Oxcarbazepine versus phenytoin monotherapy for epilepsy

 

Abstract

Background

Worldwide, phenytoin is a commonly used antiepileptic drug. Oxcarbazepine is one of the newer antiepileptic drugs and has similar chemical properties to its parent compound carbamazepine. For the new drugs such as oxcarbazepine, it is important to know how they compare with standard treatments.

Objectives

To review the best evidence comparing oxcarbazepine and phenytoin when used as monotherapy in patients with epilepsy.

Search methods

We searched the Cochrane Epilepsy Group's Specialized Register (4 April 2008), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2008), and MEDLINE (1950 to March week 4, 2008). No language restrictions were imposed. We checked the reference lists of included studies for additional reports of relevant studies. We also contacted pharmaceutical companies to try and identify any unpublished studies.

Selection criteria

Randomized controlled trials in children or adults with epilepsy. Trials must have included a comparison of oxcarbazepine monotherapy with phenytoin monotherapy.

Data collection and analysis

This was an individual patient data review. Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information.
Outcomes were (a) time on allocated treatment; (b) time to achieve 6, 12 and 24-month remission; (c) time to first seizure post randomization; (d) quality of life measures if available. Clinical heterogeneity was assessed by reviewing differences across trials in characteristics of randomized patients, dosing protocols and trial design. Data were analysed on an intention to treat basis. Stratified logrank tests were used to obtain study-specific and overall estimates of hazard ratios (with 95% confidence intervals), where a HR > 1 indicates that an event is more likely on phenytoin.

Main results

Individual patient data were available for 480 patients from two trials, representing 100% of the patients recruited into the two trials that met our inclusion criteria. By convention, for the outcomes time to withdrawal of allocated treatment and time to first seizure a hazards ratio (HR) > 1 indicates a clinical advantage for oxcarbazepine and for time to 6 and 12-month remission a HR > 1 indicates a clinical advantage for phenytoin. The main overall results (HR, 95% confidence interval (CI)) were: (i) time to withdrawal of allocated treatment 1.64 (1.09 to 2.47), (ii) time to 6-month remission 0.89 (0.66 to 1.22), (iii) time to 12-month remission 0.92 (0.62 to 1.37), (iv) time to first seizure 1.07 (0.83 to 1.39). The overall results indicate that oxcarbazepine is significantly better than phenytoin for time to treatment withdrawal, but suggest no overall difference between oxcarbazepine and phenytoin for other outcomes. Results stratified by seizure type indicate no significant advantage for either drug for patients with generalized onset seizures, but a potentially important advantage in time to withdrawal for oxcarbazepine for patients with partial onset seizures: HR 1.92 (95% CI 1.17 to 3.16). The age distribution of adults classified as having generalized epilepsy suggests a significant number of patients may have had their epilepsy misclassified.

Authors' conclusions

For patients with partial onset seizures oxcarbazepine is significantly less likely to be withdrawn, but current data do not allow a statement as to whether oxcarbazepine is equivalent, superior or inferior to phenytoin in terms of seizure control. Guidelines recommend carbamazepine as a first line treatment for patients with partial onset seizures and more evidence is needed regarding the comparative effects of oxcarbazepine and carbamazepine to further inform policy. For patients with generalized onset tonic-clonic seizures, valproate is considered the first line standard treatment and the results of this review do not inform current treatment policy. Misclassification of patients' epilepsy type may have confounded the results of this review.

 

Plain language summary

Oxcarbazepine versus phenytoin monotherapy for epilepsy

Oxcarbazepine is less likely to fail than phenytoin when used as monotherapy for partial onset seizures.

Epilepsy is a disorder where recurrent seizures are caused by abnormal electrical discharges from the brain. Most seizures can be controlled by a single antiepileptic drug. The review of trials found that the new drug, oxcarbazepine, used as a single treatment, is more effective and tolerable than phenytoin, used as a single treatment, for patients with partial epilepsy.

 

摘要

背景

以Oxcarbazepine或Phenytoin作為癲癇的單一藥物治療之比較

Phenytoin是一種全球常用抗癲癇藥物。Oxcarbazepine是一種較新的抗癲癇藥物，具有和其母體化合物Carbamazepine相似的化學特性。對於Oxcarbazepine這樣的新藥，知道該藥物和標準治療之間的區別是相當重要的。

目標

這裏回顧了比較使用Carbamazepine和Valproate作為單一藥物治療癲癇的最佳證據。

搜尋策略

我們搜尋了Cochrane Epilepsy Group's Specialized Register(2005年12月)以及Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library，2005年第3期) 和MEDLINE (1966年2005年9月)。沒有設定任何語言限制。我們檢視了收錄試驗的參考文獻清單，以獲取額外的相關研究報告。我們也聯繫製藥公司，試圖找出尚未發表的研究。

選擇標準

選擇對患有癲癇的兒童或成年人所進行的隨機對照試驗。試驗必須包括對Oxcarbazepine單一療法和Phenytoin單一藥物治療的比較。

資料收集與分析

本研究是取自臨床試驗中個別病患資料的回顧。兩位回顧作者單獨評估試驗品質及摘錄數據。我們聯繫臨床試驗報告的作者以獲得更多資訊。治療成果的收集包括 (a) 持續使用治療藥物的時間；(b) 開始治療後至達成連續6、12與24個月緩解的時間； (c) 開始隨機分配治療後至首次癲癇發作的時間； (d) 生活品質的評估(如果可取得的話)。透過回顧各個臨床試驗所隨機選出的病患的特性、劑量調整的方式和試驗設計等方面，來評估它們的異質性。資料的分析採用intention to treat方法。我們使用stratified logrank tests來估計hazard ratios與95% confidence intervals，其中HR>1表示該事件較可能發生在使用Phenytoin時。

主要結論

我們從2個試驗中取得其中480位受試者的相關資料，佔所有2個符合我們選擇條件的試驗中所有病患的100%。會議決議對開始治療後至停止試驗用藥時間和開始隨機分配治療後至首次癲癇發作的時間等兩項治療成果而言，R>1表示使用Oxcarbazepine有臨床優勢；而對開始治療後至達成連續6及12個月緩解的時間來說，R>1表示使用phenytoin具有臨床優勢。各項治療成果的HR與95% confidence interval(CI)如下: (i) 開始治療後至停止試驗用藥時間為1.64 (1.09 – 2.47)；(ii) 開始治療後至達成連續6個月緩解的時間為0.89 (0.66 – 1.22)；(iii) 開始治療後至達成連續12個月緩解的時間為0.92 (0.62 – 1.37)；(iv) 開始隨機分配治療後至首次癲癇發作的時間為1.07 (0.83 – 1.39)。總體結果顯示，除了在開始治療後至停止試驗用藥時間方面，xcarbazepine明顯優於Phenytoin，在其他治療成果上兩者沒有出現整體差異。根據發作類型加以分析的結果指出，任何一種藥物對於全盤發作型癲癇症的患者沒有明顯優勢，但Oxcarbazepine對局部發作型癲癇患者的停藥時間方面，具有潛在重要優勢，其HR為1.92 (95% CI 1.17 – 3.16)。然而因有許多成人病患被歸類在全盤發作型癲癇症，這代表可能有相當數目的病患其癲癇分類並不正確。

作者結論

對局部發作型癲癇患者而言，Oxcarbazepine比起Phenytoin較不會被停藥，但現有的資料無法提供Oxcarbazepine與 Phenytoin在癲癇發作的控制上面，兩者療效優劣或相等的結論。目前的治療指引建議將Carbamazepine作為局部發作型癲癇病患的第一線治療，因此我們需要更多有關Oxcarbazepine與Carbamazepine相互比較的證據，來進一步提供治療指引的訂定。針對全盤型強直陣攣發作的病患，Valproate被認定是第一線的標準治療，但是本回顧的結果並未提供這方面的相關證據。 至於對癲癇類型的錯誤劃分可能會混淆本回顧的結果。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

當作為單一療來治療局部發作型癲癇時， Oxcarbazepine比起Phenytoin較不會被停藥。癲癇是一種由於大腦放電異常引起的反覆發作的疾病。多數的癲癇發作可以使用單一種抗癲癇藥物得到控制。本回顧發現新的抗癲癇藥物Oxcarbazepine，作為單一療法來治療局部發作型癲癇患者時，比Phenytoin的單一藥物治療可能更有效且耐受性更佳。