咪喹莫特治疗宫颈和阴道上皮内瘤变：系统评价和荟萃分析。

Imiquimod for Cervical and Vaginal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis.

机构信息

From the Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, and the Department of Pharmacoepidemiology and the Department of Health Promotion and Human Behavior, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, the Department of General Medicine, Oita University Faculty of Medicine, Oita, and the Department of Obstetrics and Gynecology, Shizuoka General Hospital, Shizuoka, Japan; and the Institute of Primary Health Care (BIHAM) and the Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

Each author has confirmed compliance with the journal's requirements for authorship.

出版信息

Obstet Gynecol. 2023 Aug 1;142(2):307-318. doi: 10.1097/AOG.0000000000005256. Epub 2023 Jul 5.

DOI:10.1097/AOG.0000000000005256

PMID:37411024

Abstract

OBJECTIVE

To evaluate the treatment efficacy and the risk of adverse events of imiquimod for cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia (VAIN), compared with placebo or no intervention.

DATA SOURCES

We searched Cochrane, PubMed, ISRCTN registry, ClinicalTrials.gov , and the World Health Organization International Clinical Trials Registry Platform up to November 23, 2022.

METHODS OF STUDY SELECTION

We included randomized controlled trials and prospective nonrandomized studies with control arms that investigated the efficacy of imiquimod for histologically confirmed CIN or VAIN. The primary outcomes were histologic regression of the disease (primary efficacy outcome) and treatment discontinuation due to side effects (primary safety outcome). We estimated pooled odds ratios (ORs) of imiquimod, compared with placebo or no intervention. We also conducted a meta-analysis of the proportions of patients with adverse events in the imiquimod arms.

TABULATION, INTEGRATION, AND RESULTS: Four studies contributed to the pooled OR for the primary efficacy outcome. An additional four studies were available for meta-analyses of proportions in the imiquimod arm. Imiquimod was associated with increased probability of regression (pooled OR 4.05, 95% CI 2.08-7.89). Pooled OR for CIN in the three studies was 4.27 (95% CI 2.11-8.66); results of one study were available for VAIN (OR, 2.67, 95% CI 0.36-19.71). Pooled probability for primary safety outcome in the imiquimod arm was 0.07 (95% CI 0.03-0.14). The pooled probabilities (95% CI) of secondary outcomes were 0.51 (0.20-0.81) for fever, 0.53 (0.31-0.73) for arthralgia or myalgia, 0.31 (0.18-0.47) for abdominal pain, 0.28 (0.09-0.61) for abnormal vaginal discharge or genital bleeding, 0.48 (0.16-0.82) for vulvovaginal pain, and 0.02 (0.01-0.06) for vaginal ulceration.

CONCLUSION

Imiquimod was found to be effective for CIN, whereas data on VAIN were limited. Although local and systemic complications are common, treatment discontinuation is infrequent. Thus, imiquimod is potentially an alternative therapy to surgery for CIN.

SYSTEMATIC REVIEW REGISTRATION

PROSPERO, CRD42022377982.

摘要

目的

评估咪喹莫特治疗宫颈上皮内瘤变（CIN）和阴道上皮内瘤变（VAIN）的疗效和不良事件风险，与安慰剂或不干预相比。

数据来源

截至 2022 年 11 月 23 日，我们检索了 Cochrane、PubMed、ISRCTN 注册处、ClinicalTrials.gov 和世界卫生组织国际临床试验注册平台。

研究选择方法

我们纳入了随机对照试验和前瞻性非随机研究，这些研究均设有对照组，以评估咪喹莫特治疗组织学确诊的 CIN 或 VAIN 的疗效。主要结局是疾病的组织学缓解（主要疗效结局）和因副作用而停止治疗（主要安全性结局）。我们估计了咪喹莫特与安慰剂或不干预相比的汇总优势比（OR）。我们还对咪喹莫特组不良事件患者的比例进行了荟萃分析。

列表、综合和结果：四项研究为主要疗效结局的汇总 OR 提供了数据。另外四项研究可用于咪喹莫特组比例的荟萃分析。咪喹莫特与更高的缓解概率相关（汇总 OR 4.05，95%CI 2.08-7.89）。三项研究中 CIN 的汇总 OR 为 4.27（95%CI 2.11-8.66）；一项研究提供了 VAIN 的结果（OR，2.67，95%CI 0.36-19.71）。咪喹莫特组主要安全性结局的汇总概率为 0.07（95%CI 0.03-0.14）。次要结局的汇总概率（95%CI）为发热 0.51（0.20-0.81）、关节痛或肌痛 0.53（0.31-0.73）、腹痛 0.31（0.18-0.47）、阴道分泌物异常或生殖器出血 0.28（0.09-0.61）、外阴阴道疼痛 0.48（0.16-0.82）和阴道溃疡 0.02（0.01-0.06）。