Second monotherapy in childhood absence epilepsy
Avital Cnaan, Shlomo Shinnar, Ravindra Arya, Peter C Adamson, Peggy O Clark, Dennis Dlugos, Deborah G Hirtz, David Masur, Tracy A Glauser, Childhood Absence Epilepsy Study Group, Harry Abram, Ellen Albers, Samar J Bahna, Karen Ballaban-Gil, Jose Barrera, Tekolla Belaineh, Mary Bertrand, Hal Blumenfeld, Sarah Borror, Charlie Borzy, Susan Brantz, Candace Cardoza, Kevin Chapman, Harry T Chugani, Robert R Clancy, Peggy O Clark, Yong Collins, Terrie Conklin, Joan A Conry, Patricia K Crumrine, Jason Czachor, M Susan Dean, Sandra Dewar, Michael Duchowny, Deborah Dye, Tammy Eaton, Mary Jo Elgie, Michelle Ellis, Roy Elterman, Daniella Escobedo, Andrew Francis, L Matthew Frank, Tracy A Glauser, Hilary Gray, La June Grayson, May L Griebel, Laurie Guidry, Samantha Hagopian, Jennifer Haky, Amelia Halac, Angel Hernandez, Lee Howard, Krisa Hoyle Elgin, Pong Kankirawatana, Kent R Kelley, Juli Kidd, Divya Khurana, Paul M Levisohn, Donna Lowery, Mary Lou Maher, Angela Martinez, Karen McEwen, Sarah J McVey, Mary Miceli, Daniel K Miles, Jennifer Monahan, Elena Morales, Dianne Morus, Cyndi Mott, JoAnn Narus, Mark Nespeca, Edward Novotny Jr, Suzanne Oken, Juliann Paolicchi, Bryan Philbrook, Tami Quintero, Amber Reese-Porter, Jong M Rho, Tracee Ridley-Pryor, Angela Riggs, Colin Roberts, Kathy Romine, Veronique Ruppe, Russell P Saneto, Raman Sankar, Mark S Scher, Rebecca Schultz, Michael Schwabe, Dina Schwam, Sagar Shah, Gregory Sharp, Rolla Shbarou, Ruth C Shinnar, Shlomo Shinnar, Marcio Sotero de Menezes, Donovan Stock, Christina Lopez Talley, Susanna Taylor, Mamello Tekateka, Doris A Trauner, Edwin Trevathan, William R Turk, Colin B Van Orman, GeorgAnn Vanderjagt, Mary Warde, Jorge Vidaurre, Arie Weinstock, Nanastasia Welnick, Rhonda Werner, James Wheless, Angus A Wilfong, Korwyn Willliams, Shelley Williams, Teresa Williams, Jennifer Williamson, Khaled Zamel, Mary Zupanc, Avital Cnaan, Shlomo Shinnar, Ravindra Arya, Peter C Adamson, Peggy O Clark, Dennis Dlugos, Deborah G Hirtz, David Masur, Tracy A Glauser, Childhood Absence Epilepsy Study Group, Harry Abram, Ellen Albers, Samar J Bahna, Karen Ballaban-Gil, Jose Barrera, Tekolla Belaineh, Mary Bertrand, Hal Blumenfeld, Sarah Borror, Charlie Borzy, Susan Brantz, Candace Cardoza, Kevin Chapman, Harry T Chugani, Robert R Clancy, Peggy O Clark, Yong Collins, Terrie Conklin, Joan A Conry, Patricia K Crumrine, Jason Czachor, M Susan Dean, Sandra Dewar, Michael Duchowny, Deborah Dye, Tammy Eaton, Mary Jo Elgie, Michelle Ellis, Roy Elterman, Daniella Escobedo, Andrew Francis, L Matthew Frank, Tracy A Glauser, Hilary Gray, La June Grayson, May L Griebel, Laurie Guidry, Samantha Hagopian, Jennifer Haky, Amelia Halac, Angel Hernandez, Lee Howard, Krisa Hoyle Elgin, Pong Kankirawatana, Kent R Kelley, Juli Kidd, Divya Khurana, Paul M Levisohn, Donna Lowery, Mary Lou Maher, Angela Martinez, Karen McEwen, Sarah J McVey, Mary Miceli, Daniel K Miles, Jennifer Monahan, Elena Morales, Dianne Morus, Cyndi Mott, JoAnn Narus, Mark Nespeca, Edward Novotny Jr, Suzanne Oken, Juliann Paolicchi, Bryan Philbrook, Tami Quintero, Amber Reese-Porter, Jong M Rho, Tracee Ridley-Pryor, Angela Riggs, Colin Roberts, Kathy Romine, Veronique Ruppe, Russell P Saneto, Raman Sankar, Mark S Scher, Rebecca Schultz, Michael Schwabe, Dina Schwam, Sagar Shah, Gregory Sharp, Rolla Shbarou, Ruth C Shinnar, Shlomo Shinnar, Marcio Sotero de Menezes, Donovan Stock, Christina Lopez Talley, Susanna Taylor, Mamello Tekateka, Doris A Trauner, Edwin Trevathan, William R Turk, Colin B Van Orman, GeorgAnn Vanderjagt, Mary Warde, Jorge Vidaurre, Arie Weinstock, Nanastasia Welnick, Rhonda Werner, James Wheless, Angus A Wilfong, Korwyn Willliams, Shelley Williams, Teresa Williams, Jennifer Williamson, Khaled Zamel, Mary Zupanc
Abstract
Objective: To determine optimal second monotherapy for children with childhood absence epilepsy (CAE) experiencing initial treatment failure.
Methods: Children with CAE experiencing treatment failure during the double-blind phase of a randomized controlled trial comparing ethosuximide, valproic acid, and lamotrigine were randomized to open-label second monotherapy with one of the 2 other study therapies. Primary study outcome was freedom from failure proportion at week 16-20 and month 12 visits after randomization. Secondary study outcome was percentage of participants experiencing attentional dysfunction at these visits.
Results: A total of 208 children were enrolled, randomized, and received second therapy. At both week 16-20 visit and month 12 visit, ethosuximide's (63%, 57%) and valproic acid's (65%, 49%) freedom from failure proportions were similar to each other and higher than lamotrigine's (45%, 36%, p = 0.051 and p = 0.062). At both time points, ethosuximide and valproic acid had superior seizure control compared to lamotrigine (p < 0.0001). At both the week 16-20 and month 12 visits, attentional dysfunction was numerically more common with valproic acid than with ethosuximide or lamotrigine. For each medication, second monotherapy freedom from failure proportions demonstrated noninferiority to initial monotherapy freedom from failure proportions.
Conclusions: As second monotherapy, ethosuximide and valproic acid, demonstrated higher freedom from failure proportions and greater efficacy than lamotrigine; valproic acid was associated with more attentional dysfunction. Ethosuximide is the optimal second monotherapy for children with CAE not responding to initial therapy with other medications.
Clinicaltrialsgov identifier: NCT00088452.
Classification of evidence: This study provides Class III evidence that for children with CAE experiencing initial treatment failure, second monotherapy with ethosuximide or valproic acid is superior to lamotrigine.
© 2016 American Academy of Neurology.
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Source: PubMed