Starting a new anti-seizure medication in drug-resistant epilepsy: Add-on or substitute?
Adolescent
Adult
Aged
Aged, 80 and over
Anticonvulsants
/ therapeutic use
Drug Resistant Epilepsy
/ drug therapy
Drug Substitution
/ statistics & numerical data
Drug Therapy, Combination
/ statistics & numerical data
Female
Humans
Logistic Models
Longitudinal Studies
Male
Middle Aged
Prospective Studies
Young Adult
anti-seizure medications
drug-resistant
epilepsy
outcomes
substitution
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
24
08
2020
revised:
01
11
2020
accepted:
02
11
2020
pubmed:
26
11
2020
medline:
20
4
2021
entrez:
25
11
2020
Statut:
ppublish
Résumé
Randomized studies in drug-resistant epilepsy (DRE) typically involve addition of a new anti-seizure medication (ASM). However, in clinical practice, if the patient is already taking multiple ASMs, then substitution of one of the current ASMs commonly occurs, despite little evidence supporting this approach. Longitudinal prospective study of seizure outcome after commencing a previously untried ASM in patients with DRE. Multivariable time-to-event and logistic regression models were used to evaluate outcomes by whether the new ASM was introduced by addition or substitution. A total of 816 ASM changes in 436 adult patients with DRE between 2010 and 2018 were analyzed. The new ASM was added on 407 (50.1%) occasions and substituted on 409 (49.9%). Mean patient follow-up was 3.2 years. Substitution was more likely if the new ASM was enzyme-inducing or in patients with a greater number of concurrent ASMs. ASM add-on was more likely if a γ-aminobutyric acid (GABA) agonist was introduced or if the patient had previously trialed a higher number of ASMs. The rate of discontinuation due to lack of tolerability was similar between the add-on and substitution groups. No difference between the add-on and substitution ASM introduction strategies was observed for the primary outcome of ≥50% seizure reduction at 12 months. Adding or substituting a new ASM in DRE has the same influence on seizure outcomes. The findings confirm that ASM alterations in DRE can be individualized according to concurrent ASM therapy and patient characteristics.
Substances chimiques
Anticonvulsants
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
228-237Subventions
Organisme : UCB
Informations de copyright
© 2020 International League Against Epilepsy.
Références
Chen Z, Brodie MJ, Liew D, Kwan P. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol. 2018;75(3):279-86.
Callaghan BC, Anand K, Hesdorffer D, Allen Hauser W, French JA. Likelihood of seizure remission in an adult population with refractory epilepsy. Ann Neurol. 2007;62(4):382-9.
Luciano AL, Shorvon SD. Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann Neurol. 2007;62(4):375-81.
Neligan A, Bell GS, Elsayed M, Sander JW, Shorvon SD. Treatment changes in a cohort of people with apparently drug-resistant epilepsy: an extended follow-up. J Neurol Neurosurg Psychiatry. 2012;83(8):810-3.
St Louis E. Truly rational polytherapy: maximizing efficacy and minimizing drug interactions, drug load, and adverse effects. Curr Neuropharmacol. 2009;7(2):96-105.
French JA, Faught E. Rational polytherapy. Epilepsia. 2009;50(Suppl 8):63-8.
Krauss GL, Sperling MR. Treating patients with medically resistant epilepsy. Neurol Clin Pract. 2011;1(1):14-23.
Beyenburg S, Stavem K, Schmidt D. Placebo-corrected efficacy of modern antiepileptic drugs for refractory epilepsy: systematic review and meta-analysis. Epilepsia. 2010;51(1):7-26.
Canevini MP, De Sarro G, Galimberti CA, Gatti G, Licchetta L, Malerba A, et al. Relationship between adverse effects of antiepileptic drugs, number of coprescribed drugs, and drug load in a large cohort of consecutive patients with drug-refractory epilepsy: Adverse Effects and Drug Load. Epilepsia. 2010;51(5):797-804.
WHO. WHOCC - ATC/DDD Index. Available from: https://www.whocc.no/atc_ddd_index/?code=N03A&showdescription=nofiles/1534/atc_ddd_index.html
Mula M, Zaccara G, Galimberti CA, Ferrò B, Canevini MP, Mascia A, et al. Validated outcome of treatment changes according to International League Against Epilepsy criteria in adults with drug-resistant focal epilepsy. Epilepsia. 2019;60(6):1114-23.
DeGiorgio CM, Markovic D, Mazumder R, Moseley BD. Ranking the leading risk factors for sudden unexpected death in epilepsy. Front Neurol. 2017;8:473.
Hao X, Chen Z, Yan B, Kwan P, Zhou D. Impact of drug manipulation on seizure freedom in adults with uncontrolled epilepsy: a prospective controlled study in Rural China. CNS Drugs. 2017;31(3):237-43.
Jette N, Hemming K, Hutton J, Marson AG. Topiramate add-on for drug-resistant partial epilepsy. In: The Cochrane C, editor. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 2002. p. CD001417.
Marson AG, Al-Kharusi AM, Alwaidh M, , Appleton R, Baker GA, Chadwick DW, et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1000-15.
Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1016-26.
Sen A, Jette N, Husain M, Sander JW. Epilepsy in older people. Lancet. 2020;395(10225):735-48.
Riss J, Cloyd J, Gates J, Collins S. Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008;118(2):69-86.
Callaghan B, Schlesinger M, Rodemer W, Pollard J, Hesdorffer D, Allen Hauser W, French J. Remission and relapse in a drug-resistant epilepsy population followed prospectively. Epilepsia. 2011;52(3):619-26.
Foldvary-Schaefer N, Fong JS, Morrison S, Wang L, Bena J. Lacosamide tolerability in adult patients with partial-onset seizures: Impact of planned reduction and mechanism of action of concomitant antiepileptic drugs. Epilepsy Behav. 2016;57(Pt A):155-60.
Hu Y, Lu Y, Yu W, Shen D, Xiao Z, Xi Z, Wang X. Long-term retention rate of topiramate as initial monotherapy in Chinese patients with newly diagnosed epilepsy: a prospective, observational study. Epilepsy Res. 2010;90(3):278-84.
Jacob L, Hamer HM, Kostev K. Persistence with antiepileptic drugs in epilepsy patients treated in neurological practices in Germany. Epilepsy Behav. 2017;73:204-7.
Bonnett L, Smith CT, Smith D, Williamson P, Chadwick D, Marson AG. Prognostic factors for time to treatment failure and time to 12 months of remission for patients with focal epilepsy: post-hoc, subgroup analyses of data from the SANAD trial. Lancet Neurol. 2012;11(4):331-40.
Margolis JM, Chu BC, Wang ZJ, Copher R, Cavazos JE. Effectiveness of antiepileptic drug combination therapy for partial-onset seizures based on mechanisms of action. JAMA Neurol. 2014;71(8):985-93.
Chen B, Choi H, Hirsch LJ, Moeller J, Javed A, Kato K, et al. Cosmetic side effects of antiepileptic drugs in adults with epilepsy. Epilepsy Behav. 2015;42:129-37.
Martínez-Lizana E, Gil-Lopez F, Donaire A, Aparicio J, Brandt A, Carreño M. Outcome of treatment changes in patients with drug-resistant chronic epilepsy: a tertiary center experience. Epilepsy Res. 2017;136:97-102.
Sachdeo R. Monotherapy clinical trial design. Neurology. 2007;69(24 Suppl 3):S23-7.
Beydoun A, Kutluay E. Conversion to monotherapy. Neurology. 2003;60(11 Suppl 4):S13.
French JA, Wang S, Warnock B, Temkin N. Historical control monotherapy design in the treatment of epilepsy: historical control monotherapy. Epilepsia. 2010;51(10):1936-43.
Semah F, Thomas P, Coulbaut S, Derambure P. Early add-on treatment vs alternative monotherapy in patients with partial epilepsy. Epileptic Dis Int Epilepsy J Videotape. 2014;16(2):165-74.
Beghi E, Gatti G, Tonini C, Ben-Menachem E, Chadwick DW, Nikanorova M, et al. Adjunctive therapy versus alternative monotherapy in patients with partial epilepsy failing on a single drug: a multicentre, randomised, pragmatic controlled trial. Epilepsy Res. 2003;57(1):1-13.
Wang X, He R, Zeng Q, Wang Y, Zhu P, Bao Y, et al. Substitution has better efficacy than add-on therapy for patients with focal epilepsy after their first antiepileptic drug treatments fail. Seizure. 2019;64:23-8.
Perucca P, Carter J, Vahle V, Gilliam FG. Adverse antiepileptic drug effects. Neurology. 2009;72(14):1223-9.
Franco V, Canevini MP, De Sarro G, Fattore C, Fedele G, Galimberti CA, et al. Does screening for adverse effects improve health outcomes in epilepsy? A randomized trial. Neurology. 2020;95(3):e239-46.