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

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• 作者：Laura Bonnett ; MmathStat^a ; Catrin Tudur Smith ; PhD^a ; David Smith ; MD^c ; Paula Williamson ; PhD^a ; Prof David Chadwick ; MD^c ; Prof Anthony G Marson ; MD^b ; ^{a.g.marson@liverpool.ac.uk}
• 刊名：Lancet Neurology
• 出版年：2012
• 期刊代码：300_14744422
• 类别：med
• 出版时间：April, 2012
• 卷：11
• 期：4
• 页码：331-340
• 文件大小：431 K

摘要

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Summary

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路86, 95%CI 0路75-0路99), treatment history (taking non-SANAD antiepileptic drugs [other than those listed above] vs treatment naive, 1路27, 1路05-1路53), age (eg, older than 71 years vs 10 years or younger, 0路68, 0路51-0路91), total number of seizures (eg, four to 11 seizures vs two or fewer, 1路08, 1路05-1路11), electroencephalogram results (epileptiform abnormality vs normal, 1路26, 1路07-1路50), seizure type (eg, secondary generalised vs simple or complex partial only, 0路78, 0路66-0路91), site of onset (not localised vs temporal lobe, 1路25, 1路06-1路47), and treatment (lamotrigine vs carbamazepine, 0路76, 0路61-0路95). Significant factors for time to 12 months of remission were sex (male vs female, 1路19, 1路05-1路35), treatment history (taking a non-SANAD antiepileptic drug vs treatment naive, 0路64, 0路52-0路78), age (eg, older than 71 years vs 10 years or younger, 1路60, 1路26-2路03), time from first seizure (60-239 months vs 鈮? months, 1路14, 1路01-1路29; >240 months vs 鈮? months, 1路39, 1路04-1路86), neurological insult (present vs absent, 0路75, 0路61-0路93), total number of seizures before randomisation (eg, four to 11 vs two or fewer, 0路87, 0路85-0路90), and treatment (gabapentin vs carbamazepine, 0路71, 0路59-0路86; topiramate vs carbamazepine, 0路81, 0路68-0路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).