Cargando…

Conversion to eslicarbazepine acetate monotherapy: A pooled analysis of 2 phase III studies

OBJECTIVE: To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy. METHODS: This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following...

Descripción completa

Detalles Bibliográficos
Autores principales: Sperling, Michael R., French, Jacqueline, Jacobson, Mercedes P., Pazdera, Ladislav, Gough, Mallory, Cheng, Hailong, Grinnell, Todd, Blum, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826334/
https://www.ncbi.nlm.nih.gov/pubmed/26911639
http://dx.doi.org/10.1212/WNL.0000000000002497
_version_ 1782426321904730112
author Sperling, Michael R.
French, Jacqueline
Jacobson, Mercedes P.
Pazdera, Ladislav
Gough, Mallory
Cheng, Hailong
Grinnell, Todd
Blum, David
author_facet Sperling, Michael R.
French, Jacqueline
Jacobson, Mercedes P.
Pazdera, Ladislav
Gough, Mallory
Cheng, Hailong
Grinnell, Todd
Blum, David
author_sort Sperling, Michael R.
collection PubMed
description OBJECTIVE: To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy. METHODS: This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control). In each study, treatment was considered effective if the upper 95% confidence limit for exit rate was lower than the historical control threshold (65.3%). RESULTS: Pooled exit rates were as follows: ESL 1,600 mg = 20.6% (95% confidence interval: 15.6%–26.8%); ESL 1,200 mg = 30.8% (23.0%–40.5%). Use of 2 baseline AEDs or rescue medication, US location, epilepsy duration ≥20 years, and higher maximum baseline seizure frequency were associated with higher exit risks. Median percent reductions in standardized seizure frequency between baseline and the 18-week double-blind period were as follows: ESL 1,600 mg = 43.2%; ESL 1,200 mg = 35.7%; baseline carbamazepine use was associated with smaller reductions. Safety profiles were similar between ESL doses. CONCLUSIONS: Exit rates for ESL monotherapy (1,600 mg and 1,200 mg once daily) were lower than the historical control threshold, irrespective of baseline AED use and region, with no additional safety concerns identified. Clinical factors and location clearly influence treatment responses in conversion-to-monotherapy trials. CLASSIFICATION OF EVIDENCE: This pooled analysis provides Class IV evidence that for adults with medically uncontrolled partial-onset seizures, ESL monotherapy is well tolerated and effective.
format Online
Article
Text
id pubmed-4826334
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Lippincott Williams & Wilkins
record_format MEDLINE/PubMed
spelling pubmed-48263342016-04-21 Conversion to eslicarbazepine acetate monotherapy: A pooled analysis of 2 phase III studies Sperling, Michael R. French, Jacqueline Jacobson, Mercedes P. Pazdera, Ladislav Gough, Mallory Cheng, Hailong Grinnell, Todd Blum, David Neurology Article OBJECTIVE: To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy. METHODS: This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control). In each study, treatment was considered effective if the upper 95% confidence limit for exit rate was lower than the historical control threshold (65.3%). RESULTS: Pooled exit rates were as follows: ESL 1,600 mg = 20.6% (95% confidence interval: 15.6%–26.8%); ESL 1,200 mg = 30.8% (23.0%–40.5%). Use of 2 baseline AEDs or rescue medication, US location, epilepsy duration ≥20 years, and higher maximum baseline seizure frequency were associated with higher exit risks. Median percent reductions in standardized seizure frequency between baseline and the 18-week double-blind period were as follows: ESL 1,600 mg = 43.2%; ESL 1,200 mg = 35.7%; baseline carbamazepine use was associated with smaller reductions. Safety profiles were similar between ESL doses. CONCLUSIONS: Exit rates for ESL monotherapy (1,600 mg and 1,200 mg once daily) were lower than the historical control threshold, irrespective of baseline AED use and region, with no additional safety concerns identified. Clinical factors and location clearly influence treatment responses in conversion-to-monotherapy trials. CLASSIFICATION OF EVIDENCE: This pooled analysis provides Class IV evidence that for adults with medically uncontrolled partial-onset seizures, ESL monotherapy is well tolerated and effective. Lippincott Williams & Wilkins 2016-03-22 /pmc/articles/PMC4826334/ /pubmed/26911639 http://dx.doi.org/10.1212/WNL.0000000000002497 Text en © 2016 American Academy of Neurology This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
spellingShingle Article
Sperling, Michael R.
French, Jacqueline
Jacobson, Mercedes P.
Pazdera, Ladislav
Gough, Mallory
Cheng, Hailong
Grinnell, Todd
Blum, David
Conversion to eslicarbazepine acetate monotherapy: A pooled analysis of 2 phase III studies
title Conversion to eslicarbazepine acetate monotherapy: A pooled analysis of 2 phase III studies
title_full Conversion to eslicarbazepine acetate monotherapy: A pooled analysis of 2 phase III studies
title_fullStr Conversion to eslicarbazepine acetate monotherapy: A pooled analysis of 2 phase III studies
title_full_unstemmed Conversion to eslicarbazepine acetate monotherapy: A pooled analysis of 2 phase III studies
title_short Conversion to eslicarbazepine acetate monotherapy: A pooled analysis of 2 phase III studies
title_sort conversion to eslicarbazepine acetate monotherapy: a pooled analysis of 2 phase iii studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826334/
https://www.ncbi.nlm.nih.gov/pubmed/26911639
http://dx.doi.org/10.1212/WNL.0000000000002497
work_keys_str_mv AT sperlingmichaelr conversiontoeslicarbazepineacetatemonotherapyapooledanalysisof2phaseiiistudies
AT frenchjacqueline conversiontoeslicarbazepineacetatemonotherapyapooledanalysisof2phaseiiistudies
AT jacobsonmercedesp conversiontoeslicarbazepineacetatemonotherapyapooledanalysisof2phaseiiistudies
AT pazderaladislav conversiontoeslicarbazepineacetatemonotherapyapooledanalysisof2phaseiiistudies
AT goughmallory conversiontoeslicarbazepineacetatemonotherapyapooledanalysisof2phaseiiistudies
AT chenghailong conversiontoeslicarbazepineacetatemonotherapyapooledanalysisof2phaseiiistudies
AT grinnelltodd conversiontoeslicarbazepineacetatemonotherapyapooledanalysisof2phaseiiistudies
AT blumdavid conversiontoeslicarbazepineacetatemonotherapyapooledanalysisof2phaseiiistudies