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.

The Use of Decision-Analytic Models in Atopic Eczema: A Systematic Review and Critical Appraisal.

OBJECTIVE: The objective of this systematic review was to identify and assess the quality of published economic decision-analytic models within atopic eczema against best practice guidelines, with the intention of informing future decision-analytic models within this condition. METHODS: A systematic search of the following online databases was performed: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, NHS Economic Evaluation Database, EconLit, Scopus, Health Technology Assessment, Cost-Effectiveness Analysis Registry and Web of Science. Papers were eligible for inclusion if they described a decision-analytic model evaluating both the costs and benefits associated with an intervention or prevention for atopic eczema. Data were extracted using a standardised form by two independent reviewers, whilst quality was assessed using the model-specific Philips criteria. RESULTS: Twenty-four models were identified, evaluating either preventions (n = 12) or interventions (n = 12): 14 reported using a Markov modelling approach, four utilised decision trees and one a discrete event simulation, whilst five did not specify the approach. The majority, 22 studies, reported that the intervention was dominant or cost effective, given the assumptions and analytical perspective taken. Notably, the models tended to be short-term (16 used a time horizon of ≤1 year), often providing little justification for the limited time horizon chosen. The methodological and reporting quality of the studies was generally weak, with only seven studies fulfilling more than 50% of their applicable Philips criteria. CONCLUSIONS: This is the first systematic review of decision models in eczema. Whilst the majority of models reported favourable outcomes in terms of the cost effectiveness of the new intervention, the usefulness of these findings for decision-making is questionable. In particular, there is considerable scope for increasing the range of interventions evaluated, for improving modelling structures and reporting quality.

Interventions for hyperhidrosis in secondary care: a systematic review and value-of-information analysis.

BACKGROUND: Hyperhidrosis is uncontrollable excessive sweating that occurs at rest, regardless of temperature. The symptoms of hyperhidrosis can significantly affect quality of life. The management of hyperhidrosis is uncertain and variable. OBJECTIVE: To establish the expected value of undertaking additional research to determine the most effective interventions for the management of refractory primary hyperhidrosis in secondary care. METHODS: A systematic review and economic model, including a value-of-information (VOI) analysis. Treatments to be prescribed by dermatologists and minor surgical treatments for hyperhidrosis of the hands, feet and axillae were reviewed; as endoscopic thoracic sympathectomy (ETS) is incontestably an end-of-line treatment, it was not reviewed further. Fifteen databases (e.g. CENTRAL, PubMed and PsycINFO), conference proceedings and trial registers were searched from inception to July 2016. Systematic review methods were followed. Pairwise meta-analyses were conducted for comparisons between botulinum toxin (BTX) injections and placebo for axillary hyperhidrosis, but otherwise, owing to evidence limitations, data were synthesised narratively. A decision-analytic model assessed the cost-effectiveness and VOI of five treatments (iontophoresis, medication, BTX, curettage, ETS) in 64 different sequences for axillary hyperhidrosis only. RESULTS AND CONCLUSIONS: Fifty studies were included in the effectiveness review: 32 randomised controlled trials (RCTs), 17 non-RCTs and one large prospective case series. Most studies were small, rated as having a high risk of bias and poorly reported. The interventions assessed in the review were iontophoresis, BTX, anticholinergic medications, curettage and newer energy-based technologies that damage the sweat gland (e.g. laser, microwave). There is moderate-quality evidence of a large statistically significant effect of BTX on axillary hyperhidrosis symptoms, compared with placebo. There was weak but consistent evidence for iontophoresis for palmar hyperhidrosis. Evidence for other interventions was of low or very low quality. For axillary hyperhidrosis cost-effectiveness results indicated that iontophoresis, BTX, medication, curettage and ETS was the most cost-effective sequence (probability 0.8), with an incremental cost-effectiveness ratio of £9304 per quality-adjusted life-year. Uncertainty associated with study bias was not reflected in the economic results. Patients and clinicians attending an end-of-project workshop were satisfied with the sequence of treatments for axillary hyperhidrosis identified as being cost-effective. All patient advisors considered that the Hyperhidrosis Quality of Life Index was superior to other tools commonly used in hyperhidrosis research for assessing quality of life. LIMITATIONS: The evidence for the clinical effectiveness and safety of second-line treatments for primary hyperhidrosis is limited. This meant that there was insufficient evidence to draw conclusions for most interventions assessed and the cost-effectiveness analysis was restricted to hyperhidrosis of the axilla. FUTURE WORK: Based on anecdotal evidence and inference from evidence for the axillae, participants agreed that a trial of BTX (with anaesthesia) compared with iontophoresis for palmar hyperhidrosis would be most useful. The VOI analysis indicates that further research into the effectiveness of existing medications might be worthwhile, but it is unclear that such trials are of clinical importance. Research that established a robust estimate of the annual incidence of axillary hyperhidrosis in the UK population would reduce the uncertainty in future VOI analyses. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015027803. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Economic evidence for the prevention and treatment of atopic eczema: a protocol for a systematic review.

BACKGROUND: Eczema, synonymous with atopic eczema or atopic dermatitis, is a chronic skin disease that has a similar impact on health-related quality of life as other chronic diseases. The proposed research aims to provide a comprehensive systematic assessment of the economic evidence base available to inform economic modelling and decision making on interventions to prevent and treat eczema at any stage of the life course. Whilst the Global Resource of Eczema Trials (GREAT) database collects together the effectiveness evidence for eczema, there is currently no such systematic resource on the economics of eczema. It is important to gain an overview of the current state of the art of economic methods in the field of eczema in order to strengthen the economic evidence base further. METHODS/DESIGN: The proposed study is a systematic review of the economic evidence surrounding interventions for the prevention and treatment of eczema. Relevant search terms will be used to search MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, National Health Service (NHS) Economic Evaluation Database, Health Technology Assessment, Cumulative Index to Nursing and Allied Health Literature, EconLit, Scopus, Cost-Effectiveness Analysis Registry and Web of Science in order to identify relevant evidence. To be eligible for inclusion studies will be primary empirical studies evaluating the cost, utility or full economic evaluation of interventions for preventing or treating eczema. Two reviewers will independently assess studies for eligibility and perform data abstraction. Evidence tables will be produced presenting details of study characteristics, costing methods, outcome methods and quality assessment. The methodological quality of studies will be assessed using accepted checklists. DISCUSSION: The systematic review is being undertaken to identify the type of economic evidence available, summarise the results of the available economic evidence and critically appraise the quality of economic evidence currently available to inform future economic modelling and resource allocation decisions about interventions to prevent or treat eczema. We aim to use the review to offer guidance about how to gather economic evidence in studies of eczema and/or what further research is necessary in order to inform this. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015024633.