, covering a wide range of interventions, had fewer than 50 participants. All of the studies assessed repigmentation, however only five reported on all of our three primary outcomes which were quality of life, > 75% repigmentation and adverse effects. Of our secondary outcomes, six studies measured cessation of spread but none assessed long-term permanence of repigmentation resulting from treatment at two years follow-up.Most of the studies assessed combination therapies which generally reported better results. New interventions include seven new surgical interventions.We analysed the data from 25 studies which assessed our primary outcomes. We used the effect measures risk ratio (RR), and odds ratio (OR) with their 95% confidence intervals (CI) and where N is the number of participants in the study.We were only able to analyse one of nine studies assessing quality of life and this showed no statistically significant improvement between the comparators.Nine analyses from eight studies reported >75% repigmentation. In the following studies the repigmentation was better in the combination therapy group: calcipotriol plus PUVA (psoralen with UVA light) versus PUVA (paired OR 4.25, 95% CI 1.43 to 12.64, one study, N = 27); hydrocortisone-17-butyrate plus excimer laser versus excimer laser alone (RR 2.57, 95% CI 1.20 to 5.50, one study, N = 84); oral minipulse of prednisolone (OMP) plus NB-UVB (narrowband UVB) versus OMP alone (RR 7.41, 95% CI 1.03 to 53.26, one study, N = 47); azathioprine with PUVA versus PUVA alone (RR 17.77, 95% CI 1.08 to 291.82, one study, N = 58) and 8-Methoxypsoralen (8-MOP ) plus sunlight versus psoralen (RR 2.50, 95% CI 1.06 to 5.91, one study, N = 168). In these three studies ginkgo biloba was better than placebo (RR 4.40, 95% CI 1.08 to 17.95, one study, N = 47); clobetasol propionate was better than PUVAsol (PUVA with sunlight) (RR 4.70, 95% CI 1.14 to 19.39, one study, N = 45); split skin grafts with PUVAsol was better than minipunch grafts with PUVAsol (RR 1.89, 95% CI 1.25 to 2.85, one study, N = 64).We performed one meta-analysis of three studies, in which we found a non-significant 60% increase in the proportion of participants achieving >75% repigmentation in favour of NB-UVB compared to PUVA (RR 1.60, 95% CI 0.74 to 3.45; I² = 0%).Studies assessing topical preparations, in particular topical corticosteroids, reported most adverse effects. However, in combination studies it was difficult to ascertain which treatment caused these effects. We performed two analyses from a pooled analysis of three studies on adverse effects. Where NB-UVB was compared to PUVA, the NB-UVB group reported less observations of nausea in three studies (RR 0.13, 95% CI 0.02 to 0.69; I² = 0% three studies, N = 156) and erythema in two studies (RR 0.73, 95% CI 0.55 to 0.98; I² = 0%, two studies, N = 106), but not itching in two studies (RR 0.57, 95% CI 0.20 to 1.60; I² = 0%, two studies, N = 106).Very few studies only assessed children or included segmental vitiligo. We found one study of psychological interventions but we could not include the outcomes in our statistical analyses. We found no studies evaluating micropigmentation, depigmentation, or cosmetic camouflage. AUTHORS' CONCLUSIONS: This review has found some evidence from individual studies to support existing therapies for vitiligo, but the usefulness of the findings is limited by the different designs and outcome measurements and lack of quality of life measures. There is a need for follow-up studies to assess permanence of repigmentation as well as high- quality randomised trials using standardised measures and which also address quality of life.

Vitiligo: concise evidence based guidelines on diagnosis and management.

Vitiligo is a common disease that causes a great degree of psychological distress. In its classical forms it is easily recognised and diagnosed. This review provides an evidence based outline of the management of vitiligo, particularly with the non-specialist in mind. Treatments for vitiligo are generally unsatisfactory. The initial approach to a patient who is thought to have vitiligo is to make a definite diagnosis, offer psychological support, and suggest supportive treatments such as the use of camouflage cosmetics and sunscreens, or in some cases after discussion the option of no treatment. Active therapies open to the non-specialist, after an explanation of potential side effects, include the topical use of potent or highly potent steroids or calcineurin inhibitors for a defined period of time (usually 2 months), following which an assessment is made to establish whether or not there has been a response. Patients whose condition is difficult to diagnose, unresponsive to straightforward treatments, or is causing psychological distress, are usually referred to a dermatologist. Specialist dermatology units have at their disposal phototherapy, either narrow band ultraviolet B or in some cases photochemotherapy, which is the most effective treatment presently available and can be considered for symmetrical types of vitiligo. Depigmenting treatments and possibly surgical approaches may be appropriate for vitiligo in selected cases. There is no evidence that presently available systemic treatments are helpful and safe in vitiligo. There is a need for further research into the causes of vitiligo, and into discovering better treatments.

Interventions for vitiligo.

BACKGROUND: Around one per cent of the world's population has vitiligo, a disease which causes white patches on the skin. There are a variety of treatments available, most of which are unsatisfactory. OBJECTIVES: To assess all interventions used to manage vitiligo. SEARCH STRATEGY: In November 2009 we updated searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 4, 2009), MEDLINE, EMBASE, AMED, PsycINFO, LILACS and ongoing trials databases. SELECTION CRITERIA: Randomised controlled trials (RCTs). DATA COLLECTION AND ANALYSIS: At least 2 review authors independently assessed study eligibility and methodological quality, and carried out data extraction. Two of the 57 included studies could be combined for meta-analysis. MAIN RESULTS: In this update, 57 trials, including 19 from the original review, were assessed with 3139 participants. Most of the RCTs, which covered a wide range of interventions, had fewer than 50 participants. All of the studies assessed repigmentation, 6 measured cessation of spread, and 5 investigated the effect of treatment on quality of life.Most of the studies assessed combination therapies which generally reported better results. New interventions include monochromatic excimer light (MEL), Polypodium leucotomos, melanocyte transplantation, oral antioxidants, Chinese zengse pill, and pimecrolimus. We analysed the data from 28 studies that met our outcome criteria of improvement in quality of life and greater than 75% repigmentation.Fifteen analyses from studies comparing various interventions showed a statistically significant difference between the proportions of participants achieving more than 75% repigmentation. The majority of analyses showing statistically significant differences were from studies that assessed combination interventions which generally included some form of light treatment.Topical preparations, in particular corticosteroids, reported most adverse effects. However, in the combination studies it was difficult to ascertain which treatment caused these effects. None of the studies was able to demonstrate long-term benefits. Very few studies were conducted on children or included segmental vitiligo. We found one study of psychological interventions and none evaluating micropigmentation, depigmentation, or cosmetic camouflage. AUTHORS' CONCLUSIONS: This review has found some evidence from individual studies to support existing therapies for vitiligo, but the usefulness of the findings is limited by the different designs and outcome measurements and lack of quality of life measures. There is a need for follow-up studies to assess permanence of repigmentation as well as high quality randomised trials using standardised measures and which also address quality of life.

Therapeutic interventions for vitiligo.

BACKGROUND: Current treatments for vitiligo, a common pigmentary disorder affecting around 1% of the world's population, are largely unsatisfactory. OBJECTIVE: We sought to report a Cochrane review of all interventions for the treatment of vitiligo. METHODS: We systematically searched a range of databases for randomized controlled trials. At least two reviewers independently assessed study eligibility, methodological quality, and extracted data. RESULTS: Nineteen trials were included. We found moderate evidence of the benefit of topical steroids. Our search uncovered limited to moderate evidence for various types and regimens of phototherapy (ultraviolet [UV] A and UVB) used alone or in combination with oral and topical treatments. Topical khellin combined with UVA should be questioned in view of the lack of available evidence of benefit. There is limited evidence of the benefit of topical tacrolimus and topical calcipotriol used in conjunction with UV light, and for oral ginkgo biloba, and thin split-thickness grafts. LIMITATIONS: Studies generally were poorly designed and reported. CONCLUSIONS: Variations in study design and different outcome measures limit the evidence for the different therapeutic options. The best evidence from individual trials showed short-term benefit from topical steroids and various forms of UV light with topical preparations. Long-term follow-up and patient-centered outcomes should be incorporated in study design and psychologic interventions need more attention.