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TOPLINE:

Patients with multiple sclerosis (MS) have almost double the risk for seizures, with the risk even greater with sphingosine-1-phosphate receptor (S1PR) modulators, results of a new meta-analysis of randomized controlled trials (RCTs) suggest. Those with a progressive disease phenotype are at particularly high seizure risk.

METHODOLOGY:

  • The meta-analysis included 63 phase 3 RCTs with 53,535 patients.
  • Most of the studies included in the meta-analysis investigated disease-modifying treatments compared with placebo or an active comparator such as interferon beta, teriflunomide, and dimethyl fumarate, in terms of relapse rate and/or disability progression.
  • Researchers extracted relevant information from studies, including MS subtype (clinically isolated syndrome, relapsing-remitting, primary progressive, or secondary progressive MS), mean Expanded Disability Status Scale (EDSS) score, lesion volume on T2-hyperintense sequence, normalized brain volume, and number of seizures or epilepsy events.
  • They calculated the pooled effect size of studies on the incidence rate of seizure or epilepsy as the number of events per patient-years and explored which variables influenced the pooled effect size.

TAKEAWAY:

  • A total of 120 patients experienced epileptic seizure events over a median follow-up of 2 years, resulting in a pooled incidence rate of 68.0 (95% CI, 49.1-86.9) per 100,000 patient-years, which investigators noted is significantly higher than the general population rate of 34.6.
  • Higher seizure incidence rates were found among patients with progressive disease courses, longer time since clinical onset, higher EDSS scores, and lower normalized brain volume; age and T2 lesion volume did not affect the pooled effect size.
  • Patients treated with S1PR modulators (fingolimod, ozanimod, ponesimod, and siponimod) had more than double the risk for seizure compared with placebo or comparators (estimated incident seizure risk ratio, 2.45; P = .008).

IN PRACTICE:

“Our findings underscore epilepsy as a significant comorbidity in MS and emphasize the necessity for further research into its triggers, preventive measures and treatment strategies,” the authors wrote.

SOURCE:

The study, led by Valeria Pozzilli, Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine and Surgery, Campus Bio-Medico University, Roma, Italy, was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.

LIMITATIONS:

As none of the included RCTs considered epilepsy an exclusion criterion, patients with comorbid epilepsy may have been enrolled in these studies. There was significant diversity in reporting of adverse events across studies. While this study’s statistical methodology was robust, the findings can’t be applied directly to individuals due to the risk for ecological fallacy.

DISCLOSURES:

Pozzilli had no relevant conflicts of interests. See paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

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TOPLINE:

Patients with multiple sclerosis (MS) have almost double the risk for seizures, with the risk even greater with sphingosine-1-phosphate receptor (S1PR) modulators, results of a new meta-analysis of randomized controlled trials (RCTs) suggest. Those with a progressive disease phenotype are at particularly high seizure risk.

METHODOLOGY:

  • The meta-analysis included 63 phase 3 RCTs with 53,535 patients.
  • Most of the studies included in the meta-analysis investigated disease-modifying treatments compared with placebo or an active comparator such as interferon beta, teriflunomide, and dimethyl fumarate, in terms of relapse rate and/or disability progression.
  • Researchers extracted relevant information from studies, including MS subtype (clinically isolated syndrome, relapsing-remitting, primary progressive, or secondary progressive MS), mean Expanded Disability Status Scale (EDSS) score, lesion volume on T2-hyperintense sequence, normalized brain volume, and number of seizures or epilepsy events.
  • They calculated the pooled effect size of studies on the incidence rate of seizure or epilepsy as the number of events per patient-years and explored which variables influenced the pooled effect size.

TAKEAWAY:

  • A total of 120 patients experienced epileptic seizure events over a median follow-up of 2 years, resulting in a pooled incidence rate of 68.0 (95% CI, 49.1-86.9) per 100,000 patient-years, which investigators noted is significantly higher than the general population rate of 34.6.
  • Higher seizure incidence rates were found among patients with progressive disease courses, longer time since clinical onset, higher EDSS scores, and lower normalized brain volume; age and T2 lesion volume did not affect the pooled effect size.
  • Patients treated with S1PR modulators (fingolimod, ozanimod, ponesimod, and siponimod) had more than double the risk for seizure compared with placebo or comparators (estimated incident seizure risk ratio, 2.45; P = .008).

IN PRACTICE:

“Our findings underscore epilepsy as a significant comorbidity in MS and emphasize the necessity for further research into its triggers, preventive measures and treatment strategies,” the authors wrote.

SOURCE:

The study, led by Valeria Pozzilli, Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine and Surgery, Campus Bio-Medico University, Roma, Italy, was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.

LIMITATIONS:

As none of the included RCTs considered epilepsy an exclusion criterion, patients with comorbid epilepsy may have been enrolled in these studies. There was significant diversity in reporting of adverse events across studies. While this study’s statistical methodology was robust, the findings can’t be applied directly to individuals due to the risk for ecological fallacy.

DISCLOSURES:

Pozzilli had no relevant conflicts of interests. See paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

 

TOPLINE:

Patients with multiple sclerosis (MS) have almost double the risk for seizures, with the risk even greater with sphingosine-1-phosphate receptor (S1PR) modulators, results of a new meta-analysis of randomized controlled trials (RCTs) suggest. Those with a progressive disease phenotype are at particularly high seizure risk.

METHODOLOGY:

  • The meta-analysis included 63 phase 3 RCTs with 53,535 patients.
  • Most of the studies included in the meta-analysis investigated disease-modifying treatments compared with placebo or an active comparator such as interferon beta, teriflunomide, and dimethyl fumarate, in terms of relapse rate and/or disability progression.
  • Researchers extracted relevant information from studies, including MS subtype (clinically isolated syndrome, relapsing-remitting, primary progressive, or secondary progressive MS), mean Expanded Disability Status Scale (EDSS) score, lesion volume on T2-hyperintense sequence, normalized brain volume, and number of seizures or epilepsy events.
  • They calculated the pooled effect size of studies on the incidence rate of seizure or epilepsy as the number of events per patient-years and explored which variables influenced the pooled effect size.

TAKEAWAY:

  • A total of 120 patients experienced epileptic seizure events over a median follow-up of 2 years, resulting in a pooled incidence rate of 68.0 (95% CI, 49.1-86.9) per 100,000 patient-years, which investigators noted is significantly higher than the general population rate of 34.6.
  • Higher seizure incidence rates were found among patients with progressive disease courses, longer time since clinical onset, higher EDSS scores, and lower normalized brain volume; age and T2 lesion volume did not affect the pooled effect size.
  • Patients treated with S1PR modulators (fingolimod, ozanimod, ponesimod, and siponimod) had more than double the risk for seizure compared with placebo or comparators (estimated incident seizure risk ratio, 2.45; P = .008).

IN PRACTICE:

“Our findings underscore epilepsy as a significant comorbidity in MS and emphasize the necessity for further research into its triggers, preventive measures and treatment strategies,” the authors wrote.

SOURCE:

The study, led by Valeria Pozzilli, Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine and Surgery, Campus Bio-Medico University, Roma, Italy, was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.

LIMITATIONS:

As none of the included RCTs considered epilepsy an exclusion criterion, patients with comorbid epilepsy may have been enrolled in these studies. There was significant diversity in reporting of adverse events across studies. While this study’s statistical methodology was robust, the findings can’t be applied directly to individuals due to the risk for ecological fallacy.

DISCLOSURES:

Pozzilli had no relevant conflicts of interests. See paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

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