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Comparative Long-Term Effectiveness of a Monotherapy with Five Antiepileptic Drugs for Focal Epilepsy in Adult Patients: A Prospective Cohort Study.

Zeng QY, Fan TT, Zhu P, He RQ, Bao YX, Zheng RY, Xu HQ - PLoS ONE (2015)

Bottom Line: For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs.LTG was significantly better than CBZ (1.44 [1.15-1.82]) and OXC (LTG vs.OXC, 0.76 [0.63-0.93]); OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40]).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, P.R. China.

ABSTRACT

Objective: To evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs) for monotherapy of adult patients with focal epilepsy in routine clinical practice.

Methods: Adult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ), valproate (VPA), lamotrigine (LTG), topiramate (TPM), or oxcarbazepine (OXC) as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD), were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure.

Results: This study included 654 patients: CBZ (n=125), VPA (n=151), LTG (n=135), TPM (n=76), and OXC (n=167). The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]); TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74]), and OXC was better than VPA (0.86 [0.78-0.96]). After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82]) and OXC (LTG vs. OXC, 0.76 [0.63-0.93]); OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40]).

Conclusion: LTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not.

No MeSH data available.


Related in: MedlinePlus

Study flow diagram.apatients missing outcome data: patients who did not complete effectiveness/safety assessment at least for one time after being prescribed with AEDs; bpatients with poor compliance: patients who discontinued AEDs by themselves with a single discontinuing time less than two weeks but the accumulated one >20% of the total observational period. Patients who did not take AEDs according to the prescribed doses and the doses they took were also lower than the initial target doses (ITDs); cLost: lost to follow-up before treatment failure; dAEs: treatment failure because of adverse events; eLE: treatment failure because of lack of efficacy; fOthers: other reasons leading to treatment failure: pregnancy, poor economic conditions, non-compliance and deaths related to seizures; gContinue: continue treatment on AEDs; hLost: including one person who died without relation to AED medication; CBZ: carbamazepine; VPA: valproate; LTG: lamotrigine; TPM: topiramate; OXC: oxcarbazepine.
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pone.0131566.g001: Study flow diagram.apatients missing outcome data: patients who did not complete effectiveness/safety assessment at least for one time after being prescribed with AEDs; bpatients with poor compliance: patients who discontinued AEDs by themselves with a single discontinuing time less than two weeks but the accumulated one >20% of the total observational period. Patients who did not take AEDs according to the prescribed doses and the doses they took were also lower than the initial target doses (ITDs); cLost: lost to follow-up before treatment failure; dAEs: treatment failure because of adverse events; eLE: treatment failure because of lack of efficacy; fOthers: other reasons leading to treatment failure: pregnancy, poor economic conditions, non-compliance and deaths related to seizures; gContinue: continue treatment on AEDs; hLost: including one person who died without relation to AED medication; CBZ: carbamazepine; VPA: valproate; LTG: lamotrigine; TPM: topiramate; OXC: oxcarbazepine.

Mentions: Intention-to-treat (ITT) analysis was used to analyze the primary and tolerability outcome, and primary outcome was also analyzed using per-protocol (PP) analysis whose population was defined as the remaining one after excluding patients who were lost to follow-up before treatment failure in ITT analysis(The analysis population is shown in Fig 1). The censored patients in Kaplan-Meier analysis and Cox regression were defined as follows: patients who were lost to follow-up, or died but whose death were not related to AED medication before their outcomes (treatment failure, seizure remission, and first seizure) were observed and the outcomes were still not observed at the last visit of this study (for primary and secondary outcomes) or when treatment failure occurred (only for secondary outcomes). The statistical significance level was set at P = 0.05 using two-sided tests.


Comparative Long-Term Effectiveness of a Monotherapy with Five Antiepileptic Drugs for Focal Epilepsy in Adult Patients: A Prospective Cohort Study.

Zeng QY, Fan TT, Zhu P, He RQ, Bao YX, Zheng RY, Xu HQ - PLoS ONE (2015)

Study flow diagram.apatients missing outcome data: patients who did not complete effectiveness/safety assessment at least for one time after being prescribed with AEDs; bpatients with poor compliance: patients who discontinued AEDs by themselves with a single discontinuing time less than two weeks but the accumulated one >20% of the total observational period. Patients who did not take AEDs according to the prescribed doses and the doses they took were also lower than the initial target doses (ITDs); cLost: lost to follow-up before treatment failure; dAEs: treatment failure because of adverse events; eLE: treatment failure because of lack of efficacy; fOthers: other reasons leading to treatment failure: pregnancy, poor economic conditions, non-compliance and deaths related to seizures; gContinue: continue treatment on AEDs; hLost: including one person who died without relation to AED medication; CBZ: carbamazepine; VPA: valproate; LTG: lamotrigine; TPM: topiramate; OXC: oxcarbazepine.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4493091&req=5

pone.0131566.g001: Study flow diagram.apatients missing outcome data: patients who did not complete effectiveness/safety assessment at least for one time after being prescribed with AEDs; bpatients with poor compliance: patients who discontinued AEDs by themselves with a single discontinuing time less than two weeks but the accumulated one >20% of the total observational period. Patients who did not take AEDs according to the prescribed doses and the doses they took were also lower than the initial target doses (ITDs); cLost: lost to follow-up before treatment failure; dAEs: treatment failure because of adverse events; eLE: treatment failure because of lack of efficacy; fOthers: other reasons leading to treatment failure: pregnancy, poor economic conditions, non-compliance and deaths related to seizures; gContinue: continue treatment on AEDs; hLost: including one person who died without relation to AED medication; CBZ: carbamazepine; VPA: valproate; LTG: lamotrigine; TPM: topiramate; OXC: oxcarbazepine.
Mentions: Intention-to-treat (ITT) analysis was used to analyze the primary and tolerability outcome, and primary outcome was also analyzed using per-protocol (PP) analysis whose population was defined as the remaining one after excluding patients who were lost to follow-up before treatment failure in ITT analysis(The analysis population is shown in Fig 1). The censored patients in Kaplan-Meier analysis and Cox regression were defined as follows: patients who were lost to follow-up, or died but whose death were not related to AED medication before their outcomes (treatment failure, seizure remission, and first seizure) were observed and the outcomes were still not observed at the last visit of this study (for primary and secondary outcomes) or when treatment failure occurred (only for secondary outcomes). The statistical significance level was set at P = 0.05 using two-sided tests.

Bottom Line: For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs.LTG was significantly better than CBZ (1.44 [1.15-1.82]) and OXC (LTG vs.OXC, 0.76 [0.63-0.93]); OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40]).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, P.R. China.

ABSTRACT

Objective: To evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs) for monotherapy of adult patients with focal epilepsy in routine clinical practice.

Methods: Adult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ), valproate (VPA), lamotrigine (LTG), topiramate (TPM), or oxcarbazepine (OXC) as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD), were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure.

Results: This study included 654 patients: CBZ (n=125), VPA (n=151), LTG (n=135), TPM (n=76), and OXC (n=167). The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]); TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74]), and OXC was better than VPA (0.86 [0.78-0.96]). After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82]) and OXC (LTG vs. OXC, 0.76 [0.63-0.93]); OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40]).

Conclusion: LTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not.

No MeSH data available.


Related in: MedlinePlus