One systematic review of phototherapy and photochemotherapy for psoriasis (search date 1999, 51 RCTs, 2864 people),25 one meta-analysis of squamous cell carcinoma risk from PUVA (search date 1998, nine studies, 12 142 people)30 and one meta-analysis of balneophototherapy (search date 2000, three RCTs, 119 people)33 have been published. A further 12 RCTs were identified by the current search.
Clearance with BBUVB
BBUVB has not been compared directly with placebo. In one case series (n = 87), clearance
(defined as >80% reduction in psoriasis severity score) was obtained in 81% of people with psoriasis given BBUVB four times weekly in a mean of 24 treatment sessions.34 The investigators noted however that clearance was significantly less likely in people with >50% body surface area involvement. In another series (n = 165) clearance (defined as complete resolution of at least 90% of psoriasis present before treatment) was achieved in a mean of 27 treatment sessions in 81% of the 128 people who had BBUVB at least three times weekly.35 The optimal frequency of therapy is unknown but an uncontrolled study found no difference in response rate between three- and five-times-weekly regimens (n = 46).36 A recent small RCT (n = 20) has highlighted the importance of optimising UVB dosimetry for each patient in order to achieve optimal response rates with BBUVB.37
One RCT (n = 94) examined the value of maintenance therapy with BBUVB after initial clearance followed by consolidation with up to six treatments in the 3 weeks after clearance. Patients randomised to receive weekly maintenance therapy thereafter were calculated to have a 75% chance of remaining clear (no more than 3% increase in body surface area involved) for a further 16 weeks and >50% chance of still being clear at 23 weeks. By contrast, a quarter of patients who discontinued therapy had relapsed by 8 weeks and only 28% were still clear at 23 weeks.35
The efficacy of NBUVB has been compared with BBUVB in four small RCTs which, with one exception, failed to show clear superiority of one over the other.25,38 In the case of the exception, nine of ten patients cleared more rapidly on the half of the body randomised to receive NBUVB.
In the remaining patient NBUVB and BBUVB were equally effective.38 In two of the studies, however, clearance could be achieved with a 6-10-fold reduction in UV irradiance. (In the third study, greater irradiances were given to the patients receiving NBUVB than to those receiving BBUVB because of a high rate of interruption of therapy in the latter group as a result of episodes of burning.) One RCT (n = 21) has compared three- versus five-times-weekly NBUVB therapy and concluded that, although clearance could be achieved more quickly with five-times-weekly treatments (median 35 versus 40 days), this was at the expense of a greater number of treatment sessions (median 23-5 versus 17), a greater overall UVB irradiance (median 94 versus 64 x minimal erythema dose) and greater inconvenience to the patients. The authors therefore recommended the three-times-weekly regimen.39
Maintenance of remission with NBUVB
Longer term maintenance studies with this newer form of treatment have not been reported.
Clearance with heliotherapy (natural sunlight)
Many people with psoriasis report that their skin improves greatly after exposure to natural sunlight. In one RCT with an open crossover design, 95 Finns with psoriasis were randomised to receive a 4-week heliotherapy course in the Canary Islands during the Finnish winter either immediately or after a delay of 12 months. Exposure was gradually increased over the 4 weeks from 0-5-1-0 hour of midday sunshine to a maximum of 6 hours daily sunshine. All patients were kept under review for 24 months. All conventional antipsoriatic therapy was allowed in the observation period before and after heliotherapy. Over 90% of patients achieved clearance of psoriasis following 4 weeks' heliotherapy. In the 12 months following treatment the mean cumulative period for which patients required active therapy was 25 weeks in both groups; this was much less than the 38 weeks in the group observed for 12 months before heliotherapy (P<0-001). The reduction was mainly due to a reduction in the use of topical corticosteroids and systemic retinoids. Nevertheless, 54% of patients had relapsed to pretreatment severity levels by 6 months and only 15% had not reached 50% of their pretreatment score by this time.40
Balneophototherapy is popular in some countries, particularly in Europe, for the treatment of severe psoriasis. It involves bathing in spa waters containing a variety of concentrations of minerals and salt before artificial UVB irradiation. A systematic review (search date 2000, n = 119) found no evidence of superiority of spa waters or salt water over tap water.27 A recent RCT (n = 71) comparing balneophototherapy using high mineral content saline spa water followed by NBUVB phototherapy with NBUVB phototherapy alone found no evidence of benefit from the spa water.41
Thirty-eight people with mild-to-moderate psoriasis (median modified PASI score 4-4) were treated three times weekly for 4 weeks with a modified commercial low-UVB-emission UVA sunbed unit. Patients were randomised to receive UVA-filtered visible light to one half of the body and UVA to the other. In over half the patients (53%), the response of the UVA treated side was the same or worse than the visible light treated side. Despite the apparently minimal improvements seen (median reduction in pretreatment disease severity scores by 11% and 5%, respectively), 64% of patients felt that the response was sufficiently good to warrant using a sunbed again to treat their psoriasis.42
PUVA has not been compared directly with placebo but two large prospective studies have been published. The first, in 1308 people with psoriasis with a mean 33% body surface area involvement, achieved clearance with 29 exposures or fewer in 69% people given oral PUVA twice or three times weekly; a further 19% cleared with longer treatment courses.43 In the second study, where more aggressive dosing was used and where patients were treated four times weekly, clearance was achieved in 65% of 3175 people with severe psoriasis in an average of 20 treatments; a further 24% improved markedly.44 Comparable results have been obtained in patients treated in the oral PUVA arm of RCTs; for instance, a 74% clearance rate was achieved in a median of 16-5 exposures in 50 patients receiving twice-weekly oral PUVA.45 A higher and more rapid response rate was seen in another RCT where people had possibly less extensive psoriasis than in the studies quoted above (mean 26-29% body surface area involvement), clearance of psoriasis being achieved in a mean of 14.6 treatments in 91% of 113 patients randomised to receive oral PUVA three times weekly.46 Several studies have examined the effects of different doses and types of psoralen. One RCT (n = 56) has shown that when 8-methoxypsoralen is given at a dose of 40 mg rather than 10 mg, not only is there a greater success rate (rate difference 0-72, CI 0-54 to 0-90) but success can be achieved with a significantly lower cumulative UVA dose (mean (range): 54 (14-5-115) versus 77 (46-113) J/cm2). Another RCT (n = 106) has shown that when 5-methoxypsoralen is given at 1-2 mg/kg rather than 0-6 mg/kg, a similar reduction in cumulative UVA dose can be achieved (means ± SD: 53 ± 33 versus 132 ± 87 J/cm2). The two psoralens have been compared and were found in one study to have comparable efficacy at the higher doses given above. In another, however, 5-methoxypsoralen appeared to be less effective, possibly because peak plasma levels had not been reached at the time UVA was administered. The incidence of side-effects (severe erythema, pruritus and nausea) was much lower with 5- than with 8-methoxypsoralen (6% versus 38%).25 Different incremental schedules for UVA dosing have been advocated based either on skin type (assessed by recalled susceptibility to sunburn) or on phototesting for minimal phototoxic dose. Two RCTs failed to demonstrate a clear advantage of one method over the other.25
The largest RCT, involving 1005 people whose psoriasis had been cleared by oral PUVA, found that maintenance treatment reduced relapse at 18 months from 62% with no maintenance to 27%, 30% and 34% of patients receiving maintenance treatments once every 1, 2 and 3 weeks, respectively.43 In view of the concerns over cumulative UVA dose in patients receiving PUVA, long-term maintenance therapy is no longer recommended.32
As an alternative to oral ingestion, psoralen may be applied directly to the skin. For people with widespread psoriasis this is achieved by adding psoralen to bath water in which the body is immersed before UVA irradiation. This may be useful particularly where a person cannot tolerate oral psoralen, usually because of nausea. Three RCTs have compared bath PUVA with oral PUVA in a total of 171 people with widespread plaque psoriasis.47-49 All three studies concluded that bath PUVA was of similar efficacy to oral PUVA. All found that less UVA was required to achieve clearance when bath PUVA was employed (reported reductions in mean UVA dose ranged from 60% to 80%). The biological significance of this is unknown, although some evidence suggests that the risk of squamous cell carcinoma may be lower following bath PUVA (see Drawbacks below).28
The systematic review identified three RCTs involving psoralen and natural sun.25 Clearance was achieved in 12 of 20 Indians with psoriasis who were randomised to a regimen of oral 8-methoxypsoralen 40 mg followed 150-180 minutes later by exposure of the skin to direct Indian sunlight for 25-30 minutes; 18 of the 20 (90%) showed a marked improvement or better.50 No improvement was seen in the 20 people randomised to placebo capsules and sunlight. On the other hand Parrish found that white-skinned people with psoriasis improved with sunlight alone. Although response rates were better with 8-methoxypsoralen, 0-6 mg/kg, and sunlight, some patients had severe phototoxic burns.51 Psoralen and sunlight therapy may be of value for darker-skinned people in parts of the world where access to alternative treatments is limited.
Five controlled trials were identified, but it was possible to extract a response rate from only three of these. In 100 people with chronic plaque psoriasis randomised to twice-weekly treatment with either NBUVB or PUVA, clearance was achieved in a significantly greater proportion of those treated with PUVA (84%) than in those treated with NBUVB (63%) (odds ratio in favour of PUVA 3-04; CI 1-18 to 7-84) with significantly fewer treatments (median number of treatments for clearance: 16-7 with PUVA versus 25-3 with NBUVB; ratio of medians 1-52; CI 1-24 to 1-86). Only 12% of those treated with NBUVB were clear of psoriasis 6 months after finishing treatment, compared with 35% for PUVA.52 Others have argued, however, that optimal responses with NBUVB require three-times-weekly administration.53 In a small randomised left-right comparison of bath PUVA and NBUVB administered three times weekly to 28 people, clearance was achieved in 75% of sides receiving NBUVB compared with 54% of sides receiving bath PUVA (intention-to-treat analysis; 95% CI for difference between treatments 4% to 37%);53 however, only 18 patients completed the study. In a larger parallel-group RCT in which 54 patients with >10% coverage with psoriasis were randomised to standard regimens of PUVA (twice weekly) or NBUVB (three times weekly), no difference in response was found. Clearance was achieved in medians of 66 days (interquartile range 50-5-116) and 67 days (43-94-75), with medians of 19 (13-5-27-5) and 25-5 (17-2-35-8) treatments, respectively; relapse rates were similar (193 and 191 days to reach 50% of baseline severity score).26 The authors thought that NBUVB probably had a more favourable adverse effect profile than PUVA, and so recommended that NBUVB should be preferred. Another RCT compared twice-weekly PUVA with twice-weekly psoralen plus NBUVB in 100 people with psoriasis; clearance rates were similar (success rate difference -0-12, 95% CI -0-28-0-04).45
In one RCT (n = 40) good or excellent responses were seen in 80% of people treated with PUVA and in 55% of those given etretinate at an initial dose of 50-60 mg daily and then reduced according to response and side-effects.54
Retinoids + UVB versus UVB alone
See systemic retinoids.
Retinoids + PUVA (RePUVA) versus PUVA alone
See systemic retinoids.
PUVA or UVB versus other systemic therapies
No RCTs comparing phototherapy with other systemic therapies such as ciclosporin or methotrexate were identified.
In a comparison of a standard regimen using daily anthralin paste with PUVA three times weekly (n = 224), clearance was achieved in 91% of the 113 in the PUVA group but in only 82% of the anthralin group; clearing, however, took longer with PUVA (mean ± SEM 34-4 ± 1-8) than with anthralin (20-4 ± 0-9).5C
Combinations of PUVA or UVB with topical therapies versus phototherapy alone
The combination of calcipotriol cream twice daily and BBUVB twice weekly was compared with placebo cream and three-times-weekly BBUVB over 12 weeks in 164 patients with extensive psoriasis. Three-quarters of patients in each group achieved an 80% reduction in psoriasis severity score. The calcipotriol group required fewer exposures (12 versus 19) and less cumulative UVB irradiance (median 1570 versus 5430 mJ/cm2).55 In another RCT (n = 53) in which all participants received low-dose NBUVB phototherapy, just under half were randomised to receive calcipotriol ointment, 50 microgram/g twice daily, to affected skin. Low-dose NBUVB phototherapy was found to be effective but the addition of calcipotriol ointment did not improve treatment outcome.56 Some evidence indicates that the addition of topical corticosteroids to either UVB or PUVA therapy is of no benefit.25 Although the Goeckerman regimen of tar and UVB phototherapy has been widely used since the 1920s, little RCT evidence exists on whether the combination is better than phototherapy alone.25 Five small RCTs with conflicting results have compared different combinations of anthralin and phototherapy.25,57 The evidence is insufficient to evaluate whether combination therapy is more effective than either component alone.
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