A randomized controlled trial of narrowband ultraviolet B vs bath-psoralen plus ultraviolet A photochemotherapy for psoriasis.

BACKGROUND: In 1991, consensus guidelines recommended psoralen plus ultraviolet A photochemotherapy (PUVA) for those requiring second-line therapy for psoriasis. Narrowband (TL-01) UVB has since become more widely available, replacing the less effective broadband sources. Objectives To compare the efficacy of TL-01 UVB phototherapy and trimethoxypsoralen (TMP) bath-PUVA for chronic plaque psoriasis. PARTICIPANTS AND METHODS: A randomized, observer-masked, intraindividually controlled, paired (half-body) study was done in the Photo(chemo)therapy Unit in Ninewells Hospital and Medical School, Dundee. The study comprised 28 patients (skin phototypes I-III) with chronic plaque psoriasis. Each patient's body halves (sagittal plane) were treated independently, one-half with TL-01 UVB, the other with bath-PUVA. Both treatments were administered according to standard, optimized regimens. Treatment was continued until clearance or minimal residual activity (MRA), or a maximum of 30 treatments. The main outcome measures were treatments and time to clearance/MRA, the proportion reaching clearance/MRA, change in psoriasis severity score (scaling, erythema and induration) and remission durations. RESULTS: Of 18 who completed the study, all reached clearance/MRA with TL-01, but three were still not clear after 30 PUVA exposures. TL-01 achieved clearance/MRA a median of 11 (6.5-25; P = 0.001) days more quickly than PUVA, but required a median of 24.5 compared with 19 exposures [95% confidence interval (CI) for difference 1.5-5.5; P = 0.01]. Ten patients were withdrawn (four because of inadequate response of PUVA-treated halves). Analysed on an intention-to-treat basis, 21 of 28 (75%) of all participants reached clearance/MRA with TL-01 compared with 15 of 28 (54%) with PUVA (95% CI for difference 4-37%; P = 0.03). Remission durations did not differ. CONCLUSIONS: When administered according to these regimens in a skin phototype I-III population, TL-01 UVB is more efficacious than TMP bath-PUVA in the treatment of chronic plaque psoriasis.

Time course of skin photosensitivity following trimethylpsoralen bath PUVA.

One aspect of bath photochemotherapy (PUVA) that requires clarification is the duration of psoralen-induced cutaneous photosensitisation under conditions simulating clinical use. Using a half back comparison study technique, we investigated the persistence of trimethylpsoralen (TMP)-induced photosensitivity in skin irradiated to simulate a first PUVA exposure compared with un-irradiated skin. Baseline UVA minimal erythema dose and minimal phototoxic dose (MPD) were determined in 13 healthy volunteers. After readings at 72 h, subjects were bathed in TMP bath water for 15 min and one half of the back was immediately exposed to 40% of the MPD. Test sites (1.5 cm2) on both halves of the back were then irradiated with a UVA dose series at 15 min, 5, 10, 24, 34, 48 and 72 h after the bath. MPD readings were recorded visually at 72 h after each UVA exposure. The UVA MED was >25 J/cm2 in all the subjects. At each time point, a phototoxic index (PI) was calculated as UVA MED/MPD. In un-irradiated skin, photosensitivity returned to normal (PI=1) within 24 h after the TMP bath. In contrast, skin pre-irradiated to simulate the first PUVA treatment was still significantly photosensitive (PI=2.3; P=0.002) at 48 h. Contrary to previous recommendations, these data suggest that patients should be advised to avoid ambient or artificial sources of UVA throughout their course of TMP bath PUVA to reduce the risk of phototoxic erythema.

Narrowband ultraviolet B (TL-01) phototherapy for psoriasis: which incremental regimen?

Narrowband (311-313 nm) ultraviolet B phototherapy with the Philips TL-01 lamp is used increasingly in the treatment of psoriasis with little information available on the optimum irradiation regimen. We compared a high and a low incremental dose regimen in 20 patients with symmetrical chronic plaque psoriasis using a randomized half body study and thrice weekly exposures. Paired trunk, leg and arm plaques of psoriasis were scored blind prior to and at each treatment for scaling, erythema and induration. Patients were treated to clearance or minimal residual activity and followed up until relapse. The low increment regimen achieved a 10% reduction in the median cumulative dose to clearance (16,401 vs. 18,246 mJ/cm2) with one extra treatment in 50% of the patients. However, the duration of treatment (median 53.5 days) was identical for both regimens except for one patient because there were 50% fewer episodes of erythema requiring postponement of treatment with the low increment regimen. We now favour the low increment regimen for phototherapy in our psoriasis population.

Narrow-band (TL-01) ultraviolet B phototherapy for chronic plaque psoriasis: three times or five times weekly treatment?

Three and five times weekly narrow-band TL-01 (311-313 nm) ultraviolet (UV) B phototherapy regimens for chronic plaque psoriasis were compared in a randomized, observer-blinded, half-body, within-patient paired study. Twenty-one patients [13 men, eight women, age range 21-68 years, skin phototypes I (two patients), II (14) and III (five)] entered the study. Sixteen reached clearance or minimal residual activity (MRA) on both sides. Of the other five, three withdrew because they did not reach clearance or MRA on the 5x weekly side by a maximum of 30 treatments, one when he was satisfied with moderate improvement and one because of repeated failure to attend. Those who completed treatment reached clearance or MRA after a median of 35 days with 5x weekly treatment compared with 40 days with 3x weekly treatment (P = 0.007), but required a median of 23.5 compared with 17 UVB exposures (P = 0.001) and 94 minimal erythema dose multiples (MEDs) compared with 64 MEDs (P = 0.01). Fifteen (of 16) developed at least one episode of well-demarcated erythema during 5x weekly treatment compared with just three of 16 treated 3x weekly (P < 0.001). There was no significant difference between regimens in duration of remission. For this skin phototype I-III population, the more rapid clearance of psoriasis with 5x weekly phototherapy is not, for the majority of patients, sufficient to justify the extra exposures and higher UVB dose. We no longer use 5x weekly phototherapy for psoriasis.

Bath PUVA--an investigation of the distribution of trioxsalen (TMP) and 8-methoxypsoralen (8-MOP) in bathwater.

Trioxsalen (TMP) bath PUVA avoids the side effects of nausea and headache associated with oral 8-methoxypsoralen (8-MOP) treatment and allows shorter irradiation times that can be advantageous in some patients. However we noted that a number of patients developed unusual patterns of phototoxic burning. We thought that this was related to an uneven distribution of the TMP in the bathwater and for this reason, a study of bath water TMP concentrations achieved using different TMP preparations was undertaken. The distribution of 8-MOP in an 8-MOP bath was also measured for comparison. Our results confirm that an uneven distribution of TMP is achieved using TMP capsules or suspension and would explain our observed patterns of burning. With an ethanolic solution of TMP, or the commercial equivalent Tripsor, or with Puvasoralen-8 (an 8-MOP preparation), a homogeneous psoralen distribution is achieved, and they are therefore preferable for use in bath PUVA.

8-MOP PUVA for psoriasis: a comparison of a minimal phototoxic dose-based regimen with a skin-type approach.

Two ultraviolet A (UVA) regimens for oral 8-methoxypsoralen (8-MOP) photochemotherapy (PUVA) for moderate/severe chronic plaque psoriasis using a half body study technique were compared. Each patient received both regimens. A higher-dose regimen based on minimal phototoxic dose (MPD) with percentage incremental increases was given to one-half of the body. The other half received a lower dose regimen based on skin type with fixed incremental UVA increases. Patients were treated twice weekly. Symmetrical plaques were scored to determine the rate of resolution with each regimen. In addition, the number of treatments, cumulative UVA dose and number of days in treatment to achieve overall clearance were recorded. Patients were reviewed monthly for 1 year to record remission data. Thirty-three patients completed the study. Both regimens were effective and well tolerated. With the MPD-based approach, the number of exposures was significantly less for patients with skin types I and II but not III. Although the cumulative UVA dose was higher with the MPD regimen for all skin types studied, the reduced number of exposures required for clearance for skin types I and II but not III, combined with the security of individualized MPD testing, has practical attractions. MPD testing also identified five patients who required an increased psoralen dose and six patients who required a reduction of the initial UVA dose with the skin type regimen. Forty-two percent were still clear 1 year after treatment and there was no significant difference in the number of days in remission between the regimens for those whose psoriasis had recurred. The reduction in the number of exposures required for clearance with the MPD-based regimen may be safer and more cost effective in the long term.

Failure of coconut oil to accelerate psoriasis clearance in narrow-band UVB phototherapy or photochemotherapy.

Despite a widely held belief that the use of emollients prior to broad-band UVB irradiation accelerates clearance of psoriasis, only one single-blind controlled study exists in support of this. No similar study has been carried out with photochemotherapy (PUVA) or narrow-band UVB (311-313 nm) phototherapy. As some emollients absorb UV radiation, and thereby inhibit psoriasis clearance, there is a need to identify emollients suitable for pre-irradiation use. Coconut oil may be useful in this respect. In two randomized groups of patients with chronic plaque psoriasis undergoing either routine PUVA (n = 14) or narrow-band UVB phototherapy (n = 15), a single-blind controlled (half-body) study was undertaken to assess the effect of pre-irradiation application of coconut oil. Patients were given PUVA twice weekly, or TL-01 therapy thrice weekly. The initial UV dose was 70% of previously determined minimal phototoxic (MPD) or minimal erythema doses (MED), with 40% incremental steps at each visit (reduced if adverse effects occurred). Psoriasis severity was scored on each side after every three treatments. No significant acceleration of psoriasis clearance was seen in either group. We do not, therefore, recommend the routine use of emollients prior to PUVA or TL-01 therapy when using near erythemogenic irradiation regimens.