[Table, Recommendations and link to evidence]. - Psoriasis

Recommendations on phototherapy	65. Consider topical adjunctive therapy in people receiving phototherapy with broadband or narrowband UVB who: have plaques at sites that are resistant or show an inadequate response (for example, the lower leg) to phototherapy alone, or at difficult-to-treat or high-need, covered sites (for example, flexures and the scalp), and/or do not wish to take systemic drugs or in whom systemic drugs are contraindicated. 66. Do not routinely use phototherapy (narrowband UVB, broadband UVB or PUVA) as maintenance therapy. 67. Ensure that all phototherapy equipment is safety-checked and maintained in line with local and national policy^ppp. 68. Healthcare professionals who are giving phototherapy should be trained and competent in its use and should ensure an appropriate clinical governance framework is in place to promote adherence to the indications for and contraindications to treatment, dosimetry and national policy on safety standards for phototherapy^ppp.
Future research recommendations	16. In people with psoriasis, when inducing remission, what are the clinical effectiveness (including duration of remission and psychological benefit), cost effectiveness, safety, tolerability and patient acceptability of complex topical therapies with or without NBUVB compared to a short course of systemic therapy (for example, ciclosporin)?
Relative values of different outcomes	The outcomes were not prioritised for considering imprecision, as so few of the outcomes required decisions about imprecision.
Trade off between clinical benefits and harms	The topical treatments are messy and inconvenient in terms of application and additional time, and minimal or no benefit was evident either in terms of reduced UV exposure or improved efficacy when used as adjunctive therapy with UVB, so for the majority of patients adjunctive topical therapy is not be justified. See ‘other considerations’ section for additional discussion of risk/benefit trade off and special situations where topical therapy is indicated.
Economic considerations	There was no economic evidence to inform the GDG on the comparative cost-effectiveness of combination strategies such as Goeckerman’s regimen (crude coal tar plus UVB), Ingram’s regimen (dithranol plus UVB), or vitamin D or vitamin D analogue and UVB compared to any of their components alone. The clinical evidence suggested that there may be some additional benefit gained from combining these topicals with UVB compared to UVB alone or the topical alone, but the results are subject to substantial uncertainty. The clinical evidence also suggested that combination therapy with topicals and UVB may reduce either the time to clearance or the number of treatments to clearance or both; however, these results varied across trials and do not allow for any firm conclusions to be drawn. In the absence of any formal economic analysis, the GDG considered the cost of the topicals themselves and the cost of the time and expertise needed for their effective application. Costs for these interventions vary substantially and involve a high degree of specialist supervision, and there is inconclusive evidence regarding the incremental benefit of such combinations. The GDG could not be certain that these treatment strategies represented better value for NHS resources over other UVB therapy alone; therefore they chose not to recommend it routinely for all patients. Despite the limited and inconclusive evidence, the GDG believed there to be a role for these safe and historical mainstays of psoriasis treatment in the management of some patients. They believed that the addition of crude coal tar, dithranol, or vitamin D or vitamin D analogue to UVB therapy may provide additional benefits at a reasonable additional cost for patients whose psoriasis is concentrated at sites that are difficult to treat with UVB therapy or topicals alone. They also considered the use of these combination regimens likely to be cost-effective compared to continued UVB therapy or topicals alone among people not wishing or unable to be escalated to systemic non-biological or biological therapy.
Quality of evidence	Overall there was a lack of consistency in the findings, with most studies having serious or very serious limitations. The follow-up time in the studies was variable and often inappropriately short (not reflective of clinical practice) and the variable definitions of outcomes reported and the different intervention schedules employed made it difficult to draw conclusions. There was also a lack of evidence for the important outcome of relapse and for safety data. Overall, adding UVB to topical therapy appears to provide clinical benefit compared with topical therapy alone which provides evidence to support the recommendation ‘offer NBUVB phototherapy to people with chronic plaque or guttate pattern psoriasis that are inadequately controlled with topical treatments alone. Treatment with NBUVB phototherapy should be given two or three times weekly depending on patient preference. Patients should be aware that time to response may be shorter with three times weekly NBUVB’ (see 9.1.6). The key studies were those that compared UVB plus topicals with UVB alone, to establish the added benefit of adjunctive topical therapy among those who require phototherapy: In the Ramsey study comparing BBUVB plus vitamin D analogue vs. BBUVB alone the intervention group were given BBUVB twice weekly whereas the control group were given BBUVB three times weekly, making it difficult to comment on efficacy or UV-sparing effect as any difference could be due to treatment frequency rather than the adjunctive topical therapy; no clinically relevant difference was seen in the time to achieve remission. The studies addressing the value of NBUVB plus vitamin D analogue vs. NBUVB alone show no overall benefit of adding vitamin D analogue as a UV sparing agent; some of the studies suggested there may be some benefit in terms of improved response rates but the quality of the evidence was poor; these uncertain benefits need to be balanced against the increased cost and inconvenience of topical therapy with vitamin D analogues. One study (Rim) demonstrated that the benefit of adding a topical vitamin D analogue was greater for the extremities than the trunk, which is in line with clinical experience that the lower legs often take longer to respond to UVB. BBUVB plus concomitant therapy with vitamin D analogue does appear to reduce number of UV treatments (but these differences in terms of absolute number of UVB treatments were not deemed to be clinically significant) and improve efficacy. It is possible that the difference in findings between NB and BBUVB reflect differences in efficacy between the two forms of UVB treatment (i.e. a greater increase in efficacy is seen with BBUVB when adding a vitamin D analogue because the baseline efficacy is lower, although please note the findings from chapter 9.1.2 where NBUVB and BBUVB were of similar efficacy). BBUVB is not widely used to treat psoriasis having been superseded by NBUVB. The studies of adjunctive tar or dithranol with UVB were too few and of insufficient quality to be confident about the value or otherwise of these therapies in conjunction with UVB therapy.
Other considerations	Some ointment based topicals can block UV light and need to be applied after phototherapy. The GDG noted the lack of information about timing of ointment application in the studies. The GDG recognised that some healthcare professionals may be using vitamin D or vitamin D analogues as an adjunct to UVB in the belief that it is safer for patients, and this is not supported by the evidence. However, the studies addressing this question were too short and of insufficient quality to be confident that adjunctive therapy is not of value, and therefore the GDG felt justified in making a recommendation. UVB phototherapy is an effective and widely used treatment for psoriasis, but there is an outstanding question about the additional benefit of adjunctive topical therapy either self-applied or in a day care, specialist setting. From clinical experience, the traditional Ingram’s/Goeckerman’s regimens were cited as being effective and helpful in the management of psoriasis in people who did not wish to take, or could not take, systemic therapies. GDG experience, and to a degree, the limited evidence available, suggest that these complex topical interventions are effective and induce durable remission in an important proportion of patients. Some patients value the daily contact with specialist nurse expertise and social support provided in day care settings, and/or want to avoid or cannot use systemic therapy. The GDG felt it would be helpful to delineate the specific groups in whom UVB with adjunctive therapy could be beneficial, including: those who are not making satisfactory progress on UVB alone those who do not wish to take systemic drugs, or in whom systemic drugs are contraindicated those with plaques at resistant sites, for example the lower leg, or at sites not exposed to UVB, for example the scalp, flexures and genitals. The value of additional NBUVB is unclear. Dithranol/crude coal tar with or without NBUVB is widely used in dermatology practice but is expensive to deliver. The place of these interventions in the context of modern practice is not clear, nor is the value of co-therapy with NBUVB. The GDG agreed that evaluating the clinical effectiveness, cost effectiveness and tolerability of dithranol/crude coal tar in day care/inpatient settings compared to NBUVB alone and compared to short-term systemic therapy (for example, ciclosporin) would be justified.

ppp: See: British Association Of Dermatologists: Working Party Report On Minimum Standards For Phototherapy Services.

From: 9, Phototherapy

Psoriasis: Assessment and Management of Psoriasis.

NICE Clinical Guidelines, No. 153.

National Clinical Guideline Centre (UK).

London: Royal College of Physicians (UK); 2012 Oct.

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