Dataset Information

Comparative efficacy and tolerability of anti-epileptic drugs for refractory focal epilepsy: systematic review and network meta-analysis reveals the need for long term comparator trials.

ABSTRACT:

Aims

To evaluate the comparative efficacy (50% reduction in seizure frequency) and tolerability (premature withdrawal due to adverse events) of anti-epileptic drugs (AEDs) for refractory epilepsy.

Methods

We searched Cochrane Central Register of Controlled Trials (Cochrane Library 2009, issue 2) including Epilepsy Group's specialized register, MEDLINE (1950 to March 2009), EMBASE (1980 to March 2009), and Current Contents Connect (1998 to March 2009) to conduct a systematic review of published studies, developed a treatment network and undertook a network meta-analysis.

Results

Forty-three eligible trials with 6346 patients and 12 interventions, including placebo, contributed to the analysis. Only three direct drug comparator trials were identified, the remaining 40 trials being placebo-controlled. Conventional random-effects meta-analysis indicated all drugs were superior in efficacy to placebo (overall odds ratio (OR] 3.78, 95% CI 3.14, 4.55) but did not permit firm distinction between drugs on the basis of the efficacy or tolerability. A Bayesian network meta-analysis prioritized oxcarbazepine, topiramate and pregabalin on the basis of short term efficacy. However, sodium valproate, levetiracetam, gabapentin and vigabatrin were prioritized on the basis of short-term efficacy and tolerability, with the caveat that vigabatrin is recognized as being associated with serious visual disturbance with chronic use.

Conclusion

Of the wide range of AEDs licensed for the treatment of refractory epilepsy, sodium valproate, levetiracetam and gabapentin demonstrated the best balance of efficacy and tolerability. Until regulators mandate greater use of active comparator trials with longer term follow-up, network meta-analysis provides the only available means to quantify these clinically important parameters.

SUBMITTER: Bodalia PN

PROVIDER: S-EPMC3853525 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Publications

Comparative efficacy and tolerability of anti-epileptic drugs for refractory focal epilepsy: systematic review and network meta-analysis reveals the need for long term comparator trials.

Bodalia Pritesh N PN Grosso Anthony M AM Sofat Reecha R Macallister Raymond J RJ Smeeth Liam L Dhillon Soraya S Casas Juan-Pablo JP Wonderling David D Hingorani Aroon D AD

British journal of clinical pharmacology 20131101 5

<h4>Aims</h4>To evaluate the comparative efficacy (50% reduction in seizure frequency) and tolerability (premature withdrawal due to adverse events) of anti-epileptic drugs (AEDs) for refractory epilepsy.<h4>Methods</h4>We searched Cochrane Central Register of Controlled Trials (Cochrane Library 2009, issue 2) including Epilepsy Group's specialized register, MEDLINE (1950 to March 2009), EMBASE (1980 to March 2009), and Current Contents Connect (1998 to March 2009) to conduct a systematic review ...[more]

PMID: 23351090

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Project description:ObjectiveAmong standard treatments for infantile spasms, adrenocorticotropic hormone (ACTH) is reported as the best treatment, but ACTH is ineffective in one-half of the patients. To establish precision medicine, we examined pharmacoresistance of focal epileptic spasms (ES), generalized ES, and generalized ES combined with focal seizures, diagnosed based on the revised seizure classification of ILAE in 2017.MethodsWe conducted a retrospective nationwide study in Japan on the long-term seizure outcome of ES. Long-term seizure outcome was evaluated by seizure-free rate, seizure-free period, and Kaplan-Meier curve. Seizure-free was defined as seizure control for longer than 2 months.ResultsFrom the medical history of 501 patients, 325 patients had generalized ES only (GES group) at the start of the first treatment, 125 patients had generalized ES after focal seizure onset (FS-GES group), seven patients had focal ES after focal seizure onset (FS-FES group), and 24 patients had generalized ES combined with focal seizures after focal seizure onset (FS-GES + FS group). Seizure-free period of ES (generalized ES and focal ES) [mean (95% confidence interval)] was 2.7 (0.0-5.4) months in GES group, 1.1 (0.1-2.2) months in FS-GES group, 1.0 (0.2-1.9) months in FS-GES + FS group, and 0.1 (-0.2-0.5) months in FS-FES group. Seizure-free rate, seizure-free period, and Kaplan-Meier curve of generalized ES were almost the same in GES group and FS-GES group, with characteristics of superior response to ACTH. Mean seizure-free period of generalized ES combined with focal seizures was significantly shorter in FS-GES + FS group than in GES group. Mean seizure-free period of focal ES in FS-FES group was extremely short with exceedingly early relapse.SignificancePharmacoresistance was different in generalized ES, focal ES, and generalized ES combined with focal seizures. ES with focal features or with focal seizures may have focal lesions, thus consider surgical options earlier in the course.

Dataset Information

Comparative efficacy and tolerability of anti-epileptic drugs for refractory focal epilepsy: systematic review and network meta-analysis reveals the need for long term comparator trials.

Aims

Methods

Results

Conclusion

Publications

Comparative efficacy and tolerability of anti-epileptic drugs for refractory focal epilepsy: systematic review and network meta-analysis reveals the need for long term comparator trials.

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