0.03%他克莫司软膏治疗儿童特应性皮炎的疗效观察

目的:观察外用0.03%他克莫司软膏治疗儿童特应性皮炎的临床疗效和安全性。方法:将60例患者随机分为2组,每组30例,分别对两组患者外用0.03%他克莫司软膏和赋形剂,每天1次,疗程为3周。比较两组疗效。结果:他克莫司软膏组和外用赋形剂的对照组的有效率分别为85.7%和36.7%,两组比较差异有统计学意义(2=12.58,P0.05)。治疗组中7.14%的患者局部有刺激反应,症状于1周后消失。结论:他克莫司软膏用于治疗儿童特应性皮炎疗效明显,个别病例出现局部瘙痒不良反应。     

他克莫司软膏治疗特应性皮炎疗效观察及患者生活质量评价

目的:评价0.03%和0.1%他克莫司软膏治疗中国成人和儿童中、重度特应性皮炎(AD)患者后其生活质量的改善情况。方法:采用多中心、双盲、随机、赋形剂平行对照的方法对327例中、重度AD患者给予0.03%和0.1%他克莫司软膏治疗3周,在治疗前、后采用皮肤病学生活质量指数量表对患者进行生活质量评价。结果:3周后成人组总体生活质量评分及症状、日常活动和休闲3个方面评分的改善有统计学差异(P<0.05)。儿童组总体生活质量评分及症状、休闲、学校、假期、日常活动、睡眠和治疗的影响各方面改善均有统计学差异(P<0.05)。幼儿组各方面的改善无统计学差异(P>0.05)。结论:0.03%和0.1%他克莫司软膏治疗中国成人和儿童中、重度AD患者3周后,成人及儿童(>4岁)患者的生活质量均有显著改善。     

他克莫司软膏治疗儿童特应性皮炎的临床疗效评价

特应性皮炎(AD)又名异位性皮炎、遗传过敏性皮炎,是指具有明显体质和家族遗传特点,处于自然发生的过敏状态,当再接触诱发因素时而发生的过敏性疾病,多起病于婴儿期或儿童期.我科自2007年8月-2008年10月应用0.03%他克莫司软膏治疗儿童AD 72例,取得了满意的疗效,现将临床观察结果报告如下.     

他克莫司软膏治疗儿童特应性皮炎疗效和依从性评价

目的评价0.03%他克莫司软膏治疗儿童轻、中度特应性皮炎(AD)的疗效和安全性及依从性。方法采用随机双盲平行对照方法将入选的60例AD患儿分为对照组和试验组,每组各30例。试验组患儿外用0.03%他克莫司软膏,对照组患儿外用凡士林乳膏、夫西地酸软膏,两组均连续治疗3周,采用AD评分评价疗效。结果试验组患儿瘙痒、症状积分下降明显大于对照组(P<0.05);症状控制时间和临床治愈用药时间明显短于对照组(P<0.05)。试验组和对照组治疗的有效率分别为93.3%和69.5%,两组疗效比较差异有统计学意义(P<0.05);试验组和对照组依从率分别为100%和76.7%,两组比较差异具有统计学意义(P<0.05)。结论 0.03%他克莫司软膏治疗儿童轻、中度AD安全而有效,患儿依从性良好。     

他克莫司软膏治疗儿童特应性皮炎疗效和安全性研究

目的评价0．03％他克莫司软膏治疗儿童中、重度特应性皮炎的疗效和安全性。方法采用多中心．随机、双肓、赋形剂平行对照的临床研究,受试者每日2次外搽0.03％他克莫司软膏或赋形剂,疗程3周,于治疗前及治疗后第1、2、3周各随访1次,进行疗效和安全性评价。结果 5个中心共有139例中、重度儿童特应性皮炎患者纳入疗效分析。治疗结束时,0.03％他克莫司软膏组治疗有效率为84.6％,明显高于赋形剂组的29.0％(P<0．001)。其他疗效评估指标包括湿疹面积与严重度指数、皮损受累面积百分比、症状/体征总评分、研究者对治疗临床反应总评、患者／监护人对瘙痒自我评分。在治疗后第1、2、3周0.03％他克莫司软膏组明显优于赋形剂组,且均于治疗后第1周始即明显改善(P=0.002～P<0．001)。0.03％他克莫司软膏组药物相关不良反应发生率为32.9％,赋形剂组为37.7％,主要表现为皮肤灼热、瘙痒／瘙痒加重或刺痛等局部刺激反应。结论 0.03％他克莫司软膏对治疗儿童特应性皮炎具有良好的疗效和安全性。     

他克莫司软膏治疗特应性皮炎疗效和安全性评价

目的：系统评价外用他克莫司软膏治疗特应性皮炎（AD）的临床疗效及安全性。方法：计算机检索Cochrane图书馆、Cochrane协作网皮肤病专业试验数据库、Medline、OVID数据库和中文生物医学期刊数据库．收集所有外用他克莫司与安慰剂、氢化可的松的随机对照试验（RCT）,对其进行系统评价。结果：共纳入RCT13篇论文,共5320例患者。Meta分析治疗有效率,结果显示：0．03％和0．1％他克莫司在12周疗程内疗效均优于安慰剂;0．03％和0．1％他克莫司3周疗程均高于1％醋酸氢化可的松,均不高于0．1％丁酸氢化可的松,但0．1％他克莫司在6个月疗程时疗效优于合用1％醋酸氢化可的松（用于头面部）和0．1％丁酸氢化可的松（用于躯干和四肢）;0．1％他克莫司在疗程12周内疗效优于0．03％他克莫司。最常见的不良反应是皮肤刺激和烧灼感。结论：他克莫司软膏治疗AD效果优于安慰剂及弱效糖皮质激素,长期疗效可能超过中强效糖皮质激素。目前外用他克莫司临床上是安全的,但尚需进行更多长期的RCT。     

他克莫司软膏治疗成人特应性皮炎

目的研究他克莫司软膏治疗成人特应性皮炎(AD)的疗效与安全性.方法采用随机、双盲、赋形剂对照临床研究方法,将44例成人AD患者随机分为3组,按111比例分别接受0.1%(0.1%组)、0.03%(0.03%组)他克莫司软膏和赋形剂(赋形剂组)治疗.观察治疗第1、2和3周的临床疗效和不良反应.结果他克莫司软膏0.1%组和0.03%组的有效率分别为86.7%(13/15)和78.6%(11/14),均明显高于赋形剂组(42.9%,6/14),差异非常显著(P＜0.001).总体疗效比较0.1%组优于0.03%组,差异显著(P=0.043).治疗后第1、2、3周0.1%组和0.03%组的主要症状-体征指标平均值均明显低于赋形剂组,组间差异显著(P＜0.05～P＜0.001).治疗后患者的生活质量明显改善.药物相关不良反应主要为一过性局部刺激,但组间比较无统计学意义(P＞0.05),3组均未出现严重不良反应.结论他克莫司软膏治疗成人特应性皮炎安全有效.     

他克莫司软膏治疗儿童特应性皮炎的临床研究

目的　评价他克莫司软膏治疗儿童特应性皮炎 (AD)的疗效与安全性。方法　采用随机、双盲、赋形剂对照临床研究方法,将 36例儿童AD患者随机分为两组,按 1∶1比例分别接受 0. 03%他克莫司软膏或赋形剂治疗,观察治疗第 1, 2和 3周的临床疗效和不良反应。结果　0. 03%他克莫司软膏组有效率为 83. 3% (15 /18),明显高于赋形剂组的 27. 8% (5 /18),差异非常显著(P<0. 001);总体疗效比较,他克莫司软膏组亦优于赋形剂组 (P=0. 002);治疗后第 1,2, 3周患者的主要症状 /体征指标平均值均明显低于赋形剂组,组间差异显著(P<0.01~P<0. 05),治疗后患者的生活质量亦明显改善。药物相关不良反应主要表现为一过性局部刺激,组间比较差异无显著性 (P>0. 05)。两组患者均未出现严重不良反应。结论　0. 03%他克莫司软膏治疗儿童特应性皮炎安全有效。     

他克莫司软膏治疗成人特应性皮炎疗效和安全性研究

目的 评价0.1%和0.03%他克莫司软膏治疗成人中、重度特应性皮炎的疗效和安全性。方法 采用多中心、随机双盲、赋形剂平行对照的临床研究,受试者每日2次外搽0.1%或0.03%他克莫司软膏或赋形剂。疗程3周,于治疗前及治疗后第1、2、3周各访视1次,进行疗效和安全性评价。结果 6个中心共有211例中、重度特应性皮炎患者纳入疗效分析。治疗结束时,0.1%和0.03%他克莫司软膏组治疗有效率分别为88.4%和77.8%,均明显高于赋形剂组的30.0%(P<0.001)。治疗后第1、2、3周,0.1%和0.03%他克莫司软膏组湿疹面积与严重度指数、皮损受累面积百分比、症状/体征总评分、研究者对治疗临床反应总评、患者对瘙痒自我评分均明显优于赋形剂组,且多于治疗后第1周始即明显改善(P=0.002-P<0.001),0.1%他克莫司软膏组疗效优于0.03%他克莫司软膏组。0.1%和0.03%他克莫司软膏组药物相关性不良反应发生率分别为47.3%和40.0%,均高于赋形剂组的28.2%,主要表现为皮肤灼热、瘙痒/瘙痒加重或刺痛等局部刺激反应。结论 0.1%和0.03%他克莫司软膏对治疗成人特应性皮炎具有良好的疗效和安全性。     

0.03%他克莫司软膏治疗面部脂溢性皮炎临床疗效观察

目的探讨外用0.03%他克莫司软膏治疗面部脂溢性皮炎临床疗效和安全性。方法将78例患者随机分成两组,治疗组40例,外用0.03%他克莫司软膏2次/d;对照组38例,外用丁苯羟酸软膏。疗程均为4周。结果治疗组和对照组临床有效率分别为87.50%和60.53%,治疗组疗效优于对照组。治疗组7例局部出现刺激症状,均发生在用药后1周内。他克莫司组不良反应发生率高于丁苯羟酸组,但二者差异无显著性(P>0.05)。结论他克莫司软膏治疗面部脂溢性皮炎安全、有效。     

Twice‐weekly treatment with tacrolimus 0.03% ointment in children with atopic dermatitis: clinical efficacy and economic impact over 12 months

Background Rational healthcare decision‐making based on clinical and economic evidence is essential to provide the best possible care for patients with atopic dermatitis (AD). Objective To evaluate treatment outcomes, resource use and cost associated with twice‐weekly tacrolimus 0.03% ointment treatment vs. standard flare‐only therapy in children with moderate‐to‐severe AD. Methods In a pan‐European, Phase III multicentre randomized clinical trial, children with mild‐to‐severe AD were randomized to 0.03% tacrolimus ointment or vehicle twice weekly for 12 months. Disease flares were treated using open‐label tacrolimus 0.03% ointment twice daily. Clinical efficacy data were evaluated in a subgroup of 153 children with moderate‐to‐severe AD, with resource use data – collected prospectively using caregiver questionnaires – available from 146 children. Pooled costs of resource use were determined using German unit cost data. Direct and indirect costs were considered from third‐party payer, patient and caregiver, and societal perspectives. Results Twice‐weekly tacrolimus ointment reduced the number of flares compared with standard therapy (P < 0.001) and prolonged time to first flare (146 vs. 17 days, P < 0.001). Mean ± SD annual costs per patient for standard and twice‐weekly therapy respectively were €2002 ± 2315 vs. €1571 ± 1122 for severe AD and €1136 ± 1494 vs. €1233 ± 1507 for moderate AD. Conclusions In children with AD, twice‐weekly treatment with tacrolimus 0.03% ointment reduces the number of flares and prolongs time spent free from flares with no additional cost in children with moderate AD, and may be cost‐saving in those with severe AD.     

Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study

Background Long‐term treatment for atopic dermatitis (AD) using low‐dose, intermittent, topical anti‐inflammatory agents may control acute disease and prevent exacerbations. Objectives This 12‐month, European, multicentre, randomized study investigated if proactive, twice‐weekly application of 0·03% tacrolimus ointment can keep AD in remission and reduce the incidence of disease exacerbation (DE) in children. Patients and methods During the initial open‐label period, 267 children with AD applied 0·03% tacrolimus ointment twice daily for up to 6 weeks to all affected areas. When an Investigator Global Assessment (IGA) score of ≤ 2 was achieved, the patient entered the disease control period (DCP) and was randomized to receive tacrolimus (n = 125) or vehicle ointment (n = 125) twice weekly for 12 months. Exacerbations were treated with 0·03% tacrolimus ointment twice daily until an IGA ≤ 2 was regained, then randomized treatment was restarted. Results The outcome measure was the number of DEs during the DCP that required substantial therapeutic intervention. Proactive application of 0·03% tacrolimus ointment significantly reduced the number of DEs during the DCP that required substantial therapeutic intervention (median difference: 1·0; P < 0·001; Wilcoxon rank‐sum test), the percentage of DE treatment days (median difference: 6·2; P < 0·001; Wilcoxon rank‐sum test), and increased the time to first DE requiring intervention (median: 173 vs. 38 days; P < 0·001; stratified log‐rank test). Differences in quality of life scores were not significant between groups. The adverse event profile was similar for both treatment approaches. Conclusions Twice‐weekly proactive application of 0·03% tacrolimus ointment over 12 months was effective for most paediatric study patients in preventing, delaying and reducing the occurrence of AD exacerbations.     

A 4-year follow-up study of atopic dermatitis therapy with 0.1% tacrolimus ointment in children and adult patients

Background For the treatment of a chronic disease like atopic dermatitis, sustained tolerability and efficacy of the applied medication are essential. Objectives The present open‐label, noncomparative study was conducted to obtain information on the long‐term safety and efficacy of 0·1% tacrolimus ointment. Methods Patients aged 2 years or older with an affected body surface area of more than 5%, who previously participated in a clinical trial on tacrolimus ointment, were eligible for this study. The treatment area was defined by the investigator at study entry. Both children and adults applied continuously or intermittently 0·1% tacrolimus ointment twice daily during episodes of active disease plus an additional week after remission over a follow‐up period of up to 4 years. Results The intent‐to‐treat population comprised 782 patients, with a median age of 22 years (range 2–72). Patients remained in the study for up to 4 years. Approximately half of the patients discontinued the study prematurely; the median follow‐up was 1422 days. Median tacrolimus ointment use was 31·2 g during the first week; ointment use decreased during the first year and then remained stable for the remainder of the study. The median cumulative tacrolimus use was 271·5 g at month 6, 462·5 g at month 12, 739·9 g at month 24, 1029·3 g at month 36 and 1320·8 g at month 48. Altogether 51·8% of patients discontinued the study prematurely; the main reasons were withdrawal of consent (13·3%), loss to follow‐up (11·3%) and lack of efficacy (9·4%). Adverse events led to study discontinuation in 3·7% of the patients. The most frequent application site events were skin burning and pruritus. These events were most often reported in adult patients during the initial treatment period; prevalence decreased after the first week and remained at a low level throughout the study. Nonapplication site events occurred with stable incidences throughout the study period. In general, calculated daily hazard rates did not indicate an increased risk of adverse events with prolonged treatment. The total affected body surface area decreased substantially upon onset of treatment and efficacy of treatment was maintained until the end of the study with smaller but continuous improvements throughout the follow‐up period. Overall, 75% of the patients and 76% of the investigators rated their satisfaction with the treatment as excellent, very good or good at the end of the study or at the time of premature discontinuation. Conclusions The safety profile of intermittent or continuous long‐term application of 0·1% tacrolimus ointment for up to 4 years was consistent with that which has been established from shorter studies and gave no reason for concern. In addition, 0·1% tacrolimus ointment demonstrated sustained efficacy as reflected by the expression of high satisfaction with treatment by both patients and investigators.     

Skin and systemic pharmacokinetics of tacrolimus following topical application of tacrolimus ointment in adults with moderate to severe atopic dermatitis

Background  Systemic exposure to tacrolimus following topical application of tacrolimus ointment is minimal. There are, however, no data on the distribution of tacrolimus in the skin.
Objectives  To assess the distribution of tacrolimus in the skin and the systemic pharmacokinetics of tacrolimus in adults with moderate to severe atopic dermatitis after first and repeated application of tacrolimus ointment.
Methods  We investigated skin distribution of topically applied tacrolimus and systemic pharmacokinetics of percutaneously absorbed tacrolimus in adults with atopic dermatitis after topical application of tacrolimus 0·1% ointment twice daily for 2 weeks. Tacrolimus concentrations were assessed in full-thickness skin biopsies and blood samples.
Results  Of 14 patients, 11 completed treatment and were analysed. Mean ± SD tacrolimus concentrations in the skin at 24 h after first and last ointment applications were 94 ± 20 and 595 ± 98 ng cm⁻³, respectively. At 168 h after stopping treatment, values were 97% lower than at 24 h after last application. Tacrolimus concentration decreased with increasing skin depth. Systemic tacrolimus exposure after ointment application was low and highly variable, with 31% of samples below the limit of quantification (0·025 ng mL⁻¹) and 94% below 1 ng mL⁻¹. Blood concentrations at 24 h after the first and last ointment applications were 750 and 1800 times lower, respectively, than those in skin. Physicians' assessments showed that tacrolimus ointment was effective and well tolerated.
Conclusions  Tacrolimus was primarily partitioned in the skin, with minimal systemic absorption after topical application, in patients with atopic dermatitis.     

Cost-effectiveness of tacrolimus ointment vs. standard treatment in patients with moderate and severe atopic dermatitis: a health-economic model simulation based on a patient survey and clinical trial data

BACKGROUND: Atopic dermatitis (AD) affects health and quality of life (QoL) and also has great impact on both healthcare costs and costs to society. OBJECTIVES: The aim of the study was to analyse the cost-effectiveness of treatment with tacrolimus ointment vs. standard treatment in patients with moderate to severe AD. METHODS: A Markov simulation model was constructed capturing several key features of AD and its treatment: disease severity, treatment alternatives, and QoL. The model was populated with data from three sources: (i) efficacy data from a randomized controlled trial including patients with moderate to severe AD treated with either tacrolimus ointment or standard treatment (corticosteroids), (ii) resource utilization and QoL data from a patient survey including 161 Swedish patients with AD, and (iii) official price lists. Costs were calculated according to disease severity for the two treatment alternatives using the perspective of the Swedish healthcare sector. Two analyses were performed, one based on the quantity of medication used in the trial and one based on the survey data. The relationship between effectiveness of tacrolimus ointment and the amount of medication used was tested in sensitivity analyses. RESULTS: In the model simulations patients with severe AD treated with tacrolimus ointment experienced on average 4.6 more AD-free weeks per year than patients given standard treatment. The corresponding figure for patients with moderate AD was 6.5 more AD-free weeks per year. The cost-effectiveness ratios [cost per Quality Adjusted Life Year (QALY) gained] for treatment with tacrolimus ointment vs. standard treatment were 2,334 British pound for moderate AD and 3,875 British pound for severe AD when treatment patterns from the survey were assumed, and 8,269 British pound for moderate AD and 12,304 British pound for severe AD when treatment patterns from the clinical trial were assumed. The results of sensitivity analyses were all well within limits to be considered cost-effective. CONCLUSIONS: Estimates of the incremental cost-effectiveness ratio are far below the currently discussed threshold in Sweden, corresponding to approximately 48,700 British pound per QALY gained, and equivalent thresholds in other countries. Treatment with tacrolimus ointment in patients with moderate and severe AD can therefore be considered cost-effective.     

0.03%他克莫司软膏治疗眼睑皮炎临床疗效观察

目的探讨0.03%他克莫司软膏治疗眼睑部皮炎的疗效。方法 26例患者外用0.03%他克莫司软膏,2次/d,共2周。于治疗前及治疗后第3天,第1、2周和停药后1月各随访1次。结果 26例患者治疗后3天、1周、2周及停药1个月后临床痊愈率分别为57.69%,76.94%,92.30%,73.08%。对红斑、瘙痒的控制起效迅速,而脱屑及肥厚改变较缓。4例(15.38%)患者局部有灼热感,均发生在治疗初3天。停药1个月后共有7例(26.92%)患者复发。结论 0.03%他克莫司软膏治疗眼睑部皮炎起效快,疗效明显,长期使用的安全性需大样本观察研究。     

0.03% Tacrolimus ointment applied once or twice daily is more efficacious than 1% hydrocortisone acetate in children with moderate to severe atopic dermatitis: results of a randomized double-blind controlled trial

BACKGROUND: Topical corticosteroids are the usual treatment for atopic dermatitis (AD) in children but can have side-effects. OBJECTIVES: This study compared the efficacy and safety of 0.03% tacrolimus ointment applied once or twice daily over a 3-week period with the twice daily application of 1% hydrocortisone acetate (HA) ointment in children with moderate to severe AD. PATIENTS AND METHODS: Patients applied ointment daily to all affected body surface areas. The primary study endpoint was the percentage change in the modified Eczema Area and Severity Index (mEASI) between baseline and treatment end. RESULTS: Six hundred and twenty-four patients, aged 2-15 years, applied 0.03% tacrolimus ointment once daily (n = 207), twice daily (n = 210) or 1% HA twice daily (n = 207). By the end of treatment, application of 0.03% tacrolimus ointment both once or twice daily resulted in significantly greater median percentage decreases in mEASI (66.7% and 76.7%, respectively) compared with 1% HA (47.6%; P < 0.001). Furthermore, the median percentage decrease in mEASI was significantly greater for patients applying 0.03% tacrolimus twice daily compared with once daily (P = 0.007). Patients with severe AD benefited especially from twice daily application of 0.03% tacrolimus ointment compared with once daily application (P = 0.001). Transient mild to moderate skin burning occurred significantly more often in the 0.03% tacrolimus groups (P = 0.028) but resolved in most cases within 3-4 days. Laboratory parameters showed no clinically relevant changes. CONCLUSIONS: 0.03% tacrolimus ointment applied once or twice daily is significantly more efficacious than 1% HA in treating moderate-severe AD in children. Twice daily application of 0.03% tacrolimus ointment results in the greatest improvement in mEASI, and is especially effective in patients with severe baseline disease.