Schlager Justin Gabriel, Rosumeck Stefanie, Werner Ricardo Niklas, Jacobs Anja, Schmitt Jochen, Schlager Christoph, Nast Alexander
Division of Evidence Based Medicine, Department of Dermatology, Venerology and Allergology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany, 10117.
Cochrane Database Syst Rev. 2016 Feb 26;2(2):CD009687. doi: 10.1002/14651858.CD009687.pub2.
People with chronic plaque psoriasis often have lesions on the scalp. Hair makes the scalp difficult to treat and the adjacent facial skin is particularly sensitive to topical treatments.
To assess the efficacy and safety of topical treatments for scalp psoriasis.
We searched the following databases up to August 2015: the Cochrane Skin Group Specialised Register, CENTRAL (2015, Issue 7), MEDLINE (from 1946), EMBASE (from 1974) and LILACS (from 1982). We also searched five trials registers, screened abstracts of six psoriasis-specific conferences and checked the reference lists of included studies for further references to relevant randomised controlled trials.
Randomised controlled trials (RCTs) with a parallel-group, cross-over or within-patient design of topical treatments for people of all ages with scalp psoriasis.
Two authors independently carried out study selection, data extraction and 'Risk of bias' assessment. Disagreements were settled by reference to a third author.To assess the quality of evidence, we focused on the following outcomes: 'clearance' or 'response' as assessed by the investigator global assessment (IGA), improvement in quality of life, adverse events requiring withdrawal of treatment and 'response' as assessed by the patient global assessment (PGA).We expressed the results of the single studies as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes, and mean differences (MD) with 95% CI for continuous outcomes. If studies were sufficiently homogeneous, we meta-analysed the data by using the random-effects model. Where it was not possible to calculate a point estimate for a single study, we described the data qualitatively. We also presented the number needed to treat to benefit (NNTB).We categorised topical corticosteroids according to the German classification of corticosteroid potency as mild, moderate, high and very high.
We included 59 RCTs with a total of 11,561 participants. Thirty studies were either conducted or sponsored by the manufacturer of the study medication. The risk of bias varied considerably among the included studies. For instance, most authors did not state the randomisation method and few addressed allocation concealment. Most findings were limited to short-term treatments, since most studies were conducted for less than six months. Only one trial investigated long-term therapy (12 months). Although we found a wide variety of different interventions, we limited the grading of the quality of evidence to three major comparisons: steroid versus vitamin D, two-compound combination of steroid and vitamin D versus steroid monotherapy and versus vitamin D.In terms of clearance, as assessed by the IGA, steroids were better than vitamin D (RR 1.82; 95% CI 1.52 to 2.18; four studies, 2180 participants, NNTB = 8; 95% CI 7 to 11; moderate quality evidence). Statistically, the two-compound combination was superior to steroid monotherapy, however the additional benefit was small (RR 1.22; 95% CI 1.08 to 1.36; four studies, 2474 participants, NNTB = 17; 95% CI 11 to 41; moderate quality evidence). The two-compound combination was more effective than vitamin D alone (RR 2.28; 95% CI 1.87 to 2.78; four studies, 2008 participants, NNTB = 6; 95% CI 5 to 7; high quality evidence).In terms of treatment response, as assessed by the IGA, corticosteroids were more effective than vitamin D (RR 2.09; 95% CI 1.80 to 2.41; three studies, 1827 participants; NNTB = 4; 95% CI 4 to 5; high quality evidence). The two-compound combination was better than steroid monotherapy, but the additional benefit was small (RR 1.15; 95% CI 1.06 to 1.25; three studies, 2444 participants, NNTB = 13; 95% CI 9 to 24; moderate quality evidence). It was also more effective than vitamin D alone (RR 2.31; 95% CI 1.75 to 3.04; four studies, 2222 participants, NNTB = 3; 95% CI 3 to 4; moderate quality evidence).Reporting of quality of life data was poor and data were insufficient to be included for meta-analysis.Steroids caused fewer withdrawals due to adverse events than vitamin D (RR 0.22; 95% CI 0.11 to 0.42; four studies, 2291 participants; moderate quality evidence). The two-compound combination and steroid monotherapy did not differ in the number of adverse events leading withdrawal (RR 0.88; 95% CI 0.42 to 1.88; three studies, 2433 participants; moderate quality evidence). The two-compound combination led to fewer withdrawals due to adverse events than vitamin D (RR 0.19; 95% CI 0.11 to 0.36; three studies, 1970 participants; high quality evidence). No study reported the type of adverse event requiring withdrawal.In terms of treatment response, as assessed by the PGA, steroids were more effective than vitamin D (RR 1.48; 95% CI 1.28 to 1.72; three studies, 1827 participants; NNTB = 5; 95% CI 5 to 7; moderate quality evidence). Statistically, the two-compound combination was better than steroid monotherapy, however the benefit was not clinically important (RR 1.13; 95% CI 1.06 to 1.20; two studies, 2226 participants; NNTB = 13; 95% CI 9 to 26; high quality evidence). The two-compound combination was more effective than vitamin D (RR 1.76; 95% CI 1.46 to 2.12; four studies, 2222 participants; NNTB = 4; 95% CI 3 to 6; moderate quality evidence).Common adverse events with these three interventions were local irritation, skin pain and folliculitis. Systemic adverse events were rare and probably not drug-related.In addition to the results of the major three comparisons we found that the two-compound combination, steroids and vitamin D monotherapy were more effective than the vehicle. Steroids of moderate, high and very high potency tended to be similarly effective and well tolerated. There are inherent limitations in this review concerning the evaluation of salicylic acid, tar, dithranol or other topical treatments.
AUTHORS' CONCLUSIONS: The two-compound combination as well as corticosteroid monotherapy were more effective and safer than vitamin D monotherapy. Given the similar safety profile and only slim benefit of the two-compound combination over the steroid alone, monotherapy with generic topical steroids may be fully acceptable for short-term therapy.Future RCTs should investigate how specific therapies improve the participants' quality of life. Long-term assessments are needed (i.e. 6 to 12 months).
慢性斑块状银屑病患者头皮常出现皮损。头发使头皮难以治疗,且相邻的面部皮肤对局部治疗尤为敏感。
评估头皮银屑病局部治疗的疗效和安全性。
截至2015年8月,我们检索了以下数据库:Cochrane皮肤组专业注册库、CENTRAL(2015年第7期)、MEDLINE(始于1946年)、EMBASE(始于1974年)和LILACS(始于1982年)。我们还检索了五个试验注册库,筛选了六个银屑病专题会议的摘要,并检查了纳入研究的参考文献列表,以进一步查找相关随机对照试验的参考文献。
针对各年龄段头皮银屑病患者的局部治疗的平行组、交叉或患者内设计的随机对照试验(RCT)。
两位作者独立进行研究选择、数据提取和“偏倚风险”评估。分歧通过参考第三位作者解决。为评估证据质量,我们关注以下结果:研究者整体评估(IGA)评估的“清除”或“反应”、生活质量改善、需要停药的不良事件以及患者整体评估(PGA)评估的“反应”。我们将单项研究的结果表示为二分类结局的风险比(RR)及其95%置信区间(CI),连续结局的均值差(MD)及其95%CI。如果研究足够同质,我们使用随机效应模型对数据进行荟萃分析。如果无法为单项研究计算点估计值,我们将对数据进行定性描述。我们还给出了治疗获益所需的治疗人数(NNTB)。我们根据德国皮质类固醇效力分类将局部皮质类固醇分为轻度、中度、高度和极高度。
我们纳入了59项RCT,共11561名参与者。30项研究由研究药物的制造商进行或资助。纳入研究中的偏倚风险差异很大。例如,大多数作者未说明随机化方法,很少涉及分配隐藏。大多数研究结果仅限于短期治疗,因为大多数研究进行时间少于六个月。只有一项试验研究了长期治疗(12个月)。尽管我们发现了多种不同的干预措施,但我们将证据质量分级限制在三项主要比较:类固醇与维生素D、类固醇和维生素D的复方组合与类固醇单药治疗以及与维生素D单药治疗。
就IGA评估的清除情况而言,类固醇优于维生素D(RR 1.82;95%CI 1.52至2.18;四项研究,2180名参与者,NNTB = 8;95%CI 7至11;中等质量证据)。从统计学上看,复方组合优于类固醇单药治疗,然而额外获益较小(RR 1.22;95%CI 1.08至1.36;四项研究,2474名参与者,NNTB = 17;95%CI 11至41;中等质量证据)。复方组合比单独使用维生素D更有效(RR 2.28;95%CI 1.87至2.78;四项研究,2008名参与者,NNTB = 6;95%CI 5至7;高质量证据)。
就IGA评估的治疗反应而言,皮质类固醇比维生素D更有效(RR 2.09;95%CI 1.80至2.41;三项研究,1827名参与者;NNTB = 4;95%CI 4至5;高质量证据)。复方组合比类固醇单药治疗更好,但额外获益较小(RR 1.15;95%CI 1.06至1.25;三项研究,2444名参与者,NNTB = 13;95%CI 9至24;中等质量证据)。它也比单独使用维生素D更有效(RR 2.31;95%CI 1.75至3.04;四项研究,2222名参与者,NNTB = 3;95%CI 3至4;中等质量证据)。
生活质量数据的报告较差,数据不足以纳入荟萃分析。
类固醇因不良事件导致的停药比维生素D少(RR 0.22;95%CI 0.11至0.42;四项研究,2291名参与者;中等质量证据)。复方组合和类固醇单药治疗在导致停药的不良事件数量上没有差异(RR 0.88;95%CI 0.42至1.88;三项研究,2433名参与者;中等质量证据)。复方组合因不良事件导致的停药比维生素D少(RR 0.19;95%CI 0.11至0.36;三项研究,1970名参与者;高质量证据)。没有研究报告需要停药的不良事件类型。
就PGA评估的治疗反应而言,类固醇比维生素D更有效(RR 1.48;95%CI 1.28至1.72;三项研究,1827名参与者;NNTB = 5;95%CI 5至7;中等质量证据)。从统计学上看,复方组合比类固醇单药治疗更好,然而获益在临床上并不重要(RR 1.13;95%CI 1.06至1.20;两项研究,2226名参与者;NNTB = 13;95%CI 9至26;高质量证据)。复方组合比维生素D更有效(RR 1.76;95%CI 1.46至2.12;四项研究,2222名参与者;NNTB = 4;95%CI 3至6;中等质量证据)。
这三种干预措施常见的不良事件是局部刺激、皮肤疼痛和毛囊炎。全身性不良事件很少见,可能与药物无关。
除了三项主要比较的结果外,我们发现复方组合、类固醇和维生素D单药治疗比赋形剂更有效。中度、高度和极高度效力的类固醇往往疗效相似且耐受性良好。本综述在评估水杨酸、焦油、蒽林或其他局部治疗方面存在固有局限性。
复方组合以及皮质类固醇单药治疗比维生素D单药治疗更有效且更安全。鉴于复方组合与单独使用类固醇的安全性相似且额外获益甚微,通用局部类固醇单药治疗可能完全适用于短期治疗。
未来的RCT应研究特定疗法如何改善参与者的生活质量。需要进行长期评估(即6至12个月)。