Meta-analysis of adverse events in clinical studies with antisense oligonucleotide therapies

Antisense oligonucleotides (ASOs) are increasingly being used as a platform to target various diseases. Currently, there are 13 USFDA- or EMA-approved ASO therapies. Adverse events resulting from ASO treatments are assessed on a per drug basis, but for many ongoing ASO developments targeting N-of-1 mutations, conventional randomized clinical trials to assess safety cannot be performed. Here, we conducted a systematic review and meta-analysis of adverse events in clinical studies conducting trials of ASO therapies. The study aims to provide better insight into the safety aspects of ASO design choices and to summarize knowledge of the safety aspects of ASOs so that we can better inform researchers and physicians of possible adverse events that can occur during (N-of-1) ASO treatments. Our results provide a list of common adverse events and event rates obtained from pooled data from both approved and non-approved ASO drugs, and we include recommendations that can provide insights into the nature of ASO-induced adverse events in future trials.