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In‐depth analysis of data from the RAS‐ALS study reveals new insights in rasagiline treatment for amyotrophic lateral sclerosis.

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Title: In‐depth analysis of data from the RAS‐ALS study reveals new insights in rasagiline treatment for amyotrophic lateral sclerosis.
Authors: Schuster, Joachim (AUTHOR), Dreyhaupt, Jens (AUTHOR), Mönkemöller, Karla (AUTHOR), Dupuis, Luc (AUTHOR), Dieterlé, Stéphane (AUTHOR), Weishaupt, Jochen H. (AUTHOR), Kassubek, Jan (AUTHOR), Petri, Susanne (AUTHOR), Meyer, Thomas (AUTHOR), Grosskreutz, Julian (AUTHOR), Schrank, Berthold (AUTHOR), Boentert, Matthias (AUTHOR), Emmer, Alexander (AUTHOR), Hermann, Andreas (AUTHOR), Zeller, Daniel (AUTHOR), Prudlo, Johannes (AUTHOR), Winkler, Andrea S. (AUTHOR), Grehl, Torsten (AUTHOR), Heneka, Michael T. (AUTHOR), Johannesen, Siw (AUTHOR)
Source: European Journal of Neurology. Apr2024, Vol. 31 Issue 4, p1-11. 11p.
Subjects: Amyotrophic lateral sclerosis, Single nucleotide polymorphisms, Data analysis, Randomized controlled trials, Statistical power analysis
Abstract: Background and purpose: In 2016, we concluded a randomized controlled trial testing 1 mg rasagiline per day add‐on to standard therapy in 252 amyotrophic lateral sclerosis (ALS) patients. This article aims at better characterizing ALS patients who could possibly benefit from rasagiline by reporting new subgroup analysis and genetic data. Methods: We performed further exploratory in‐depth analyses of the study population and investigated the relevance of single nucleotide polymorphisms (SNPs) related to the dopaminergic system. Results: Placebo‐treated patients with very slow disease progression (loss of Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised [ALSFRS‐R] per month before randomization of ≤0.328 points) showed a per se survival probability after 24 months of 0.85 (95% confidence interval = 0.65–0.94). The large group of intermediate to fast progressing ALS patients showed a prolonged survival in the rasagiline group compared to placebo after 6 and 12 months (p = 0.02, p = 0.04), and a reduced decline of ALSFRS‐R after 18 months (p = 0.049). SNP genotypes in the MAOB gene and DRD2 gene did not show clear associations with rasagiline treatment effects. Conclusions: These results underline the need to consider individual disease progression at baseline in future ALS studies. Very slow disease progressors compromise the statistical power of studies with treatment durations of 12–18 months using clinical endpoints. Analysis of MAOB and DRD2 SNPs revealed no clear relationship to any outcome parameter. More insights are expected from future studies elucidating whether patients with DRD2CC genotype (Rs2283265) show a pronounced benefit from treatment with rasagiline, pointing to the opportunities precision medicine could open up for ALS patients in the future. [ABSTRACT FROM AUTHOR]
Copyright of European Journal of Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: In‐depth analysis of data from the RAS‐ALS study reveals new insights in rasagiline treatment for amyotrophic lateral sclerosis.
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  Data: <searchLink fieldCode="AR" term="%22Schuster%2C+Joachim%22">Schuster, Joachim</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dreyhaupt%2C+Jens%22">Dreyhaupt, Jens</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mönkemöller%2C+Karla%22">Mönkemöller, Karla</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dupuis%2C+Luc%22">Dupuis, Luc</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dieterlé%2C+Stéphane%22">Dieterlé, Stéphane</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Weishaupt%2C+Jochen+H%2E%22">Weishaupt, Jochen H.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kassubek%2C+Jan%22">Kassubek, Jan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Petri%2C+Susanne%22">Petri, Susanne</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Meyer%2C+Thomas%22">Meyer, Thomas</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Grosskreutz%2C+Julian%22">Grosskreutz, Julian</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Schrank%2C+Berthold%22">Schrank, Berthold</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Boentert%2C+Matthias%22">Boentert, Matthias</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Emmer%2C+Alexander%22">Emmer, Alexander</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hermann%2C+Andreas%22">Hermann, Andreas</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zeller%2C+Daniel%22">Zeller, Daniel</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Prudlo%2C+Johannes%22">Prudlo, Johannes</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Winkler%2C+Andrea+S%2E%22">Winkler, Andrea S.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Grehl%2C+Torsten%22">Grehl, Torsten</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Heneka%2C+Michael+T%2E%22">Heneka, Michael T.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Johannesen%2C+Siw%22">Johannesen, Siw</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Journal+of+Neurology%22">European Journal of Neurology</searchLink>. Apr2024, Vol. 31 Issue 4, p1-11. 11p.
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  Data: <searchLink fieldCode="DE" term="%22Amyotrophic+lateral+sclerosis%22">Amyotrophic lateral sclerosis</searchLink><br /><searchLink fieldCode="DE" term="%22Single+nucleotide+polymorphisms%22">Single nucleotide polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Data+analysis%22">Data analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Randomized+controlled+trials%22">Randomized controlled trials</searchLink><br /><searchLink fieldCode="DE" term="%22Statistical+power+analysis%22">Statistical power analysis</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background and purpose: In 2016, we concluded a randomized controlled trial testing 1 mg rasagiline per day add‐on to standard therapy in 252 amyotrophic lateral sclerosis (ALS) patients. This article aims at better characterizing ALS patients who could possibly benefit from rasagiline by reporting new subgroup analysis and genetic data. Methods: We performed further exploratory in‐depth analyses of the study population and investigated the relevance of single nucleotide polymorphisms (SNPs) related to the dopaminergic system. Results: Placebo‐treated patients with very slow disease progression (loss of Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised [ALSFRS‐R] per month before randomization of ≤0.328 points) showed a per se survival probability after 24 months of 0.85 (95% confidence interval = 0.65–0.94). The large group of intermediate to fast progressing ALS patients showed a prolonged survival in the rasagiline group compared to placebo after 6 and 12 months (p = 0.02, p = 0.04), and a reduced decline of ALSFRS‐R after 18 months (p = 0.049). SNP genotypes in the MAOB gene and DRD2 gene did not show clear associations with rasagiline treatment effects. Conclusions: These results underline the need to consider individual disease progression at baseline in future ALS studies. Very slow disease progressors compromise the statistical power of studies with treatment durations of 12–18 months using clinical endpoints. Analysis of MAOB and DRD2 SNPs revealed no clear relationship to any outcome parameter. More insights are expected from future studies elucidating whether patients with DRD2CC genotype (Rs2283265) show a pronounced benefit from treatment with rasagiline, pointing to the opportunities precision medicine could open up for ALS patients in the future. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of European Journal of Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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