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. 2024 Apr;82(4):1-7.
doi: 10.1055/s-0044-1781463. Epub 2024 Apr 5.

Real-life experience with inotersen at CEPARM, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro

Moises Dias  1   2 , Luiz Felipe Pinto  2 , Marcus Vinícius Pinto  2   3 , Renata Gervais  1   2 , Paula Accioli  2 , Gabriela Amorim  2 , Mariana Guedes  2 , Carlos Perez Gomes  1   2 , Roberto Coury Pedrosa  2   4 , Márcia Waddington-Cruz  5
Affiliations

Real-life experience with inotersen at CEPARM, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro

Moises Dias et al. Arq Neuropsiquiatr. 2024 Apr.

Abstract
in English, Portuguese

Background: Hereditary transthyretin amyloidosis (ATTRv) is an inherited, progressive, and fatal disease still largely underdiagnosed. Mutations in the transthyretin (TTR) gene cause the TTR protein to destabilize, misfold, aggregate, and deposit in body tissues, which makes ATTRv a disease with heterogeneous clinical phenotype.

Objective: To describe the long-term efficacy and safety of inotersen therapy in patients with ATTRv peripheral neuropathy (ATTRv-PN).

Methods: Patients who completed the NEURO-TTR pivotal study and the NEURO-TTR OLE open-label extension study migrated to the present study and were followed-up for at least 18 more months to an average of 67 months and up to 76 months since day 1 of the inotersen therapy (D1-first dose of inotersen). Disease progression was evaluated by standard measures.

Results: Ten ATTRv-PN patients with Val30Met mutation were included. The mean disease duration on D1 was of 3 years, and the mean age of the patients was of 46.8 years. During an additional 18-month follow up, neurological function, based on the Neuropathy Impairment Score and the Polyneuropathy Disability Score, functionality aspects (Karnofsky Performance Status), and nutritional and cardiac aspects were maintained. No new safety signs have been noted.

Conclusion: The treatment with inotersen was effective and well tolerated for the average of 67 months and up to 76 months. Our results are consistent with those of larger phase-III trials.

Antecedentes: Amiloidose hereditária por transtirretina (ATTRv) é uma doença hereditária, progressiva e fatal ainda largamente subdiagnosticada. Mutações no gene transtirretina (TTR) promovem desestabilização, desdobramento, agregação e depósito da proteína TTR em tecidos do corpo, o que faz da ATTRv uma doença de fenótipo clínico heterogêneo.

Objetivo: Descrever a eficácia e segurança da terapia com inotersena no longo prazo em pacientes com neuropatia periférica ATTRv (ATTRv-PN). MéTODOS: Pacientes que completaram o estudo pivotal NEURO-TTR e o estudo de extensão aberta NEURO-TTR OLE migraram para este estudo e foram acompanhados por no mínimo 18 meses adicionais, em média por 67 meses, e por até 76 meses, desde o dia 1 da terapia com inotersena (D1–primeira dose de inotersena). A progressão da doença foi avaliada por medidas padronizadas.

Resultados: Dez pacientes com ATTRv-PN com mutação Val30Met foram incluídos. A duração média da doença no D1 era de 3 anos, e a média de idade dos pacientes era de 46,8 anos. Durante o período de acompanhamento adicional de 18 meses, a função neurológica, baseada no Neuropathy Impairment Score e no Polyneuropathy Disability Score, os aspectos de funcionalidade (Karnofsky Performance Status), nutricional e cardíacos estavam mantidos. Não se observou nenhum novo sinal de segurança. CONCLUSãO: O tratamento com inotersena foi eficaz e bem tolerado por 67 meses em média, e por até 76 meses. Nossos resultados são consistentes com os de estudos maiores de fase III.

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Conflict of interest statement

MWC received honoraria from NHI, Prothena, FoldRx, Ionis Pharmaceuticals, Akcea Therapeutics, Pfizer, Alnylan Pharmaceuticals, PTC Therapeutics, SOBI, and Genzyme for travel expenses, as a consultant member and as principal investigator in clinical trials. No potential competing interest was reported by the other authors.

Figures

Figure 1
Figure 1
Evolution of individual data from day 1 (D1) through the last evaluation (LE) on the Polyneuropathy Disability (PND) score.
Figure 2
Figure 2
Evolution of individual data from D1 through the LE on the Neuropathy Impairment Score (NIS). Note: D1 from Patient #1 is not available due to missing data; the last NIS evaluation of Patient #8 is not available due to a remote visit.
Figure 3
Figure 3
Delta of NIS and NIS trendline.
Figure 4
Figure 4
Evolution of individual data from D1 through the LE last evaluation regarding the Karnofsky Performance Status (KPS).
Figure 5
Figure 5
Individual data from D1 through the LE regarding the Body Mass Index (BMI). Note: The LE of Patient #8is not available due to a remote visit.
See this image and copyright information in PMC

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