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。     

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.     

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。     

他克莫司软膏治疗成人特应性皮炎随机对照试验的Meta分析

目的:评价局部应用他克莫司治疗成人特应性皮炎(AD)的疗效和安全性.方法:计算机检索Ovid:http://gateway.ovid.com/:Cochrane图书馆(2008年第1期)、检索MEDLINE(1966～2007年),Embase数据库(1974～2007年),http://www.cnki.net/index.htm,纳入他克莫司治疗AD的随机对照试验,两名研究者独立进行各临床试验的质量评估.采用Cochrane协作网提供的RevMan 4.2.8进行统计分析.结果:共纳入6个随机对照试验(RCT),包括1 441例临床诊断为中、重度AD患者.Meta分析显示:0.03%、0.1%他克莫司软膏治疗特应性皮炎有较好疗效,0.1%他克莫司软膏疗效优于0.03%者,OR为0.65(0.48, 0.86),0.1%他克莫司软膏疗效与0.1%丁酸氢化可的松相似.主要的不良反应轻微,多为灼热感和瘙痒.结论:局部应用他克莫司治疗成人AD安全有效.     

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。     

他克莫司软膏治疗成人中、重度特应性皮炎的临床研究

目的:比较0.1%,0.03%他克莫司软膏与赋形剂治疗中、重度特应性皮炎(AD)的疗效和安全性.方法:采用随机、双盲、赋形剂平行对照临床研究方法,入选病例按1:1:1比例分为三组,分别随机接受0.1%,0.03%他克莫司软膏或赋形剂治疗,每天2次外搽患处,共3周.结果:有效率:他克莫司软膏0.1%组和0.03%组分别为88.9%和87.5%,赋形剂组为25%;治愈率:他克莫司软膏0.1%组和0.03%组分别为55.6%和50%,赋形剂组为25%,差异有统计学意义(P＜0.05).结论:他克莫司软膏(0.1%和0.03%)治疗成人中、重度特应性皮炎疗效好,安全和耐受性均良好.     

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。     

他克莫司软膏治疗成人中重度特应性皮炎的疗效和安全性观察

目的观察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。方法采用随机双盲、赋形剂平行对照的临床试验,共入组54例成人中重度特应性皮炎患者,年龄18~65岁,共用药3周,其中49例患者完成本试验。结果治疗结束时0.1%和0.03%他克莫司软膏痊愈率分别为46.7%(7/15)和23.5%(4/17),显效率分别为46.7%(7/15)和47.1%(8/17),与赋形剂组的痊愈率17.7%(3/17)和显效率11.8%(2/17)相比,差异有统计学意义;0.1%和0.03%他克莫司软膏治疗有效率分别为93.3%(14/15)和70.6%(12/17),均明显高于赋形剂对照组的29.4%(5/17),差异具有高度统计学意义。在0.1%和0.03%他克莫司软膏中,主要不良反应表现为用药部位出现瘙痒(38.9%和27.8%)、灼热感(33.3%和16.7%)、刺痛(16.7%和22.2%)等,严重程度多为轻到中度,并且均为一过性。治疗前后实验室检查也无明显异常改变。结论0.1%和0.03%他克莫司软膏是一种安全、有效的治疗成人中、重度特应性皮炎的药膏。     

0.03%他克莫司软膏治疗儿童特应性皮炎的疗效观察及生活质量评价

目的:评价0.03%他克莫司软膏治疗儿童特应性皮炎的疗效和安全性。方法:采用随机、双盲、平行对照方法,分别对两组儿童特应性皮炎患者外用0.03%他克莫司软膏和赋形剂,疗程为3周。每周对患儿进行随访观察,并在治疗前、后对5～17岁患者作皮肤病学生活质量指数(DLQI)问卷调查。结果:0.03%他克莫司软膏组和对照组的有效率分别为85.0%和33.3%,两组疗效比较差异有非常显著性(P<0.001)。问卷调查表明患者治疗后生活质量明显改善。结论:0.03%他克莫司软膏治疗儿童特应性皮炎安全、有效,治疗后患者的生活质量明显改善。     

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.     

A single‐center open‐label long‐term comparison of tacrolimus ointment and topical corticosteroids for treatment of atopic dermatitis

Background: Atopic dermatitis is a chronic or recurrent inflammatory skin disease that often requires treatment over years. According to its severity, atopic dermatitis is often managed with use of emollients, topical corticosteroids, topical calcineurin inhibitors or systemic agents. This long‐term study compares the efficacy of tacrolimus 0.1% ointment with topical corticosteroids as standard therapy in patients with moderate atopic dermatitis. Patients and methods: 50 patients were enrolled. They were allocated to treatment groups by the investigator (tacrolimus group or standard group), and followed over a period of six to twenty months. Efficacy was evaluated by the Eczema Area Severity Index (EASI), the percentage of affected body surface area, and the score of Rajka and Langeland. In addition, ointment usage was documented and analyzed. Results: The improvement of the skin condition was statistically significant in both groups. The comparison of the two groups, however, did not show a statistically significant advantage of one or the other treatment. Ointment usage was slightly higher in the standard group. Conclusions: The efficacy of tacrolimus 0.1% ointment was confirmed. In terms of emollient usage, no regular pattern could be demonstrated.     

Characteristics and completeness of clinical trial registrations in psoriasis and atopic dermatitis

BACKGROUND: Controversy over the failure to publish results of clinical trials linking antidepressant treatment to suicidal behaviour in adolescents has increased interest in clinical trial registration. OBJECTIVE: To assess numbers, characteristics and completeness of registrations of trials for psoriasis and atopic dermatitis registered at two web-based trial registries: ClinicalTrials.gov and isrctn.org. METHODS: In this cross-sectional study we identified trials by searching ClinicalTrials.gov and isrctn.org on 18 January 2006 for trials registered up to 31 December 2005. We included only trials of therapeutic interventions for atopic dermatitis or psoriasis. We ascertained the date of submission of registration, the funding source of the trial, and whether a registration listed the specific name of the intervention studied, the specific outcome measure used (e.g. "Psoriasis Area and Severity Index"), the criterion used to gauge success on the outcome measure (e.g. > or = 75% decrease), and the time at which the outcome would be assessed (e.g. at 12 weeks). RESULTS: There were 156 registered trials, including 128 (82%) at ClinicalTrials.gov [36 (23%) in atopic dermatitis, 92 (59%) in psoriasis] and 28 (18%) at isrctn.org [23 (15%) in atopic dermatitis, 5 (3%) in psoriasis]. Pharmaceutical companies funded 87 trials (56%), federal or governmental agencies 28 (18%), universities or organizations 21 (13%), and a combination of funders 20 (13%). Of atopic dermatitis trials (13 of 36) and (24 of 92) of psoriasis trials at ClinicalTrials.gov were registered in September 2005. The specific name of the intervention studied was listed in 150 registrations (96%), 89 (57%) listed the specific measure used, 69 (44%) listed the criteria to gauge success and 62 (40%) listed the time of assessment. CONCLUSIONS: While trial registrations in atopic dermatitis and psoriasis are increasing, more complete information in these registrations may increase their value for dermatologists and their patients.