Inotersen (Tegsedi) is indicated for adults with hereditary transthyretin-mediated amyloidosis (hATTR) with stage I or stage II polyneuropathy. Inotersen is administered through subcutaneous injection at a dose of 284 mg (300 mg inotersen sodium)/1.5 mL once every week using a single-dose pre-filled syringe. Oral supplementation with the recommended daily allowance of vitamin A (3,000 IU vitamin A per day) should be continued while on treatment alongside regular monitoring of platelet counts to inform dose adjustments. The recommended frequency of monitoring varies according to platelet count levels, ranging from daily to every two weeks. The price of inotersen is $8,076.92 per pre-filled syringe, which results in an annual cost of approximately $420,000.
The manufacturer submitted a cost-utility analysis comparing inotersen with best supportive care (BSC). BSC was defined as management of symptoms and support of function of failing organs. The analysis was conducted from the perspective of the Canadian publicly funded health care payer over a lifetime time horizon (41 years) with cycles defined as every four weeks. Future costs and benefits were discounted at 1.5%. A Markov model was developed with patients transitioning through three health stages based on ambulatory status and an absorbing death state. Patients in Coutinho stage I or II begin inotersen according to the baseline characteristics reported in the NEURO-TTR and were assumed to discontinue treatment upon reaching stage III. The clinical efficacy data used in the model came from the NEURO-TTR study by mapping Norfolk total quality-of-life (TQoL) values to the Coutinho disease stages. Utilities for each health state were found in the literature and converted in an attempt to represent Canadian health state preferences. Health-state utilities were further adjusted by treatment-specific time-dependent utilities based on a regression analysis of the Norfolk TQoL score reported in NEURO-TTR mapped to the EuroQol 5-Dimensions health status questionnaire (EQ-5D). Health-state costs were estimated based on interviews with Canadian clinicians. No treatment costs were assumed in patients on BSC; rather, the manufacturer assumed that patients who were on or had discontinued inotersen would have a 43% reduction in health-state costs across all Coutinho disease stages to reflect the reduction in health care resource use expected in patients with current or past exposure to inotersen.
The manufacturer reported that inotersen was $1,064,922 more costly than BSC and more effective, with 2.03 additional QALYs, resulting in an incremental cost-utility ratio (ICUR) of $523,448 per QALY gained. In this analysis, inotersen had a 0% probability of being the most likely cost-effective intervention at any willingness-to-pay threshold below $400,000 per QALY gained.
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