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

Abstract

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.