OBJECTIVE: To identify people with epilepsy who will not achieve a 12-month seizure remission within 5 years of starting treatment. METHODS: The Standard and New Antiepileptic Drug (SANAD) study is the largest prospective study in patients with epilepsy to date. We applied a recently developed multivariable approach to the SANAD dataset that takes into account not only baseline covariates describing a patient's history before diagnosis but also follow-up data as predictor variables. RESULTS: Changes in number of seizures and treatment history were the most informative time-dependent predictors and were associated with history of neurologic insult, epilepsy type, age at start of treatment, sex, and having a first-degree relative with epilepsy. Our model classified 95% of patients. Of those classified, 95% of patients observed not to achieve remission at 5 years were correctly classified (95% confidence interval [CI] 89.5%-100%), with 51% identified by 3 years and 90% within 4 years of follow-up. Ninety-seven percent (95% CI 93.3%-98.8%) of patients observed to achieve a remission within 5 years were correctly classified. Of those predicted not to achieve remission, 76% (95% CI 58.5%-88.2%) truly did not achieve remission (positive predictive value). The predictive model achieved similar accuracy levels via external validation in 2 independent United Kingdom-based datasets. CONCLUSION: Our approach generates up-to-date predictions of the patient's risk of not achieving seizure remission whenever new clinical information becomes available that could influence patient counseling and management decisions.

From the Departments of Biostatistics Faculty of Mathematics and Physics Charles University Prague Czech Republic

Neurology. 2018 Nov 27;91(22):989-990. doi: 10.1212/WNL.0000000000006561. PubMed

Epilepsy Curr. 2019 Sep;19(5):299-301. doi: 10.1177/1535759719868466. PubMed

Zobrazit více v PubMed

Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy. N Engl J Med 2011;365:919–926. PubMed

Kwan P, Arzimanoglou A, Berg AT, et al. . Definition of drug resistant epilepsy: consensus proposal by the ad hoc task force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010;51:1069–1077. PubMed

Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000;342:314–319. PubMed

Hitiris N, Mohanraj R, Norrie J, Sills GJ, Brodie MJ. Predictors of pharmacoresistant epilepsy. Epilepsy Res 2007;75:192–196. PubMed

Sillanpää M, Schmidt D. Predicting antiepileptic drug response in children with epilepsy. Expert Rev Neurother 2011;11:877. PubMed

Wassenaar M, Leijten FS, Egberts TC, Moons KG, Uijl SG. Prognostic factors for medically intractable epilepsy: a systematic review. Epilepsy Res 2013;106:301–310. PubMed

Sillanpää M, Schmidt D. Long-term outcome of medically treated epilepsy. Seizure 2017;44:211–216. PubMed

Arts WF, Brouwer OF, Peters AB, et al. . Course and prognosis of childhood epilepsy: 5-year follow-up of the Dutch Study of Epilepsy in Childhood. Brain 2004;127:1774–1784. PubMed

Huang L, Li S, He D, Bao W, Li L. A predictive risk model for medical intractability in epilepsy. Epilepsy Behav 2014;37:282–286. PubMed

Sillanpää M, Schmidt D. Early seizure frequency and aetiology predict long-term medical outcome in childhood-onset epilepsy. Brain 2009;132:989–998. PubMed

Marson AG, Al-Kharusi AM, Alwaidh M, et al. . The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet 2007;369:1016–1026. PubMed PMC

Marson AG, Al-Kharusi AM, Alwaidh M, 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;369:1000–1015. PubMed PMC

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;11:331–340. PubMed

Bonnett LJ, Smith CT, Smith D, Williamson PR, Chadwick D, Marson AG. Time to 12-month remission and treatment failure for generalised and unclassified epilepsy. J Neurol Neurosurg Psychiatry 2014;85:603–610. PubMed PMC

Marson A, Jacoby A, Johnson A, et al. . Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures: a randomised controlled trial. Lancet 2005;365:2007–2013. PubMed

Hart Y, Sander J, Sharvon S. National general practice study of epilepsy and epileptic seizures: objectives and study methodology of the largest reported prospective cohort study of epilepsy: National General Practice Study of Epilepsy and Epileptic Seizures (NGPSE). Neuroepidemiology 1988;8:221–227. PubMed

Vere D. MRC guidelines for good clinical practice in clinical trials. J Med Ethics 1999;25:280.

Shukralla AA, Tudur-Smith C, Powell GA, Williamson PR, Marson AG. Reporting of adverse events in randomised controlled trials of antiepileptic drugs using the CONSORT criteria for reporting harms. Epilepsy Res 2011;97:20–29. PubMed

Hughes DM, Komárek A, Czanner G, Garcia-Fiñana M. Dynamic longitudinal discriminant analysis using multiple longitudinal markers of different types. Stat Methods Med Res 2018;27:2060–2080. PubMed PMC

Plummer M. Penalized loss functions for bayesian model comparison. Biostatistics 2008;9:523–539. PubMed

Hughes DM, Komárek A, Bonnett LJ, Czanner G, García‐Fiñana M. Dynamic classification using credible intervals in longitudinal discriminant analysis. Stat Med 2017;36:3858–3874. PubMed PMC

Steyerberg E. Clinical Prediction Models: A Practical Approach to Development, Validation, and Updating. Berlin: Springer Science & Business Media; 2008.

Kim LG, Johnson TL, Marson AG, Chadwick DW; MRC MESS Study Group. Prediction of risk of seizure recurrence after a single seizure and early epilepsy: further results from the MESS trial. Lancet Neurol 2006;5:317–322. PubMed

Bonnett LJ, Marson AG, Johnson A, et al. . External validation of a prognostic model for seizure recurrence following a first unprovoked seizure and implications for driving. PLoS One 2014;9:e99063. PubMed PMC

Szaflarski JP, Martin RC, Faught E, et al. . Quality indicator for epilepsy treatment 15 (QUIET-15): intervening after recurrent seizures in the elderly. Epilepsy Behav 2017;70:253–258. PubMed PMC

Cockerell OC, Sander J, Hart YM, Shorvon SD, Johnson A. Remission of epilepsy: results from the National General Practice Study of Epilepsy. Lancet 1995;346:140–144. PubMed