Efficacy and Safety of Imiquimod for Verruca Planae: a Systematic Review
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Global Dermatology Research Article ISSN: 2056-7863 Efficacy and safety of imiquimod for verruca planae: A systematic review Xin-rui Zhang#, Bi-huan Xiao#, Rui-qun Qi*, and Xing-hua Gao* Department of Dermatology, No 1 Hospital of China Medical University, Shenyang 110001, PR China #These authors contributed equally to this work Abstract Objective: To assess the efficacy and safety of imiquimod for treating verruca planae. Methods: We searched the Pubmed, Cochrane Register of Controlled Trials, EMbase, CBM, CNKI and Wanfang databases (Chinese) to collect randomized controlled trials (RCTs). We screened the retrieved studies according to the predefined inclusion and exclusion criteria, evaluated the quality of include studies, and performed meta-analyses using the Cochrane Collaboration’s RevMan 5.1. Software. Results: Twenty-six RCTs involving 2169 patients with verruca planae were included and assessed. At the end of the 6th and ≥8th week, the effective rate of topical imiquimod was obviously higher than that of control [ RR=1.42, 95%CI (1.27, 1.60), P <0.00001; RR=1.43, 95%CI (1.22,1.67), P<0.00001]. The effective rate of imiquimod cream was higher than tretinoin cream, tazarotene gel and other antiviral drugs. [RR=1.41, 95%CI (1.25, 1.59), P <0.00001; RR=1.76, 95%CI (1.48, 2.10), P<0.00001; RR=1.71, 95%CI (1.29, 2.26), P =0.0002]. However, the effectiverate of imiquimod cream was lower than 5-ALA-PDT (RR=0.6, 95%CI (0.5, 0.71), P<0.00001). Conclusions: The limited evidence demonstrates that topical imiquimod is safe and efficient. More multiple central RCTs with large samples are required to verify these conclusions. Introduction with other treatment methods. Verruca planae are warts caused by the human papilloma virus Outcome indicator (HPV), mostly by HPV type3, 10, 28 and 41. They primarily affect Cured: skin lesions completely disappeared or decreased >90%. children and young adults [1]. The treatment cycle is usually prolonged. Significantly improved: skin lesions decreased >60% (or >70%); Current treatment options are anti-viral, immune-modulation and Improved: over 30%, but less than 70% of decrease of skin lesions; destruction of the infected tissue. Invalid: less than 30% in decrease of kin lesions. The effective rate is Imiquimod is a low molecular weight, synthetic immune response the sum of cured and significantly improved by the total number of the modifier which does not exert its antiviral effects directly on virus- tested patients. infected cells. Imiquimod induces the production of antiviral cytokines that enhance cellular immunity necessary for the control or elimination Data sources and searches of HPV infection. Imiquimod is often prescribed for condyloma To identify relevant studies, three reviewers (Z.X.R, X.B.H, H.X.J) acuminatum [2]. In recent years, there are reports that it has been used systematically searched MEDLINE, Cochrane Central Register of for flat warts and molluscum contagiosum, with satisfactory curative Controlled Trials, Embase, China National Knowledge Infrastructure effect [3]. Here we performed a systematic review on the efficacy and database (CNKI), China Biology Medicine disc (CBM) and Wanfang safety of imiquimod cream in the treatment of verruca planae in order Data Knowledge Service Platform. Search terms were based on specific to provide the evidence for clinical decision. agents (“Imiquimod,” “Verruca Planae,” “Plane Warts,” “Flat Warts,” Materials and methods Eligibility criteria Correspondence to: Rui-qun Qi, MD, PhD, Department of Dermatology, No 1 Inclusion and exclusion criteria were determined before the search Hospital of China Medical University, Shenyang 110001, China, Tel: +86 24 8328 2742; Fax: +86 24 8328 2742; E-mail: [email protected] was conducted. We included studies comparing the efficacy and safety of Imiquimod with other drugs on patients with verruca planae. Xing-hua Gao, MD, PhD, Department of Dermatology, No 1 Hospital of China Included studies must be randomized controlled trial (RCT). Case Medical University, Shenyang 110001, China, Tel: +86 24 8328 2326; Fax: +86 24 reports, reviews and document of incomplete data were excluded. 8328 2326; E-mail: [email protected] Key words: imiquimod, verruca planae, plane warts, flat warts, systematic review, Intervention measure randomized controlled trial The test group for 5% imiquimod cream alone or in combination Received: July 01, 2016; Accepted: August 03, 2016; Published: August 05, 2016 Glob Dermatol, 2016 doi: 10.15761/GOD.1000189 Volume 3(5): 363-370 Zhang XR (2016) Efficacy and safety of imiquimod for verruca planae: A systematic review “Systematic review,” “Randomized controlled trial,” “Treatment”). was assessed using the I2 test. And I2 value >50% was considered there existed substantial heterogeneity. In such a case, random effects model Study selection was used. Results were expressed with relative risk (RR) and 95% To determine eligibility for inclusion in the review, we searched all confidence interval (CI) and the test level α=0.05. Publication bias was titles and abstracts that analyses the efficacy of imiquimod for treating displayed graphically by using funnel plots (Figures 1 and 2). verruca planae with control group. There were no limitations on the study design, participant’s age, gender, or nationality. We identified 68 Result articles in the initial search. Two of them were in English, others in Characteristics of the included publications Chinese. Through manual review of the citations from these articles, we removed 39 articles including general reviews, case reports, The basic characteristics of the included studies were shown in investigative research, commentaries and other non-clinical trials. We Table 1, including the total number of cases, the number of excluded identified 28 original studies that were eligible for inclusion criteria and the lost, the age, course of disease, the number of effective cases assessment. After reviewing the full text of these 28 studies, we excluded and the intervention measures. 2 articles of non RCT nature. In the end, we selected 26 studies that Quality assessment met the inclusion criteria for this systematic review [4-29]. The search processes are presented in chart in Figure 1. All included studies were referred to the randomized grouping, and only 4 studies [4,9,10,20] described the details. All the studies Data extraction were unclear in reporting allocation concealment and blinding. 5 Studies were selected independently by two researchers who used studies [5,7,8,14,29] reported the number of withdraw. Assessment of the same criteria. The third researcher was involved in the discussion methodological quality of included studies was presented in Figure 2. if there were controversial issues. If the information is not complete Therapeutic evaluation or not clear, we contact original author to obtain the information and determine whether the study will be included. Total effect: Twenty six RCTs involving 2169 patients with verruca planae were included and assessed. Results showed that the effective rate Quality assessment of topical imiquimod combined with intramuscular injection or other We used RevMan 5.1 (Review Manager Version 5.1) to analyze the oral drugs in the treatment of flat wart was obviously higher than using quality of the data, including random sequence generation, allocation other drugs alone. (RR=1.35 (95% CI 1.181.54.), P<0.00001) (Figure 3), concealment, blinding of participants and personnel, blinding of 10 studies [4,10-11,17-18,20-21,23,27,29] described the efficacy at the outcome assessment, incomplete outcome data, selective reporting and end of 4 weeks. As there exist statistical heterogeneity among the studies other bias (Figure 2). (P<0.00001, I²=82%), meta-analysis was performed using a random effects model. The results showed that the efficacy of test group was Data synthesis and analysis significantly higher than that in control group. The difference had no We analysed the data using RevMan 5.1.Chi square test was used statistical significance. (RR=1.81, 95%CI (0.91, 1.54), P=0.21) (Figure to test for heterogeneity. The degree of heterogeneity between studies 4A.2.1.1.). 6 studies [5,17-18,20-22] described the efficacy at the end Figure 1. Flowchart of literature search and study selection. Glob Dermatol, 2016 doi: 10.15761/GOD.1000189 Volume 3(5): 363-370 Zhang XR (2016) Efficacy and safety of imiquimod for verruca planae: A systematic review Figure 2. Assessment of methodological quality of included studies (2A.Risk of bias graph; 2B. Risk of bias summary). of 6 weeks. As there was no statistical heterogeneity (P=0.08, I²=48%), only tretinoin cream once per day; results showed that the effective meta-analysis was performed using a fixed effects model. The results rate in imiquimod group was significantly higher than tretinoin showed that the efficacy in the test group was significantly higher than cream group (RR=1.41, 95%CI (1.25, 1.59), P<0.00001); the effective that in control group (RR=1.42, 95%CI (1.27, 1.60), P<0.00001) (Figure rate of imiquimod combined with BCG-PSN group was higher than 4B), 19 studies [4,6-21,24-26,28] described the efficacy at the end of 8 that of tretinoin cream combined with BCG-PSN group (RR=1.56, weeks. As there existed statistical heterogeneity (P<0.00001, I²=80%), 95%CI (1.27, 1.91), P<0.0001); the effective rate of imiquimod alone meta-analysis was performed using a random effects model. The results or in combination with tretinoin cream group was higher than that of showed that the efficacy in the test group was significantly higher than tretinoin cream alone group (RR=1.32, 95%CI (1.14, 1.54), P =0.0003) that in control group (RR=1.43, 95%CI (1.22, 1.67), P<0.00001] (Figure (Figure 5A.3.1.1.).