Seizure recurrence and remission after switching antiepileptic drugs.
Seizure recurrence and remission after switching antiepileptic drugs.
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DOI：
10.1111/j.1528-1167.2012.03652.x
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发表时间：
2013-01
期刊：
影响因子：
5.6
通讯作者：
Sperling MR
中科院分区：
文献类型：
--
作者：
Wang SP;Mintzer S;Skidmore CT;Zhan T;Stuckert E;Nei M;Sperling MR
在接受系列抗癫痫药物试验的患者中进行的癫痫发作结局研究均未得到控制，未考虑可能混淆药物作用阐明的疾病状态自发变化。此外，尽管在临床实践中常规进行抗癫痫药物转换，但从未有研究观察过无癫痫患者转换抗癫痫药物后的结局。我们的目标是使用匹配的病例队列设计来解决这两个问题。我们随访了服用苯妥英钠或卡马西平单药治疗局灶性癫痫的患者，这些患者正在交叉使用一种新的药物，作为抗惊厥治疗代谢影响研究的一部分。许多药物没有副作用，但由于副作用或对长期不良后果的担忧而被转换。每例患者均与两名癫痫发作状态相同的对照组相匹配，这两名对照组均接受抗惊厥药单药治疗，且未转换药物。随后6个月内无癫痫发作是主要终点。其中病例组43例，对照组86例。23例病例患者在使用旧药物时无癫痫发作; 5例（21.7%）在药物转换后癫痫发作复发，而46例匹配对照中有2例（4.3%）。20例患者在使用旧药物时发生癫痫发作; 6例（30%）在药物转换后缓解，而8/40例匹配对照（20%）。两组在基线时抗惊厥药物治疗失败的数量不同，这是预后的最重要因素。经过统计学调整后，如果改用新药，无癫痫患者癫痫复发的几率高出6.53倍（95% CI 1.02 - 61.19; p=0.06）。如果非无癫痫发作患者继续使用相同药物，其缓解几率是转换药物的1.66倍，但不显著（95% CI 0.36 - 8.42; p=0.532）。剂量变化、药物机制和无不良反应持续时间均对结果无任何影响。虽然绝大多数无复发的患者在改用另一种药物时仍然如此，但约有六分之一的患者因这种变化而复发。相反，我们的研究设计提供了第一个证据，表明耐药患者的大多数改善可能是由于自发缓解，而不是新药的引入。这些发现对于比较抗癫痫药物疗效的两种竞争模型具有相互矛盾的影响，这需要进一步的研究来阐述。
Studies of seizure outcome in patients undergoing serial antiepileptic drug trials have all been uncontrolled, with no account made for the spontaneous changes in disease state that could confound the elucidation of drug effects. In addition, no study has ever looked at outcome following antiepileptic drug switch in seizure-free patients, despite the fact that this is done routinely in clinical practice. We aimed to address both of these issues using a matched case-cohort design. We followed patients taking phenytoin or carbamazepine in monotherapy for focal epilepsy who were being crossed over to a newer agent as part of studies on the metabolic effects of anticonvulsant therapy. Many had been seizure-free but were being switched nonetheless due to side effects or concerns about long-term adverse consequences. Each patient was matched with two controls of the same seizure status who were on anticonvulsant monotherapy and whose drug was not switched. Seizure freedom over the ensuing 6 months was the primary endpoint. There were 43 cases and 86 matched controls. Twenty-three case patients had been seizure-free on their old drug; 5 (21.7%) had seizure recurrence after drug switch compared to 2/46 matched controls (4.3%). Twenty case patients were having seizures on their old drug; 6 (30%) entered remission after drug switch, compared to 8/40 matched controls (20%). The two groups differed at baseline in number of anticonvulsants previously failed, which was the most important factor for prognosis. After statistical adjustment to account for this, seizure-free patients had 6.53 times higher odds of seizure recurrence if switched to a new drug (95% CI 1.02 – 61.19; p=0.06). Non-seizure-free patients had 1.66 times higher odds of remission if they remained on the same drug compared to switching, though this was not significant (95% CI 0.36 – 8.42; p=0.532). Neither dose changes, nor drug mechanism, nor duration of seizure-freedom had any bearing upon the results. While the large majority of seizure-free patients remain so when switched to another agent, about one-sixth have a recurrence attributable to the change. Conversely, our study design provides the first evidence to suggest that most improvements in drug-resistant patients are likely due to spontaneous remissions, not new drug introductions. These findings have conflicting implications for two competing models of comparative antiepileptic drug efficacy, which will require further study to elaborate.
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影响因子：
168.9
作者：
Marson, Anthony G.;Al-Kharusi, Asya M.;Alwaidh, Muna;Appleton, Richard;Baker, Gus A.;Chadwick, David W.;Cramp, Celia;Cockerell, Oliver C.;Cooper, Paul N.;Doughty, Julie;Eaton, Barbara;Gamble, Carrot;Goulding, Peter J.;Howell, Stephen J. L.;Hughes, Adrian;Jackson, Margaret;Jacoby, Ann;Kellett, Mark;Lawson, Geoffrey R.;Leach, John Paul;Nicolaides, Paola;Roberts, Richard;Shackley, Phil;Shen, Jing;Smith, David F.;Smith, Philip E. M.;Smith, Catrin Tudur;Vanoli, Alessandra;Williamson, Paula R.
通讯作者：
Williamson, Paula R.
影响因子：
11.2
作者：
Callaghan, Brian C.;Anand, Kishlay;French, Jacqueline A.
通讯作者：
French, Jacqueline A.
影响因子：
5.6
作者：
McLean, MJ;Bukhari, AA;Wamil, AW
通讯作者：
Wamil, AW
影响因子：
3.5
作者：
Privitera, MD;Brodie, MJ;Wang, S
通讯作者：
Wang, S
影响因子：
11.2
作者：
Mintzer, Scott;Skidmore, Christopher T.;Sperling, Michael R.
通讯作者：
Sperling, Michael R.