| Autor: |
Timothy M, Miller, Merit E, Cudkowicz, Angela, Genge, Pamela J, Shaw, Gen, Sobue, Robert C, Bucelli, Adriano, Chiò, Philip, Van Damme, Albert C, Ludolph, Jonathan D, Glass, Jinsy A, Andrews, Suma, Babu, Michael, Benatar, Christopher J, McDermott, Thos, Cochrane, Sowmya, Chary, Sheena, Chew, Han, Zhu, Fan, Wu, Ivan, Nestorov, Danielle, Graham, Peng, Sun, Manjit, McNeill, Laura, Fanning, Toby A, Ferguson, Stephanie, Fradette, Cathy, Zhong |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
The New England journal of medicine. 387(12) |
| ISSN: |
1533-4406 |
| Popis: |
The intrathecally administered antisense oligonucleotide tofersen reduces synthesis of the superoxide dismutase 1 (SOD1) protein and is being studied in patients with amyotrophic lateral sclerosis (ALS) associated with mutations inIn this phase 3 trial, we randomly assigned adults withA total of 72 participants received tofersen (39 predicted to have faster progression), and 36 received placebo (21 predicted to have faster progression). Tofersen led to greater reductions in concentrations of SOD1 in CSF and of neurofilament light chains in plasma than placebo. In the faster-progression subgroup (primary analysis), the change to week 28 in the ALSFRS-R score was -6.98 with tofersen and -8.14 with placebo (difference, 1.2 points; 95% confidence interval [CI], -3.2 to 5.5; P = 0.97). Results for secondary clinical end points did not differ significantly between the two groups. A total of 95 participants (88%) entered the open-label extension. At 52 weeks, the change in the ALSFRS-R score was -6.0 in the early-start cohort and -9.5 in the delayed-start cohort (difference, 3.5 points; 95% CI, 0.4 to 6.7); non-multiplicity-adjusted differences favoring early-start tofersen were seen for other end points. Lumbar puncture-related adverse events were common. Neurologic serious adverse events occurred in 7% of tofersen recipients.In persons with |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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