Ashcroft Darren M, Dimmock Paul, Garside Ruth, Stein Ken, Williams Hywel C
School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester M13 9PL.
BMJ. 2005 Mar 5;330(7490):516. doi: 10.1136/bmj.38376.439653.D3. Epub 2005 Feb 24.
To determine the efficacy and tolerability of topical pimecrolimus and tacrolimus compared with other treatments for atopic dermatitis.
Systematic review and meta-analysis.
Electronic searches of the Cochrane Library, Medline, and Embase.
Randomised controlled trials of topical pimecrolimus or tacrolimus reporting efficacy outcomes or tolerability.
investigators' global assessment of response; patients' global assessment of response; proportions of patients with flares of atopic dermatitis; and improvements in quality of life. Tolerability: overall rates of withdrawal; withdrawal due to adverse events; and proportions of patients with burning of the skin and skin infections.
4186 of 6897 participants in 25 randomised controlled trials received pimecrolimus or tacrolimus. Both drugs were significantly more effective than a vehicle control. Tacrolimus 0.1% was as effective as potent topical corticosteroids at three weeks and more effective than combined treatment with hydrocortisone butyrate 0.1% (potent used on trunk) plus hydrocortisone acetate 1% (weak used on face) at 12 weeks (number needed to treat (NNT) = 6). Tacrolimus 0.1% was also more effective than hydrocortisone acetate 1% (NNT = 4). In comparison, tacrolimus 0.03% was more effective than hydrocortisone acetate 1% (NNT = 5) but less effective than hydrocortisone butyrate 0.1% (NNT = -8). Direct comparisons of tacrolimus 0.03% and tacrolimus 0.1% consistently favoured the higher strength formulation, but efficacy differed significantly between the two strengths only after 12 weeks' treatment (rate ratio 0.80, 95% confidence interval 0.65 to 0.99). Pimecrolimus was far less effective than betamethasone valerate 0.1% (NNT = -3 at three weeks). Pimecrolimus and tacrolimus caused significantly more skin burning than topical corticosteroids. Rates of skin infections in any of the comparisons did not differ.
Both topical pimecrolimus and topical tacrolimus are more effective than placebo treatments for atopic dermatitis, but in the absence of studies that show long term safety gains, any advantage over topical corticosteroids is unclear. Topical tacrolimus is similar to potent topical corticosteroids and may have a place for long term use in patients with resistant atopic dermatitis on sites where side effects from topical corticosteroids might develop quickly. In the absence of key comparisons with mild corticosteroids, the clinical need for topical pimecrolimus is unclear. The usefulness of either treatment in patients who have failed to respond adequately to topical corticosteroids is also unclear.
确定与其他治疗特应性皮炎的方法相比，外用匹美莫司和他克莫司的疗效和耐受性。
系统评价和荟萃分析。
对Cochrane图书馆、Medline和Embase进行电子检索。
外用匹美莫司或他克莫司的随机对照试验，报告疗效结果或耐受性。
研究者对反应的整体评估；患者对反应的整体评估；特应性皮炎发作患者的比例；以及生活质量的改善。耐受性：总体撤药率；因不良事件撤药；以及皮肤烧灼感和皮肤感染患者的比例。
25项随机对照试验中的6897名参与者中有4186名接受了匹美莫司或他克莫司治疗。两种药物均比赋形剂对照显著更有效。0.1%他克莫司在3周时与强效外用糖皮质激素效果相同，在12周时比0.1%丁酸氢化可的松（用于躯干的强效药物）加1%醋酸氢化可的松（用于面部的弱效药物）联合治疗更有效（治疗所需人数（NNT）=6）。0.1%他克莫司也比1%醋酸氢化可的松更有效（NNT = 4）。相比之下，0.03%他克莫司比1%醋酸氢化可的松更有效（NNT = 5），但比0.1%丁酸氢化可的松效果差（NNT = -8）。0.03%他克莫司和0.1%他克莫司的直接比较始终支持较高强度的制剂，但仅在治疗12周后两种强度的疗效才有显著差异（率比0.80，95%置信区间0.65至0.99）。匹美莫司远比0.1%戊酸倍他米松效果差（3周时NNT = -3）。匹美莫司和他克莫司引起的皮肤烧灼感比外用糖皮质激素显著更多。任何比较中的皮肤感染率均无差异。
外用匹美莫司和外用他克莫司治疗特应性皮炎均比安慰剂治疗更有效，但由于缺乏显示长期安全性获益的研究，其相对于外用糖皮质激素的任何优势尚不清楚。外用他克莫司与强效外用糖皮质激素相似，对于外用糖皮质激素副作用可能迅速出现的部位，对难治性特应性皮炎患者可能有长期使用的价值。由于缺乏与弱效糖皮质激素的关键比较，外用匹美莫司的临床需求尚不清楚。对于外用糖皮质激素反应不佳的患者，这两种治疗方法的有效性也不明确。
