Randomized Controlled Trial of Topical Corticosteroid and Home-based Narrowband Ultraviolet B for Active and Limited Vitiligo

Results of the Hi-Light Vitiligo Trial

K.S. Thomas; J.M. Batchelor; P. Akram; J.R. Chalmers; R.H. Haines; G.D. Meakin; L. Duley; J.C. Ravenscroft; A. Rogers; T.H. Sach; M. Santer; W. Tan; J. White; M.E. Whitton; H.C. Williams; S.T. Cheung; H. Hamad; A. Wright; J.R. Ingram; N.J. Levell; J.M.R. Goulding; A. Makrygeorgou; A. Bewley; M. Ogboli; J. Stainforth; A. Ferguson; B. Laguda; S. Wahie; R. Ellis; J. Azad; A. Rajasekaran; V. Eleftheriadou; A.A. Montgomery

Disclosures

The British Journal of Dermatology. 2021;184(5):828-839. 

In This Article

Discussion

The HI-Light trial was a large, pragmatic trial of home interventions for people with active, limited vitiligo. Combination treatment with handheld NB-UVB and potent TCS is likely to be superior to potent TCS alone (number needed to treat = 10), although the CIs around this result were quite wide. We did not find clear evidence that handheld NB-UVB monotherapy was better than TCS monotherapy. Results for percentage repigmentation (the most commonly used outcome in vitiligo trials)[40] were consistent with the participant-reported primary outcome using the VNS.

Both interventions were well tolerated. Erythema (grade 3 or 4) was the most frequently observed adverse event, but these episodes were managed effectively and were limited to the small areas being treated. Given the large total number of NB-UVB treatments given across these groups, we feel that this is an acceptable level of erythemas and it is not suggestive of a significant safety risk. The incidence of clinical skin thinning was very low despite the relatively long-term intermittent use of potent TCS, including on the face.

All sensitivity analyses were supportive of the main findings and participants who adhered to the treatment regimen (≥ 75%) were more likely to achieve treatment success. There was no difference between the rates of success in the treatment groups that could be attributed to age, skin type or duration of vitiligo.

The number of participants achieving a treatment success with the trial interventions was low but consistent with findings from other trials. A meta-analysis of studies assessing phototherapy (whole body, as opposed to handheld) for vitiligo[41] reported that around 19% of patients achieved a 'marked response' (> 75% repigmentation) after 6 months of treatment with NB-UVB monotherapy. Participants in our study achieved similar rates of treatment success, as measured using the VNS (18% for NB-UVB, 28% for combination at 6 months). The better response rates for vitiligo on the head and neck seen in our study are also consistent with previous findings.[41]

There are no other studies that have compared a combination of NB-UVB and mometasone furoate with mometasone furoate alone, so direct comparison with a combination of treatments is not possible. The participants in our study used mometasone furoate on alternate weeks for 9 months, which differs from other published studies.[37] We used this alternate-week regimen on the basis of feasibility work that suggested that this would be more acceptable than once-daily application over a 9-month treatment period.

The Cochrane systematic review of interventions for vitiligo[37] identified a study comparing the combination of NB-UVB and clobetasol propionate (a more potent TCS) with NB-UVB alone. That study suggested that combination treatment might be more effective. However, the study was too small for the results to be conclusive; the relative risk ratio for achieving > 75% repigmentation was 1·38 (95% CI 0·71–2·68).[42]

Previous small studies of home-based handheld phototherapy devices for vitiligo have demonstrated their safety;[23,24] our larger study confirms this. A recently published study of patients undergoing long-term NB-UVB treatment (mean number of treatments = 211) reported no increase in skin cancer risk, suggesting that treatment can safely be continued for longer periods than in our study, although most patients in the study of Momen and Sarkany had skin types IV–VI.[43]

This was a large, pragmatic trial that controlled for the most common causes of bias. The patient-reported primary outcome ensured that treatment success reflected the views of participants, and was supported by blinded outcome assessment using digital images.

As found in other vitiligo trials,[37] retention throughout the trial was challenging, with just over 70% of participants providing primary outcome data at 9 months, and < 50% providing secondary outcome data by 21 months. As loss to follow-up was higher than originally anticipated, the trial lacked power to provide a high level of precision around the point estimates.

The most significant drop in the number of participants remaining in the trial was from baseline to the first follow-up at 3 months. Many participants commented that the time burden was the main reason for them doing so. Participants who adhered to the treatment regimen ≥ 75% of the time were more likely to achieve treatment success. This requires a significant time commitment, which some participants found challenging. In clinical practice, following such a treatment regimen may not be feasible for some individuals.

This trial has good external validity as it was a large, pragmatic trial with few exclusions, although participants with widespread vitiligo were excluded. People with all skin types and of all ethnicities were included in the trial as this reflected the types of patients typically presenting for vitiligo treatment within the UK health service. We did not exclude participants with lighter skin types, as vitiligo can cause considerable distress in such people, as well as in those with darker skin types.[44]

For people with vitiligo requiring second-line therapy, combination treatment with potent TCS and NB-UVB may be helpful. Patients should be informed that only about one-quarter of those seeking treatment are likely to achieve a substantial treatment response, that considerable time commitment is required, and that response is likely to be slow.

This trial found considerable output variation between individual NB-UVB devices,[32] which demonstrates the need for quality assurance testing prior to use. We would recommend that any member of the public purchasing such a device seek specialist dermatologist advice and quality assurance before use.

Safety data provide reassurance that mometasone furoate 0·1% used intermittently 'one week on, one week off' for up to 9 months is safe for both children and adults. This potent TCS was helpful in stopping the spread of active disease and was successful in one in six cases, supporting its use as first-line therapy. Health economic analysis and a process evaluation study were conducted alongside this trial and are reported separately.[32] Forty per cent of participants reported loss of treatment response after stopping treatments, therefore research into strategies to maintain treatment response is needed.

In conclusion, combination therapy with NB-UVB and potent TCS is likely to result in improved treatment response compared with potent TCS alone, for people with localized nonsegmental vitiligo. Both treatments are relatively safe and well tolerated, but were only successful in around one-quarter of participants.

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