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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
Open accessAbstract
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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: National Institute for Health Research (UK).
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There is no evidence to suggest that one syndrome or cause responds better to one specific treatment than to another.
“Although focal epilepsies can be classified according to site of seizure onset and cause, there is no evidence to suggest that one syndrome or cause responds better to one specific treatment than to another.8”
From The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial (2021) · cites this paper as [8]
The Interpretation (page unavailable) says that predictors of seizure control have not yet been established, which is consistent with the claim’s general caution. The Prognostic modelling section classifies focal epilepsy by site of onset, but our copy does not establish that no syndrome or cause responds preferentially to a particular treatment. (LLM, conf=0.72)
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Marson, A., Burnside, G., Appleton, R., Smith, D., Leach, J. P., Sills, G., Tudur-Smith, C., Plumpton, C., Hughes, D. A., Williamson, P., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00247-6 · Cited by 208
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Metadata
- Authors
- Bonnett, L., Smith, C. T., Smith, D., Williamson, P., Chadwick, D., & Marson, A. G.
- Affiliations
- University of Liverpool (GB)
- Walton Centre (GB)
- Corresponding author
- Marson, Anthony G
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 11
- Issue
- 4
- Pages
- 331-340
- ISSN
- 1474-4422 (ISSN-L)
- OpenAlex
- W2129184868
- Cited by
- 69
- References
- 2
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 14 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 7 · 2016: 9 · 2015: 4 · 2014: 2 · 2013: 7 · 2012: 4
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Lancet Neurology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute for Health Research (NIHR) (RP-PG-0606-1062)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
- Keywords
- focal epilepsy, prognostic factors, treatment failure, seizure remission, antiepileptic drugs, carbamazepine, lamotrigine, gabapentin, oxcarbazepine, topiramate, seizure control, seizure types, temporal lobe epilepsy, seizure frequency, sex differences, adverse events, treatment-naive patients
- MeSH terms
- Gabapentin, Lamotrigine, Topiramate, Oxcarbazepine, Adolescent, Adult, Aged, Amines, Anticonvulsants, Carbamazepine, Child, Cyclohexanecarboxylic Acids, Epilepsies, Partial, Female, Fructose, gamma-Aminobutyric Acid, Humans, Male, Middle Aged, Prognosis, Time Factors, Triazines, Treatment Failure, Disease-Free Survival, Young Adult
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