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Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis.

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Title: Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis.
Authors: Hamad, Abdullah Ashraf (AUTHOR), Alkhawaldeh, Ibraheem M. (AUTHOR), Nashwan, Abdulqadir J. (AUTHOR), Meshref, Mostafa (AUTHOR), Imam, Yahia (AUTHOR)
Source: Neurological Sciences. May2025, Vol. 46 Issue 5, p1977-1985. 9p.
Subjects: Amyotrophic lateral sclerosis, Vital capacity (Respiration), Cerebrospinal fluid, Genetic mutation, Patient safety
Abstract: Objective: Tofersen, an antisense oligonucleotide, has recently received FDA and EMA approval for treating amyotrophic lateral sclerosis (ALS) in adults with SOD1 gene mutations. This systematic review and meta-analysis synthesized evidence on tofersen's safety and efficacy in patients with SOD1-related ALS. Methods: A comprehensive search of three databases was conducted from inception through October 2024. Eligible studies included clinical trials, observational studies, and case studies. Meta-analyses were conducted using a random-effects model in RevMan. Results: Twelve studies involving 195 patients treated with tofersen met the inclusion criteria, comprising two randomized controlled trials (RCTs), five cohort studies, one case series, and four case reports. Tofersen demonstrated promising effects, notably reducing SOD1 levels in cerebrospinal fluid and neurofilament light chain (NfL) in plasma, a biomarker strongly correlated with ALS progression and survival. Meta-analysis of RCTs showed a significantly lower rate of decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores from baseline in the tofersen group compared to placebo (SMD = 0.44, 95% CI [0.05 to 0.83], P = 0.03) and a significant reduction in the decline of predicted Slow Vital Capacity (P = 0.005). In a pre-post meta-analysis of five studies, a significant decrease in ALS progression rate (ALSFRS-R decline rate) was observed (MD = -0.28, 95% CI [-0.40 to -0.15], P < 0.0001). Reported adverse events were consistent with ALS progression or procedural effects. Conclusion: Current evidence suggests that tofersen effectively reduces SOD1 and NfL levels and slow disease progression in SOD1 ALS, showing promise as a targeted therapeutic option. [ABSTRACT FROM AUTHOR]
Copyright of Neurological Sciences is the property of Springer Nature 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.)
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  Data: Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis.
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  Data: &lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Hamad%2C+Abdullah+Ashraf%22&quot;&gt;Hamad, Abdullah Ashraf&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Alkhawaldeh%2C+Ibraheem+M%2E%22&quot;&gt;Alkhawaldeh, Ibraheem M.&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Nashwan%2C+Abdulqadir+J%2E%22&quot;&gt;Nashwan, Abdulqadir J.&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Meshref%2C+Mostafa%22&quot;&gt;Meshref, Mostafa&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Imam%2C+Yahia%22&quot;&gt;Imam, Yahia&lt;/searchLink&gt; (AUTHOR)
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22Neurological+Sciences%22&quot;&gt;Neurological Sciences&lt;/searchLink&gt;. May2025, Vol. 46 Issue 5, p1977-1985. 9p.
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  Data: &lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Amyotrophic+lateral+sclerosis%22&quot;&gt;Amyotrophic lateral sclerosis&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Vital+capacity+%28Respiration%29%22&quot;&gt;Vital capacity (Respiration)&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Cerebrospinal+fluid%22&quot;&gt;Cerebrospinal fluid&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Genetic+mutation%22&quot;&gt;Genetic mutation&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Patient+safety%22&quot;&gt;Patient safety&lt;/searchLink&gt;
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  Data: Objective: Tofersen, an antisense oligonucleotide, has recently received FDA and EMA approval for treating amyotrophic lateral sclerosis (ALS) in adults with SOD1 gene mutations. This systematic review and meta-analysis synthesized evidence on tofersen&#39;s safety and efficacy in patients with SOD1-related ALS. Methods: A comprehensive search of three databases was conducted from inception through October 2024. Eligible studies included clinical trials, observational studies, and case studies. Meta-analyses were conducted using a random-effects model in RevMan. Results: Twelve studies involving 195 patients treated with tofersen met the inclusion criteria, comprising two randomized controlled trials (RCTs), five cohort studies, one case series, and four case reports. Tofersen demonstrated promising effects, notably reducing SOD1 levels in cerebrospinal fluid and neurofilament light chain (NfL) in plasma, a biomarker strongly correlated with ALS progression and survival. Meta-analysis of RCTs showed a significantly lower rate of decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores from baseline in the tofersen group compared to placebo (SMD = 0.44, 95% CI [0.05 to 0.83], P = 0.03) and a significant reduction in the decline of predicted Slow Vital Capacity (P = 0.005). In a pre-post meta-analysis of five studies, a significant decrease in ALS progression rate (ALSFRS-R decline rate) was observed (MD = -0.28, 95% CI [-0.40 to -0.15], P &lt; 0.0001). Reported adverse events were consistent with ALS progression or procedural effects. Conclusion: Current evidence suggests that tofersen effectively reduces SOD1 and NfL levels and slow disease progression in SOD1 ALS, showing promise as a targeted therapeutic option. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder&#39;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.&lt;/i&gt; (Copyright applies to all Abstracts.)
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        Value: 10.1007/s10072-025-07994-2
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      – Code: eng
        Text: English
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        PageCount: 9
        StartPage: 1977
    Subjects:
      – SubjectFull: Amyotrophic lateral sclerosis
        Type: general
      – SubjectFull: Vital capacity (Respiration)
        Type: general
      – SubjectFull: Cerebrospinal fluid
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      – SubjectFull: Genetic mutation
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      – SubjectFull: Patient safety
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      – TitleFull: Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis.
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              M: 05
              Text: May2025
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