title: 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.
abstract: BACKGROUND
  Epilepsy is a heterogeneous disorder, with outcomes ranging from immediate remission after taking a first antiepileptic drug to frequent unremitting seizures with multiple treatment failures. Few prognostic models enable prediction of outcome; we therefore aimed to use data from the SANAD study to predict outcome overall and for patients receiving specific treatments.
  
  
  METHODS
  The SANAD study was a randomised controlled trial in which standard antiepileptic drugs were compared with new treatments. Arm A included patients for whom carbamazepine was considered the first-line treatment, most of whom were newly diagnosed with focal epilepsy. Patients were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Outcomes were time to treatment failure overall, because of inadequate seizure control, and because of adverse events, and time to 12 months of remission from seizures. In this post-hoc study we used regression multivariable modelling to investigate how clinical factors affect the probability of treatment failure and the probability of achieving 12 months of remission.
  
  
  RESULTS
  For time to treatment failure, we identified several significant risk factors: sex (male vs female, hazard ratio [HR] 0·86, 95% CI 0·75-0·99), treatment history (taking non-SANAD antiepileptic drugs [other than those listed above] vs treatment naive, 1·27, 1·05-1·53), age (eg, older than 71 years vs 10 years or younger, 0·68, 0·51-0·91), total number of seizures (eg, four to 11 seizures vs two or fewer, 1·08, 1·05-1·11), electroencephalogram results (epileptiform abnormality vs normal, 1·26, 1·07-1·50), seizure type (eg, secondary generalised vs simple or complex partial only, 0·78, 0·66-0·91), site of onset (not localised vs temporal lobe, 1·25, 1·06-1·47), and treatment (lamotrigine vs carbamazepine, 0·76, 0·61-0·95). Significant factors for time to 12 months of remission were sex (male vs female, 1·19, 1·05-1·35), treatment history (taking a non-SANAD antiepileptic drug vs treatment naive, 0·64, 0·52-0·78), age (eg, older than 71 years vs 10 years or younger, 1·60, 1·26-2·03), time from first seizure (60-239 months vs ≥2 months, 1·14, 1·01-1·29; >240 months vs ≤2 months, 1·39, 1·04-1·86), neurological insult (present vs absent, 0·75, 0·61-0·93), total number of seizures before randomisation (eg, four to 11 vs two or fewer, 0·87, 0·85-0·90), and treatment (gabapentin vs carbamazepine, 0·71, 0·59-0·86; topiramate vs carbamazepine, 0·81, 0·68-0·98).
  
  
  CONCLUSIONS
  We present a thorough investigation of prognostic factors from a large randomised controlled trial in patients starting antiepileptic monotherapy. If validated, our models could aid in individual patient risk stratification and the design and analysis of epilepsy trials.
  
  
  BACKGROUND
  National Institute for Health Research (UK).
authors.affiliation: Department of Biostatistics, University of Liverpool, Liverpool, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Bonnett
authors.forename: Catrin Tudur
authors.initials: CT
authors.lastname: Smith
authors.forename: David
authors.initials: D
authors.lastname: Smith
authors.forename: Paula
authors.initials: P
authors.lastname: Williamson
authors.forename: David
authors.initials: D
authors.lastname: Chadwick
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Marson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000588:Amines / Q000009:adverse effects / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002220:Carbamazepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D002648:Child; D003509:Cyclohexanecarboxylic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077206:Gabapentin; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D000078330:Oxcarbazepine; D011379:Prognosis; D013997:Time Factors; D000077236:Topiramate; D017211:Treatment Failure; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000077213:Lamotrigine; D000078330:Oxcarbazepine