Summary

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• Inotersen (Tegsedi) is an antisense oligonucleotide designed to reduce the production of transthyretin and is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.
• Four systematic reviews/meta-analyses compared Tegsedi with other treatments such as tafamidis, patisiran, and diflunisal.
• Compared to Tegsedi, tafamidis slightly reduces the progression of peripheral neuropathy but may not significantly improve the quality of life; patisiran shows substantial improvement in disability progression and quality of life after 18 months; diflunisal might reduce disability progression more than placebo, but its effect on quality-of-life remains unclear.
• The safety profile for Tegsedi includes a slight increase in mortality rate and the occurrence of severe adverse events when compared to placebo, leading to more discontinuations due to adverse effects.
• A network meta-analysis was considered unfeasible due to cross-trial heterogeneity among these drugs, indicating that direct comparisons are challenging without head-to-head trials.
• No specific information regarding population types or subgroup considerations beyond the distinction between hereditary and wild-type forms was provided by the studies reviewed.