Is the combination of calcipotriol and PUVA effective in vitiligo?

OBJECTIVE: The objective was to compare the effectiveness of psoralen plus ultraviolet A (PUVA) and the combination of PUVA and topical calcipotriol in the treatment of vitiligo. BACKGROUND: There are several reports on the response rate of patients with vitiligo treated with the combination of PUVA and calcipotriol or calcipotriol alone. SUBJECTS AND METHODS: Twenty-two patients with generalized vitiligo were taken into the study. PUVA treatment was applied on a twice-weekly schedule. Calcipotriol cream was applied to one of the two symmetrical lesions of each patient twice daily. RESULTS: Our results showed that the addition of topical calcipotriol to PUVA treatment did not lead to a significant increase in response rate of patients with vitiligo compared with PUVA treatment alone.     

Experience with calcipotriol as adjunctive treatment for vitiligo in patients who do not respond to PUVA alone: a preliminary study

BACKGROUND: PUVA therapy remains a primary treatment for vitiligo, despite unsatisfactory results. Because of calcipotriol's reported effects on melanocytes and on immunomodulatory and inflammatory mediators we wondered whether adding calcipotriol to PUVA would be more effective than PUVA alone in treating vitiligo. OBJECTIVE: We sought to determine whether the combination of topical calcipotriol and PUVA therapy increases the responsiveness of patients with vitiligo refractory to PUVA alone. METHODS: Twenty-one patients with vitiligo refractory to previous PUVA therapy were studied. Patients received 60 sessions of PUVA 3 times a week and 0.005% topical calcipotriol twice daily. Patients were monitored for repigmentation overall and on the trunk, extremities, and acral regions. RESULTS: Starting at the median of the 17th treatment session, some degree of repigmentation was observed in 71.5% of the patients. After treatment, cosmetically acceptable overall repigmentation was observed in 29% of patients; repigmentation of lesions on the trunk, extremities, and acral region was noted in 36%, 58%, and 0% of patients, respectively. Adverse reactions were mild and tolerable. CONCLUSION: The combination of PUVA and calcipotriol may be effective therapy and should be further investigated for the treatment of vitiligo.     

Is the efficacy of psoralen plus ultraviolet A therapy for vitiligo enhanced by concurrent topical calcipotriol? A placebo‐controlled double‐blind study

BACKGROUND: Encouraging results of previous uncontrolled trials suggest that calcipotriol may potentiate the efficacy of psoralen plus ultraviolet (UV) A (PUVA) therapy in patients with vitiligo. OBJECTIVES: We performed a placebo-controlled double-blind study to investigate whether the effectiveness of PUVA treatment could be enhanced by combination with topical calcipotriol in the treatment of vitiligo. METHODS: Thirty-five patients with generalized vitiligo enrolled in the study. Symmetrical lesions of similar dimensions and with no spontaneous repigmentation on arms, legs or trunk were selected as reference lesions. In this randomized left-right comparison study, calcipotriol 0.05 mg g(-1) cream or placebo was applied to the reference lesions 1 h before PUVA treatment (oral 8-methoxypsoralen and conventional UVA units) twice weekly. Patients were examined at weekly intervals. The mean number of sessions and the cumulative UVA dosage for initial and complete repigmentation were calculated. RESULTS: Twenty-seven patients (nine women, 18 men; mean +/- SEM age 29.8 +/- 13.5 years) were evaluated. The mean +/- SEM cumulative UVA dose and number of UVA exposures for initial repigmentation were 52.52 +/- 6.10 J cm(-2) and 9.33 +/- 0.65 on the calcipotriol side, and 78.20 +/- 7.88 J cm(-2) and 12.00 +/- 0.81 on the placebo side, respectively (P < 0.001). For complete repigmentation, respective values were 232.79 +/- 14.97 J cm(-2) and 27.40 +/- 1.47 on the calcipotriol side and 259.93 +/- 13.71 J cm(-2) and 30.07 +/- 1.34 on the placebo side (P = 0.001). Treatment with calcipotriol and PUVA resulted in significantly higher percentages of repigmentation for both initial (81%) and complete pigmentation (63%), compared with placebo and PUVA (7% and 15%, respectively). CONCLUSIONS: Our results have shown that concurrent topical calcipotriol potentiates the efficacy of PUVA in the treatment of vitiligo, and that this combination achieves earlier pigmentation with a lower total UVA dosage.     

Narrow-band ultraviolet B as monotherapy and in combination with topical calcipotriol in the treatment of vitiligo

Vitiligo is a common, idiopathic, acquired, depigmenting disease characterized by loss of normal melanin pigments in the skin. The most interesting treatment methods for extensive vitiligo involve psoralen plus ultraviolet A (PUVA) therapy and ultraviolet (UV)-B phototherapy, particularly narrow-band UV-B. In this randomized and comparative study, we investigated the safety and efficacy of narrow band ultraviolet B as monotherapy and in combination with topical calcipotriol in the treatment of generalized vitiligo. Of the 40 vitiligo patients enrolled in the study, 15 were treated with the calcipotriol plus narrow-band UV-B (NBUVB) and 25 with narrow band UV-B alone. The patients were randomized into two NBUVB treatment groups. The first group, consisting of 24 patients (all male), received only NBUVB treatment; the second group, consisting of 13 patients (all male) applied 0.05% topical calcipotriol ointments twice daily. Both groups were irradiated with NBUVB (311 nm). In the NBUVB group, the percentage of the body surface affected was reduced from 27.21 +/- 10.41% to 16.25 +/- 8.54% after a mean of 30 treatment sessions. The mean repigmentation percentage was 41.6 +/- 19.4%. In clinical evaluation (moderate and marked/complete response was accepted as an effective treatment), 19 patients (19/24; 79.17%) had clinically good results. In the NBUVB plus calcipotriol group, the percentage of the body surface affected was reduced from 23.35 +/- 6.5% to 13.23 +/- 7.05% after a mean of 30 treatment sessions. The mean repigmentation percentage was 45.01 +/- 19.15%. In clinical evaluation (moderate and marked/complete response was accepted as an effective treatment), 10 patients (10/13; 76.92%) had clinically good results. Statistically significant intragroup reductions from the baseline percentage of the body surface affected were seen at the endpoint of treatment for the two treatment groups (P < 0.001). However, there was no statistically significant difference between the two treatment groups at the end of therapy with respect to the reduction of repigmentation rates (P > 0.05). The present study reconfirmed the efficacy of NBUVB phototherapy in vitiligo. It can be a therapeutic option considered in the management of patients with vitiligo. However, addition of topical calcipotriol to NBUVB did not show any advantage.     

Combination of narrow band UVB and topical calcipotriol for the treatment of vitiligo

BACKGROUND: Narrow band ultraviolet B (NB-UVB) phototherapy has been used successfully for the treatment of vitiligo. Recently, topical calcipotriol has also been claimed to be effective, either as monotherapy or as a part of combination therapies. OBJECTIVE: The aim of the present study was to compare the clinical efficacy of NB-UVB and NB-UVB plus topical calcipotriol in the treatment of vitiligo. METHODS: NB-UVB treatment was given to 24 patients with generalized vitiligo three times weekly. Topical calcipotriol cream was only applied to the lesions located on the right side of the body. Treatment was continued for 6 months. Treatment efficacy was evaluated by determining the average response rates of the lesions at 3-month intervals. RESULTS: The average response rates of patients receiving combination of NB-UVB plus calcipotriol and NB-UVB alone were 51 +/- 19.6% and 39 +/- 18.9%, respectively. The median cumulative UVB dose and number of UVB exposures for initial repigmentation were 6345 mj/cm(2) (range; 2930-30980) and 18 (range; 12-67) for the combination therapy, and 8867.5 mj/cm(2) (range; 2500-30980) and 24 (range; 15-67) for the narrow band UVB therapy, respectively. CONCLUSIONS: These findings indicate that concurrent topical calcipotriol potentates the efficacy of NB-UVB in the treatment of vitiligo. This combination not only provides earlier pigmentation with lower total UVB dosage and less adverse UVB effects, but also reduces the duration and cost of treatment as well.     

Clinical study of repigmentation patterns with different treatment modalities and their correlation with speed and stability of repigmentation in 352 vitiliginous patches

Because the etiopathogenesis of depigmentation in vitiligo is still obscure, the source of pigmentation in the repigmentating lesion and its stability is also not fully known. Several authors have shown on histopathology and electron microscopy predominantly a perifollicular spread of pigment. The aim of this study was to clinically assess the types of repigmentation patterns obtained with different treatment modalities and their correlation with speed and stability of repigmentation. A total of 125 patients with vitiligo on treatment with psoralens (topical and systemic psoralen-UVA [PUVA]), steroids (both topical and systemic), and topical calcipotriol, alone or in combination were enrolled. Representative lesions of vitiligo excluding mucosal sites were selected in each patient and photographed at baseline. Repigmentation was assessed and labeled as marginal, perifollicular, diffuse, or combined. The preselected patches were evaluated at 3 months to assess the speed of repigmentation. Retention of pigment (stability) was noted at 6 months, after the stoppage of active treatment. Of the 352 vitiligo patches selected, 194 (55%) showed predominant perifollicular repigmentation, of which a majority (127; 65.5%) were on systemic PUVA and 35 (18%) were on topical PUVA. Diffuse pigmentation was observed in 98 patches (27.8%) of which 66 (67.3%) were on topical steroids. Marginal repigmentation was seen in 15, of which the majority (80%) were on systemic PUVA and topical calcipotriol. Of the 28 total lesions showing marked repigmentation at 3 months, 22 lesions pigmented in a diffuse manner, 2 in a perifollicular pattern, and 4 showed a combined type of repigmentation. On follow-up, marginal repigmentation was the most stable (93.3%), followed by perifollicular (91.7%) and combined type (84.4%). Diffuse repigmentation was the least stable (78.5%). Psoralens predominantly exhibit a perifollicular pattern of repigmentation and steroids (topical/systemic), a diffuse type. The speed of repigmentation is much faster when initial repigmentation is of the diffuse type as compared with follicular repigmentation. The marginal and perifollicular repigmentation is more stable than the diffuse type of repigmentation.     

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.     

Narrow-band UVB311 nm vs. broad-band UVB therapy in combination with topical calcipotriol vs. placebo in vitiligo

BACKGROUND: Recently, it has been shown that UVB phototherapy may be more effective than UVA in the treatment of vitiligo. Currently, however, no studies have compared the efficacy of UVB311 nm and broad-band UVB therapy. Calcipotriol has recently been reported to be effective adjunctive treatment for vitiligo, enhancing the efficacy of 8-methoxypsoralen plus UVA (PUVA) therapy. METHODS: Ten patients were enrolled in the study; nine completed the 12 months of therapy. The upper part of the body was treated twice weekly with UVB311 nm and the lower part with broad-band UVB. Calcipotriol was applied onto the vitiligo lesions of the right side of the body and placebo on the left side. Repigmentation was documented by photography, planimetry, and Vitiligo Disease Activity (VIDA) score. The quality of life was measured by the Dermatology Life Quality Index (DLQI). RESULTS: After 7-16 weeks, six of the nine patients showed initial repigmentation on the side treated with UVB311 nm. After 6 months of treatment, none of the patients showed repigmentation on the areas treated with broad-band UVB, which prompted us to apply UVB311 nm all over the body. At the end of 12 months, two patients showed > 75% repigmentation, two showed 51-75%, two showed 26-50%, and three showed 0-25%. In all patients with progressive vitiligo (seven of the nine patients), disease activity was stopped. Remarkably, vitiligo lesions treated with calcipotriol initially showed delayed repigmentation compared with control areas; however, there was no therapeutic difference between calcipotriol and placebo, both in combination with UVB311 nm, by the end of the study. The DLQI score improved significantly by an average of 28%. Conclusion UVB311 nm therapy was effective in the treatment of vitiligo, whereas broad-band UVB had no effect. Combination with calcipotriol ointment was not superior to UVB311 nm monotherapy. The quality of life significantly improved with narrow-band UVB311 nm phototherapy.     

Treatment of vitiligo by topical calcipotriol

OBJECTIVE: Evaluation of the efficiency of topical calcipotriol monotherapy in vitiligo. MATERIALS AND METHODS: This was a prospective, right/left comparative, open study at the Dermatology Department at the University Hospital in Nice, France. Twenty-four patients with localized or generalized vitiligo with symmetrical lesions were included. The main outcome measure was the evaluation of the percentage of repigmentation in treated target lesions and untreated control lesions for each patient. RESULTS AND CONCLUSIONS: Topical calcipotriol in monotherapy is not an effective treatment of vitiligo.     

A comparative study on the use of fractional CO2 laser with tacrolimus or calcipotriol or narrow band ultraviolet‐B in treatment of stable nonsegmental vitiligo

Conventional methods of treatment for vitiligo are often unsatisfactory to the patients and time consuming, new treatment modalities are needed. This study was conducted to evaluate the efficacy and safety of fractional carbon dioxide (CO₂) laser therapy followed by narrow band ultraviolet‐B (NB‐UVB) phototherapy, topical tacrolimus or topical calcipotriol on stable nonsegmental vitiligo. Thirty patients with stable nonsegmental vitiligo were evaluated. All patients were subjected to three sessions of fractional CO₂ laser 1 month apart. Patients were divided into three groups (each group 10 patients). Group (A) treated with tacrolimus ointment twice daily for 3 months, group (B) treated with calcipotriol ointment twice daily for 3 months, and group (C) treated with NB‐UVB twice weekly for 3 months. Outcomes were evaluated by calculating vitiligo area scoring index (VASI) score change, percentage of repigmentation, patient satisfaction, and adverse effects. There was a statistical significant decrease in VASI score after treatment in the three groups. The VASI change and % of regimentation was higher in group (C) treated by laser and NB‐UVB and this was significantly higher than group (B) treated with laser and calcipotriol. Otherwise, there was no statistical significant difference between other treatment groups. In concluion, NB‐UVB phototherapy, topical tacrolimus, or topical calcipotriol in combination with fractional CO₂ laser could be used effectively and safely as an alternative modality for treatment of vitiligo. The combination of fractional CO₂ laser and NB‐UVB was found to be more effective.     

Calcipotriol and PUVA as treatment for vitiligo

We performed a prospective study to evaluate efficacy of the combination of calcipotriol and psoralen plus ultraviolet A (PUVA) in the treatment of vitiligo. Twenty-three patients with essentially bilateral symmetrical lesions of vitiligo were included. Calcipotriol (0.005 %) ointment was applied twice daily over the right side of the body, and the other side was not treated. PUVA was performed three times per week. All patients received at least forty five sessions of PUVA. Patients were evaluated clinically and photographed all fifteen weeks. At the fifteenth session, 69 percent of the patients had minimal to moderate improvement on the calcipotriol side compared to 52 percent on the PUVA-only side (p = 0.015). At the forty-fifth session, 52 percent showed marked improvement on the calcipotriol side compared to 30 percent on the PUVA-only side (p = 0.13), with more intense repigmentation on calcipotriol-treated areas. Treatment was well tolerated, and no adverse effect was noted. This combination was an effective treatment for vitiligo, especially in initiating repigmentation.     

Calcipotriene and corticosteroid combination therapy for vitiligo

Corticosteroids and photochemotherapy, using a combination of psoralen and ultraviolet A (PUVA) exposure, are the most widely prescribed therapies for vitiligo. These treatments are not uniformly effective and many patients have inadequate responses. Calcipotriene has been shown to be effective in adults and children with psoriasis when used as monotherapy and in combination with corticosteroids and phototherapy. We hypothesized that since the mechanisms of action for calcipotriene and corticosteroids are different, patients may develop more repigmentation with a combination of the two agents, while decreasing the side effects from both agents. Twelve patients with vitiligo (average age 13.1 years) were advised to use topical corticosteroids in the morning and topical calcipotriene in the evening. Of the 12 patients, 83% responded to therapy, with an average of 95% repigmentation by body surface area. Four of the patients who responded had previously failed trials of topical corticosteroids alone. All of the patients in this group had repigmentation. Eyelid and facial skin responded best to this therapy. None of the patients had adverse reactions to the treatment. Our results show that topical calcipotriene in combination with corticosteroids can repigment vitiligo, even in those patients who were previous topical corticosteroid failures.     

Narrowband ultraviolet B radiation therapy for recalcitrant vitiligo in Asians

BACKGROUND: Narrowband ultraviolet B (NBUVB) has recently been reported to be effective therapy for vitiligo. However, reports on its efficacy in recalcitrant vitiligo are lacking. OBJECTIVE: Our objective was to assess the efficacy of NBUVB in patients with vitiligo who did not respond to either topical therapy or oral psoralen plus ultraviolet A (PUVA). METHOD: This was a retrospective analysis of patients with vitiligo who were treated with NBUVB from February 1998 to January 2001. They received NBUVB treatment 2 times per week, with an initial dose of 100 mJ/cm(2). The dose was increased by 10% to 20% per treatment for 20 treatments. The dose was then increased by 2% to 5% per treatment until 50% repigmentation was observed or persistent erythema developed. The treatment was continued until maximum repigmentation was achieved. The treatment was terminated if the patient showed less than 25% improvement after 40 to 50 exposures. RESULTS: There were 60 patients: 22 men and 38 women, aged 11 to 61 years. The mean duration of vitiligo was 8.2 +/- 7.1 years. There were 53 cases of generalized and 7 cases of localized vitiligo. The lesions covered from less than 5% to 50% of body surface. Twenty-five patients were skin type III, 33 patients were skin type IV, and 2 patients were skin type V. Every case had been previously treated with topical steroid with or without topical psoralen with solar light exposure. Thirty-six patients (60%) had been treated with oral PUVA before NBUVB therapy. After NBUVB treatment, 25 of 60 patients (42%) achieved more than 50% repigmentation on face, trunk, arms, and legs. However, hand and foot lesions showed less than 25% repigmentation in all cases. There was no significant difference between the responders and nonresponders in age, sex, duration of diseases, and skin type. The response rate of patients who had not been previously treated with PUVA was significantly higher than that of patients who had been previously treated with PUVA (67% vs 36%, P =.003). CONCLUSION: This retrospective, open study demonstrated that NBUVB therapy was effective in 42% of Asian patients with recalcitrant vitiligo without serious side effect. The only clinical parameter that could differentiate nonresponders from responders was previous exposure to PUVA.     

Calcipotriol/Betamethasone Dipropionate

The two-compound product containing calcipotriol 50 microg/g plus betamethasone dipropionate 0.5 mg/g (Dovobet, Daivobet) [referred to here as calcipotriol/betamethasone dipropionate], is a topical treatment for psoriasis vulgaris, combining a vitamin D analog and a corticosteroid. For most adult patients with psoriasis vulgaris on the trunk and limbs, up to 4 weeks of therapy with calcipotriol/betamethasone dipropionate provides an effective and well tolerated treatment. In clinical trials, patients with a mean baseline psoriasis area and severity index (PASI) of 9.5-10.9 experienced a mean 65.0-74.4% PASI improvement within 4 weeks, significantly better than improvements with calcipotriol 50 microg/g monotherapy, betamethasone dipropionate 0.5 mg/g monotherapy, or placebo. In addition, in 6.4%-20.1% of patients, lesions cleared. In patients who were subsequently treated with calcipotriol maintenance therapy, benefits were retained for at least 4 weeks. The safety of calcipotriol/betamethasone dipropionate in patients treated for up to 1 year was generally good; fewer than 5% of patients experienced adverse events possibly associated with long-term corticosteroid use.     

Effect of topical calcipotriol, betamethasone dipropionate and their combination in the treatment of localized vitiligo

BACKGROUND: Treatment of vitiligo is a challenge. Steroids are known to be effective but are associated with serious adverse effects. Many uncontrolled studies have shown calcipotriol to be a promising therapeutic modality in vitiligo. OBJECTIVE: To conduct a randomized trial to evaluate the effect of topical calcipotriol ointment (0.005%) and betamethasone dipropionate (0.05%) cream, given alone or in combination, in treatment of localized vitiligo. METHODS: Forty-nine patients with vitiligo affecting 5% of their skin were recruited. Patients were randomized into three groups. Group I patients were treated with betamethasone dipropionate (0.05%) cream twice daily. Group II patients were treated with calcipotriol ointment (0.005%) twice daily, and group III with betamethasone dipropionate (0.05%) in the morning and calcipotriol (0.005%) in the evening. RESULTS: Forty-five patients completed the study period of 3 months with 15 patients in each group. No patient achieved excellent (> 75%) pigmentation. Marked (50% to 75%) repigmentation was observed in 2 (13.3%), 1 (6.7%) and 4 (26.7%) patients in groups I, II and III, respectively. Moderate (25-50%) repigmentation was observed in 7 (46.7%), 5 (33.3%) and 7 (46.7%) patients in groups I, II and III, respectively. Patients with < 25% pigmentation were termed as minimal pigmentation or no response. The mean time for initial pigmentation to appear was 9.04 +/- 2.0 weeks in group I, 10.18 +/- 1.6 weeks in group II and 5.17 +/- 2.4 weeks in group III (P < 0.01). The acquired pigmentation in the lesions was more stable in group III as compared with patients in groups II and I (P < 0.01). Side-effects in the form of atrophy and lesional burning sensations were more common in group I when compared with groups II and III (P < 0.05). CONCLUSION: Combined therapy appeared to give a significantly faster onset of repigmentation along with better stability of the achieved pigmentation and with lesser number of side-effects.     

The efficacy of calcipotriol + acitretin combination therapy for psoriasis: comparison with acitretin monotherapy

Background: Although the use of an oral retinoid as monotherapy is an effective treatment for psoriasis, it is usually used in combination with other topical or systemic therapies including topical corticosteroids, UVB phototherapy, psoralens + UVA (PUVA) chemotherapy and cyclosporine mainly in an effort to reduce or avoid adverse effects. Aim: To compare the efficacy of the calcipotriol + acitretin combination treatment with acitretin alone over a long period in Korean patients with psoriasis. Methods: A randomized, bilateral paired comparison was conducted involving 40 patients with psoriasis who received calcipotriol + acitretin combination therapy and 20 psoriasis patients who received acitretin alone. The initial dose of acitretin was 10 or 20 mg/day. The dose was adjusted at each visit (2, 4 and 6 weeks) in steps of 10mg according to patient responsiveness and adverse effects. The maximum dose was 40 mg/day. The treatment duration for all patients ranged from 4–52 weeks. After 12 weeks, the efficacy of therapy, according to Psoriasis Area and Severity Index scores, was assessed. At the end of the study (52 weeks), we selected patients who had achieved complete clearance and compared the duration of treatment and total dose of acitretin used in both groups. Results: After 12 weeks, 16 patients (40%) achieved complete clearance in the calcipotriol + acitretin group and 3 patients (15%) in the acitretin monotherapy group (p < 0.05). After 52 weeks, 24 patients (60%) in the calcipotriol + acitretin group and 8 patients (40%) in the acitretin monotherapy group achieved complete clearance. The duration of treatment and total dose of retinoid required to achieve clearance were slightly lower in the calcipotriol + acitretin combination group, however, this was not statistically significant. With the exception of liver enzyme elevation (which affected more patients in the acitretin monotherapy group than in the combination group), adverse effects were not significantly different. Discussion: Our results showed that calcipotriol might enhance the clinical outcome of systemic acitretin therapy. More large, well-controlled, long-term studies need to be conducted to determine whether there is indeed a beneficial effect of the addition of calcipotriol to acitretin treatment and whether this effect is maintained over long-term periods.     

Combination TL01 ultraviolet B phototherapy and topical calcipotriol for psoriasis: a prospective randomized placebo-controlled clinical trial

BACKGROUND: Previous studies have demonstrated the ultraviolet (UV)-sparing effect of combining topical calcipotriol with broadband UVB in the treatment of psoriasis. OBJECTIVES: To determine if the combination of narrowband TL01 UVB phototherapy and topical calcipotriol produces the same UVB-sparing effect. METHODS: This was a randomized, placebo-controlled, blinded clinical trial. Fifty psoriasis patients were recruited, 25 of whom were randomized into the active group who received TL01 phototherapy together with twice-daily application of calcipotriol cream 50 microg g(-1). The control group received TL01 phototherapy and twice-daily application of a topical emollient as placebo. TL01 phototherapy was given three times per week starting at 70% minimal erythema dose with 20% increments as tolerated for up to approximately 20 sessions. Patients were assessed using the Psoriasis Area and Severity Index (PASI) and Psoriasis Disability Index (PDI). They were evaluated at treatment sessions 8, 14 and 20, and followed up at 5 and 10 weeks post-treatment. Statistical analysis was performed using a two-tailed t-test. RESULTS: There were no significant differences in demographic characteristics and baseline PASI and PDI scores between the two groups. The mean PASI score declined significantly (P < 0.01) for both groups after treatment. The difference in mean PASI score reduction from baseline between the two groups was only significant during the first eight sessions, with a net reduction of 3.6 (95% confidence interval 1.0-6.2, P = 0.008) in the active group relative to the control group. The mean PDI score declined significantly (P < 0.05) for both groups, but there was no statistical difference in mean PDI score reduction between the two groups (P = 0.8) at the end of treatment. The mean cumulative UVB dose for the active group was significantly lower (P < 0.02) at 16 204 mJ cm-2 compared with 21 082 mJ cm-2 for the control group. CONCLUSIONS: We conclude that combining TL01 phototherapy with topical calcipotriol cream has a UVB-sparing effect.     

Open trial of topical tacalcitol [1 alpha 24(OH)2D3] and solar irradiation for vitiligo vulgaris: upregulation of c-Kit mRNA by cultured melanocytes

Vitiligo vulgaris is a common skin disease, however some cases show poor clinical responses to topical steroid ointment or PUVA therapy. Such regimens are generally avoided in the treatment of facial lesions or in pediatric cases because of the undesirable side effects. To confirm the excellent response to combination therapy with topical vitamin D3 ointment and solar irradiation for vitiligo achieved in the initial patients, we conducted an open trial on other patients, most of whom had poor clinical responses to the prior therapies. Fifteen patients (9 men and 6 women) with vitiligo vulgaris were enrolled in this study. Each patient was instructed to sunbathe for 30 minutes within 1 hour after topical application of the tacalcitol [1 alpha 24(OH)(2)D(3)] ointment or cream to the skin lesions every day. Six of 15 patients showed a fair and excellent clinical response to the combination therapy (more than 30% clearance of the vitiligo). The clinical effect was more apparent in patients with a history of less than 5 years of vitiligo (4 of 6 cases) in contrast to those with a history of more than 5 years (2 of 9 cases). In vitro experiments revealed that tacalcitol upregulated the expression of c-Kit mRNA by melanocytes irradiated with linear polarized infrared, UVA or short period solar irradiation. These results suggest that combination therapy with topical vitamin D(3) ointment and solar irradiation can be used as an alternate therapy for vitiligo vulgaris.     

Topical calcipotriol plus oral fumaric acid is more effective and faster acting than oral fumaric acid monotherapy in the treatment of severe chronic plaque psoriasis vulgaris

BACKGROUND: Calcipotriol is an established topical therapy for psoriasis vulgaris. OBJECTIVE: This study aimed to investigate whether the addition of calcipotriol to fumaric acid ester (FAE) monotherapy had an additive efficacy and an FAE-sparing effect in patients with severe plaque psoriasis. METHODS: This multicentre, randomised, double-blind, vehicle-controlled study included 143 patients for up to 13 weeks treatment. Group A received FAE tablets (Fumaderm) with an increasing daily dosage from 105 to 1,075 mg + ointment vehicle. Group B received FAE tablets + calcipotriol ointment (50 microg/g). Ointments were applied twice daily. Clinical response was assessed using percentage changes in the Psoriasis Area and Severity Index (PASI), from baseline to treatment end. RESULTS: The mean percentage change in the PASI was -76.1% in group B and -51.9% in group A, the difference between treatments was -24.2% (95% CI from -34.2 to -14.2%; p < 0.001). Group B responded more rapidly to treatment. Investigators' and patients' overall efficacy assessments were significantly more favourable for group B (p < or = 0.001). Group B was prescribed less FAE than group A. This difference was greatest at the last visit (mean daily dose 529 and 685 mg, respectively; p = 0.006). Overall adverse events in the two groups were similar. CONCLUSION: This study shows that the combination of calcipotriol and FAEs is significantly more effective and faster acting than FAE monotherapy in the treatment of severe plaque psoriasis. The combination has a slight FEA-sparing effect and therefore a superior benefit/risk ratio.     

Rationale for use and clinical responsiveness of hexafluoro-1,25-dihydroxyvitamin D3 for the treatment of plaque psoriasis: a pilot study

BACKGROUND: Vitamin D analogues are useful in topical therapy of psoriasis. OBJECTIVES: To evaluate the effect of hexafluoro-1,25-dihydroxyvitamin D3 (F6-1,25(OH)2D3) in treatment of psoriasis. METHODS: Fifteen patients with plaque-type psoriasis were enrolled in a single centre double-blind, right/left comparison, placebo-controlled study, and received 0.1 g of petrolatum containing 5 microg of F6-1,25(OH)2D3 or 0.1 g of petrolatum (placebo) for 3 months. After completion of this double-blind study, a subset of these patients (n = 12) applied F6-1,25(OH)2D3 ointment (50 microg g-1 of petrolatum) to all their lesions (total area, 100-5000 cm2, mean area: 3300 m2) for 2 months as a single application at night. RESULTS: The mean severity score in the right/left-sided controlled topical F6-1,25(OH)2D3 (50 microg g-1) therapy group showed a decrease of 85%. In contrast, the mean severity score for the placebo-treated areas showed a decrease of 45% (P < 0.001). In the 12 patients who subsequently applied F6-1,25(OH)2D3 (50 microg g-1) ointment to all of their lesions, 91.6% showed moderate to excellent improvement. The mean Psoriasis Area and Severity Index score decreased by 44.9% (from 33.6 +/- 15 to 18.5 +/- 13). No effect on calcium homeostasis was noted. Adverse events included mild irritation in two patients that resolved during therapy. CONCLUSIONS: Topical F6-1,25(OH)2D3 is a safe and effective once a day treatment for psoriasis.