Indirect treatment comparison of the efficacy of patisiran and inotersen for hereditary transthyretin-mediated amyloidosis with polyneuropathy

Expert Opinion on Pharmacotherapy, 2021


Patisiran and inotersen are two therapies approved for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy, a rapidly progressive disease with a substantial clinical burden. This analysis indirectly compares the efficacy of patisiran and inotersen on neuropathy and quality of life (QOL).


Published results from the NEURO-TTR study of inotersen and individual patient data from the APOLLO study of patisiran were used. Indirect comparisons were conducted for 15-month changes in neuropathy and QOL endpoints: modified Neuropathy Impairment Score +7 (mNIS+7Ionis,), Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire, body mass index (BMI), and Polyneuropathy Disability (PND) score. Analyses were conducted under different assumptions about the impact of missing data and to adjust for baseline differences between studies.


Patisiran showed significantly greater treatment effects than inotersen for mNIS+7Ionis (mean difference: -12.3 [95% confidence interval: -21.4, -3.3]), Norfolk QOL-DN (-11.3 [-19.8, -2.9]), and BMI (1.0 [0.4, 1.7]). The proportion of patients with improvement or no change from baseline on PND score was higher for patisiran-treated patients (odds ratio: 8.9 [4.6, 17.5]). Results were consistent and robust across analyses and methods.


Patisiran demonstrated greater treatment effects on neuropathy and QOL than inotersen in patients with hATTR amyloidosis with polyneuropathy.

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Gorevic P, Franklin J, Chen J, Sajeev G, Wang JCH, Lin H