他克莫司软膏治疗成人和儿童特应性皮炎51例

目的:评价他克莫司软膏治疗特应性皮炎的疗效和安全性。方法:运用随机双盲平行对照方法,将成人特应性皮炎分为3组(每组均15例),分别外用0.1%,0.03%他克莫司软膏和赋形剂;将儿童特应性皮炎分为2组,分别外用0.03%他克莫司软膏(21例)和赋形剂(21例)。每日2次,疗程为3wk。结果:成人他克莫司软膏0.1%组、0.03%组和赋形剂对照组的有效率分别为100%,80%和27%;儿童他克莫司软膏0.03%组和赋形剂对照组的有效率分别为85%和33%。成人和儿童他克莫司软膏治疗组的有效率均显著高于赋形剂组(P<0.01),症状和体征显著缓解。成人他克莫司软膏0.1%组,0.03%组和赋形剂对照组不良反应发生率分别为47%,40%和27%(P>0.05)。不良反应主要为用药部位的灼热、瘙痒、红斑等,大部分可自行消退。结论:0.1%和0.03%他克莫司软膏治疗成人特应性皮炎及0.03%他克莫司软膏治疗儿童特应性皮炎是有效和安全的。     

他克莫司软膏治疗儿童中重度特应性皮炎随机双盲对照临床研究

目的 观察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 用随机双盲安慰剂平行对照临床试验，共人组30例儿童中重度特应性皮炎患者，用药3周，其中29例患者完成本试验。结果 治疗结束时，0．03％他克莫司软膏组痊愈率、显效率和有效率分别为35．7％（5／14），50．0％（7／14）和85．7％（12／14），与安慰组痊愈率6．7％（1／15）、显效率13．3％（2／15）和有效率为20．0％（3／15）相比，差异均有统计学意义。试验组主要药物不良反应多为轻到中度，且均为一过性；实验室检查治疗前后也未见明显异常。结论0．03％他克莫司软膏治疗儿童中重度特应性皮炎安全有效。     

0．03％他克莫司软膏治疗面部激素依赖性皮炎临床观察

目的：观察0．03％他克莫司软膏治疗面部激素依赖性皮炎的疗效与依从性。方法：将50例面部激素依赖性皮炎患者随机分为2组,观察组外用0．03％他克莫司软膏,对照组口服西替利嗪、四环素联合局部冷湿敷,连续使用2周,第2周结束评价临床疗效与依从性。结果：观察组与对照组的有效率分别为83．3％和44．4％（P〈0．05）;依从率分别为96．0％和72．0％（P〈0．05）。结论：0．03％他克莫司软膏治疗面部激素依赖性皮炎具有较好疗效,且依从性好。     

0．03％他克莫司软膏治疗面部糖皮质激素依赖性皮炎20例疗效观察

目的 观察外用0．03％他克莫司软膏治疗面部激素依赖性皮炎的临床疗效。方法应用0．03％他克莫司软膏及Vit E软膏分别治疗两组面部激素依赖性皮炎患者，2次／d，共4周，于治疗后1、2,4周和停药后2周各随访1次。结果 治疗组中疗后1、2．4周和停药后2周有效率明显高于对照组。治疗组中30％于治疗早期有局部刺激症状，均于1周内消失，不影响继续治疗。结论 0．03％他克莫司软膏治疗面部激素依赖性皮炎起效快，疗效优，不良反应轻微。     

不同浓度他克莫司软膏治疗特应性皮炎疗效及对患者炎性因子水平影响

摘 要 目的:比较不同浓度他克莫司软膏对特应性皮炎患者白细胞介素-6（IL-6）和白细胞介素-10（IL-10）表达水平的影响,及其疗效与安全性。方法：特应性皮炎患者96例随机分为观察组（0.1%他克莫司软膏外涂皮损部位,早晚各1次）和对照组（0.03%他克莫司软膏外涂皮损部位,早晚各1次）,两组疗程均为3周。比较两组患者治疗前后血清IL-6、IL-10水平,皮损的面积、症状、体征及药品不良反应,评估患者临床疗效。结果：观察组总有效率为97.92%,明显高于对照组的79.17%（P＜0.05）。治疗后,两组患者严重指数（EASI）、受累面积占体表面积百分比(BSA)和体征／瘙痒症状评分均较治疗前下降（P＜0.05）;且观察组下降值均大于对照组（P＜0.05）。治疗后两组血清IL-6、IL-10水平均较前明显降低（P＜0.05）;且观察组明显低于对照组（P＜0.05）。两组药品不良反应发生率比较,差异无统计学意义（P＞0.05）。结论：采用0.1%他克莫司软膏用于治疗特应性皮炎疗效优于0.03%他克莫司软膏,能显著改善患者皮损情况和症状体征,降低血清IL 6和IL 10水平,且安全性好。     

他克莫司软膏治疗斑块状寻常型银屑病18例

目的 观察他克莫司软膏治疗斑块状寻常型银屑病的，临床疗效及安全性。方法 将36例斑块状银屑病患者随机分治疗组和对照组各18例，治疗组采用0．1％他克莫司软膏和尿素软膏外涂，bid，共治疗4周；对照组用糠酸莫美松软膏和尿素软膏外涂，bid，共治疗4周。用PASI积分评价疗效，并观察不良反应。结果 治疗组治疗结束时有效率为94．4％，对照组为66．7％（P〈0．05）。治疗组起效时间平均约为10d，对照组为14d。治疗组发生皮肤刺激反应5例（27．8％）。结论 他克莫司软膏外用治疗斑块状寻常型银屑病具有良好疗效和安全性。     

他克莫司治疗特应性皮炎的疗效观察

目的观察他克莫司治疗特应性皮炎的疗效。方法根据不同年龄外用0.03%和0.1%他克莫司,每日2次,共用3周,治疗前、治疗后1周和3周观察记录症状评分及副作用。结果治疗组总有效率为93.3%,对照组为64.7%%（P〈0.05）。结论他克莫司软膏治疗特应性皮炎效果好、副作用少。     

FDA咨询委员会要求Elidel和Protopic增加黑框警示

美国FDA儿科咨询委员会建议治疗儿童特应性皮炎的两种神经钙蛋白抑制剂增加黑框警示和用药指南(MedGuides)。这两种有问题的药品是Novartis公司的Elidel(pimecrolimus)1％霜剂和藤泽公司的Protopic(tacrolimus，他克莫司)0．03％和0．1％软膏。     

他克莫司对儿童特应性皮炎疗效及体表马拉色菌定植的影响

目的 评价他克莫司软膏对特应性皮炎患儿体表马拉色菌定植的影响.方法 将特应性皮炎患儿随机分为2组,均给予氯雷他定片口服作为基础治疗,治疗组同时给予0.03％他克莫司软膏,对照组同时给予维生素E乳,每日2次,疗程3周,根据SCORAD积分下降指数做疗效判定.比较治疗前、治疗第7d、14 d、21 d及治疗结束后第14d、28 d时的SCORAD积分及皮损表面马拉色菌定植密度;对马拉色菌定植密度与疾病严重程度进行Pearson相关性分析.结果 治疗结束时,治疗组SCORAD积分显著下降,治疗组和对照组的有效率分别为95.65％和66.67％（P＜0.05）.治疗结束后第28 d时,治疗组有1例复发,治疗总有效率为91.30％,对照组有3例复发,有效率为50％,治疗组复发率低于对照组（P＜0.05）.马拉色菌定植密度与SCORAD积分在治疗前后无明显相关性（P＞0.05）.治疗组第7d、14d、21 d时马拉色菌定植密度较对照组低（P均＜0.05）.结论 0.03％他克莫司软膏治疗儿童特应性皮炎有效、安全,复发率低,并可以减少皮损表面马拉色菌定植.     

用中药药浴联合他克莫司软膏治疗儿童特应性皮炎有效性和安全性的随机单盲临床试验疗效观察

目的评价中药药浴联合他克莫司软膏外用治疗儿童特应性皮炎的临床疗效及安全性。方法本试验采用随机、单盲、阳性平行对照试验将45例儿童患者采用随机数字表分成治疗组和对照组。治疗组23例,对照组22例。治疗组采用中药药浴治疗联合外用0.03%他克莫司软膏外用。对照组单用0.03%他克莫司软膏外用。结果 4周疗程结束后,两组间有效率差异有显著性(u=-2.411,P<0.05)。两组初诊时SCORAD积分值比较无统计学差异(t=0.557,P>0.05),治疗4周后SCORAD积分值比较,差异具有显著性(u=-2.411,P<0.05)。结论中药药浴联合0.03%他克莫司软膏较单用0.03%他克莫司软膏治疗特应性皮炎疗效较优,复发率低,安全性好,值得临床推广。     

Tacrolimus ointment: a review of its use in atopic dermatitis and its clinical potential in other inflammatory skin conditions

Tacrolimus ointment (Protopic) is a topically applied macrolide lactone immunomodulator effective in the treatment of atopic dermatitis. Its mechanism of action primarily involves calcineurin inhibition, which interrupts cytokine gene expression and leads to the downregulation of T-cell activity. Tacrolimus ointment (0.03% and 0.1% for adults and 0.03% for children) is an effective treatment for atopic dermatitis of the trunk and limbs, as well as sensitive skin areas such as the face. Its efficacy is similar to or greater than that of hydrocortisone acetate 1%, hydrocortisone butyrate 0.1% and betamethsone valerate 0.12% ointments and pimecrolimus 1% cream. Systemic absorption of tacrolimus from the ointment is minimal, and adverse events, which are mostly associated with the application site and include skin burning and pruritus, tend to resolve early in treatment. Unlike topical corticosteroids, tacrolimus ointment is not associated with skin atrophy, and it is a well tolerated treatment for adults or children with atopic dermatitis, particularly when long-term treatment is indicated or the face or skin-fold regions are involved.     

Pharmacokinetics of tacrolimus following topical application of tacrolimus ointment in adult and pediatric patients with moderate to severe atopic dermatitis

OBJECTIVE: To characterize the pharmacokinetics of tacrolimus after topical application in adult and pediatric patients with moderate to severe atopic dermatitis from all clinical trials in which tacrolimus blood levels were obtained. METHODS: Tacrolimus ointment 0.03% or 0.1% was applied twice daily. In the adult and pediatric pharmacokinetic studies, serial blood samples were obtained after single and repeated topical application. During the 12 clinical efficacy trials of tacrolimus ointment, single blood samples were obtained at various times relative to tacrolimus ointment application. RESULTS: In the pharmacokinetic studies, 89% to 95% of tacrolimus whole blood concentration samples were less than 1 ng/mL; mean maximum concentrations ranged from 0.2 to 1.6 ng/mL and mean area under the blood concentration-time curves (0-12 hours) ranged from 1.4 to 13.1 ng x hr/mL. Likewise, in the clinical efficacy trials, the majority (85%-99%) of tacrolimus concentration samples were less than 1 ng/mL. CONCLUSIONS: Tacrolimus ointment is associated with minimal systemic absorption and no evidence of systemic accumulation in patients with moderate to severe atopic dermatitis and extensive disease.     

Comparison of the efficacy and safety of 0.1% tacrolimus ointment with topical corticosteroids in adult patients with atopic dermatitis: review of randomised, double-blind clinical studies conducted in Japan

Tacrolimus (FK506) ointment is widely used in the treatment of patients with atopic dermatitis. The drug exerts its action by down-regulating antigen-specific T-cell activities and associated proinflammatory cytokine production. A number of clinical studies have evaluated the efficacy and safety of 0.1% tacrolimus ointment compared with vehicle or topical corticosteroids in adult patients with atopic dermatitis. These studies have suggested that topical tacrolimus has a rapid onset of action and exerts sustained therapeutic effects, with an efficacy similar to that of moderate to potent topical corticosteroids, but without causing skin atrophy. Two phase III randomised, controlled clinical trials have been conducted in Japanese adult patients with atopic dermatitis to compare the efficacy and safety of topical 0.1% tacrolimus with topical corticosteroid ointments. In the first study, patients with moderate or severe atopic dermatitis on the trunk and extremities were randomised to 3 weeks of treatment with topical 0.1% tacrolimus or the mid-potency topical corticosteroid 0.12% betamethasone valerate. Over 90% of the patients in each study group experienced at least a moderate improvement at the end of the study. In the second study, patients with moderate or severe atopic dermatitis on the head or neck were randomised to 1 week of treatment with 0.1% tacrolimus or the mild-potency corticosteroid 0.1% alclometasone dipropionate. Significantly greater improvements in individual symptom scores were observed with topical tacrolimus compared with alclometasone dipropionate, with overall global improvement at 1 week being statistically superior with tacrolimus. Furthermore, in a long-term open-label study involving 568 patients, at least a moderate global improvement in symptoms was observed in 85% of patients at 6 weeks, increasing to 91% at both 26 weeks and 52 weeks; this rate was maintained throughout the 2-year duration of the study. 0.1% tacrolimus ointment was considered to be safe in the majority of patients. The most prevalent adverse reactions were local application site irritations, which generally resolved with continued therapy. In summary, these findings suggest that 0.1% tacrolimus ointment is an effective and safe nonsteroidal alternative therapy for adult patients with atopic dermatitis.     

Tacrolimus ointment: new preparation. Too many unknowns

(1) Drug therapy for exacerbations of atopic dermatitis (atopic eczema) should only be considered when simple measures and emollients are inadequate. The first-line option is a topical corticosteroid with a level of potency appropriate for the affected site and the patient's age. (2) Tacrolimus, an immunosuppressant used orally or parenterally to prevent graft rejection, is now marketed in France as an ointment, in two dose strengths, for the treatment of atopic dermatitis. It is approved for use when topical corticosteroids fail, in patients aged at least two years. (3) According to a comparative trial in adults, tacrolimus, when used as a first-line treatment, is no more effective than a class II (strong) topical corticosteroid. Several clinical trials show that it is better than the excipient in both adults and children. The 0.1% strength seems to be slightly more active than the 0.03% strength in adults. (4) It is not known whether tacrolimus is effective after topical corticosteroid failure. (5) In comparative trials the main systemic adverse events in patients using tacrolimus ointment were flu-like syndromes and headache. Local adverse events included burning or pruritus at the site of application in about 50% of patients. These local effects are due to both the excipient and tacrolimus. (6) Severe skin infections and skin cancer cannot be ruled out as serious side effects. (7) Tacrolimus uptake through the skin exposes patients to systemic adverse effects and drug interactions. (8) In practice, patients with atopic dermatitis, however severe, have no reason to use tacrolimus, at least pending studies showing it is effective after topical corticosteroid failure.     

Topical tacrolimus for the treatment of inflammatory skin diseases

Chronic inflammatory skin disorders, such as atopic eczema, can cause considerable impairment of life quality. Their treatment is mainly driven by systemic or topical glucocorticosteroids which have the risk of many side effects. Recently, immunosuppressive macrolides which act via the inhibition of cytokine expression in T-lymphocytes have been shown to exert good therapeutic potency in inflammatory skin disorders. Cyclosporin, widely used in transplantation medicine, is also effective in psoriasis and atopic eczema but is not suitable for topical treatment. Tacrolimus (FK506) has been found to be 10-100 times more potent than cyclosporin and to penetrate skin much better due to a lower molecular weight. Initial clinical investigations have shown efficacy of topical tacrolimus in patients with atopic eczema. Large multi-centre studies have proven that long-term therapy with 0.03% and 0.1% tacrolimus ointment reveals effectiveness and safety both in adults and in children with severe atopic eczema. A burning sensation at the site of application is the most frequently observed local side effect. Relevant systemic adverse events were not detected. In Japan and the US, the drug is already licensed for the treatment of atopic eczema. The European admission for the pharmaceutical market is expected in the year 2002. Tacrolimus represents a milestone in topical therapy of inflammatory skin disorders which has so far been dominated by corticosteroid formulations and gives hope for the development of further topical immunosuppressive agents of its class in the future.     

他克莫司软膏在儿童口周皮炎中的临床应用

目的分析0.03%他克莫司软膏在儿童口周皮炎治疗中的应用价值。方法儿童口周皮炎患儿70例,年龄2～14岁,随机分为观察组及对照组。观察组给予0.03%他克莫司软膏联合保湿软膏每日外用1次治疗。对照组采用保湿乳膏每日外用2次治疗。两组疗程均为4周。比较两组患儿治疗后1、2、4周治疗效果。结果观察组有效率高于对照组(P<0.01),观察组2周、4周的有效率明显高于1周(P<0.05)。观察组的药物不良反应发生率为13.9%(5/36),主要表现为轻微的红斑、烧灼及痒痛感。结论 0.03%他克莫司软膏治疗儿童口周皮炎疗效确切,安全性高。     

Topical [symbol: see text] tacrolimus--a role in atopic dermatitis?

Conventional treatment of atopic dermatitis includes the regular, frequent use of emollients, and intermittent application of topical corticosteroids to control acute 'flares'. [symbol: see text] Tacrolimus (pronounced ta-kro-li-mus), which is available for systemic use for the prevention of organ rejection following allogenic liver and kidney transplantation, is now formulated as an immunosuppressant ointment (Protopic-Fujisawa). This is licensed for use in adults and children aged 2 years and over with moderate to severe atopic dermatitis inadequately responsive to conventional therapy. Promotion states that, in these groups, tacrolimus is "at least as effective as topical steroids" and "without the potential side effects of conventional therapy". Here we consider the place of tacrolimus ointment in the management of atopic dermatitis.     

Long-term safety of tacrolimus ointment in atopic dermatitis

Background: Tacrolimus ointment has shown efficacy as monotherapy in both short- and long-term studies in atopic dermatitis. Absorption of tacrolimus after topical application is dependent on the barrier function of the skin. Absorption through the intact epidermis is very low and eczematic skin a little higher. In comparison to systemic tacrolimus used for prevention and treatment of rejection after organ transplantation, the bioavailability of topical tacrolimus in patients with atopic dermatitis is between 3 and 4%. Long-term safety studies of up to 4 years have not shown adverse events associated with systemic use of immunosuppressive agents, that is, increased risk of infections, lymphomas or skin cancers. Despite these findings, many physicians remain concerned about possible long-term malignancies associated with long-term treatment with a topical calcineurin inhibitor. Objective: To identify in the published literature possible long-term safety issues associated with topical tacrolimus treatment. Methods: PubMed was used to identify studies of atopic dermatitis therapy in which tacrolimus ointment was used for at least 6 months. We evaluated the safety data available from these studies. In addition, some safety data were evaluated from clinical follow-up of our own patients who have used tacrolimus ointment intermittently for up to 14 years. Conclusions: During a follow-up period of 4 years in clinical studies, no increased risk of infections or cancer was associated with long-term use of tacrolimus ointment. Only short-term adverse events were detected. They included increased burning and stinging of the skin, and a temporary increase in skin infections. No signs of immunosuppression were observed after 1 – 4 years of intermittent treatment with tacrolimus ointment.