钙泊三醇倍他米松软膏联合卡泊三醇软膏序贯治疗寻常型银屑病疗效评价

目的：评价钙泊三醇倍他米松软膏联合卡泊三醇软膏治疗寻常型银屑病的临床疗效。方法：30例银屑病患者全身左右侧皮损随机分为治疗组或对照组。治疗组外用钙泊三醇倍他米松软膏和卡泊三醇软膏;对照组外用卡泊三醇软膏。治疗第2、4、8周末进行疗效评价。结果：治疗2、4、8周后治疗组有效率（53.33%、70%和86.67%）均明显高于对照组（30%、46.67%和66.67%）,组间差异均有统计学意义（P〈0.05）。结论：钙泊三醇倍他米松软膏联合卡泊三醇软膏治疗寻常型银屑病疗效较单独使用卡泊三醇好。     

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.     

Consistency of data in six phase III clinical studies of a two-compound product containing calcipotriol and betamethasone dipropionate ointment for the treatment of psoriasis

BACKGROUND: Calcipotriol and betamethasone dipropionate are both proven products in the topical treatment of psoriasis. The efficacy and tolerability of a new ointment containing these two compounds has been assessed in six phase III clinical studies. OBJECTIVE: To compare the results obtained in the clinical studies of the new calcipotriol/betamethasone dipropionate ointment. METHODS: A total of 6050 patients with psoriasis took part in the six randomized, double-blind studies. The two-compound product was compared with each of the active constituents, either in the new ointment vehicle or in the marketed formulation. RESULTS: After 4 weeks of treatment the mean reduction in the Psoriasis Area and Severity Index (PASI) ranged from 65 to 74% with the two-compound product applied once or twice daily, from 46 to 59% with calcipotriol alone and from 57 to 63% with betamethasone dipropionate alone. The tolerability profile of the two-compound product was similar to betamethasone dipropionate monotherapy and better than calcipotriol alone. CONCLUSION: The new two-compound product containing calcipotriol and betamethasone dipropionate was found to consistently provide rapid, highly effective treatment of psoriasis vulgaris.     

Significant one week efficacy of a calcipotriol plus betamethasone dipropionate scalp formulation

Background A two‐compound scalp formulation containing calcipotriol (50 μg/g) and betamethasone (0.5 mg/g; as dipropionate) (Xamiol^®, Taclonex Scalp^®) has been shown to be an effective and safe treatment for scalp psoriasis. Objective The aim of this study was to investigate the clinical efficacy of the two‐compound scalp formulation after 1 week of treatment. Methods Pooled data from two large pivotal phase III trials with 2920 patients receiving once‐daily treatment for up to 8 weeks with either the two‐compound scalp formulation (n = 1108), betamethasone dipropionate (n = 1118), calcipotriol (n = 558), or the vehicle (n = 136) were analysed. Results The percentage of patients who had ‘absent’ or ‘very mild’ disease according to Investigator’s Global Assessment after 1 week of treatment was significantly higher with the two‐compound scalp formulation (30.6%) compared to betamethasone (24.1%; P < 0.001), calcipotriol (10.0%; P < 0.001) or vehicle (6.9%; P < 0.001). Conclusion This data indicates that the two‐compound scalp formulation demonstrated significant efficacy already after 1 week, with a faster onset of effect than either of the individual components in the same vehicle, in the treatment of scalp psoriasis.     

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.     

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 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.     

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.     

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.     

钙泊三醇软膏治疗稳定期斑块型银屑病20例临床观察

银屑病是一种顽固性皮肤病，其病理改变主要为表皮过度增生及不完全分化，我科自１９９６年４月—１９９７年１月共对２０例银屑病患者外用钙泊三醇（大力士）软膏治疗，效果较满意，现报告如下。临床资料本组２０例男１３例，女７例，年龄３０—６０岁，病程２—３０年，...     

钙泊三醇倍他米松软膏治疗斑块状银屑病疗效评价

目的:评价钙泊三醇倍他米松软膏治疗斑块状银屑病的临床疗效。方法:治疗组(70例)给予钙泊三醇倍他米松软膏外用,对照组(56例)给予钙泊三醇软膏外用和5%松馏油软膏封包。结果:6周后治疗组有效率为88.57%,对照组有效率为75.00%,不良反应发生率分别为10.00%和23.75%,差异均有统计学意义(均P0.05)。结论:钙泊三醇倍他米松软膏外用治疗斑块状银屑病有效且相对安全。     

Effective treatment and improvement of quality of life in patients with scalp psoriasis by topical use of calcipotriol/betamethasone (Xamiol®‐gel): results

Background: Quality of life of patients with scalp psoriasis is greatly impaired due to itch and scaling. To control the disease long‐term therapy is necessary and treatment success is greatly dependent on compliance. Patients and Methods: In a prospective, non‐interventional trial in German dermatological practices 721 patients with scalp psoriasis received Xamiol^® gel (calcipotriol 50 μg/g, betamethasone 0,5 mg/g) topically for 4 weeks. Severity was assessed by physician's global assessment (PGA) and quality of life by using a scalp‐specific questionnaire at the beginning of the study and after 4 weeks of treatment. Results: The mean disease severity of scalp psoriasis (PGA) improved from 4.26 to 2.49 (–41.8 %, p < 0.0001) during 4 weeks of treatment and quality of life improved from 10.57 to 3.22 (–69.5 %, p < 0.0001). Among patients with pre‐treatment 89.5 % of patients and 87.9 % of dermatologists judged treatment response to Xamiol^® gel as better/much better compared to previous therapy. Tolerability of Xamiol^® gel was rated good/very good by 98 % of dermatologists and patients, respectively. The use of Xamiol^® gel was found easy/very easy by 90.4 % of the patients. Conclusions: Due to the major improvement of quality of life and quick onset of improvement together with the high acceptance by the patients Xamiol^® gel may be regarded as the topical treatment of choice for scalp psoriasis.     

脉冲染料激光联合卡泊三醇倍他米松乳膏治疗甲银屑病一例并文献复习

甲银屑病的局部药物和物理治疗是目前治疗轻、中度甲银屑病研究的方向。本文报道595nm脉冲染料激光(Pulsed dye laser, PDL)联合卡泊三醇倍他米松乳膏治疗甲银屑病1例,并对PDL治疗甲银屑病的相关文献进行复习。     

A novel vehicle for the treatment of psoriasis

This study evaluates the effectiveness of the topical use of an aerosol foam combination of calcipotriol 50 μg/g plus betamethasone dipropionate 0.5 mg/g (Cal/BD foam, Enstilar®) in adults with moderate plaque psoriasis. A total of 120 male and female adult psoriasis patients (53.3% male) from two Italian dermatological units were enrolled in an 8‐week prospective study performed between November 2018 and January 2019. Psoriasis Area and Severity Index (PASI) was evaluated at baseline (T0) and 4 weeks (T4) of daily application, and a further evaluation was carried out 4 weeks after suspension (T8). Furthermore, the Dermatology Life Quality Index (DLQI) was evaluated at baseline and after 4 weeks of treatment (T4). At baseline, patients presented a mean PASI of 7 (7.0 ± 2.1). After 4 weeks (T4) of once‐daily application, an important improvement in PASI was observed (1.1 ± 0.3). At Week 4, DLQI was reduced by 5.5 points from baseline (mean: 12 ± 3.1 at T0 vs 6.5 ± 1.8 at T4). Four weeks after suspension (T8), mean PASI was 2.6 ± 1.9, which was stable compared to the previous evaluation; only 8.3% of the treated patients showed worsening of plaque psoriasis. This study suggested that the Cal/BD aerosol foam is an effective topical therapy to treat plaque psoriasis.     

A phase IIIb,multicentre, randomized,double‐blind,vehicle‐controlled study of the efficacy and safety of adalimumab with and without calcipotriol/betamethasone topical treatment in patients with moderate to severe psoriasis: the BELIEVE study

Background Data are lacking on the use of topical therapies in combination with tumour necrosis factor blockers for the treatment of psoriasis. Objectives To assess the efficacy and safety of adalimumab (ADA) with topical calcipotriol/betamethasone (C/B) in patients with psoriasis resembling those treated in routine clinical practice. Methods A 16‐week, randomized, vehicle‐controlled trial was conducted in patients with moderate to severe psoriasis and previous failure, intolerance or contraindications to two or more systemic treatments. All patients received ADA (80 mg, week 0; 40 mg every other week, weeks 1–15) in addition to either topical C/B or drug‐free vehicle applied once daily for 4 weeks, and as needed thereafter. The primary endpoint was 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75) at week 16. Results A total of 730 patients received either ADA + C/B (n = 366) or ADA + vehicle (n = 364). PASI 75 response was initially higher with the combination therapy [14·8% for ADA + C/B vs. 5·8% for ADA + vehicle at week 2 (P < 0·001); and 40·7% vs. 32·4%, respectively, at week 4 (P = 0·021)]. After week 4, the trend was towards a higher response with ADA monotherapy, with no statistical difference in the PASI 75 response at week 16 (64·8% for ADA + C/B vs. 70·9% for ADA monotherapy, P = 0·086). Safety findings were consistent with previous ADA trials. Conclusions ADA + C/B resulted in more rapid and higher efficacy within the first 4 weeks; thereafter, the trend was towards a higher response with ADA monotherapy. There was no statistical difference in the PASI 75 response at week 16. Both treatment regimens were well tolerated.     

他扎罗汀倍他米松乳膏治疗斑块状银屑病后两种延长治疗方案的疗效和安全性的多中心临床观察

目的 探索使用他扎罗汀倍他米松乳膏治疗斑块状银屑病4周后有效但未达基愈患者的后续用药方案.方法 本研究采用多中心、随机、开放、平行、对照设计.232例完成0.05％/0.05％他扎罗汀倍他米松乳膏4周治疗,银屑病面积与严重性指数(PASI评分)改善在50％ ～ 90％但未达基愈的斑块状银屑病受试者,在第5周时1:1随机...     

钙泊三醇倍他米松软膏在银屑病治疗中的应用

钙泊三醇倍他米松软膏是卡泊三醇（50 μg/g）和倍他米松（0.5 mg/g）的复方制剂,两种活性成分通过不同的细胞受体发挥协同互补的药效学活性［１］。由于卡泊三醇和倍他米松保持稳定所需的pH值不同,卡泊三醇需要碱性环境来保持稳定性,而倍他米松需要的是酸性环境,因此两者混合时不能相容［2］。为此研发人员开发出了一种独特的、稳定的赋形剂克服两者不能相容的障碍,最终形成含有稳定活性成分的制剂。目前钙泊三醇倍他米松软膏已被应用于银屑病等皮肤病治疗中,我们概述近10年钙泊三醇倍他米松软膏在银屑病治疗中的应用……     

不同浓度配比的他扎罗汀倍他米松乳膏治疗寻常型银屑病的疗效观察

【摘要】 目的 探索不同浓度配比的他扎罗汀倍他米松乳膏治疗寻常型银屑病的疗效和安全性,筛选人体使用的最佳药物配比浓度。方法 采用多中心、随机、双盲、多剂量对照研究设计,2008年12月至2009年4月,中国医学科学院皮肤病医院等7个研究中心共纳入180例寻常型银屑病患者,按1∶1∶1∶1∶1比例随机分配进入4个试验组（他扎罗汀/二丙酸倍他米松浓度配比分别为0.025%/0.025%、0.05%/0.025%、0.025%/0.05%、0.05%/0.05%,简称为试验1、2、3和4组）和对照组（基质）,每日用药1次,持续4周。用药后第1、2、4周分别评价各组药物的疗效和安全性。多组计量资料比较采用方差分析和LSD-t检验,多组分类资料的比较用χ2检验或Fisher精确概率检验,采用CMH法分析各组的银屑病皮损面积和严重程度指数（PASI）反应率数据。结果 用药4周,试验1、2、3、4组和对照组改善达PASI75的患者分别为11例（30.56%）、12例（33.33%）、12例（33.33%）、19例（52.78%）和2例（5.56%）,各试验组达PASI75的患者比例均显著高于对照组（均P < 0.012 7）;此外,试验药物1、2、4组达PASI90的患者比例亦显著高于对照组（均P < 0.012 7）。用药4周,试验1、2、3、4组PASI评分下降率分别达59.52% ± 26.79%、57.19% ± 31.98%、56.85% ± 30.46%和68.21% ± 37.20%,均显著高于对照组（20.07% ± 28.55%）（LSD-t = 5.36、5.05、5.00、6.55,均P < 0.001）。试验4组的综合疗效表现更突出。试验1、2、3、4组和对照组药物耐受性良好,分别发生不良反应11例（30.56%）、8例（22.22%）、2例（5.56%）、4例（11.11%）和2例（5.56%）,试验1组不良反应发生率显著高于对照组（P = 0.012）,试验2、3、4组与对照组比较差异无统计学意义（均P > 0.05）。结论 0.05%/0.05%他扎罗汀倍他米松乳膏可作为后继治疗寻常型银屑病临床研究的推荐配比浓度。