Abstract: Individual participant data were available for 480 out of a total of 517 participants (93%), from two out of three included trials. For remission outcomes, a HR of less than one indicated an advantage for phenytoin; and for first seizure and treatment failure outcomes, a HR of less than one indicated an advantage for oxcarbazepine. The results for time to treatment failure for any reason related to treatment showed a potential advantage of oxcarbazepine over phenytoin, but this was not statistically significant (pooled HR adjusted for epilepsy type: 0.78 95% CI 0.53 to 1.14, 476 participants, two trials, moderate-quality evidence). Our analysis showed that treatment failure due to adverse events occurred later on with oxcarbazepine than phenytoin (pooled HR for all participants: 0.22 (95% CI 0.10 to 0.51, 480 participants, two trials, high-quality evidence). Our analysis of time to treatment failure due to lack of efficacy showed no clear difference between the drugs (pooled HR for all participants: 1.17 (95% CI 0.31 to 4.35), 480 participants, two trials, moderate-quality evidence). We found no clear or statistically significant differences between drugs for any of the secondary outcomes of the review: time to first seizure post-randomisation (pooled HR adjusted for epilepsy type: 0.97 95% CI 0.75 to 1.26, 468 participants, two trials, moderate-quality evidence); time to 12-month remission (pooled HR adjusted for epilepsy type 1.04 95% CI 0.77 to 1.41, 468 participants, two trials, moderate-quality evidence) and time to six-month remission (pooled HR adjusted for epilepsy type: 1.06 95% CI 0.82 to 1.36, 468 participants, two trials, moderate-quality evidence). The most common adverse events reported in more than 10% of participants on either drug were somnolence (28% of total participants, with similar rates for both drugs), headache (15% of total participants, with similar rates for both drugs), dizziness (14.5% of total participants, reported by slightly more participants on phenytoin (18%) than oxcarbazepine (11%)) and gum hyperplasia (reported by substantially more participants on phenytoin (18%) than oxcarbazepine (2%)). The results of this review are applicable mainly to individuals with focal onset seizures; 70% of included individuals experienced seizures of this type at baseline. The two studies included in IPD meta-analysis were generally of good methodological quality but the design of the studies may have biased the results for the secondary outcomes (time to first seizure post-randomisation, time to six-month and 12-month remission) as seizure recurrence data were not collected following treatment failure or withdrawal from the study. In addition, misclassification of epilepsy type may have impacted on results, particularly for individuals with generalised onset seizures. High-quality evidence provided by this review indicates that treatment failure due to adverse events occurs significantly later with oxcarbazepine than phenytoin. For individuals with focal onset seizures, moderate-quality evidence suggests that oxcarbazepine may be superior to phenytoin in terms of treatment failure for any reason, seizure recurrence and seizure remission. Therefore, oxcarbazepine may be a preferable alternative treatment than phenytoin, particularly for individuals with focal onset seizures. The evidence in this review which relates to individuals with generalised onset seizures is of low quality and does not inform current treatment policy. We recommend that future trials should be designed to the highest quality possible with regards to choice of population, classification of seizure type, duration of follow-up (including continued follow-up after failure or withdrawal of randomised treatment), choice of outcomes and analysis, and presentation of results.

Plain-language summary: We assessed the evidence from three studies (specifically, randomised controlled trials) comparing oxcarbazepine with phenytoin. We were able to combine information for 480 people from two of the three trials. For the remaining 37 people from one trial, information was not available to use in this review. The evidence is current to 20 August 2018. Results The review found that people taking oxcarbazepine stop taking treatment because of side effects significantly later than people taking phenytoin. Our results also showed that people with focal onset seizures taking phenytoin may stop taking treatment for any reason earlier than people with focal onset seizures taking oxcarbazepine. The results also suggest that people with focal onset seizures taking oxcarbazepine may experience a repeat seizure later, and achieve freedom from seizures earlier, than people with focal onset seizures taking phenytoin. There was no clear difference between the drugs in terms of withdrawal from the treatment, seizure recurrence and seizure remission for individuals with generalised onset seizures. Quality of the evidence The two studies included in analysis were well designed but no information about seizures was recorded after people stopped taking their trial medication, which may have impacted on the results of the study. Most people (70%) included in the studies within this review had focal onset seizures, so the results are mainly relevant to people with this epilepsy type. Also up to 30% of the people in the trials used in our results may have been wrongly classified as having generalised seizures, which may have impacted on the results. For these reasons, we judged the quality of the evidence provided by this review to be of moderate quality for people with focal onset seizures, and low quality for people with generalised onset seizures. Conclusions For people with focal onset seizures, oxcarbazepine may be a preferable treatment to phenytoin, but more information is needed for people with generalised onset seizures to choose between these medications. We recommend that all future trials comparing these medications, or any other antiepileptic medications, should be designed using high-quality methods. Seizure types of people included in trials should also be classified very carefully.