Eugen Trinka1, Wan Tsong2, Sydney Toupin3, Anna Patten4, Katy Wilson5, Jaana Isojarvi6, Daniel James7. 1. FRCP Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Harrerstrasse 79, A-5020, Salzburg, Austria. Electronic address: eugen@trinka.at. 2. Formerly Eisai Inc, 100 Tice Blvd, Woodcliff Lake, NJ, 07677, United States. Electronic address: wtsong.esi@gmail.com. 3. Quantics Biostatistics, Exchange Tower, 19 Canning Street Fourth Floor, Edinburgh, EH3 8EG, United Kingdom. Electronic address: sydney.toupin@outlook.com. 4. Eisai Ltd. European Knowledge Centre, Mosquito Way, Hatfield, Hertfordshire, AL10 9SN, United Kingdom. Electronic address: Anna_Patten@eisai.net. 5. York Health Economics Consortium, Enterprise House, Innovation Way, University of York, York, YO10 5NQ, United Kingdom. Electronic address: katy.wilson@york.ac.uk. 6. York Health Economics Consortium, Enterprise House, Innovation Way, University of York, York, YO10 5NQ, United Kingdom. Electronic address: jaana.isojarvi@york.ac.uk. 7. Quantics Biostatistics, Exchange Tower, 19 Canning Street Fourth Floor, Edinburgh, EH3 8EG, United Kingdom. Electronic address: Daniel.James@quantics.co.uk.
Abstract
PURPOSE: To date, there has not been a single randomized controlled trial (RCT) conducted to directly compare the efficacy and safety of perampanel to brivaracetam in the adjunctive treatment of focal-onset seizures. This study makes these comparisons through the use of indirect treatment comparison (ITC) methods. METHODS: A systematic review was conducted to identify RCTs that evaluated either one of perampanel or brivaracetam in the treatment of patients with focal-onset seizures. The Bucher ITC method was then used to compare efficacy and safety outcomes between perampanel and brivaracetam. Additional subgroup analyses, by levetiracetam usage (prior or concomitant), were conducted. RESULTS: Eight RCTs (four comparing perampanel to placebo, four comparing brivaracetam to placebo) were included in the ITC. For patients taking concomitant levetiracetam, perampanel showed a significantly better responder rate compared to brivaracetam [relative risk (RR) and 95 % confidence interval (CI): 2.62 (1.15, 5.99)]. For patients who had previously, or never, taken levetiracetam, there was no difference in the responder rate. In the overall population, both perampanel and brivaracetam were more effective than placebo in terms of responder rate, seizure freedom, and secondarily generalized tonic-clonic seizure responder rate; however, for these outcomes, no evidence of a difference between perampanel and brivaracetam was found. Patients taking brivaracetam showed significantly less dizziness compared to patients taking perampanel. No differences for any other safety outcome were found. CONCLUSION: Perampanel and brivaracetam are effective for the adjunctive treatment of focal-onset seizures and display similar adverse event profiles. Perampanel demonstrated an improved focal-onset seizure responder rate compared to brivaracetam in patients taking concomitant levetiracetam. This may be due to the similarity in the mechanism of action between brivaracetam and levetiracetam.
PURPOSE: To date, there has not been a single randomized controlled trial (RCT) conducted to directly compare the efficacy and safety of perampanel to brivaracetam in the adjunctive treatment of focal-onset seizures. This study makes these comparisons through the use of indirect treatment comparison (ITC) methods. METHODS: A systematic review was conducted to identify RCTs that evaluated either one of perampanel or brivaracetam in the treatment of patients with focal-onset seizures. The Bucher ITC method was then used to compare efficacy and safety outcomes between perampanel and brivaracetam. Additional subgroup analyses, by levetiracetam usage (prior or concomitant), were conducted. RESULTS: Eight RCTs (four comparing perampanel to placebo, four comparing brivaracetam to placebo) were included in the ITC. For patients taking concomitant levetiracetam, perampanel showed a significantly better responder rate compared to brivaracetam [relative risk (RR) and 95 % confidence interval (CI): 2.62 (1.15, 5.99)]. For patients who had previously, or never, taken levetiracetam, there was no difference in the responder rate. In the overall population, both perampanel and brivaracetam were more effective than placebo in terms of responder rate, seizure freedom, and secondarily generalized tonic-clonic seizure responder rate; however, for these outcomes, no evidence of a difference between perampanel and brivaracetam was found. Patients taking brivaracetam showed significantly less dizziness compared to patients taking perampanel. No differences for any other safety outcome were found. CONCLUSION:Perampanel and brivaracetam are effective for the adjunctive treatment of focal-onset seizures and display similar adverse event profiles. Perampanel demonstrated an improved focal-onset seizure responder rate compared to brivaracetam in patients taking concomitant levetiracetam. This may be due to the similarity in the mechanism of action between brivaracetam and levetiracetam.