Reporting of outcomes in randomized controlled trials on nail psoriasis: a systematic review

One of the important complications of the skin disease, psoriasis, is the appearance of changes in the nails. These range from the formation of small pits across the surface of the nail to painful separation of the nail plate from the underlying nail bed and disfiguring enlargement and thickening of the nail itself. Given this wide range of changes in appearance it is important that, in assessing the results of treatment, researchers can use simple, but accurate, criteria for measuring changes in psoriatic nails under treatment; these are known as core outcome sets. This study, organised by investigators from the departments of dermatology in the Universities of Amsterdam and Nijmegen in the Netherlands, surveyed 65 clinical trials focussing on nail psoriasis, all of which used assessment measures for nail changes in psoriasis, the commonest of which is called the nail psoriasis severity index. However, they found that several different methods were used in the various studies. A detailed analysis of these studies has identified a number of variations in the methods used which make the results of different treatments difficult to compare. This is particularly because there was no standard way of expressing the final scores of the severity of nail disease found in these studies and also that the different aspects of severity were rated differently. Some of these assessment scoring systems have not been validated (substantiated) either. The authors call for a rethink of the use of nail assessments in psoriasis and highlight the need to develop new methods which are sufficiently robust to stand up to close scrutiny. These should allow investigators to assess the different changes seen in the diseased nails in a standardised way, so that results of different studies can be compared. They suggest that a consensus group should be established to carry out this work.     

Efficacy and tolerability of biologic and nonbiologic systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials

Background The comparative efficacy and tolerability of conventional and biologic treatments for moderate‐to‐severe plaque psoriasis are unknown. Objectives To perform a systematic review and meta‐analysis of randomized controlled trials (RCTs) reporting efficacy of systemic treatments approved for moderate‐to‐severe psoriasis by means of the Psoriasis Area and Severity Index (PASI). Methods We identified relevant articles by systematic electronic searches (Cochrane Library, Medline, Embase, Scopus). Efficacy was defined as proportion of participants with ≥ 75% decrease in PASI (PASI‐75) at primary efficacy measurement (week 8–16). PASI‐75 response rates of double‐blind placebo‐controlled trials were summarized as risk differences (RDs) and pooled using random effects models. Tolerability was assessed from rates of withdrawals and adverse events. Results Twenty‐four RCTs totalling 9384 patients were analysed qualitatively. Sixteen double‐blind placebo‐controlled trials were eligible for meta‐analysis. Infliximab was significantly superior to all other interventions [RD 77%, 95% confidence interval (CI) 72–81%]. Adalimumab (RD 64%, 95% CI 61–68%) was superior to ciclosporin (RD 33%, 95% CI 13–52%), efalizumab (RD 24%, 95% CI 19–30%), etanercept 50 mg twice weekly (RD 44%, 95% CI 40–48%) and etanercept 25 mg twice weekly (RD 30%, 95% CI 25–35%). Efalizumab was significantly less efficacious than fumaric acid esters (RD 48%, 95% CI 32–64%). Rates of withdrawals due to adverse events were highest for methotrexate and fumaric acid esters. Conclusions The efficacy of systemic agents approved for moderate‐to‐severe psoriasis differs considerably both within and between biologics and nonbiologics. Infliximab is most efficacious, followed by adalimumab. Patients receiving infliximab have an excess chance of 77% over placebo to achieve PASI‐75 response. Published evidence questions regulatory guidelines that recommend biologics as second‐line therapy for moderate‐to‐severe plaque psoriasis.     

Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials

Background Ustekinumab, a novel monoclonal antibody for the treatment of moderate to severe plaque‐type psoriasis, has recently received regulatory approval in Europe, bringing the total number of biologic agents licensed in this indication to five. To assist treatment selection in daily practice it is essential to understand the benefit/risk profile of these agents and in the absence of a clinical trial comparing all available biologics a number of reviews have used statistical techniques to generate estimates of the comparative effectiveness of these therapies through the available network of randomized clinical trials. These estimates have previously been published for a limited range of psoriasis biologic treatments, although, to date no review has compared all the currently available agents in Europe. Objectives To estimate the comparative effectiveness of all biologic agents indicated in the treatment of moderate to severe psoriasis currently available in Europe based on the primary trial endpoints. Methods A number of databases were searched for details of randomized controlled trials of available biologics in the treatment of plaque‐type psoriasis in adults. Comparative effectiveness was estimated based on the reported Psoriasis Area and Severity Index (PASI) 50, 75 and 90 response rates. A network meta‐analysis conducted on the ordered probit scale and implemented as a Bayesian hierarchical model provided estimates for the probability of response and relative risk vs. placebo, based on all observed comparisons. Results Twenty trials were included in the meta‐analysis including patients with a mean disease duration of 18–22 years. Based on the indirect comparison and given a placebo PASI 50 response of 13%, infliximab had the highest predicted mean probability of response at PASI levels 50 (93%), 75 (80%) and 90 (54%), followed by ustekinumab 90 mg at 90%, 74% and 46%, respectively, and then ustekinumab 45 mg, adalimumab, etanercept and efalizumab. Conclusions The ordered probit model allowed a quantitative comparison of all currently licensed biologics, providing estimates on comparative effectiveness and a suggested ranking of treatments that is of potential use to decision‐makers. However, the analysis is based on indirect comparisons of the primary endpoint reported from short‐term randomized trials.     

Gabapentin for uremic pruritus: a systematic review of randomized controlled trials

Uremic pruritus is one of the most prevalent and bothersome dermatologic symptoms in patients with end-stage renal disease. Some studies suggest a possible neuropathic cause of uremic pruritus. Gabapentin, an anticonvulsant, may control pruritus with neuropathic origin. The objectives of this study were to assess the efficacy of gabapentin in reducing pruritus scores of patients with uremic pruritus and evaluate its safety among dialysis patients. Meta-analysis of randomized controlled trials, using gabapentin as treatment for uremic pruritus among hemodialysis patients was included and analyzed using Review Manager Version 5.1.4 software. Seven out of 17 screened articles were included, with a total of 315 participants. Meta-analysis of the incidence of improved pruritus scores after treatment from four studies (n = 171) showed that treatment with gabapentin decreased the severity of uremic pruritus as compared to the placebo (risk ratio = 0.18; 95% confidence interval: 0.09, 0.33; I² = 4%: P =< 0.00001). Six studies (n = 290) presented with incidence of adverse drug events such as dizziness, drowsiness, and somnolence. In the pooled analysis, treatment with gabapentin was associated with a higher incidence of adverse drug events compared to the comparator drugs, but the results were not significant (risk ratio = 1.3, 95% confidence interval: 0.81, 2.11; P = 0.28, I² = 37%). The results of this systematic review suggest that gabapentin is efficacious and safe in improving uremic pruritus among dialysis patients.     

Homeopathy for eczema: a systematic review of controlled clinical trials

Background Homeopathy is often advocated for patients with eczema. Objectives This article systematically reviews the evidence from controlled clinical trials of any type of homeopathic treatment for any type of eczema. Methods Electronic searches were conducted in Medline, Embase and the Cochrane Library with no restrictions on time or language. In addition, the bibliographies of the retrieved articles and our departmental files were hand searched. All controlled trials of homeopathy in patients with eczema were considered. Their methodological quality was estimated using the Jadad score. Results One randomized and two nonrandomized clinical trials met the inclusion criteria. All were methodologically weak. None demonstrated the efficacy of homeopathy. Conclusions The evidence from controlled clinical trials therefore fails to show that homeopathy is an efficacious treatment for eczema.     

Safety and efficacy of topical nitric oxide-releasing berdazimer gel for molluscum contagiosum clearance: A systematic review and meta-analysis of randomized controlled trials

Molluscum contagiosum (MC) is a contagious infection that, although benign, can become an aesthetic burden and lead to other opportunistic infections, secondary dermatitis, and self-isolation. Currently, several treatment options are available for MC, including the newly investigated nitric oxide-releasing berdazimer gel, leading this review to evaluate randomized controlled trials (RCT) comparing berdazimer gel with a vehicle for treating MC. The meta-analysis included three reports and four RCT involving 1854 patients, with 1106 (59.6%) randomized to receive berdazimer. Our findings suggest that berdazimer is effective in the management of MC lesions, but the increased clearance of lesions and reduction of scarring must be weighed against the potential for topical adverse effects, particularly when considering the use of this therapy in pediatric patients.     

Azelaic acid in the treatment of papulopustular rosacea: a systematic review of randomized controlled trials

OBJECTIVE: To evaluate the clinical efficacy of topical 20% azelaic acid cream and 15% azelaic acid gel compared with their respective vehicles and metronidazole gel in the treatment of papulopustular rosacea. DATA SOURCES: Electronic searches of MEDLINE, EMBASE, BIOSIS, and SciSearch through July or August 2004 and the Cochrane Central Register of Controlled Trials through 2004 (issue 3). We performed hand searches of reference lists, conference proceedings, and clinical trial databases. Experts in rosacea and azelaic acid were contacted. STUDY SELECTION: Randomized controlled trials involving topical azelaic acid (cream or gel) for the treatment of rosacea compared with placebo or other topical treatments. Two authors independently examined the studies identified by the searches. Ten studies were identified, of which 5 were included (873 patients). DATA EXTRACTION: Two authors independently extracted data from the included studies, then jointly assessed methodological quality using a quality assessment scale. DATA SYNTHESIS: Because standard deviation data were not available for 4 of the 5 studies, a meta-analysis could not be conducted. Four of the 5 studies demonstrated significant decreases in mean inflammatory lesion count and erythema severity after treatment with azelaic acid compared with vehicle. None of the studies showed any significant decrease in telangiectasia severity. CONCLUSIONS: Azelaic acid in 20% cream and 15% gel formulations appears to be effective in the treatment of papulopustular rosacea, particularly in regard to decreases in mean inflammatory lesion count and erythema severity. Compared with metronidazole, azelaic acid appears to be an equally effective, if not better, treatment option.     

Placebo response in phase 2 and 3 trials of systemic and biological therapies for atopic dermatitis—a systematic review and meta-analysis

A growing number of clinical trials of biological and systemic therapies have been conducted within adult atopic dermatitis (AD). No study has yet examined and meta-analysed the pooled placebo response in AD. We performed a systematic review and meta-analysis to examine the placebo response in clinical trials evaluating the effect of systemic and biological therapies in adult AD and compared it to results from clinical trials in psoriasis. Two screeners independently searched the databases ClinicalTrials.gov, Embase, Pubmed and Web of Science. A total of 2058 articles were identified, of which 78 were full-text reviewed. Overall, 25 trials were included in the qualitative analysis, of which 24 were further included in the quantitative analysis. At 12-week follow-up, EASI50, EASI75 and EASI90 placebo responses were 39.9% [95% confidence interval (CI), 36.7–43.2], 20.9% (95% CI, 18.2–23.8) and 9.0% (95% CI, 6.7–11.6), respectively. At week 12, the pooled proportion of placebo-treated AD patients that obtained EASI50, EASI75 and EASI90 was significantly higher than the pooled proportion of placebo-treated psoriasis patients obtaining PASI50, PASI75 and PASI90 (P < 0.05). Our findings emphasize the fluctuating nature of AD and show that correct and consistent use of topical treatments strongly reduces disease severity.     

生物制剂治疗银屑病患者出现严重感染的风险评估:一项系统性回顾与荟萃分析

<正>肿瘤坏死因子抑制剂英夫利昔单抗、依那西普和阿达木单抗是目前用于治疗银屑病常用的3种生物制剂,新药优特克单抗是IL-12和IL-23拮抗剂,苏金单抗是IL-17受体拮抗剂。生物制剂通过抑制细胞因子,调控银屑病患者紊乱的免疫系统,从而发挥疗效。肿瘤坏死因子等细胞因子在细胞感染免疫应答和肉芽肿形成过程中是不可或缺的重要一员,因此生物治疗是否存在引起严重感染的风险     

环孢素维持治疗银屑病随机对照研究的文献分析

检索MEDLINE、Embase、Cochrane图书馆、SinoMed、CNKI和万方数据库中1974年1月1日至2018年7月1日环孢素维持治疗银屑病的随机对照临床研究,评价不同环孢素给药方案治疗银屑病的疗效和安全性。共纳入9篇随机临床对照试验文献,均报道环孢素治疗银屑病有效,其中2篇文献研究发现连续治疗方案在长达24周的维持治疗期内是安全有效的,2篇发现间断治疗比连续治疗更安全有效。     

Outcome measures for vulval skin conditions: a systematic review of randomized controlled trials

Symptoms and signs of vulval skin disorders are common. These conditions can have a considerable impact on quality of life, restricting physical activities and causing difficulty in everyday activities and may also affect social, psychosexual and psychological well‐being. There are no standardized measures routinely used to assess the impact of vulval disease on daily life. To report outcome measures used in clinically based randomized controlled trials (RCTs) investigating therapeutic interventions in vulval disease. The Medline, EMBASE and CENTRAL databases were searched to identify RCTs of vulval skin conditions written in English. Studies with laboratory tests or survival rates as the primary outcome, or those investigating menopausal symptoms or infections were excluded. Twenty‐eight published RCTs were included. The vulval conditions represented were vulvodynia (n = 14), lichen sclerosus (n = 9), vulval intraepithelial neoplasia (n = 2), vulval pruritus (n = 2) and lichen planus (n = 1). The 28 RCTs measured 25 different outcomes, using 49 different scales. The method of outcome assessment was lacking on nine occasions. Only 21% (six of 28) of included trials had a clearly stated primary outcome. Patient‐reported outcomes were more commonly reported than clinician‐related outcome measures. The most commonly reported patient‐rated outcome measure was a reduction in pain (measured 15 times) and an overall improvement in symptoms using a patient global assessment (measured 11 times). The most commonly reported clinician‐rated outcome was an overall assessment of the appearance of affected sites (measured 13 times). There were no agreed standard scales used for the global assessments. Only nine of the recorded outcome measure tools were designed to assess vulval disease or sexual functioning, the remainder were general measures. There is heterogeneity in the outcome measures used when reporting therapeutic interventions in vulval disease. This field of dermatology would benefit from development of a vulval‐specific outcome measure and the establishment of a core outcome measure set.     

Topical herbal medicines for atopic eczema: a systematic review of randomized controlled trials

Despite the availability of medicines with proven efficacy, many patients use complementary or alternative medicines (CAMs) to manage atopic eczema (AE). Due to the lack of objective information on topical CAMs, this systematic review evaluates the current evidence for the efficacy and safety of topical herbal preparations in AE. Using Cochrane systematic review methodology, PubMed, the Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (via EBSCO), MEDLINE (via EBSCO), Proquest Health and Medical Complete, GREAT and CAM‐QUEST were searched from inception until June 2014. Bibliographies of retrieved studies were hand searched for further relevant trials. All controlled clinical trials of topical herbal medicines for AE in humans of any age were included regardless of the control intervention or randomization. Only English‐language publications were considered. Eight studies met the inclusion criteria. Seven investigated extracts of single plants and one an extract from multiple plants. Only two studies that showed a positive effect were considered to have a low risk of bias across all domains (those of liquorice gel and Hypericum perforatum). In these two, the test product was reported to be superior to placebo. Despite variations in diagnostic criteria and lack of validated tools for outcome assessments in one of these, the promising results may warrant continued research in better‐designed studies. No meta‐analysis was performed due to heterogeneity in all studies. There is currently insufficient evidence of efficacy for any topical herbal extract in AE. Many studies had methodological flaws and even those showing efficacy were single trials with small patient cohorts.