Factors associated with increased health‐related quality‐of‐life benefits in hereditary transthyretin amyloidosis polyneuropathy patients treated with inotersen

Introduction/Aims Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PN) is a genetic condition associated with significant morbidity and mortality. In this study we aimed to identify patient subgroups exhibiting the greatest health‐related quality of life (HRQL) benefit from inotersen treatment. Methods We examined data from the inotersen phase 2/3 randomized, controlled trial for ATTRv‐PN, NEURO‐TTR (NCT01737398, 66 weeks). LASSO regression models predicted changes in Norfolk QoL‐DN total score (TQoL, range −4 to 136; higher scores indicate poorer HRQL) from baseline in the inotersen and placebo arm, respectively. Individualized efficacy scores (ES) were calculated as differences between predicted change scores had patients received inotersen vs placebo. Patients were ranked by ES to define the greatest‐benefit subpopulation (top 50%). Characteristics of the top 50% and bottom 50% of patients were compared. Results The overall mean ± standard deviation TQoL change was −0.20 ± 19.13 for inotersen (indicating no change) and 10.77 ± 21.13 for placebo (indicating deterioration). Within the highest‐benefit patients, mean TQoL change was −11.03 ± 17.06 (improvement) for inotersen and 11.24 ± 22.97 (deterioration) for placebo (P