Real-world treatment management in hereditary transthyretin amyloidosis - an experience report and proposal for therapy switch decision criteria.

Abstract

Background: Hereditary transthyretin amyloidosis is a rapidly progressive and lethal disease. Thanks to the increasing number of disease-modifying treatments, prognosis has improved significantly. However, new challenges regarding treatment response and when to change treatment remain unanswered. The objective of this study was to evaluate rationales for treatment switches from the past and to formulate learnings for future management.

Methods: In this retrospective single center study, we analyzed real-world data of 13 patients with hereditary transthyretin amyloidosis undergoing single or multiple treatment switches before January 2024. Data involved demographic characteristics as well as reasons for treatment switches in a descriptive and exploratory manner. Available amyloid specific therapies during the study period included tafamidis 20 mg, tafamidis 61 mg, patisiran, inotersen and vutrisiran.

Results: Switches from tafamidis 20 mg were most frequently due to disease progression (83.3%). Patisiran transitions predominantly occurred following vutrisiran's approval, driven by preference for subcutaneous administration and extended dosing intervals (65.0%). Two cases of switches from inotersen were both associated with severe adverse effects.

Conclusions: In this study, reasons for treatment switches were manifold, encompassing disease progression, the occurrence of adverse events, patient preferences and/or the availability of newly approved drugs. Hence, multidimensional consideration of these reasons remains pivotal in guiding the subsequent choice of medication in particular and managing hereditary transthyretin amyloidosis in general.