自身免疫是开发基于 mRNA 的化合物的相关排除标准：临床试验登记系统回顾。

IF 9.2 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews Pub Date : 2024-11-09 DOI:10.1016/j.autrev.2024.103670

Larisa Pinte , Alina Dima , Anamaria Draghici , Maria Caraghiulea , Ioana Andreea Zamfir-Gradinaru , Cristian Baicus

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引用次数: 0

摘要

背景：基于信使 RNA（mRNA）的化合物近来已被开发为治疗各种病症，尤其是癌症和传染性疾病的最有前途的替代疗法之一。目的：回顾当前基于 mRNA 的化合物的研究情况，重点关注自身免疫性疾病和/或接受免疫抑制治疗的参与者的纳入标准：我们根据专门制定的 PICO 框架，在最重要的临床试验登记处进行了全面搜索：世界卫生组织国际临床试验注册平台（ICTRP）门户网站、ClinicalTrials.gov、Cochrane对照试验中央注册中心（CENTRAL），以及辉瑞生物技术公司和Moderna公司的官方网站。数据提取遵循 CONSORT 核对表，重点是确定自身免疫性疾病患者和接受各种免疫抑制治疗者的特定排除标准，包括每日剂量、治疗时间和入组前所需的停药期。我们酌情使用统计检验进行了描述性分析和比较分析。本综述遵循 PRISMA 指南，研究方案已在 PROSPERO 上注册（CRD42024544811）：在确定的 2818 项研究方案中，有 608 项符合资格标准，其中绝大多数（96.9%）侧重于非复制 RNA。大多数研究的目标是传染病（66.6%），主要是 COVID-19（51.3%），其次是癌症（29.1%）和其他疾病（4.3%）。60.8%的试验将患有自身免疫性疾病作为排除标准；与评估感染或其他病症的试验相比，针对癌症的试验的排除率更高（79.1% vs. 55.3% vs. 23.1%，P 结论：据我们所知，这项研究的主要目的是为癌症患者提供治疗：据我们所知，这是第一篇记录正在进行的基于 mRNA 的化合物研究的综述。这项工作凸显了在评估基于 mRNA 的化合物的临床试验中，自身免疫性疾病患者和接受免疫抑制治疗的患者所占比例较低。

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Autoimmunity, a relevant exclusion criterion in the development of mRNA-based compounds: A systematic review of clinical trials registries

Background

Messenger RNA (mRNA) -based compounds have been lately developed as one of the most promising treatment alternatives in a wide range of pathologies, especially cancers and infectious diseases.

Aim

To review the current research landscape on mRNA-based compounds, with a focus on the inclusion criteria used for participants with autoimmune diseases and/or under immunosuppressive treatments.

Methods

We conducted a comprehensive search based on PICO framework specifically formulated, throughout the most important clinical trial registries: WHO International Clinical Trials Registry Platform (ICTRP) portal, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as in the Pfizer-BioNTech and Moderna official websites.

Data extraction followed the CONSORT checklist, focusing on identifying the specific exclusion criteria for individuals with autoimmune diseases and those undergoing various immunosuppressive treatments, including daily dosages, treatment length, and required cessation periods before enrollment.

We performed descriptive and comparative analyses using statistical tests where applicable.

This review followed PRISMA guidelines, and the protocol was registered on PROSPERO (CRD42024544811).

Results

Out of 2818 study protocols identified, 608 met the eligibility criteria, the vast majority (96.9 %) focusing on non-replicating RNA.

Most targeted were infectious diseases (66.6 %), primarily COVID-19 (51.3 %), followed by cancers (29.1 %), and other conditions (4.3 %).

Having an autoimmune disease was used as an exclusion criterion in 60.8 % of trials; higher exclusion rates were observed in studies designed for cancers when compared to those assessing infections or other pathologies (79.1 % vs. 55.3 % vs. 23.1 %, p < 0.001), as well as in those using cell-based when compared to non-cell delivery systems (79.2 % vs. 57.2 %, p < 0.001).

Further, participants under immunosuppressive treatments were excluded from 77.5 % of the trials, primarily due to corticosteroid use. There is considerable variability in exclusion criteria related to immunosuppressive treatment length and cessation time prior enrollment, as well as in the daily corticosteroid dosage.

Conclusion

To the best of our knowledge, this is the first review to document the ongoing research designed for mRNA-based compounds. This work highlights the underrepresentation of patients with autoimmune diseases and those on immunosuppressive treatments in clinical trials assessing mRNA-based compounds.

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来源期刊

Autoimmunity reviews 医学-免疫学

CiteScore

24.70

自引率

4.40%

发文量

164

审稿时长

21 days

期刊介绍： Autoimmunity Reviews is a publication that features up-to-date, structured reviews on various topics in the field of autoimmunity. These reviews are written by renowned experts and include demonstrative illustrations and tables. Each article will have a clear "take-home" message for readers. The selection of articles is primarily done by the Editors-in-Chief, based on recommendations from the international Editorial Board. The topics covered in the articles span all areas of autoimmunology, aiming to bridge the gap between basic and clinical sciences. In terms of content, the contributions in basic sciences delve into the pathophysiology and mechanisms of autoimmune disorders, as well as genomics and proteomics. On the other hand, clinical contributions focus on diseases related to autoimmunity, novel therapies, and clinical associations. Autoimmunity Reviews is internationally recognized, and its articles are indexed and abstracted in prestigious databases such as PubMed/Medline, Science Citation Index Expanded, Biosciences Information Services, and Chemical Abstracts.