A randomized,observer-blinded trial of twice vs. three times weekly narrowband ultraviolet B phototherapy for chronic plaque psoriasis

BACKGROUND: The optimum treatment frequency for narrowband (TL-01) ultraviolet B (NB-UVB) in psoriasis is not yet known. We have previously found three times weekly to be preferable to five times weekly treatment in our population. OBJECTIVES: To compare twice weekly with three times weekly NB-UVB phototherapy in chronic plaque psoriasis. METHODS: In an observer-blinded, randomized comparison, patients with chronic plaque psoriasis referred from dermatology out-patient clinics in Tayside for NB-UVB phototherapy received either twice weekly (Monday and Friday) or three times weekly (Monday, Wednesday and Friday) whole-body NB-UVB phototherapy following our standard departmental treatment protocol. Treatment was continued to clearance or until the fourth treatment after minimal residual activity (MRA) was first documented. Number of days in treatment, number of treatments, total dose and time to relapse were recorded. RESULTS: In total, 113 patients were recruited, skin phototypes I-III: 58 in the twice weekly and 55 in the three times weekly group. Forty patients in the twice weekly group reached clearance/MRA, as did 44 in the three times weekly group. It took 1.5 (95% confidence interval 1.3-1.7) times longer to reach clearance/MRA with twice weekly therapy, a geometric mean of 88 vs. 58 days (P < 0.0001). Small differences in numbers of treatments and total dose to reach clearance tended to favour three times weekly therapy, but these were not significant. CONCLUSIONS: Three times weekly NB-UVB clears psoriasis significantly faster than twice weekly treatment, and therefore is preferable for most patients.     

Efficacy and safety of calcipotriol plus betamethasone dipropionate scalp formulation compared with calcipotriol scalp solution in the treatment of scalp psoriasis: a randomized controlled trial

Background Current topical therapies for scalp psoriasis are difficult or unpleasant to apply, resulting in decreased adherence and efficacy. Objectives To compare the efficacy and safety of once‐daily treatment with a combination of calcipotriol 50 μg g^?1 plus betamethasone 0·5 mg g^?1 (as dipropionate) (Xamiol^®; LEO Pharma A/S, Ballerup, Denmark) and twice‐daily calcipotriol 50 μg mL^?1 scalp solution in patients with scalp psoriasis. Methods This 8‐week, multicentre, randomized, investigator‐blind, parallel‐group study compared two‐compound calcipotriol/betamethasone scalp formulation with calcipotriol scalp solution in patients with moderately severe scalp psoriasis. Primary efficacy outcome was the proportion of patients who achieved ‘clear’ or ‘minimal’ disease severity according to investigator’s global assessment of disease severity at week 8. Secondary efficacy outcomes and adverse events were also evaluated. Relapse and rebound were assessed in an 8‐week, post‐treatment observation phase. Results In total, 207 patients received the two‐compound scalp formulation and 105 patients received calcipotriol scalp solution. The proportion of patients with ‘clear’ or ‘minimal’ disease at week 8 was significantly greater in the two‐compound scalp formulation group (68·6%) than in the calcipotriol scalp solution group (31·4%; P < 0·001). Improvement was more rapid with the two‐compound scalp formulation than with calcipotriol scalp solution. Further evidence of the superiority of the two‐compound scalp formulation over the scalp solution was demonstrated through greater improvements in clinical signs and fewer adverse events. Conclusions A once‐daily combination of calcipotriol plus betamethasone dipropionate was significantly more effective and better tolerated than twice‐daily calcipotriol scalp solution in the treatment of scalp psoriasis.     

Local effects of TL01 phototherapy in psoriasis

The mechanisms whereby narrowband ultraviolet B (UVB) (311-313 nm, TL01) phototherapy are effective in psoriasis may differ from those occurring in broadband UVB phototherapy. In the present study, changes in epidermal cells as a result of TL01 therapy were assessed in the skin of patients with psoriasis. The non-lesional skin of five subjects with plaque psoriasis was biopsied before and after a series of 12 whole-body TL01 treatments. Following appropriate staining of skin sections, the numbers of p53-positive keratinocytes, sunburn cells and Langerhans cells in the epidermis were counted. TL01 therapy induced a threefold increase in the number of p53-positive epidermal cells, a 12-fold increase in sunburn cells and a twofold decrease in Langerhans cells. The increase in epidermal p53 expression and apoptosis of keratinocytes together with the depletion of Langerhans cells in the non-lesional skin of psoriasis patients are likely to contribute to the effectiveness of TL01 phototherapy.     

Topical becocalcidiol for the treatment of psoriasis vulgaris: a randomized, placebo-controlled, double-blind, multicentre study

BACKGROUND: Becocalcidiol is a vitamin D(3) analogue which has not caused hypercalcaemia or significant irritation in preclinical trials. OBJECTIVES: To evaluate the efficacy and safety of two dosing regimens of becocalcidiol ointment (low dose = 75 microg g(-1) once daily for 8 weeks; high dose = 75 microg g(-1) twice daily for 8 weeks) in the treatment of plaque-type psoriasis. METHODS: One hundred and eighty-five subjects with chronic plaque-type psoriasis affecting 2-10% of their body surface area took part in a multicentre, double-blind, parallel-group, vehicle-controlled, randomized controlled trial comparing topical application of placebo, becocalcidiol 75 microg g(-1) once daily (low dose) or becocalcidiol twice daily (high dose) for 8 weeks. Main outcomes included Physician's Static Global Assessment of Overall Lesion Severity (PGA) score; Psoriasis Symptom Severity (PSS) score; adverse events; and laboratory assessment. RESULTS: In the intent-to-treat population at week 8, high-dose becocalcidiol was statistically superior to vehicle [P = 0.002; 95% confidence interval (CI) 6.7-32.2], with 16 of 61 (26%) subjects achieving a PGA score of clear or almost clear. Greater improvement in PSS score was seen with high-dose becocalcidiol than with vehicle, but this result did not quite achieve statistical significance (P = 0.052; 95% CI -16.2 to 0.1). In all groups, therapy was safe and well tolerated, with fewer subjects experiencing irritation than is reported in studies using calcipotriol. CONCLUSIONS: Treatment with high-dose topical becocalcidiol for 8 weeks led to almost or complete clearing of moderate plaque-type psoriasis in over a quarter of patients. Therapy was safe and well tolerated.     

Calcitriol 3 microg g-1 ointment in combination with ultraviolet B phototherapy for the treatment of plaque psoriasis: results of a comparative study

BACKGROUND: Combinations of topical treatments and ultraviolet (UV) B phototherapy for plaque psoriasis may be more beneficial than either type of treatment used alone. OBJECTIVES: To determine the efficacy of calcitriol 3 microg g-1 ointment in combination with UVB phototherapy in treating plaque psoriasis. METHODS: Calcitriol ointment with UVB was compared with vehicle plus UVB in a randomized, double-blind study in 104 patients. RESULTS: Mean global improvement scores for both groups increased over the 8-week study period; there was a statistically significant difference (P < 0.05) in favour of the calcitriol/UVB combination from week 1. At end-point, 45% of the calcitriol/UVB group showed considerable improvement or clearing of psoriasis, compared with 21% of the control group. The superiority of calcitriol plus UVB was also reflected in the global severity and Psoriasis Area and Severity Index (PASI) scores; at end-point the mean percentage decrease in PASI score was 65% for the calcitriol/UVB group and 43% for vehicle/UVB (P = 0.0014). The incidence of skin-related adverse events was low (< 12%) and similar in the two treatment groups. No clinically significant changes in blood chemistry, in particular calcium levels, occurred. The greater efficacy of combined calcitriol and phototherapy allowed a 34% decrease in total UVB exposure. CONCLUSIONS: Calcitriol 3 microg g-1 ointment and UVB phototherapy in combination provides a promising therapy for managing chronic plaque psoriasis.     

A comparison of twice-daily calcipotriol ointment with once-daily short-contact dithranol cream therapy: a randomized controlled trial of supervised treatment of psoriasis vulgaris in a day-care setting

BACKGROUND: Calcipotriol has become a first-line treatment for psoriasis. Its efficacy and safety have been shown in many comparative clinical trials carried out in outpatients. In a comparative study in patients visiting the outpatient department once every 14 days, it was shown that calcipotriol was more effective and better tolerated compared with dithranol. OBJECTIVES: To compare the clinical efficacy of calcipotriol ointment with that of dithranol cream in a supervised treatment regimen. METHODS: In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. RESULTS: This study failed to prove that calcipotriol is as efficacious as dithranol when used in a day-care setting (noninferiority test). The mean percentage reduction in Psoriasis Area and Severity Index from baseline to end of treatment was 57.0% in the calcipotriol group vs. 63.6% in the dithranol group. However, the two-sided test for superiority indicated no statistically significant difference between the treatment groups (P = 0.39). At the end of treatment, 15% of the patients treated with calcipotriol ointment and 25% of those treated with dithranol cream did not require any further treatment. Although calcipotriol ointment appeared to be more effective during the first 8 weeks, a difference was no longer apparent at 12 weeks. In comparison with the high number of drop-outs due to cutaneous side-effects in the calcipotriol group, the frequency of a tolerable degree of irritation appeared to be higher in patients treated with dithranol. However, concomitant corticosteroid treatment of dithranol irritation in seven patients may have contributed to this difference between both treatments. Moreover, patients receiving therapy with calcipotriol ointment experienced fewer application-related skin and subcutaneous tissue disorders than patients treated with dithranol cream: 21 of 53 (40%) and 37 of 52 (71%), respectively. This difference is statistically significant (P = 0.001). CONCLUSIONS: The hypothesis that calcipotriol ointment might be at least as effective as dithranol cream in the day-care setting could not be proven in the present study. Whereas calcipotriol has become a mainstay in the routine outpatient treatment of psoriasis not requiring a day-care setting, dithranol treatment, being difficult as a routine outpatient therapy, has increased efficacy and improved tolerability if the treatment is carried out in a day-care setting.     

Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized,double-blind,vehicle-controlled clinical trial

BACKGROUND: Calcipotriol and betamethasone dipropionate are both widely used, effective treatments for psoriasis. Vitamin D analogues and topical corticosteroids have different mechanisms of action in the treatment of psoriasis. A new vehicle has been developed in order to contain both calcipotriol (50 micro g g-1) and betamethasone dipropionate (0.5 mg g-1) in an ointment form. By using calcipotriol and a corticosteroid together, greater efficacy may be achieved than by using either compound alone. OBJECTIVES: The present study was conducted in order to compare the clinical efficacy and safety of the combined ointment formulation used once daily with the vehicle ointment used twice daily, calcipotriol ointment used twice daily and the combined formulation used twice daily in psoriasis vulgaris. METHODS: This was an international, multicentre, prospective, randomized, double-blind, vehicle-controlled, parallel group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment. Patients were randomized to one of four treatment groups: combined formulation once daily, combined formulation twice daily, calcipotriol twice daily or vehicle twice daily. Efficacy and safety were assessed. RESULTS: There was no statistically significant difference in the mean percentage change in the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment between the two combined formulation groups, but the difference in PASI reduction was significantly higher in the combined formulation groups (68.6% once daily, 73.8% twice daily) than in both the twice daily calcipotriol group (58.8%) and the vehicle group (26.6%). Safety data showed the frequency of adverse events to be less in the combined formulation groups than in both the calcipotriol group and the vehicle group. The proportion of patients with lesional/perilesional adverse reactions was less in the combined formulation groups and vehicle group than in the calcipotriol group (9.9% combined formulation once daily, 10.6% combined formulation twice daily, 19.8% calcipotriol, 12.5% vehicle). CONCLUSIONS: No statistically significant nor clinically relevant difference in efficacy was seen between the combined formulation used once daily and twice daily. When compared to vehicle ointment or calcipotriol ointment alone, the combined formulation was shown to be clearly more efficacious.     

Comparison of clinical effects of psoriasis treatment regimens among calcipotriol alone,narrowband ultraviolet B phototherapy alone,combination of calcipotriol and narrowband ultraviolet B phototherapy once a week,and combination of calcipotriol and narrowband ultraviolet B phototherapy more than twice a week

We compared the clinical efficacy of various psoriasis treatments among: (i) topical application of calcipotriol ointment twice daily (group I); (ii) topical application of calcipotriol ointment twice daily and narrowband ultraviolet B NB‐UVB phototherapy once a week (group II); (iii) topical application of heparinoid ointment twice daily and NB‐UVB phototherapy more than twice a week (group III); and (iv) topical application of calcipotriol ointment twice daily and NB‐UVB phototherapy more than twice a week (group IV). Ten patients were randomly selected for each group and treated by the indicated regimens for 12 weeks. All treatments were effective and significantly improved Psoriasis Area and Severity Index (PASI) scores, self‐administered PASI scores and visual analog scale scores of pruritus. Group IV showed most marked and rapid reduction in PASI and self‐PASI scores among the four regimens. Although the serum levels of interleukin (IL)‐17, IL‐20 and IL‐22 and psoriasis disability index were significantly decreased after the treatments, no significant difference was detected among the four groups. Our study indicates that combination of calcipotriol ointment plus NB‐UVB more than twice a week is superior to other treatment regimens, rapidly improving psoriasis lesions.     

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.     

A comparison of twice-daily calcipotriol ointment with once-daily short-contact dithranol cream therapy: quality-of-life outcomes of a randomized controlled trial of supervised treatment of psoriasis in a day-care setting

BACKGROUND: Calcipotriol ointment and short-contact dithranol cream therapy are well-established topical treatments for psoriasis. Quality of life, i.e. the physical, psychological, and social functioning and well-being of the patient, has become an essential outcome measure in chronic skin disease. OBJECTIVES: To compare the quality-of-life outcomes of calcipotriol ointment with that of short-contact dithranol cream in a supervised treatment regimen, and to determine the degree of improvement in quality of life these topical treatments can accomplish. METHODS: In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily in a 12-week intensive treatment programme. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. Quality of life was assessed with the Skindex-29 and the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36). RESULTS: At the end of treatment, no statistically significant differences were found between the calcipotriol and the dithranol group in any of the quality-of-life domains or scales of the Skindex-29 and the SF-36. Over time, a significant improvement of quality of life was found on all three scales of the dermatology-specific Skindex-29, predominantly of a moderate magnitude. In the calcipotriol group, a significant change of a small magnitude was found in the Physical Component Summary of the SF-36. No significant changes were found in the Mental Component Summary (or on any of the eight scales composing the questionnaire) of the SF-36. CONCLUSIONS: The hypothesis was confirmed, that no statistically significant differences in improvement of quality of life could be found between calcipotriol ointment and dithranol short-contact cream in a day-care setting. Given this result, both calcipotriol and dithranol can be welcome alternatives for the patient. Calcipotriol, being more practical and patient friendly, can be considered as a first-line approach in clinical practice. However, in patients recalcitrant to calcipotriol and/or other topical treatments, preference should be given to the dithranol regimen. Topical treatment in combination with interventions explicitly focusing on improvement of coping behaviour and psychosocial functioning may further increase the degree of improvement in the psychosocial domains of quality of life. The results of this study are likely to give further evidence to the notion that the generic SF-36 is little or not responsive to small to moderate changes in quality of life in mild to moderate psoriasis.     

The effect of inositol supplements on the psoriasis of patients taking lithium: a randomized, placebo-controlled trial

BACKGROUND: Lithium carbonate is the most widely used long-term treatment for bipolar affective disorders, but its ability to trigger and exacerbate psoriasis can become a major problem in patients for whom lithium is the only treatment option. Inositol depletion underlies the action of lithium in bipolar affective disorders and there are good theoretical reasons why the use of inositol supplements might be expected to help this group of patients. OBJECTIVES: To determine whether inositol supplements improve the psoriasis of patients on lithium therapy. METHODS: Fifteen patients with psoriasis, who were taking lithium, took part in a randomized, double-blind, placebo-controlled, crossover clinical trial comparing the effect of inositol supplements with those of a placebo (lactose). Changes in the severity of their psoriasis were measured by Psoriasis Area and Severity Index scores recorded before and after the different courses of treatment. The effect of inositol supplements on the psoriasis of 11 patients who were not taking lithium was evaluated in the same way. RESULTS: The inositol supplements had a significantly beneficial effect on the psoriasis of patients taking lithium. No such effect was detected on the psoriasis of patients not on lithium. CONCLUSIONS: The use of inositol supplements is worth considering for patients with intractable psoriasis who need to continue to take lithium for bipolar affective disorders.     

A new scalp formulation of calcipotriol plus betamethasone dipropionate compared with each of its active ingredients in the same vehicle for the treatment of scalp psoriasis: a randomized, double-blind, controlled trial

Background There is a need for new treatments for scalp psoriasis, as many topical treatments are cosmetically unacceptable and difficult to apply, resulting in poor compliance. Objectives To compare the efficacy and safety of a new, once‐daily, two‐compound scalp formulation (Xamiol^®; LEO Pharma A/S, Ballerup, Denmark) containing calcipotriol 50 μg g^?1 plus betamethasone 0·5 mg g^?1 (as dipropionate), with the active ingredients as single compounds in the same vehicle. Methods This 8‐week, multicentre, double‐blind, parallel‐group study, randomized adult patients with scalp psoriasis involving > 10% of the scalp to the two‐compound scalp formulation (n = 568), betamethasone dipropionate 0·5 mg g^?1 (n = 563), or calcipotriol 50 μg g^?1 (n = 286). The primary efficacy measure was the proportion of patients with ‘absence of disease’ or ‘very mild disease’ according to investigators’ assessments at week 8. Results The proportion of patients with ‘absence of disease’ or ‘very mild disease’ at week 8 was significantly higher in the two‐compound group (68·4%) than the betamethasone dipropionate (61·0%, P = 0·0079) or calcipotriol (43·4%, P < 0·0001) groups. The proportion of patients rating their scalp psoriasis as ‘clear’ or ‘almost clear’ was significantly higher for the two‐compound scalp formulation (69·6%) than for betamethasone dipropionate (59·9%, P = 0·0006) or calcipotriol (44·7%, P < 0·0001). The incidence of lesional/perilesional adverse events was lower in the two‐compound and betamethasone dipropionate groups than the calcipotriol group. Conclusions The two‐compound scalp formulation was well tolerated and more effective in the treatment of scalp psoriasis than either of its individual components in the same vehicle.     

Treatment of psoriasis with topical sirolimus: preclinical development and a randomized, double-blind trial

BACKGROUND: Systemically administered sirolimus has demonstrated efficacy in psoriasis in a multicentre European study. OBJECTIVES: To determine the efficacy and safety of topically applied sirolimus in treating psoriasis. METHODS: In vitro studies were followed by a pilot study designed to determine if sirolimus penetrates human skin, and by a randomized, double-blind, left-right comparative, dose-ranging study consisting of treatment with 2.2% sirolimus for 6 weeks and 8% sirolimus for an additional 6 weeks in 24 patients with stable, chronic plaque psoriasis. The primary outcome measure was clinical score. Secondary measures were ultrasound plaque thickness, plaque erythema, and computerized image analysis of immunohistochemical stains for immunocytes and proliferating cells. Pharmacokinetics and blood chemistry monitoring for safety were also performed. RESULTS: A significant reduction in the clinical score (P = 0.03) (mean score 9.1 following sirolimus vs. 11.2 in control) was achieved with topical sirolimus. Measurements of plaque thickness and erythema did not show significant improvement with treatment. Computerized image analysis of biopsies showed a significant reduction in CD4+ cells (P = 0.0054) and proliferating cells (stained by Ki-67) in the epidermis (P = 0.0153) with sirolimus treatment compared with control. CONCLUSIONS: Topically applied sirolimus penetrates normal skin and may have some antipsoriatic and immunosuppressive activity.     

昆仙胶囊治疗进行期寻常型银屑病的单中心随机双盲安慰剂对照临床试验研究

目的：评价昆仙胶囊治疗进行期寻常型银屑病的疗效及安全性。方法：按照入选和排除标准将进行期寻常型银屑病患者随机分成昆仙胶囊治疗组及安慰剂对照组,治疗周期为4周,采用PASI评分评价药物疗效。结果：共纳入病例60例,每组30例,治疗组脱落3例,对照组脱落1例。治疗组达到PASI 50、PASI 75、PASI 90的患者比例分别为74.1%、29.6%和14.8%,对照组各组患者均为0%,两组各PASI组均存在显著差异（P值分别为0.001,0.002,0.048）。治疗组和对照组中分别出现不良事件6例和1例。结论：昆仙胶囊治疗进行期寻常型银屑病疗效优于安慰剂。     

The impact of a two-compound product containing calcipotriol and betamethasone dipropionate (Daivobet/ Dovobet) on the quality of life in patients with psoriasis vulgaris: a randomized controlled trial

BACKGROUND: Psoriasis is a common disease and may have a significant impact on patients' quality of life (QoL). OBJECTIVES: To assess the impact on QoL of a new two-compound product (TCP) (Daivobet/Dovobet; LEO Pharma) which combines the topical vitamin D analogue calcipotriol (50 microg g(-1)) and the World Health Organization group III corticosteroid betamethasone dipropionate (0.5 mg g(-1)) in a single ointment vs. calcipotriol monotherapy using a placebo-controlled study design. METHODS: The Psoriasis Disability Index and the EuroQoL 5D questionnaire and visual analogue scale (VAS) were used in this study, which enrolled 828 patients with psoriasis vulgaris for treatment lasting up to 4 weeks. These QoL instruments were completed by patients before and after treatment with the TCP of calcipotriol and betamethasone dipropionate used once or twice daily, calcipotriol alone twice daily and vehicle twice daily. RESULTS: The TCP used once or twice daily and calcipotriol used twice daily were found to have statistically significant beneficial effects on patients' QoL over the course of treatment, and each was demonstrated to have a statistically significant benefit on QoL over vehicle. The TCP, applied once daily, was superior to calcipotriol twice daily in terms of reductions on the EuroQoL 5D questionnaire and VAS. CONCLUSIONS: The results suggest that calcipotriol twice daily and the new TCP applied twice daily have a substantial effect on QoL. Once-daily application of the TCP is superior to calcipotriol twice daily terms of QoL, which reflects the superior efficacy of this combination and the advantage of once-daily application when compared with twice-daily application.     

Optimizing the frequency of outpatient short-contact dithranol treatment used in combination with broadband ultraviolet B for psoriasis: a randomized, within-patient controlled trial

BACKGROUND: Recent concerns over the side-effects of psoralen plus ultraviolet (UV) A, immunosuppressive and cytotoxic treatments have led to increased interest in dithranol for treatment of psoriasis. Few studies have investigated how frequently dithranol should be applied. Dithranol-induced inflammation is maximal at 48-72 h, suggesting that daily application of dithranol may not be optimal. OBJECTIVES: To investigate the effectiveness of five times weekly application of short-contact dithranol (SCD) compared with three times weekly application in a dedicated hospital outpatient treatment unit. METHODS: A randomized, within-patient, controlled study was performed. Patients had SCD applied five times weekly to one half of the body, and three times weekly to the other side. Whole-body UVB irradiation was given 5 days a week. Patients were assessed weekly for 8 weeks. Principal outcome measures were percentage reduction in modified Psoriasis Area and Severity Index (mPASI) at the end of study and time to 50% improvement in mPASI score. RESULTS: Twenty-nine patients were recruited; four were excluded from analysis. Mean percentage reduction in mPASI score at the end of study for five times weekly application was 57.3% (95% confidence interval, CI 39.6-75.0%) and for three times weekly application was 55.4% (95% CI 37.8-73.1%; P = 0.34). Mean time to 50% improvement in mPASI for five times weekly treatment was 4.1 weeks and for three times weekly treatment was 4.0 weeks (P = 0.50). There was no difference in the frequency or severity of burning episodes for each side. CONCLUSIONS: This study suggests that three times weekly application of SCD may be as effective as five times weekly when used in conjunction with UVB administered five times weekly. Large studies of whole-body comparisons are warranted to assess further the optimal frequency of SCD and UVB therapy for psoriasis.     

The combination of calcipotriol and methotrexate compared with methotrexate and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trial

BACKGROUND: A multicentre, randomized, double-blind, vehicle-controlled, parallel-group study was carried out to study the effect of the addition of calcipotriol ointment to methotrexate (MTX) therapy in patients with psoriasis vulgaris. OBJECTIVES: To investigate whether the addition of calcipotriol to treatment with MTX has an MTX-sparing effect, and whether the combination of treatments is safe. Additionally, to compare the effect of calcipotriol or vehicle on the duration of the relapse-free interval after cessation of MTX. METHODS: Patients on maintenance therapy with MTX with controlled psoriasis were selected. The study was divided into three phases: (i) an MTX-free phase with double-blind treatment with either calcipotriol ointment or vehicle; (ii) an MTX titration phase with open MTX treatment and additional double-blind treatment with either calcipotriol or vehicle until target response; and (iii) follow-up phase: in a group of 97 patients, psoriasis was assessed using the modified psoriasis severity score, patients' assessment and safety parameters were monitored as well. RESULTS: The combined use of calcipotriol with MTX resulted in an MTX-sparing effect of 3.4 mg week-1 (phase (II) and 2.6 mg week-1 (phase I and II taken together), while still maintaining efficacy. Calcipotriol treatment increased the time to relapse of psoriasis following discontinuation of MTX: 113 days vs. 35 days. A decrease in aspartate aminotransferase and alanine aminotransferase was seen during the study of 8% (calcipotriol) and 12% (vehicle). CONCLUSIONS: The combination of calcipotriol and MTX was safe and well tolerated. The combination resulted in lower cumulative dosages of MTX compared with MTX and vehicle. Therefore the risk of side-effects is substantially decreased.     

A 52-week randomized safety study of a calcipotriol/betamethasone dipropionate two-compound product (Dovobet/Daivobet/Taclonex) in the treatment of psoriasis vulgaris

BACKGROUND: The calcipotriol/betamethasone dipropionate two-compound product Dovobet/Daivobet/Taclonex(LEO Pharma A/S, Ballerup, Denmark) has been shown to be safe and effective in the treatment of psoriasis for up to 8 weeks. As psoriasis is a chronic disease, long-term treatment may be required, so there is a need to investigate the safety of its use over a longer period of time. OBJECTIVES: To investigate the safety of two treatment regimens involving use of the two-compound product over 52 weeks in the treatment of patients with psoriasis. METHODS: Patients (n = 634) were randomized double-blind to treatment with: (i) 52 weeks of the two-compound product (two-compound group); (ii) 52 weeks of alternating 4-week periods of the two-compound product and calcipotriol (alternating group); or (iii) 4 weeks of the two-compound product followed by 48 weeks of calcipotriol (calcipotriol group). Treatments in all groups were used once daily when required. RESULTS: Adverse drug reactions (ADRs) occurred in 45 (21.7%) patients in the two-compound group, 63 (29.6%) in the alternating group and 78 (37.9%) in the calcipotriol group. The odds ratio for an ADR in the two-compound group relative to the calcipotriol group was 0.46 (95% confidence interval 0.30-0.70; P < 0.001). ADRs of concern associated with long-term topical corticosteroid use occurred in 10 (4.8%) patients in the two-compound group, six (2.8%) in the alternating group and six (2.9%) in the calcipotriol group; those with the highest incidence were skin atrophy, occurring in four (1.9%), one (0.5%) and two (1.0%) patients, respectively, and folliculitis, in three (1.4%), one (0.5%) and no patients, respectively. CONCLUSIONS: Treatment with the two-compound product for up to 52 weeks appears to be safe and well tolerated whether used on its own or alternating every 4 weeks with calcipotriol treatment.     

A randomized controlled comparison of the efficacy of Dead Sea salt balneophototherapy vs. narrowband ultraviolet B monotherapy for chronic plaque psoriasis

BACKGROUND: Dead Sea (DS) salt solution soaks are used in combination with narrowband ultraviolet B (NB-UVB) to treat psoriasis in many centres, particularly in continental Europe. No previously published controlled study has assessed DS salt + NB-UVB balneophototherapy. OBJECTIVES: To compare DS salt balneophototherapy with NB-UVB monotherapy for chronic plaque psoriasis. METHODS: Sixty patients with chronic plaque psoriasis participated in this paired, controlled study, with pretreatment DS salt soaks randomly allocated to each participant's right or left study limb. Psoriasis severity was assessed with a Scaling, Erythema and Induration score by a blinded observer. Assessments were weekly during the therapy course, and thereafter 8-weekly until relapse or for up to 1 year after clearance. RESULTS: The mean area under the psoriasis severity-time curves during treatment was not detectably lower with DS salt balneophototherapy than with NB-UVB monotherapy (P = 0.099). The psoriasis severity score fell slightly more from beginning to end of courses with DS salt balneophototherapy than with NB-UVB monotherapy (P = 0.019). There was no detectable difference in times to relapse. CONCLUSIONS: In this population the addition of pretreatment DS salt soaks to NB-UVB did not result in a clinically important improvement in clearance of psoriasis.