Effect of dosage failed of first antiepileptic drug on subsequent outcome

Martin J. Brodie, Sarah J.E. Barry, Ghazi A. Bamagous, Patrick Kwan

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Purpose: The recent definition of drug-resistant epilepsy proposed by the International League Against Epilepsy (ILAE) stipulated failure of an adequate trial of two tolerated, appropriately chosen and used antiepileptic drug (AED) schedules to achieve seizure freedom. Doses failed were not specifically discussed. We explored the effect of the doses at which the first and second AED regimens failed on subsequent outcomes in a population of adults with newly diagnosed epilepsy followed for up to 20 years. Methods: Patients in whom epilepsy was diagnosed and the first AED prescribed between July 1, 1982 and April 1, 2006, were followed until March 31, 2008. Dosage at which an AED failed was categorized according to the World Health Organization?s defined daily dose (DDD) for each drug. Cumulative incidence curves for time to final seizure freedom(no seizure for at least 1 year on unchanged dosage at last follow up) were stratified by whether the first regimen was failed at doses above or below the 25 50 or 75% cutoffs for the DDD of each AED. Key Findings: Among patients who had taken a second regimen (n = 327), those in whom the first AED failed at doses above the various cutoffs (particularly 50% and 75% DDD) had lower probability of becoming seizure-free at last follow-up (p = 0.06 for 25% DDD, p 61; 0.001 for both 50% and 75% DDD). The same difference was observed for patients who had taken a third regimen (n = 141; p = 0.23 for 25% DDD, p 61; 0.01 for 50% DDD; and p = 0.002 for 75% DDD). A trend to higher seizure-free rate was observed in patients who had taken the third regimen when both the first and second regimens failed at 61; 75% DDD. The difference remained significant after adjusting for covariates when using 50% DDD as the cutoff for patients who took a second regimen (hazard ratio 1.60, 95% confidence interval 1.08?2.37). Significance: Higher failure dosage of the first AED predicts poorer subsequent outcome. This methodology could be used to refine further the ILAE definition of drug-resistant epilepsy by exploring the doses need to fail to provide an adequate AED trial.
LanguageEnglish
Pages194-198
Number of pages5
JournalEpilepsia
Volume54
Issue number1
Early online date25 Oct 2012
DOIs
Publication statusPublished - 1 Jan 2013

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Anticonvulsants
Seizures
Epilepsy
Appointments and Schedules
Confidence Intervals
Incidence
Pharmaceutical Preparations
Population

Keywords

  • antiepileptic drugs
  • drug resistance
  • epilepsy
  • dose
  • seizures

Cite this

Brodie, Martin J. ; Barry, Sarah J.E. ; Bamagous, Ghazi A. ; Kwan, Patrick . / Effect of dosage failed of first antiepileptic drug on subsequent outcome. In: Epilepsia. 2013 ; Vol. 54, No. 1. pp. 194-198.
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Effect of dosage failed of first antiepileptic drug on subsequent outcome. / Brodie, Martin J.; Barry, Sarah J.E.; Bamagous, Ghazi A. ; Kwan, Patrick .

In: Epilepsia, Vol. 54, No. 1, 01.01.2013, p. 194-198.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of dosage failed of first antiepileptic drug on subsequent outcome

AU - Brodie, Martin J.

AU - Barry, Sarah J.E.

AU - Bamagous, Ghazi A.

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N2 - Purpose: The recent definition of drug-resistant epilepsy proposed by the International League Against Epilepsy (ILAE) stipulated failure of an adequate trial of two tolerated, appropriately chosen and used antiepileptic drug (AED) schedules to achieve seizure freedom. Doses failed were not specifically discussed. We explored the effect of the doses at which the first and second AED regimens failed on subsequent outcomes in a population of adults with newly diagnosed epilepsy followed for up to 20 years. Methods: Patients in whom epilepsy was diagnosed and the first AED prescribed between July 1, 1982 and April 1, 2006, were followed until March 31, 2008. Dosage at which an AED failed was categorized according to the World Health Organization?s defined daily dose (DDD) for each drug. Cumulative incidence curves for time to final seizure freedom(no seizure for at least 1 year on unchanged dosage at last follow up) were stratified by whether the first regimen was failed at doses above or below the 25 50 or 75% cutoffs for the DDD of each AED. Key Findings: Among patients who had taken a second regimen (n = 327), those in whom the first AED failed at doses above the various cutoffs (particularly 50% and 75% DDD) had lower probability of becoming seizure-free at last follow-up (p = 0.06 for 25% DDD, p 61; 0.001 for both 50% and 75% DDD). The same difference was observed for patients who had taken a third regimen (n = 141; p = 0.23 for 25% DDD, p 61; 0.01 for 50% DDD; and p = 0.002 for 75% DDD). A trend to higher seizure-free rate was observed in patients who had taken the third regimen when both the first and second regimens failed at 61; 75% DDD. The difference remained significant after adjusting for covariates when using 50% DDD as the cutoff for patients who took a second regimen (hazard ratio 1.60, 95% confidence interval 1.08?2.37). Significance: Higher failure dosage of the first AED predicts poorer subsequent outcome. This methodology could be used to refine further the ILAE definition of drug-resistant epilepsy by exploring the doses need to fail to provide an adequate AED trial.

AB - Purpose: The recent definition of drug-resistant epilepsy proposed by the International League Against Epilepsy (ILAE) stipulated failure of an adequate trial of two tolerated, appropriately chosen and used antiepileptic drug (AED) schedules to achieve seizure freedom. Doses failed were not specifically discussed. We explored the effect of the doses at which the first and second AED regimens failed on subsequent outcomes in a population of adults with newly diagnosed epilepsy followed for up to 20 years. Methods: Patients in whom epilepsy was diagnosed and the first AED prescribed between July 1, 1982 and April 1, 2006, were followed until March 31, 2008. Dosage at which an AED failed was categorized according to the World Health Organization?s defined daily dose (DDD) for each drug. Cumulative incidence curves for time to final seizure freedom(no seizure for at least 1 year on unchanged dosage at last follow up) were stratified by whether the first regimen was failed at doses above or below the 25 50 or 75% cutoffs for the DDD of each AED. Key Findings: Among patients who had taken a second regimen (n = 327), those in whom the first AED failed at doses above the various cutoffs (particularly 50% and 75% DDD) had lower probability of becoming seizure-free at last follow-up (p = 0.06 for 25% DDD, p 61; 0.001 for both 50% and 75% DDD). The same difference was observed for patients who had taken a third regimen (n = 141; p = 0.23 for 25% DDD, p 61; 0.01 for 50% DDD; and p = 0.002 for 75% DDD). A trend to higher seizure-free rate was observed in patients who had taken the third regimen when both the first and second regimens failed at 61; 75% DDD. The difference remained significant after adjusting for covariates when using 50% DDD as the cutoff for patients who took a second regimen (hazard ratio 1.60, 95% confidence interval 1.08?2.37). Significance: Higher failure dosage of the first AED predicts poorer subsequent outcome. This methodology could be used to refine further the ILAE definition of drug-resistant epilepsy by exploring the doses need to fail to provide an adequate AED trial.

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KW - drug resistance

KW - epilepsy

KW - dose

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