{"title":"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。","authors":"Larisa Pinte , Alina Dima , Anamaria Draghici , Maria Caraghiulea , Ioana Andreea Zamfir-Gradinaru , Cristian Baicus","doi":"10.1016/j.autrev.2024.103670","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Aim</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div><div>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.</div><div>We performed descriptive and comparative analyses using statistical tests where applicable.</div><div>This review followed PRISMA guidelines, and the protocol was registered on PROSPERO (CRD42024544811).</div></div><div><h3>Results</h3><div>Out of 2818 study protocols identified, 608 met the eligibility criteria, the vast majority (96.9 %) focusing on non-replicating RNA.</div><div>Most targeted were infectious diseases (66.6 %), primarily COVID-19 (51.3 %), followed by cancers (29.1 %), and other conditions (4.3 %).</div><div>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 %, <em>p</em> < 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).</div><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 12","pages":"Article 103670"},"PeriodicalIF":9.2000,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Autoimmunity, a relevant exclusion criterion in the development of mRNA-based compounds: A systematic review of clinical trials registries\",\"authors\":\"Larisa Pinte , Alina Dima , Anamaria Draghici , Maria Caraghiulea , Ioana Andreea Zamfir-Gradinaru , Cristian Baicus\",\"doi\":\"10.1016/j.autrev.2024.103670\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>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.</div></div><div><h3>Aim</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div><div>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.</div><div>We performed descriptive and comparative analyses using statistical tests where applicable.</div><div>This review followed PRISMA guidelines, and the protocol was registered on PROSPERO (CRD42024544811).</div></div><div><h3>Results</h3><div>Out of 2818 study protocols identified, 608 met the eligibility criteria, the vast majority (96.9 %) focusing on non-replicating RNA.</div><div>Most targeted were infectious diseases (66.6 %), primarily COVID-19 (51.3 %), followed by cancers (29.1 %), and other conditions (4.3 %).</div><div>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 %, <em>p</em> < 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).</div><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>\",\"PeriodicalId\":8664,\"journal\":{\"name\":\"Autoimmunity reviews\",\"volume\":\"23 12\",\"pages\":\"Article 103670\"},\"PeriodicalIF\":9.2000,\"publicationDate\":\"2024-11-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Autoimmunity reviews\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1568997224001617\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autoimmunity reviews","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1568997224001617","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
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.
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.
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